bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral RNA level, serum antibody responses, and transmission risk in discharged COVID-19 patients with recurrent positive SARS-CoV-2 RNA test results: a population-based observational cohort study
Authors: Yang Chao , Jiang Min , Wang Xiaohui , Tang Xiujuan , Fang Shisong , Li Hao , Zuo Le , Jiang Yixiang , Zhong Yifan , Chen Qiongcheng , Zheng Chenli , Wang Lei , Wu Shuang , Wu Weihua , Liu Hui , Yuan Jing , Liao Xuejiao , Zhang Zhen , Lin Yiman , Geng Yijie , Zhang Huan , Zheng Huanying , Wan Min , Lu Linying , Ren Xiaohu , Cui Yujun , Zou Xuan , Feng Tiejian , Xia Junjie , Yang Ruifu , Liu Yingxia , Mei Shujiang , Li Baisheng , Yang Zhengrong , Hu Qinghua
Published: July 2020

Background

Managing discharged COVID-19 (DC) patients with recurrent positive (RP) SARS-CoV-2 RNA test results is challenging. We aimed to comprehensively characterize the viral RNA level and serum antibody responses in RP-DC patients and evaluate their viral transmission risk.

Methods

A population-based observational cohort study was performed on 479 DC patients discharged from February 1 to May 5, 2020 in Shenzhen, China. We conducted RT-qPCR, antibody assays, neutralisation assays, virus isolation, whole genome sequencing (WGS), and epidemiological investigation of close contacts.

Findings

Of 479 DC patients, the 93 (19%) RP individuals, including 36 with multiple RP results, were characterised by young age (median age: 34 years, 95% confidence interval [CI]: 29–38 years). The median discharge-to-RP length was 8 days (95% CI: 7–14 days; maximum: 90 days). After readmission, RP-DC patients exhibited mild (28%) or absent (72%) symptoms, with no disease progression. The viral RNA level in RP-DC patients ranged from 1·9–5·7 log10copies/mL (median: 3·2, 95% CI: 3·1–3·5). At RP detection, the IgM, IgG, IgA, total antibody, and neutralising antibody (NAb) seropositivity rates in RP-DC patients were 38% (18/48), 98% (47/48), 63% (30/48), 100% (48/48), and 91% (39/43), respectively. Regarding antibody levels, there was no significant difference between RP-DC and non-RP-DC patients. The antibody level remained constant in RP-DC patients pre- and post-RP detection. Virus isolation of nine representative specimens returned negative results. WGS of six specimens yielded only genomic fragments. No clinical symptoms were exhibited by 96 close contacts of 23 RP-DC patients; their viral RNA (96/96) and antibody (20/20) test results were negative. After full recovery, 60% of patients (n=162, 78 no longer RP RP-DC and 84 non-RP-DC) had NAb titres of ≥1:32.

Interpretation

RP may occur in DC patients following intermittent and non-stable excretion of low viral RNA levels. RP-DC patients pose a low risk of transmitting SARS-CoV-2. An NAb titre of ≥ 1:32 may provide a reference indicator for evaluating humoral responses in COVID-19 vaccine clinical trials.

Funding

Sanming Project of Medicine in Shenzhen, China National Science and Technology Major Projects Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province of China, and Shenzhen Committee of Scientific and Technical Innovation grants.
Biophysical and dynamic characterization of a fine-tuned binding of the human Respiratory Syncytial Virus M2-1 core domain to long RNAs
Authors: Caruso Icaro P. , Guimarães Giovana C. , Machado Vitor B. , Fossey Marcelo A. , Willbold Dieter , Almeida Fabio C. L. , Souza Fátima P.
Published: July 2020

The human Respiratory Syncytial Virus (hRSV) M2-1 protein functions as a processivity and antitermination factor of the viral polymerase complex. Here it is presented the first evidence that hRSV M2-1 core domain (cdM2-1) alone has an unfolding activity for long RNAs, as well as a biophysical and dynamic characterization of the cdM2-1/RNA complex. The main contact region of cdM2-1 with RNA was the α1–α2–α5–α6 helix bundle, which suffered local conformational changes and promoted the RNA unfolding activity. This activity may be triggered by base-pairing recognition. RNA molecules wrap around the whole cdM2-1, protruding their terminals over the domain. The α2–α3 and α3–α4 loops of cdM2-1 were marked by an increase in picosecond internal motions upon RNA binding even though they are not directly involved in the interaction. The results revealed that the cdM2-1/RNA complex originates from a fine-tuned binding, contributing to unraveling interaction aspects necessary to M2-1 activity.

