bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease
Authors: Fields Melanie E. , Mirro Amy E. , Guilliams Kristin P. , Binkley Michael M. , Gil Diaz Luisa , Tan Jessica , Fellah Slim , Eldeniz Cihat , Chen Yasheng , Ford Andria L. , Shimony Joshua S. , King Allison A. , An Hongyu , Smyser Christopher D. , Lee Jin‐Moo
Published: September 2020

Objective

Children with sickle cell disease (SCD) experience cognitive deficits even when unaffected by stroke. Using functional connectivity magnetic resonance imaging (MRI) as a potential biomarker of cognitive function, we tested our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, indicated by elevated oxygen extraction fraction, would have the lowest connectivity.

Methods

We prospectively obtained brain MRIs and cognitive testing in healthy controls and children with SCD.

Results

We analyzed data from 60 participants (20 controls and 40 with sickle cell disease). There was no difference in global cognition or cognitive subdomains between cohorts. However, we found decreased functional connectivity within the sensory‐motor, lateral sensory‐motor, auditory, salience, and subcortical networks in participants with SCD compared with controls. Further, as white matter oxygen extraction fraction increased, connectivity within the visual (p = 0.008, parameter estimate = −0.760 [95% CI = −1.297, −0.224]), default mode (p = 0.012, parameter estimate = −0.417 [95% CI = −0.731, −0.104]), and cingulo‐opercular (p = 0.009, parameter estimate = −0.883 [95% CI = −1.517, −0.250]) networks decreased.

Interpretation

We conclude that there is diminished functional connectivity within these anatomically contiguous networks in children with SCD compared with controls, even when differences are not seen with cognitive testing. Increased white matter oxygen extraction fraction was associated with decreased connectivity in select networks. These data suggest that elevated oxygen extraction fraction and disrupted functional connectivity are potentially presymptomatic neuroimaging biomarkers for cognitive decline in SCD. ANN NEUROL 2020;88:995–1008
Tridentate benzimidazole ligand and its metal complexes: Synthesis, characterization, photo physical and sensor properties
Authors: Kırpık Hilal , Kose Muhammet , Ballı Julide Nacaroğlu
Published: September 2020

A tridentate bisbenzimidazole‐pyridine ligand (L‐C5) with two pentyl side‐units and its metal complexes with Mn2+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+ metal ions were synthesized and characterized. The structures of the ligand (L‐C5) and its five coordinate [Mn(L‐C5)Cl2] were elucidated by single crystal X‐ray diffraction studies. The absorption and photoluminescence properties of the compounds were studied in solution media. The ligand is highly fluorescent, and binding of the metal ions to the ligand has caused significant changes in the emission band (shift or quenching). Moreover, the effect of aggregation on UV–Vis. absorption and emission properties was examined in MeOH‐water mixtures. The ligand was found to show aggregation‐induced quenching in the MeOH‐water mixture. The ligand was also screened for its colorimetric and fluorometric sensing ability of several metal ions [Na+, K+, Mg2+, Al3+, Ca2+, Mn2+, Fe2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+, Hg2+, Pb2+]. The ligand showed selective sensing ability towards Zn2+, and the limit of detection was calculated as 3.09 × 10−7 m. The ligand also showed a distinguishable color change in the presence of Fe2+ under daylight.
Extension‐dominated improved dispersive mixing in single‐screw extrusion. Part 1: Computational and experimental validation
Authors: Pandey Vivek , Maia João M.
Published: September 2020

Extensional mixing elements (EMEs) were previously developed for twin‐screw extruders (TSEs) to incorporate extensional flows through stationary single‐plane or double‐plane hyperbolic convergence–divergence channels. In Part 1 of this work, the EME concept is extended to single‐screw extruders (SSEs), which are known for their good pumping characteristics but limited dispersive mixing capability, to enhance the latter. Flow simulations are performed to optimize the EME design for SSE. Experimental validations are performed on immiscible polymer blends (varying viscosity ratio) and nanocomposites. Morphological results show tremendous improvement in mixing capability of SSE when equipped with EME without significant throughput and pressure drop penalties. Rheological and crystallinity studies are observed to be in line with the morphological analysis. Morphological and mechanical results are benchmarked with TSE operations in Part 2 of this work.
Periodic solutions for coupled neutral Rayleigh system
Authors: Du Bo
Published: September 2020

In this paper, we study a kind of coupled neutral Rayleigh system (CNRS). Based on graph theory and coincidence degree theory, some new sufficient conditions on the existence of periodic solutions for the CNRS are established. The methods of the present paper are markedly different from the existing ones.
Optimization of Alcohol Dehydrogenase for Industrial Scale Oxidation of Lactols
Authors: Bartsch Sebastian , Brummund Jan , Köpke Sabrina , Straatman Harrie , Vogel Andreas , Schürmann Martin
Published: September 2020