IMPORTANCE

The main outcome is the molecular description of a fine-tuned binding of the cdM2-1/RNA complex and the evidence that the domain alone has an unfolding activity for long RNAs. This binding mode is essential in the understanding of the function in the full-length protein. Orthopneumovirus, as the human Respiratory Syncytial Virus (hRSV), stands out for the unique role of M2-1 as a transcriptional antitermination factor able to increase the RNA polymerase processivity.
TRANsCre-DIONE transdifferentiates scar-forming reactive astrocytes into functional motor neurons
Authors: An Heeyoung , Lee Hye-Lan , Cho Doo-Wan , Hong Jinpyo , Lee Hye Yeong , Lee Jung Moo , Woo Junsung , Lee Jaekwang , Park MinGu , Yang Young-Su , Han Su-Cheol , Ha Yoon , Lee C. Justin
Published: July 2020

In spinal cord injury (SCI), the scar-forming reactive astrocytes with upregulated GFAP proliferate aberrantly near the injury site, allowing themselves as a prime target for transdifferentiation into neurons to replenish dead neurons. However, the conventional use ofGFAPpromoter to target reactive astrocytes has two inherent problems: inadvertent conversion of normal astrocytes and low efficiency due to progressive weakening of promoter activity during transdifferentiation. Here, we report that the scar-forming reactive astrocytes are selectively transdifferentiated into neurons with 87% efficiency and 96% specificity via TRANsCre-DIONE, a combination of the split-Cre system under two different promoters ofGFAPandLcn2and a Cre-loxP-dependent inversion and expression ofNeurog2under the strongEF1αpromoter. After SCI, TRANsCre-DIONE caused transdifferentiation into Isl1-positive motor neurons, reduced astrogliosis, enhanced regeneration in surrounding cells, and a significant motor recovery. Our study proposes TRANsCre-DIONE as the next-generation therapeutic approach for patients suffering from SCI.

Highlights

TRANsCre-DIONE converts reactive astrocyte into neuron by over-expression ofNeurog2Reactive astrocytes are targeted using split-Cre under two promoters,GFAPandLcn2TRANsCre-DIONE reduces reactivity, replaces dead neurons and alleviates symptom of SCI Transdifferentiated-neurons are GABA+ in the striatum and Isl1+ in the spinal cord
Host genotype and stable differences in algal symbiont communities explain patterns of thermal stress response ofMontipora capitatafollowing thermal pre-exposure and across multiple bleaching events
Authors: Dilworth Jenna , Caruso Carlo , Kahkejian Valerie A. , Baker Andrew C. , Drury Crawford
Published: July 2020

As sea surface temperatures increase worldwide due to climate change, coral bleaching events are becoming more frequent and severe, resulting in reef degradation. Leveraging the inherent ability of reef-building corals to acclimatize to thermal stress via pre-exposure to protective temperature treatments may become an important tool in improving the resilience of coral reefs to rapid environmental change. We investigated whether historical bleaching phenotype, coral host genotype, and exposure to protective temperature treatments would affect the response of the Hawaiian coralMontipora capitatato natural thermal stress. Fragments were collected from colonies that demonstrated different bleaching responses during the 2014-2015 event in Kāne’ohe Bay (O’ahu, Hawai’i) and exposed to four different artificial temperature pre-treatments (and a control at ambient temperature). After recovery, fragments experienced a natural thermal stress event either in laboratory conditions or their native reef environment. Response to thermal stress was quantified by measuring changes in the algal symbionts’ photochemical efficiency, community composition, and relative density. Historical bleaching phenotype was reflected in stable differences in symbiont community composition, with historically bleached corals containing onlyCladocopiumsymbionts and historically non-bleached corals having mixed symbiont communities dominated byDurusdinium. Mixed-community corals lost moreCladocopiumthanCladocopium-only corals during the natural thermal stress event, and preferentially recovered withDurusdinium. Laboratory pre-treatments exposed corals to more thermal stress than anticipated, causing photochemical damage that varied significantly by genotype. While none of the treatments had a protective effect, temperature variation during treatments had a significant detrimental effect on photochemical efficiency during the thermal stress event. These results show that acclimatization potential is affected by fine-scale differences in temperature regime, host genotype, and relatively stable differences in symbiont community composition that underpin historical bleaching phenotypes inM. capitata.
In-SilicoAnalysis of Secondary Metabolites that Modulates Enzymes of Cholesterol Target
Authors: Marahatha Rishab , Basnet Saroj , Bhattarai Bibek Raj , Budhathoki Prakriti , Aryal Babita , Adhikari Bikash , Lamichhane Ganesh , Poudel Darbin Kumar , Parajuli Niranjan
Published: July 2020