Alcohol dehydrogenases (ADH) are widely used to enantioselectively reduce ketones to chiral alcohols, but their application in industrial scale oxidations is rare. Reasons are the need for an NAD(P)+ cofactor regeneration system, often low performance in oxidative reactions and the limited substrate scope of ADHs. ADHA from Candida magnoliae DSMZ 70638 is identified to efficiently catalyze the regio‐selective hydroxy‐lactone oxidations to hydroxy‐lactones. Hydroxy‐lactones are common intermediates in industrial processes to cholesterol lowering (va)statin drugs. A biocatalytic aliphatic hydroxy‐lactone oxidation process is developed using pure oxygen as oxidant reaching volumetric productivities of up to 12 g L−1 h−1, product concentrations of almost 50 g L−1 and 95% reaction yield. For co‐factor recycling a previously engineered, water‐forming NAD(P)H‐oxidase from Streptococcus mutans is used. The process is scaled up to industrial pilot plant scale and it could be demonstrated that ADH catalyzed oxidations can be developed to efficient and safe processes. However, the ADHA wild‐type enzyme is not productive enough in chlorolactol oxidation. Therefore, enzyme engineering and multi‐parameter screening is successfully applied to optimize the enzyme for the target reaction. The optimized ADHA variant shows a 17‐fold higher oxidative activity, a 26°C increased stability and is applied to develop an efficient chlorolactol oxidation process.
Does financial development influence fertility rate in South Asian economies? An empirical insight
Authors: Sethi Narayan , Jena Nihar Ranjan , Loganathan Nanthakumar
Published: September 2020

The purpose of this paper is to empirically investigate the effect of financial development on fertility rate along with other major indicators in select South Asian economies over the period 1990–2016. The study uses various statistical techniques such as Johansen–Fisher panel co‐integration approaches are employed to examine the long‐run relationship among the variables and for statistically quantile regression is employed. The study finds that the variables under consideration are found to be cointegrated, that is, they are found to be having a long‐term relationship. By using three different measures of financial sector development, it is also observed that financial sector development has invariably led to a declining fertility rate in the south Asian region during the study period.
Staging of T2 and T3 nasopharyngeal carcinoma: Proposed modifications for improving the current AJCC staging system
Authors: Cui Chunyan , Li Haojiang , Ma Huali , Dong Annan , Xie Fei , Liang Shaobo , Li Li , Zhou Jian , Xie Chuanbo , Yan Yue , Liu Lizhi
Published: September 2020

Objectives

We aimed to reconstitute T2 and T3 stage classification in nasopharyngeal carcinoma (NPC) cases and verify its utility in clinical settings.

Materials and Methods

We enrolled 792 NPC patients. Cox proportional hazards model was used to compare the effect sizes (hazard ratio [HR]) of the cranial structure invasion on survival and select the structures for up‐staging or downstaging T2 and T3 NPC. The samples were reclassified and the survival curves for T2 and T3 stages were analyzed. The proposed new staging system was validated on an external sample (n = 433).

Results

Thirteen cranial structures were examined. American Joint Committee on Cancer (AJCC) T3 stage patients with the invasion of the base of the sphenoid (HR = 2.58, 95% CI = 1.16‐5.77) or base of the pterygoid (HR = 2.00, 95% CI = 0.84‐4.77) had significantly lower hazard ratios than T2 stage patients with the invasion of soft tissues in the bilateral parapharyngeal space (HR = 5.26, 95% CI = 2.02‐13.68) and single/bilateral carotid sheath (HR = 7.78, 95% CI = 3.06‐19.76). T3 stage with the invasion of the above‐mentioned bones was reclassified as T2, and T2 stage with the invasion of the above‐mentioned soft‐tissue structures was reclassified as T3. Survival analysis showed a significant difference between the reclassified T2 and T3 stages (P < 0.001). The results were replicated in the validation samples.

Conclusion

The proposed staging system for defining T2 and T3 stage NPC appears to be superior to the AJCC 8th edition. It could improve prognosis and optimize the treatment selection.
Race modifies survival benefit of guideline‐based treatment: Implications for reducing disparities in muscle invasive bladder cancer
Authors: Washington Samuel L. , Gregorich Steven E. , Meng Maxwell V. , Suskind Anne M. , Porten Sima P.
Published: September 2020

Background

Black individuals with muscle‐invasive bladder cancer (MIBC) experienced 21% lower odds of guideline‐based treatment (GBT) and differences in treatment explain 35% of observed Black‐White differences in survival. Yet little is known of how interactions between race/ethnicity and receipt of GBT drive within‐ and between‐race survival differences.

Methods

Black, White, and Latino individuals diagnosed with nonmetastatic, locally advanced MIBC from 2004 to 2013 within the National Cancer Database were included. Guideline‐based treatment was defined as the receipt including one or more of the following treatment modalities: radical cystectomy (RC), neoadjuvant chemotherapy with RC, RC with adjuvant chemotherapy, and/or chemoradiation based on American Urological Association guidelines. Cox proportional hazards model of mortality estimated effects of GBT status, race/ethnicity, and the GBT‐by‐race/ethnicity interaction, adjusting for covariates.

Results

Of the 54 910 MIBC individuals with 125 821 person‐years of posttreatment observation (max = 11 years), 6.9% were Black, and 3.0% were Latino. Overall, 51.4%, 45.3%, and 48.5% of White, Black, and Latino individuals received GBT. Latino individuals had lower hazard of death compared to Black (HR 0.81, 95% CI 0.75‐0.87) and White individuals (HR 0.92, 95% 0.86‐0.98). With GBT, Latino and White individuals had similar outcomes (HR = 1.00, 95% 0.91‐1.10) and both fared better than Black individuals (HR = 0.88, 95% 0.79‐0.99 and HR = 0.88, 95% 0.83‐0.94, respectively). Without GBT, Latino individuals fared better than White (HR = 0.85, 95% 0.77‐0.93) and Black individuals (HR = 0.74, 95% 0.67‐0.82) while White individuals fared better than Black individuals (HR = 0.87, 95% 0.83‐0.92). Black individuals with GBT fared worse than Latinos without GBT (HR = 1.02, 95% 0.92‐1.14), although not statistically significant.

Conclusion

Low GBT levels demonstrated an “under‐allocation” of GBT to those who needed it most—Black individuals. Interventions to improve GBT allocation may mitigate race‐based survival differences observed in MIBC.
What role does substance use play in the social world of Australian people who have experienced homelessness? A critical realist mixed‐methods exploration
Authors: Bower Marlee , Perz Janette , Conroy Elizabeth
Published: September 2020

Substance use is prevalent amongst Australians who have experienced homelessness, but the social impacts of using substances amongst this group are poorly understood. This study uses a relational and critical realist approach to understand the role of substance use on the social lives of people with lived experience of homelessness. A mixed‐methods design was used to explore this question and assess the experiences of people who have exited homelessness. Recruiting across services catering to marginalised populations, 110 participants completed a cross‐sectional survey. Findings showed substance use both socially connected and disconnected participants, and that attempting abstinence required participants to negotiate and alter their social networks. To participants, being a substance “user,” or “non‐user,” was a social identity that they actively negotiated to facilitate competing social, psychological and material/embodied needs. Participants chose to engage and not engage with others to craft a social identity they valued, which had the sometimes‐negative side‐effect of limiting potential relationships, leaving users feeling isolated from their non‐users and a continued imperative to keep using. The impacts of substance use on social networks were similar for currently and formerly homeless participants, suggesting transitioning into housing may not immediately prompt a reduction in substance use or influence from substance‐using peers. Interventions with substance users with lived experience of homelessness would benefit from taking a social identity approach that incorporates an understanding of the material/embodied aspects of addiction to provide a holistic model of care that best supports the relational needs of the client.
Anti‐Diabetic Effects of Berberis kansuensis Extract on Type 2 Diabetic Rats Revealed by 1H‐NMR‐Based Metabolomics and Biochemistry Analysis
Authors: Du Huan , Li Qi , Yi Huan , Xu Tong , Xu Xin‐Mei , Kuang Ting‐Ting , Zhang Jing , Huang An‐Qing , Fan Gang
Published: September 2020

The dried stem bark of Berberis kansuensis C.K.Schneid. (Berberidaceae) was widely used to treat diabetes in traditional Tibetan medicine system. However, its anti‐diabetic mechanisms have not been elucidated. In this study, 1H‐NMR‐based metabolomics combined with biochemistry assay was applied to investigate the anti‐diabetic activities as well as underlying mechanisms of B. kansuensis extract on type 2 diabetic rats. The results showed that after 30 days treatment with B. kansuensis extract, the levels of FBG, GSP, INS, TNF‐α, IL‐1β and IL‐6 were significantly decreased in B. kansuensis group compared with the model group. Besides, a total of 28 metabolites were identified in rat serum by 1H‐NMR‐based metabolomics method, 16 of which were significantly different in the normal group compared with the model group, and eight of them were significantly reversed after B. kansuensis intervention. Further analysis of metabolic pathways indicated that therapeutic effect of B. kansuensis might be predominantly related to their ability to improve glycolysis and gluconeogenesis, citric acid cycle, lipid metabolism, amino acid metabolism and choline metabolism. The results of both metabolomics and biochemical analysis indicated that B. kansuensis extract has a potential anti‐diabetic effect on type 2 diabetic rats. Its therapeutic effect may be based on the ability of anti‐inflammation, alleviating insulin resistance and restoring several disturbed metabolic pathways.
The role of intergenerational context in recovery from complex trauma: It's all about attachment
Authors: Otu Mitch
Published: September 2020

Nicole is wheeled into the emergency room, flanked by four police officers and struggling mightily against the restraints that strap her to the gurney. One officer peels off to explain the situation: Nicole was brought in from her residential mental health treatment program after she became dysregulated with no apparent provocation, striking a male staff member in the face multiple times and attempting to elope. As Nicole settles in the ER, her mood rapidly shifts from angry and frustrated to sad and worried. During her physical examination, the ER staff notices multiple lacerations in various stages of healing scattered around Nicole's body. Nicole points to a specific laceration, noting that this was from her most recent suicide attempt. A few hours after being brought into the ER, Nicole is much calmer, with an almost vacant look in her eyes as she describes her early childhood to the psychiatry team. Without much feeling to her words, she recounts a history of being sexually abused from age 3–6 years old by one of her mother's boyfriends. Nicole describes the despair she felt because of her mother not believing her disclosures or protecting her, and the carousel of foster home, group home, and residential program placements after the Child Protective Services agency in her state removed her from the abusive situation she was living in.
Creating trauma narratives for young children
Authors: Key Danielle , Newland Rebecca
Published: September 2020

Treating young children who have experienced trauma can be a daunting task, specifically when considering the wide range of developing abilities in young children. Preschool post‐traumatic stress disorder treatment (PPT) (see Scheeringa et al., 2012) is a trauma treatment that utilizes the same principles as trauma‐focused cognitive behavioral therapy (TF‐CBT) (see Cohen et al., 2006) but is modified to be developmentally appropriate for children ages 3–6 years who have at least some memory of the trauma and are being supported by a nonoffending caregiver.
Heat‐sensitive inhibition of aqualysin 1 by protein containing wheat, maize, and barley extracts
Authors: Verbauwhede Annelien E. , Lambrecht Marlies A. , Fierens Ellen , Shegay Oksana , Brijs Kristof , Delcour Jan A.
Published: September 2020

Background and objectives

Wheat flour proteins inhibit the thermo‐active serine peptidase aqualysin 1 (Aq1) from Thermus aquaticus in a temperature‐dependent way. The impact of aqueous flour extracts (FEs) from maize, barley, or rice on Aq1 activity both in an assay and in a gluten‐starch model system (GSMS) for bread making was investigated.