Hypercholesterolemia has posed a serious threat of heart diseases and stroke worldwide. Xanthine oxidase (XO), the rate-limiting enzyme in uric acid biosynthesis, is regarded as the root of reactive oxygen species (ROS) that generates atherosclerosis and cholesterol crystals. β-Hydroxy β-methylglutaryl-coenzyme A reductase (HMGR) is a rate-limiting enzyme in cholesterol biosynthesis. Although some commercially available enzyme inhibiting drugs have effectively reduced the cholesterol level, most of them have failed to meet the requirements of being apt drug candidates. Here, we have carried out anin-silicoanalysis of secondary metabolites that have already shown good inhibitory activity against XO and HMGR. Out of 118 secondary metabolites reviewed, sixteen molecules inhibiting XO and HMGR were taken based on IC50values reportedin vitroassays. Further, receptor-based virtual screening was carried out against secondary metabolites usingGOLD Protein-Ligand Docking Software, combined with subsequent post-docking, to study the binding affinities of ligands to the enzymes. In-SilicoADMET analysis was carried out to study their pharmacokinetic properties, followed by toxicity prediction through ProTox-II. The molecular docking of amentoflavone(1)(GOLD score 70.54), and ganomycin I(9)(GOLD score 59.61) evinced that the drug has effectively bind at the competitive site of XO and HMGR, respectively. Besides, 6-paradol(3)and selgin(4)could be potential drug candidates to inhibit XO. Likewise, n-octadecanyl-O-α-D-glucopyranosyl(6’→1”)-O-α-D-glucopyranoside(10)could be potential drug candidates to maintain serum cholesterol.In-silicoADMET analysis showed that the sixteen metabolites were optimal within the categorical range in comparison to commercially available XO and HMGR inhibitors, respectively. Toxicity analysis through Protox-II revealed that 6-gingerol(2), ganoleucoin K(11), and ganoleucoin Z(12)are toxic for human use. This computational analysis supports earlier experimental evidence towards the inhibition of XO and HMGR by natural products. Further study is necessary to explore the clinical efficacy of these secondary molecules, which might be alternatives for the treatment of hypercholesterolemia.

Graphical abstract
Hijacking of the host cell Golgi byPlasmodiumliver stage parasites
Authors: De Niz Mariana , Kaiser Gesine , Zuber Benoit , Do Heo Won , Heussler Volker T. , Agop-Nersesian Carolina
Published: July 2020

The intracellular lifestyle represents a challenge for the rapidly proliferating liver stagePlasmodiumparasite. In order to scavenge host resources,Plasmodiumhas evolved the ability to target and manipulate host cell organelles. Using dynamic fluorescence-based imaging, we show a direct interplay between the pre-erythrocytic stages ofPlasmodium bergheiand the host cell Golgi during the entire liver stage development. Liver stage schizonts fragment the host cell Golgi into miniaturized stacks, which increases surface interactions with the parasite’s parasitophorous vacuole membrane. Interference with the host cell Golgi-linked vesicular machinery using specific dominant-negative Arf and Rab GTPases results in developmental arrest and diminished survival of liver stage parasites. Moreover, functional Rab11a is critical for the parasites ability to induce Golgi fragmentation. Altogether, we demonstrate that the structural and functional integrity of the host cell Golgi is necessary for optimal pre-erythrocytic development ofP. berghei. The parasite hijacks the hepatocyte’s Golgi structure to optimize its own intracellular development.
LIN-10 can promote LET-23 EGFR signaling and trafficking independently of LIN-2 and LIN-7
Authors: Gauthier Kimberley D. , Rocheleau Christian E.
Published: July 2020

DuringC. eleganslarval development, an inductive signal mediated by LET-23 EGFR (Epidermal Growth Factor Receptor) specifies three of six vulva precursor cells (VPCs) to adopt vulval cell fates. An evolutionarily conserved complex consisting of PDZ domain-containing scaffold proteins LIN-2 (CASK), LIN-7 (Lin7 or Veli), and LIN-10 (APBA1 or Mint1) (LIN-2/7/10) mediates basolateral LET-23 EGFR localization in the VPCs to permit signal transmission and development of the vulva. We recently found that the LIN-2/7/10 complex likely forms at Golgi ministacks or recycling endosomes; however, the mechanism through which the complex targets the receptor to the basolateral membrane remains unknown. Here we found that overexpression of LIN-10 or LIN-7 can compensate for loss of their complex components by promoting LET-23 EGFR signaling through previously unknown complex-independent and receptor-dependent pathways. In particular, LIN-10 can independently promote basolateral LET-23 EGFR localization, and its complex-independent function uniquely requires its PDZ domains that also regulate its localization to Golgi ministacks and recycling endosomes. These studies point to a novel complex-independent function for LIN-7 and LIN-10 that broadens our understanding of how this complex regulates targeted sorting of membrane proteins.
Electrophysiological foundations of the human default-mode network revealed by brain-wide intracranial-EEG recordings during resting-state and cognition
Authors: Das Anup , de los Angeles Carlo , Menon Vinod
Published: July 2020

Investigations using noninvasive functional magnetic resonance imaging (fMRI) have provided significant insights into the unique functional organization and profound importance of the human default mode network (DMN), yet these methods are limited in their ability to resolve network dynamics across multiple timescales. Electrophysiological techniques are critical to address these challenges, yet few studies have explored the neurophysiological underpinnings of the DMN. Here we investigate the brain-wide electrophysiological organization of the DMN in a common large-scale network framework consistent with prior fMRI studies. We used brain-wide intracranial EEG (iEEG) recordings, and evaluated intra- and cross-network interactions during the resting-state and cognition. Our analysis revealed significantly greater intra-DMN phase iEEG synchronization in the slow-wave (< 4 Hz) while DMN interactions with other brain networks was higher in all higher frequencies. Crucially, slow-wave intra-DMN synchronization was observed in the task-free resting-state and during verbal memory encoding and recall. Compared to resting-state, intra-DMN phase synchronization was significantly higher during both memory encoding and recall. Slow-wave intra-DMN phase synchronization increased during successful memory retrieval, highlighting its behavioral relevance. Finally, analysis of nonlinear dynamic causal interactions revealed that the DMN is a causal outflow network during both memory encoding and recall. Our findings identify dynamic spectro-temporal network features that allow the DMN to maintain a balance between stability and flexibility, intrinsically and during task-based cognition, provide novel insights into the neurophysiological foundations of the human DMN, and elucidate network mechanisms by which it supports cognition.
Genome-wide variation in DNA methylation linked to developmental stage and chromosomal suppression of recombination in white-throated sparrows
Authors: Sun Dan , Layman Thomas S. , Jeong Hyeonsoo , Chatterjee Paramita , Grogan Kathleen , Merritt Jennifer , Maney Donna L. , Yi Soojin V.
Published: July 2020

DNA methylation is known to play critical roles in key biological processes. Most of our knowledge on regulatory impacts of DNA methylation has come from laboratory-bred model organisms, which may not exhibit the full extent of variation found in wild populations. Here, we investigated naturally-occurring variation in DNA methylation in a wild avian species, the white-throated sparrow (Zonotrichia albicollis). This species offers exceptional opportunities for studying the link between genetic differentiation and phenotypic traits because of a non-recombining chromosome pair linked to both plumage and behavioral phenotypes. Using novel single-nucleotide resolution methylation maps and gene expression data, we show that DNA methylation and the expression of DNA methyltransferases are significantly higher in adults than in nestlings. Genes for which DNA methylation varied between nestlings and adults were implicated in development and cell differentiation and were located throughout the genome. In contrast, differential methylation between plumage morphs was localized to the non-recombining chromosome pair. One subset of CpGs on the non-recombining chromosome was extremely hypomethylated and localized to transposable elements. Changes in methylation predicted changes in gene expression for both chromosomes. In summary, we demonstrate changes in genome-wide DNA methylation that are associated with development and with specific functional categories of genes in white-throated sparrows. Moreover, we observe substantial DNA methylation reprogramming associated with the suppression of recombination, with implications for genome integrity and gene expression divergence. These results offer an unprecedented view of ongoing epigenetic reprogramming in a wild population.
The Role of IgG Subclass in Antibody-Mediated Protection against Carbapenem-ResistantKlebsiella pneumoniae
Authors: Motley Michael P. , Diago-Navarro Elizabet , Banerjee Kasturi , Inzerillo Sean , Fries Bettina C.
Published: July 2020

Monoclonal antibodies (Abs) have the potential to assist in the battle against multidrug-resistant bacteria such as Carbapenem-ResistantKlebsiella pneumoniae(CR-Kp). However, the characteristics by which these Abs function, such as the role of antibody subclass, must be determined before such modalities can be carried from the bench to the bedside. We performed a subclass switch on anti-capsular monoclonal murine IgG3(mIgG3) hybridomas and identified and purified a murine IgG1(mIgG1) hybridoma line through sib selection. We then compared the ability of the mIgG1and mIgG3antibodies to control CR-KpST258 infection bothin vitroandin vivo. We found by ELISA and flow cytometry that mIgG3has superior binding to CR-KpCPS and superior agglutinating ability compared to mIgG1. The mIgG3also predictably had better complement-mediated serum bactericidal activity than the mIgG1and also promoted neutrophil-mediated killing at concentrations lower than the mIgG1. In contrast, the mIgG1had marginally better activity in improving macrophage-mediated phagocytosis. Comparing their activities in a pulmonary infection model with wild type as well as neutropenic mice, both antibodies reduced organ burden in a non-lethal challenge, regardless of neutrophil status, with mIgG1having the highest overall burden reduction in both scenarios. However, at a lethal inoculum, both antibodies showed reduced efficacy in neutropenic mice, with mIgG3retaining the most activity. These findings suggest the viability of monoclonal Ab adjunctive therapy in neutropenic patients that cannot mount their own immune response, while also providing some insight into the relative contributions of immune mediators in CR-Kpprotection.