Findings

The degree of Aq1 inhibition by maize and barley FEs decreased at temperatures exceeding 50°C. With higher levels of FEs, higher temperatures were required to undo inhibition. Rice FEs did not inhibit Aq1. Gluten hydrolysis started at lower temperatures in GSMS containing maize FE rather than wheat FE. Incubating Aq1 with maize FE prior to inclusion in GSMS containing wheat FE decreased the onset temperature of Aq1 activity.

Conclusions

In presence of their FEs, the onset and optimal temperatures for Aq1 activity increased in the order maize, wheat, and barley. When Aq1 was incubated with maize inhibitors prior to dough making, wheat inhibitors still impacted Aq1 activity.

Significance and novelty

That maize and barley contain inhibitors inactivating Aq1 in a heat‐sensitive way different from that exerted by those in wheat is novel and relevant in the context of the production of multigrain bread products.
Lisch nodules and iris mammillations in two siblings with familial legius syndrome
Authors: Bixel Kaitlyn D. , Cano Miguel J. , Johnson Damon M. , Gomez Benjamin , Lobsinger Laura V. , Valentin Frank E. , Hsieh David T. , Rohena Luis O.
Published: September 2020

Legius syndrome is characterized by numerous café‐au‐lait macules and intertriginous freckling, but typically lacks the distinctive tumor manifestations of neurofibromatosis type 1. We report two siblings with Legius syndrome and Lisch nodules illustrating the importance of eye surveillance in these patients.
Enhancing Methanol Oxidation Reaction with Platinum‐based Catalysts using a N‐Doped Three‐dimensional Graphitic Carbon Support
Authors: Elangovan Ayyappan , Xu Jiayi , Sekar Archana , Liu Bin , Li Jun
Published: September 2020

Nitrogen‐doped graphitic carbon materials have been widely used as a catalyst support in the methanol oxidation reaction (MOR). In this study, we report the role of three‐dimensionally architectured in‐situ N‐doped vertically aligned carbon nanofibers (VACNF) as a catalyst support for MOR in acidic and alkaline media. The abundant graphitic edge sites at the sidewall of N‐doped VACNF strongly anchor the deposited platinum group metal (PGM) catalysts and induce a partial electron transfer between the PGM catalysts and support. Density Functional Theory (DFT) calculations reveal that the strong metal‐support interaction substantially increases the adsorption energy of OH, particularly near the N‐doping sites, which helps to compete and remove the adsorbed intermediate species generated during MOR. The PGM catalysts on N‐doped VACNF support exhibits CO stripping at lower potentials comparing to the commercial Vulcan carbon support and presents an enhanced electrocatalytic performance and better durability for MOR.
Dimensionality reduction of multielement glass evidence to calculate likelihood ratios
Authors: Gupta Anjali , Corzo Ruthmara , Akmeemana Anuradha , Lambert Katelyn , Jimenez Kenneth , Curran James M. , Almirall Jose R.
Published: September 2020

Dimensionality reduction of multivariate elemental concentrations of glass is reported for computing likelihood ratios (LRs). TheLRs calculated using principal component analysis (PCA) and a post hoc calibration steps result in very low (<1%) false inclusions when comparing glass samples known to originate from different sources and very low (<1%) false exclusions when comparing glass samples known to originate from the same source. TheLRs calculated using the novel PCA approach are compared with previously reportedLRs calculated using a more computationally intensive Multivariate Kernel (MVK) model followed by a calibration step using a Pool Adjacent Violators (PAV) algorithm. In both cases, the calibratedLRs limited the magnitude of the misleading evidence, providing only weak to moderate support for the incorrect hypotheses. Most of the different pairs that were found to be falsely included were explained by chemical relatedness (same manufacturer of the glass sources in very close time interval between manufacture). The computation ofLRs using dimensionality reduction of elemental concentrations using PCA may transfer to other multivariate data‐generating evidence types.
Stepwise Assembly of an Electroactive Framework from a Co6S8 Superatomic Metalloligand and Cuprous Iodide Building Units
Authors: Freeman Matthew B. , Edokobi Ozioma D. , Gillen Jonathan H. , Kocherga Margaret , Dipple Kathleen M. , Jones Daniel S. , Paley Daniel W. , Wang Le , Bejger Christopher M.
Published: September 2020

Invited for the cover of this issue is Christopher Bejger and co‐workers at UNC Charlotte, Columbia University, and Donghua University. The image depicts a pair of star clusters in the constellation Perseus as the structure of two metal clusters in the reported framework. Read the full text of the article at 10.1002/chem.20201215.
Dicarba[26]hexaporphyrinoids(1.1.1.1.1.1) with an Embedded Cyclopentene Moiety—Conformational Switching
Authors: Berlicka Anna , Stanowska Justyna , Białek Michał J. , Ślepokura Katarzyna , Latos‐Grażyński Lechosław
Published: September 2020