Importance

Carbapenem-resistantKlebsiella pneumoniaeis an urgent public health threat that causes life-threatening infections in immunocompromised hosts. Its resistance to nearly all antibiotics necessitates novel strategies to treat it, including the use of monoclonal antibodies. Monoclonal antibodies are emerging as important adjuncts to traditional pharmaceuticals, and studying how they protect against specific bacteria such asKlebsiella pneumoniaeis crucial to their development as effective therapies. Antibody subclass is often overlooked but is a major factor in how an antibody interacts with other mediators of immunity. This paper is the first to examine how the subclass of anti-capsular monoclonal antibodies can affect efficacy against CR-Kp. Additionally, this work sheds light on the viability of monoclonal antibody therapy in neutropenic patients, who are most vulnerable to CR-Kpinfection.
A Humanized Antibody against LRG1 that Inhibits Angiogenesis and Reduces Retinal Vascular Leakage
Authors: Kallenberg David , Tripathi Vineeta , Javaid Faiza , Pilotti Camilla , George Jestin , Davis Sterenn , Blackburn Jack WD , O’Connor Marie , Dowsett Laura , Bowers Chantelle E , Liyanage Sidath , Gourlaouen Morgane , Hoeh Alexandra , Mota Filipa , Selwood David , Bainbridge James , Tufail Adnan , Chudasama Vijay , Greenwood John , Moss Stephen E
Published: July 2020

Pathological angiogenesis contributes to morbidity in a number of diseases including cancer, diabetic retinopathy and the neovascular form of age-related macular degeneration, leading to significant efforts to develop effective anti-angiogenic therapeutics for these conditions. The field is dominated by inhibitors of vascular endothelial growth factor (VEGF), yet angiogenesis can also be driven and modified by other factors. We have previously demonstrated that leucine-rich alpha-2-glycoprotein 1 (LRG1) contributes to abnormal vessel growth by activating a TGFß switch. Here we report the development and characterisation of a function-blocking fully humanised IgG4 and its Fab fragment, that bind to LRG1 with high affinity and specificity and inhibit vascular leakage in the mouse model of laser-induced choroidal neovascularisation. In summary, we have developed a therapeutic antibody that targets a VEGF-independent signalling axis, which may be effective in a number of conditions either as monotherapy or in combination with other vascular targeted therapies.
Rapid, sensitive and specific SARS coronavirus-2 detection: a multi-center comparison between standard qRT-PCR and CRISPR based DETECTR
Authors: Brandsma Eelke , Verhagen Han J.M.P. , van de Laar Thijs J.W. , Claas Eric C.J. , Cornelissen Marion , van den Akker Emile
Published: July 2020

Recent advances in CRISPR-based diagnostics suggest that DETECTR, a combination of isothermal reverse transcriptase loop mediated amplification (RT-LAMP) and subsequent Cas12 bystander nuclease activation by amplicon targeting ribonucleoprotein complexes, could be a faster and cheaper alternative to qRT-PCR without sacrificing sensitivity/specificity. Here we compare qRT-PCR with DETECTR to diagnose COVID-19 on 378 patient samples and report a 95% reproducibility. Patient sample dilution assays suggest a higher analytical sensitivity of DETECTR compared to qRT-PCR, however, this was not confirmed in a large patient cohort. The data showed that both techniques are equally sensitive in detecting SARS-CoV-2 providing an added value of DETECTR to the currently used qRT-PCR platforms. For DETECTR, different gRNAs can be used simultaneously to obviate negative results due to mutations in N-gene. Lateral flow strips, suitable as a point of care test (POCT), showed a 100% correlation to the high-throughput DETECTR assay. Importantly, DETECTR was 100% specific for SARS-CoV-2 and did not detect other human coronaviruses. As there is no need for specialized equipment, DETECTR could be rapidly implemented as a complementary technically independent approach to qRT-PCR thereby increasing the testing capacity of medical microbiological laboratories and relieving the existent PCR-platforms for routine non-SARS-CoV-2 diagnostic testing.
An Analysis of Territorial Patterns in COVID-19 Mortality in France, Spain, Italy and the UK
Authors: Zavatta Roberto
Published: July 2020