Invited for the cover of this issue is Lechosław Latos‐Grażyński and co‐workers at University of Wrocław. The image depicts two essential conformations of 31,34‐dicarba[26]hexachlorins: dumbbell and rectangular with regular or doubly inverted carbocyclic rings, respectively. Read the full text of the article at 10.1002/chem.202002603.
Isoselective Polymerization of rac‐Lactide by Highly Active Sequential {ONNN} Magnesium Complexes
Authors: Rosen Tomer , Rajpurohit Jitendrasingh , Lipstman Sophia , Venditto Vincenzo , Kol Moshe
Published: September 2020

The coordination chemistry and the activities in the ring‐opening polymerization catalysis of racemic lactide (LA) of magnesium complexes of a series of {ONNN}‐type sequential monoanionic ligands are described. All ligands include pyridyl and substituted‐phenolate as peripheral groups. The ligands bearing either chiral or meso‐bipyrrolidine cores led to single diastereomeric complexes, whereas the ligands bearing a diaminoethane core led to diastereomer mixtures. All {ONNN}Mg‐X complexes [X=Cl, HMDS (hexamethyldisilazide)] led to highly active and isoselective catalysts. The complexes bearing the chiral bipyrrolidine core exhibited the highest activities (full consumption of 5000 equiv. of rac‐LA at RT within 5 min) and highest isoselectivities (Pm=0.91), as well as a living character. The complexes of the meso‐bipyrrolidine based ligands were almost as active and slightly less stereoselective, while those of the diaminoethane based ligands exhibited reduced activities and isoselectivities.
Improving the Stability of Maleimide–Thiol Conjugation for Drug Targeting
Authors: Lahnsteiner Marianne , Kastner Alexander , Mayr Josef , Roller Alexander , Keppler Bernhard K. , Kowol Christian R.
Published: September 2020

Maleimides are essential compounds for drug conjugation reactions via thiols to antibodies, peptides and other targeting units. However, one main drawback is the occurrence of thiol exchange reactions with, for example, glutathione resulting in loss of the targeting ability. A new strategy to overcome such retro‐Michael exchange processes of maleimide–thiol conjugates by stabilization of the thiosuccinimide via a transcyclization reaction is presented. This reaction enables the straightforward synthesis of stable maleimide–thiol adducts essential in drug‐conjugation applications.
Phase 1 study of the immunotoxin LMB‐100 in patients with mesothelioma and other solid tumors expressing mesothelin
Authors: Hassan Raffit , Alewine Christine , Mian Idrees , Spreafico Anna , Siu Lillian L. , Gomez‐Roca Carlos , Delord Jean‐Pierre , Italiano Antoine , Lassen Ulrik , Soria Jean‐Charles , Bahleda Rastilav , Thomas Anish , Steinberg Seth M. , Peer Cody J. , Figg William D. , Niederfellner Gerhard , Méresse Naegelen Valérie , Pastan Ira
Published: September 2020

Background

LMB‐100 is an antibody‐toxin conjugate with an antimesothelin Fab linked to a 24‐kilodalton portion of Pseudomonas exotoxin A with mutations that decrease immunogenicity. The objective of the current first‐in‐human phase 1 study was to determine the maximum tolerated dose (MTD) and safety in patients with advanced solid tumors expressing mesothelin.

Methods

Cohorts of 1 to 7 patients received intravenous LMB‐100 at 7 dose levels from 40 µg/kg to 250 µg/kg intravenously on days 1, 3, and 5 of a 21‐day cycle.

Results

Of the 25 patients accrued, 17 had mesothelioma, 3 each had ovarian or pancreatic cancer, and 2 patients had gastric cancer. Dose‐limiting toxicities occurred in 2 of 4 patients treated at a dose of 250 µg/kg (capillary leak syndrome) and in 3 of 7 patients treated at a dose of 170 µg/kg (creatinine increase). The MTD of LMB‐100 was 140 µg/kg. Of the 10 patients with mesothelioma who were treated at doses of 170 µg/kg or 140 µg/kg, 8 had stable disease and 2 developed progressive disease. Peak LMB‐100 plasma concentrations were dose‐dependent during cycle 1. The development of antidrug antibodies decreased LMB‐100 blood levels in 8 of 21 patients (38%) who received cycle 2 and 9 of 11 patients (81.8%) who received cycle 3.

Conclusions

The MTD for single‐agent LMB‐100 was found to be 140 µg/kg given on a schedule of every other day for 3 doses every 3 weeks. Although less immunogenic than the first‐generation antimesothelin immunotoxin SS1P, the majority of patients developed antidrug antibodies after 2 cycles, indicating that LMB‐100 has limited antitumor efficacy as a single agent. Phase 2 studies of LMB‐100 plus pembrolizumab currently are ongoing for patients with mesothelioma and lung cancer.

Lay Summary

Mesothelin, a cell surface antigen, is an attractive target for cancer therapy given its limited expression in normal human tissues and high expression in many human cancers. LMB‐100 is a recombinant antimesothelin immunotoxin consisting of a humanized antimesothelin antibody fragment fused to a truncated Pseudomonas exotoxin A.

In the current study, the authors determined the safety, maximum tolerated dose, and pharmacokinetics of LMB‐100, as well as the generation of antidrug antibodies.

Ongoing phase 2 clinical trials are evaluating the combination of LMB‐100 plus pembrolizumab in patients with treatment‐refractory mesothelioma and non–small cell lung cancer.
Heterogeneous expression of dopaminergic markers and Vglut2 in mouse mesodiencephalic dopaminergic nuclei A8–A13
Authors: Fougère Maxime , van der Zouwen Cornelis Immanuel , Boutin Joël , Ryczko Dimitri
Published: September 2020

Co‐transmission of glutamate by brain dopaminergic (DA) neurons was recently proposed as a potential factor influencing cell survival in models of Parkinson's disease. Intriguingly, brain DA nuclei are differentially affected in Parkinson's disease. Whether this is associated with different patterns of co‐expression of the glutamatergic phenotype along the rostrocaudal brain axis is unknown in mammals. We hypothesized that, as in zebrafish, the glutamatergic phenotype is present preferentially in the caudal mesodiencephalic DA nuclei. Here, we used in mice a cell fate mapping strategy based on reporter protein expression (ZsGreen) consecutive to previous expression of the vesicular glutamate transporter 2 (Vglut2) gene, coupled with immunofluorescence experiments against tyrosine hydroxylase (TH) or dopamine transporter (DAT). We found three expression patterns in DA cells, organized along the rostrocaudal brain axis. The first pattern (TH‐positive, DAT‐positive, ZsGreen‐positive) was found in A8–A10. The second pattern (TH‐positive, DAT‐negative, ZsGreen‐positive) was found in A11. The third pattern (TH‐positive, DAT‐negative, ZsGreen‐negative) was found in A12–A13. These patterns should help to refine the establishment of the homology of DA nuclei between vertebrate species. Our results also uncover that Vglut2 is expressed at some point during cell lifetime in DA nuclei known to degenerate in Parkinson's disease and largely absent from those that are preserved, suggesting that co‐expression of the glutamatergic phenotype in DA cells influences their survival in Parkinson's disease.
Enhancement ofreal‐timegrasp detection by cascaded deep convolutional neural networks
Authors: Weng Yaoqing , Sun Ying , Jiang Du , Tao Bo , Liu Ying , Yun Juntong , Zhou Dalin
Published: September 2020

Robot grasping technology is a hot spot in robotics research. In relatively fixed industrialized scenarios, using robots to perform grabbing tasks is efficient and lasts a long time. However, in an unstructured environment, the items are diverse, the placement posture is random, and multiple objects are stacked and occluded each other, which makes it difficult for the robot to recognize the target when it is grasped and the grasp method is complicated. Therefore, we propose an accurate, real‐time robot grasp detection method based on convolutional neural networks. A cascaded two‐stage convolutional neural network model with course to fine position and attitude was established. The R‐FCN model was used as the extraction of the candidate frame of the picking position for screening and rough angle estimation, and aiming at the insufficient accuracy of the previous methods in pose detection, an Angle‐Net model is proposed to finely estimate the picking angle. Tests on the Cornell dataset and online robot experiment results show that the method can quickly calculate the optimal gripping point and posture for irregular objects with arbitrary poses and different shapes. The accuracy and real‐time performance of the detection have been improved compared to previous methods.
Stabilization of the Closed‐Ring Isomer of Spiropyran by Amide Naphthotube in Water and Its Application in Naked‐Eye Detection of Toxic Paraoxon
Authors: Liu Wei‐Er , Quan Mao , Zhou Hang , Yang Liu‐Pan , Au‐Yeung H. Y. , Jiang Wei
Published: September 2020

The thermodynamically unstable, colourless closed‐ring isomer of spiropyran can be stabilized in water by the anti‐configurational isomer of amide naphthotube. The influence of the binding on the thermodynamics and kinetics of spiropyran have been studied. The complex was further used to prepare a test paper that allows naked‐eye detection of toxic paraoxon.
Economic policy uncertainty, stakeholder engagement, and environmental, social, and governance practices: The moderating effect of competition
Authors: Vural‐Yavaş Çiğdem
Published: September 2020

This paper investigates the effect of the economic policy uncertainty (EPU) on corporate environmental, social, and governance practices (ESG), using 6,562 firm‐year observations from 15 developed European countries covering the period from 2004 to 2017. The results show that during periods of high uncertainty, firms increase their overall ESG performance, corporate environmental performance, and performance in governance. The relationship is valid for emission, resource use, workforce, management, and corporate social responsibility (CSR) strategy subdimensions of ESG. Furthermore, during periods of high uncertainty, firms operating in concentrated industries increase their overall ESG activities and corporate environmental performance. These results suggest that firms use ESG practices as risk‐reducing activities like insurance, during high periods of uncertainty. Overall, consistent with the stakeholder theory, the results indicate that firms increase their ESG practices not only to reduce corporate risk‐taking but also to follow value‐increasing activities during periods of high uncertainty, implying an improved stakeholder engagement.
Field trials of chemical suppression of embryonic cane toads (Rhinella marina) by older conspecifics
Authors: McCann Samantha , Crossland Michael , Greenlees Matthew , Shine Richard
Published: September 2020

Laboratory experiments have shown that the viability of embryos of the invasive cane toad (Rhinella marina) can be reduced by exposure to chemical cues from older conspecific larvae. These effects (very strong in laboratory trials) may offer an exciting new approach to controlling this problematic invasive species in Australia. However, the degree to which the method works in natural environments has yet to be assessed.

Our experiments in the laboratory and in seminatural outdoor waterbodies show that chemical cues from tadpoles do indeed suppress the growth, development, and survival of conspecific larvae that are exposed as embryos and do so in a dose‐dependent manner; higher tadpole densities cause greater suppression of embryos.