This paper provides an overview of territorial patterns of COVID-19 deaths in four European countries severely affected by the pandemic, Spain, France, Italy, and the United Kingdom. The analysis focuses on cumulated COVID-19 mortality at the sub-regional level, following the territorial subdivision of countries adopted by the European Union. The paper builds upon a dataset with highly granular information on COVID- 19 deaths assembled from various sources. The analysis shows remarkable differences in territorial patterns of COVID-19 mortality, both within and across the four countries reviewed. Results somewhat differ depending on the aspect considered (concentration of deaths or mortality rates) but, in general, Italy, France and Spain display significant territorial disparities, with selected sub-regions being disproportionately affected by the pandemic. Instead, the picture is more uniform in the UK, with comparatively lower differences across the various sub- regions. These findings suggest that analyses of COVID-19 mortality at the national level (and, sometimes, even at the regional level) may conceal major differences and therefore be of limited use, both analytically and from an operational viewpoint.
Immune responses to cholera following natural infection: a review
Authors: Leung Tiffany , Matrajt Laura
Published: July 2020

Cholera is an acute, diarrheal disease caused by Vibrio cholerae O1 or 139 that is associated with a high global burden. In this review, we identify the estimated duration of immunity following cholera infection with and without clinical symptoms from available published studies. We searched Pubmed and Web of Science for studies examining the long-term infection-acquired immunity against cholera infection. We identified 22 eligible studies and categorized them as either observational, challenge, or serological. We observed in observational and challenge studies that at three years, there is strong evidence of protection. However, serological studies show that elevated humoral markers returned to baseline within one year. Although with small sample sizes, three studies found that most participants with a subclinical infection from an initial challenge with cholera had a symptomatic infection when rechallenged with a homologous biotype, suggesting that a subclinical cholera infection may confer lower protection than a clinical one. This review underscores the need to elucidate potential differences in the protection provided by clinical and subclinical cholera infections. Further, more studies are warranted to bridge the gap between the correlates of protection and cholera immunity. Understanding the duration of natural immunity to cholera can help guide control strategies and policy.
A benchmark modelling for participation-based tax increment financing
Authors: Varli Yusuf , Ovenc Gokhan
Published: July 2020

Purpose

This paper aims to present the theoretical and conceptual framework of a new method in public finance called “participation based tax increment financing (P-TIF)” by combining conventional tax increment financing (TIF) within the Sharīʿah-compliance structure.

Design/methodology/approach

This study develops a benchmark model for P-TIF, which offers a participative contract between both lender and borrower. With the help of this model, a financing schema in P-TIF is established by incorporating stochastic modelling. Possible implications and alternative options of application are also explored with a discussion of challenges.

Findings

The results mainly indicate that P-TIF promises lenders to be a part of increment from tax earnings, in return for a reduced interest rate. They show how a rise in participation of the lender in a given contract lowers the interest rate. Under the base case scenario, the interest rate is reduced to zero when the participation of the lender in tax increment is set at 50%.

Practical implications

With the feature of being interest-free, P-TIF can be implied also within the Sharīʿah-compliance framework, thanks to the model it is based on. Additionally, as the model in this paper is parametric, it can be applicable to various cases in Islamic finance.

Originality/value

To the best of our knowledge, this is the first paper in the literature in the sense that it provides a conceptual idea and respective model for TIF method within a Sharīʿah-compliance framework.
AdaptPack studio translator: translating offline programming to real palletizing robots
Authors: Carvalho de Souza João Pedro , Castro André Luiz , Rocha Luís F. , Silva Manuel F.
Published: July 2020

Purpose

This paper aims to propose a translation library capable of generating robots proprietary code after their offline programming has been performed in a software application, named AdaptPack Studio, running over a robot simulation and offline programming software package.

Design/methodology/approach

The translation library, named AdaptPack Studio Translator, is capable to generate proprietary code for the Asea Brown Boveri, FANUC, Keller und Knappich Augsburg and Yaskawa Motoman robot brands, after their offline programming has been performed in the AdaptPack Studio application.

Findings

Simulation and real tests were performed showing an improvement in the creation, operation, modularity and flexibility of new robotic palletizing systems. In particular, it was verified that the time needed to perform these tasks significantly decreased.

Practical implications

The design and setup of robotics palletizing systems are facilitated by an intuitive offline programming system and by a simple export command to the real robot, independent of its brand. In this way, industrial solutions can be developed faster, in this way, making companies more competitive.

Originality/value

The effort to build a robotic palletizing system is reduced by an intuitive offline programming system (AdaptPack Studio) and the capability to export command to the real robot using the AdaptPack Studio Translator. As a result, companies have an increase in competitiveness with a fast design framework. Furthermore, and to the best of the author’s knowledge, there is also no scientific publication formalizing and describing how to build the translators for industrial robot simulation and offline programming software packages, being this a pioneer publication in this area.
The role of customer personality in satisfaction, attitude-to-brand and loyalty in mobile services
Authors: Smith Trevor Alexander
Published: July 2020

Purpose

The purpose of this study is two-fold. First is to explore the role of some customer personality traits in explaining customer satisfaction in mobile services. Second is to explore the relationship between satisfaction and loyalty of mobile services customers, mediated by attitude-to-brand considering the fierce competition and the fast industry growth.

Design/methodology/approach

The study used a cross-sectional design and a survey of mobile service customers. For the empirical analysis, the structural equation models were applied (partial least squares).

Findings

The results suggest that customers who are agreeable, neurotic and open to new experience are more likely to be satisfied with mobile services than other personality types. In addition, the satisfaction-loyalty link is fully mediated by attitude-to-brand. Hence, satisfaction is not a direct driver of loyalty in the mobile services business and loyalty is achieved when service providers simultaneously focussed on the customers’ satisfaction and their attitudes towards brands.

Practical implications

The study identified the personality trait drivers of customer satisfaction and the path to customer loyalty in the mobile services sector. With this information, mobile service providers should be better able to target and retain customers.

Originality/value

The study offers new insights into customer behaviour by using personality traits to identify requirements for achieving customer satisfaction, customer loyalty and attitude-to-brand.
Patients with severe acute‐on‐chronic liver failure are disadvantaged by model for end‐stage liver disease‐based organ allocation policy
Authors: Sundaram Vinay , Shah Parth , Mahmud Nadim , Lindenmeyer Christina C. , Klein Andrew S. , Wong Robert J. , Karvellas Constantine J. , K. Asrani Sumeet , Jalan Rajiv
Published: July 2020

Background

Mortality for patients with acute‐on‐chronic liver failure (ACLF) may be underestimated by the model for end‐stage liver disease‐sodium (MELD‐Na) score.

Aim

To assess waitlist outcomes across varying grades of ACLF among a cohort of patients listed with a MELD‐Na score ≥35, and therefore having similar priority for liver transplantation.

Methods

We analysed the United Network for Organ Sharing (UNOS) database, years 2010‐2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression.

Results

We identified 6342 candidates at listing with a MELD‐Na score ≥35, of whom 3122 had ACLF‐3. Extra‐hepatic organ failures were present primarily in patients with four to six organ failures. Competing risks regression revealed that candidates listed with ACLF‐3 had a significantly higher risk for 90‐day waitlist mortality (Sub‐hazard ratio (SHR) = 1.41; 95% confidence interval [CI] 1.12‐1.78) relative to patients with lower ACLF grades. Subgroup analysis of ACLF‐3 revealed that both the presence of three organ failures (SHR = 1.40, 95% CI 1.20‐1.63) or four to six organ failures at listing (SHR = 3.01; 95% CI 2.54‐3.58) was associated with increased waitlist mortality. Candidates with four to six organ failures also had the lowest likelihood of receiving liver transplantation (SHR = 0.61, 95% CI 0.54‐0.68). The Share 35 rule was associated with reduced 90‐day waitlist mortality among the full cohort of patients listed with ACLF‐3 and MELD‐Na score ≥35 (SHR = 0.59; 95% CI 0.49‐0.70). However, Share 35 rule implementation was not associated with reduced waitlist mortality among patients with four to six organ failures (SHR = 0.76; 95% CI 0.58‐1.02).

Conclusions

The MELD‐Na score disadvantages patients with ACLF‐3, both with and without extra‐hepatic organ failures. Incorporation of organ failures into allocation policy warrants further exploration.
Tailored optimal posttreatment surveillance for cancer recurrence
Authors: Chen Rui , Yu Menggang
Published: July 2020

A substantial rise in the number of cancer survivors has led to urgent management questions regarding effective posttreatment imaging‐based surveillance strategies for cancer recurrence. Current surveillance guidelines provided by a number of professional societies all warn against overly aggressive surveillance, especially for low‐risk patients, but all fail to provide more specific directions to accommodate underlying heterogeneity of cancer recurrence. Therefore it is imperative to develop data‐driven strategies that can tailor the surveillance schedules to recurrence risk in this era of stricter insurance regulations, provider shortages, and rising costs of health care. Due to a lack of statistical methods for optimizing surveillance scheduling in presence of competing risks, we propose a general approach that uses an intuitive loss function for optimization of early detection of recurrence before death. The proposed strategies can tailor to patient risks of recurrence, in terms of both intensity and amount of surveillance. Using general three‐state Markov models, our method is flexible and includes earlier works as special cases. We illustrate our method in both simulation studies and an application to breast cancer surveillance.
Systematic review of barriers to, and facilitators of, the provision of high‐quality midwifery services in India
Authors: McFadden Alison , Gupta Sunanda , Marshall Joyce L. , Shinwell Shona , Sharma Bharati , McConville Fran , MacGillivray Steve
Published: July 2020

Background

The Indian government has committed to implementing high‐quality midwifery care to achieve universal health coverage and reduce the burden of maternal and perinatal mortality and morbidity. There are multiple challenges, including introducing a new cadre of midwives educated to international standards and integrating midwifery into the health system with a defined scope of practice. The objective of this review was to examine the facilitators and barriers to providing high‐quality midwifery care in India.