In seminatural outdoor waterbodies, suppressor‐exposed tadpoles were less than half as likely to survive to metamorphosis as were controls, and were much smaller when they did so and hence, less likely to survive the metamorph stage. Additionally, female cane toads were less likely to oviposit in a waterbody containing free‐ranging (but not cage‐enclosed) tadpoles, suggesting that the presence of tadpoles (rather than the chemical cues they produce) may discourage oviposition.

Broadly, our results suggest that the suppression effect documented in laboratory studies does indeed occur in the field also, and hence that we may be able to translate that approach to develop new and more effective ways to reduce rates of recruitment of peri‐urban populations of cane toads in their invasive range.
Contrasting effects of egg size and appearance on egg recognition and rejection response by Oriental reed warblers
Authors: Li Donglai , Li Xiaoshuang , Zhang Yan , Guan Shuang , Ruan Yanan
Published: September 2020

Background

Among potential hosts, the rejection of foreign eggs, which is a common and effective strategy to counter brood parasitism, depends on egg recognition. Multimodal and multicomponent recognition cues of brood parasitic eggs, which include both tactile (size, shape, and texture) and visual (size, shape, color, and maculation) cues, are potentially involved in the perception and discrimination of foreign eggs by hosts. An egg rejection experiment on the host with different types of model eggs can help to accurately assess the relative contribution of different components on egg recognition and constraints to rejection, in which videos can help identify the method of host rejection.

Methods

Here, we assessed egg recognition and rejection responses by Oriental reed warblers (Acrocephalus orientalis), one of the most common hosts of common cuckoos (Cuculus canorus) which breed in eastern China. We designed six groups of model eggs for rejection experiments in which sensory cues included three grades of size and two categories of visual mimicry.

Results

Our experiments confirmed that the multimodal traits, which included variation in size, were significant predictors of egg rejection: We detected significantly higher rejection rates of mimetic spotted model eggs than of nonmimetic blue eggs. However, large model eggs did not yield higher rejection rates and, instead, these were less likely to be rejected and more likely to be deserted compared with smaller eggs. Further video‐recording data showed that there was no significant effect of egg size on the egg recognition rate (percentage of nests with evidence of egg pecking). No evidence that the egg appearance had an effect on the method of egg rejection (ejection or nest desertion) was found.

Conclusions

Only visual signals, such as color and maculation, contributed to the recognition of foreign eggs by Oriental reed warblers as recognizable clues, but not the egg size. The egg size had an impact on the type of egg rejection. It was less feasible for the warblers to eject large eggs and that is why they opted more often for desertion as the mean of model egg rejection. The significantly lower egg rejection rate of large eggs suggested that although some of them were recognized as foreign eggs, hosts failed to reject these eggs and finally the eggs were assumed to being accepted by the commonly used nest‐checking methods.
Kinetics and modeling of growth and lactic acid production in Gundruk, a Himalayan fermented vegetable dish
Authors: Ghimire Arjun , Kumar Sah Ajit , Poudel Ranjana
Published: September 2020

Gundruk is a fermented green leafy vegetable product prepared from fresh leaves of local vegetables called Rayo—sag (Brassica campestris), mustard (Brassica juncea), and cauliflower (Brassica oleracea) indigenous to the Nepali people. Fresh gundruk was prepared in a glass jar by fermenting the Brassica juncea leaves anaerobically for 16 days and the changes in biomass, lactic acid, and pH were evaluated after every 24 hr. The viable cell count increased from 6.03 × 104 cfu/g to 9.55 × 108 cfu/g after 3 days and then decreased gradually to remain constant after 8 days with 6.31 × 107 cfu/g until the end of fermentation. The lactic acid increased by about 12.58 times in 12 days and remained constant for the rest of the fermentation period. Unlike this, pH decreased from 6.59 to 3.71 on the 9th day of fermentation and then increased slightly till the last day of fermentation. The data obtained were fitted to two most widely accepted microbial growth models: Modified Gompertz, and Logistic model and three well‐known lactic acid production models: Luedeking‐ Piret, Monteagudo et al., and Balannec et al. model for lactic acid fermentation. Based on nonlinear regression analysis, Modified Gompertz, and Monteagudo et al. model gave a better fit to describe microbial growth and lactic acid production, respectively. The growth‐associated and non‐growth‐associated coefficients were determined to be 0.1104 and 0.0042, respectively, using Monteagudo et al. model. The findings revealed that lactic acid production in gundruk is a mixed type.
Valuation of VIX and target volatility options with affine GARCH models
Authors: Cao Hongkai , Badescu Alexandru , Cui Zhenyu , Jayaraman Sarath Kumar
Published: September 2020

In this paper we propose semiclosed‐form solutions, subject to an inversion of the Fourier transform, for the price of VIX options and target volatility options under affine GARCH models based on Gaussian and Inverse Gaussian distributions. We illustrate the advantage of the proposed analytic expressions by comparing them with those obtained from benchmark Monte–Carlo simulations. The empirical performance of the two affine GARCH models is tested using different calibration exercises based on historical returns and market quotes on VIX and SPX options.
Returning individual‐specific results of a dementia prevalence study: insights from prospective participants living in Switzerland
Authors: Fadda Marta , Fiordelli Maddalena , Amati Rebecca , Falvo Ilaria , Ibnidris Aliaa , Hurst Samia , Albanese Emiliano
Published: September 2020

Objectives

To explore prospective participants' preferences regarding the return of their individual‐specific results from a dementia prevalence study (a probabilistic diagnosis of dementia).

Methods/Design

We conducted a qualitative study with 22 individuals aged 45 to 86 and resident in the Canton of Ticino (Switzerland). Participants had previously joined the validation phase of an epidemiological study into dementia and its impact.

Results

We found that individuals welcome the return of their individual‐specific results, provided these meet a number of validity, clinical, and personal utility criteria. They justify researchers' duty to return study findings with the principles of beneficence (eg, providing information that can help participants' medical decision‐making) and justice (eg, acknowledging participants' efforts to help research by sharing their personal information). Furthermore, individuals anticipate societal benefits of the return of individual specific study findings, including improved interpersonal relationships among individuals and decreased dementia‐related stigma.

Conclusions

Our findings suggest that researchers should address the return of individual‐specific study results early on during study design and involve prospective participants in identifying both the conditions under which results should be offered and the perceived individual and societal benefits returning can have.
Gain of LINC00624 Enhances Liver Cancer Progression by Disrupting the Histone Deacetylase 6/Tripartite Motif Containing 28/Zinc Finger Protein 354C Corepressor Complex
Authors: Li Zhe , Lu Xinyuan , Liu Yanfang , Zhao Jingjing , Ma Shengzhe , Yin Haoxiang , Huang Shenglin , Zhao Yingjun , He Xianghuo
Published: September 2020

Background and Aims

Long noncoding RNAs (lncRNAs) are involved in almost every stage of tumor initiation and progression. Here, we have identified an antisense lncRNA, LINC00624, that arises from the antisense strand of chromo‐domain‐helicase‐DNA‐binding protein 1‐like (CHD1L), located on chr1q21.1, with significant copy number gain and transcriptional activation of CHD1L and B‐cell CLL/lymphoma 9 protein (BCL9), in hepatocellular carcinoma (HCC).

Approach and Results

Overexpression of LINC00624 enhances tumor growth and metastasis in vitro and in vivo. Mechanistically, higher levels of LINC00624 strengthen the interaction between histone deacetylase 6 (HDAC6) and tripartite motif containing 28 (TRIM28), which accelerates HDAC6 ubiquitination and degradation. Moreover, LINC00624 binds to the RBCC domain of TRIM28, inhibits trimer formation, and weakens the interaction between TRIM28 and zinc finger protein 354C (ZNF354C). Thus, LINC00624 overexpression disrupts the formation of the HDAC6‐TRIM28‐ZNF354C transcriptional corepressor complex, resulting in the dissociation of the complex from the promoter of CHD1L and BCL9, thereby removing transcription inhibition.

Conclusions

Our findings suggest that LINC00624 acts as a molecular decoy that sequesters the HDAC6‐TRIM28‐ZNF354C transcriptional corepressor complex away from the specific genomic loci, and that it can potentially be a therapeutic target in HCC.
Impact of the COVID‐19 pandemic on maternal health services in Pakistan
Authors: Sarwer Abdullah , Javed Bilal , Soto Erik B. , Mashwani Zia‐ur‐Rehman
Published: September 2020

Throughout the world as health systems are being prepared to deal with the SARS‐CoV‐2 outbreak which will affect the management of HIV, diabetes, mental health and mainly maternal healthcare systems. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID‐19 outbreak, there has been very little concern expressed over the effects on maternal health services. It is highly likely that the present situation may exacerbate maternal mortality in suburban and rural areas. The present situation requires governments and NGOs to make necessary arrangements to support people with prenatal and postnatal care.
High‐performance work systems with internal and external contingencies: The moderating roles of organizational slack and industry instability
Authors: Kim Kwanghyun , Ok Chiho , Kang Sung‐Choon , Bae Johngseok , Kwon Kiwook
Published: September 2020

When high‐performance work systems (HPWS) positively affect firm performance, both internal and external contingencies play potentially salient roles in its influence. Our study pays attention to organizational (unabsorbed) slack and industry instability as important boundary conditions in the relationship between HPWS and firm performance. Based on 307 Korean firms in 39 industries, our research found moderating effects of unabsorbed slack and industry instability in the relationship between HPWS and firm performance. We found that HPWS's positive effect on firm performance is strongest when a firm possesses more slack resources in an unstable industry.
The non‐payout functions of deposit insurance schemes
Authors: Kozińska Magdalena
Published: September 2020

Institutional and functional development of entities responsible for the provision of deposit insurance remains a marginal area of scientific research. The literature does not offer comprehensive analyses of the organization of deposit guarantee schemes (DGS), including the identification of all their possible tasks supporting the performance of its main goal (deposit insurance). Nevertheless, the potential synergies and cost savings justify broad range of tasks that could be carried out by DGSs in order to facilitate their functioning. At the same time, the problem of the functional shape of DGS is also of utmost practical importance. Therefore, the aim of this paper is to fill the identified gap by classifying the non‐payout functions and presenting the empirical review about them. To this end, the activities of 109 deposit guarantors around the world were analyzed. The review allowed to distinguish seven DGS functions supplementary to the payout of covered deposits, as well as to examine the interdependencies between the recognized roles and evaluate in terms of the DGSs' fulfillment of their objectives. Additionally, the advantages and disadvantages of every supplementary DGS activity were presented. The analysis allowed for the distinction of desired functions of deposit guarantee schemes.