Methods

We searched 15 databases for studies relevant to the provision of midwifery care in India. The findings were mapped to two global quality frameworks to identify barriers and facilitators to providing high‐quality midwifery care in India.

Results

Thirty‐two studies were included. Key barriers were lack of competence of maternity care providers, lack of legislation recognizing midwives as autonomous professionals and limited scope of practice, social and economic barriers to women accessing services, and lack of basic health system infrastructure. Facilitators included providing more hands‐on experience during training, monitoring and supervision of staff, utilizing midwives to their full scope of practice with good referral systems, improving women's experiences of maternity care, and improving health system infrastructure.

Conclusions

The findings can be used to inform policy and practice. Overcoming the identified barriers will be critical to achieving the Government of India's plans to reduce maternal and neonatal mortality through the introduction of a new cadre of midwives. This is unlikely to be effective until the facilitators described are in place.
Effect of murine double‐minute 2 inhibitors in preclinical models of advanced clear cell carcinomas originating from ovaries and kidneys
Authors: Kawata Yoshiko , Nagasaka Kazunori , Oda Katsutoshi , Makii Chinami , Takeuchi Makoto , Oki Shinya , Honjo Harunori , Kojima Machiko , Miyagawa Yuko , Taguchi Ayumi , Tanikawa Michihiro , Sone Kenbun , Hiraike Haruko , Matsumoto Yoko , Wada‐Hiraike Osamu , Ayabe Takuya , Osuga Yutaka , Fujii Tomoyuki
Published: July 2020

Advanced clear cell carcinomas originating from both ovaries and kidneys with cancerous peritonitis have poor prognoses. Murine double‐minute 2 (MDM2) is a potential therapeutic target for clear cell ovarian carcinomas with WT TP53. Herein, we characterized the antiangiogenic and antitumor effects of the MDM2 inhibitors DS‐3032b and DS‐5272 in 6 clear cell ovarian carcinoma cell lines and 2 clear cell renal carcinoma cell lines, as well as in clear cell ovarian carcinomas s.c. xenograft and ID8 (murine ovarian cancer cells with WT TP53) cancer peritonitis mouse models. In clear cell ovarian carcinoma s.c. xenograft mouse models, DS‐3032b significantly reduced WT TP53 clear cell ovarian carcinoma‐ and clear cell renal carcinoma‐derived tumor volumes. In ID8 mouse models, DS‐5272 significantly inhibited ascites production, reduced body weight, and significantly improved overall survival. Additionally, DS‐5272 reduced the tumor burden of peritoneal dissemination and decreased CD31+ cells in a dose‐dependent manner. Furthermore, DS‐5272 significantly decreased vascular endothelial growth factor concentrations in both sera and ascites. Combined therapy with MDM2 inhibitors and everolimus showed synergistic, and dose‐reduction potential, for clear cell carcinoma treatment. Our findings suggest that MDM2 inhibitors represent promising molecular targeted therapy for clear cell carcinomas, thereby warranting further studies to evaluate the efficacy and safety of dual MDM2/mTOR inhibitors in clear cell carcinoma patients.
ABO‐incompatible living kidney transplantation
Authors: Cen Menger , Wang Rending , Kong Weiwei , Deng Hao , Lei Wenhua , Chen Jianghua
Published: July 2020

ABO‐incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody‐mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody‐mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.
Impfen bei Immunsuppression: ein Leitfaden für die dermatologische Praxis
Authors: Mohme Sophia , Schmalzing Marc , Müller Cornelia S. L. , Vogt Thomas , Goebeler Matthias , Stoevesandt Johanna
Published: July 2020

Der zunehmende Einsatz immunmodulierend wirkender Medikamente erfordert die Beachtung spezifischer Impfempfehlungen, welche durch die Ständige Impfkommission am Robert Koch‐Institut erarbeitet und regelmäßig aktualisiert werden. Dermatologische Patienten unter immunsuppressiver Therapie sollten idealerweise einen vollständigen Status bezüglich altersentsprechender Standardimpfungen aufweisen. Zusätzlich angeraten werden Indikationsimpfungen gegen saisonale Influenza und Pneumokokken sowie ab dem Alter von 50 Jahren eine Impfung mit dem adjuvantierten Zoster‐Totimpfstoff. Die Indikation für zusätzliche Impfungen, beispielsweise gegenHaemophilus influenzae B, Hepatitis B oder Meningokokken, ist abhängig von Begleiterkrankungen und individueller Exposition. Zu beachten sind darüber hinaus Einschränkungen, Kontraindikationen und zeitliche Mindestabstände für die Impfung immunsupprimierter Personen, welche maßgeblich von den eingesetzten immunsuppressiven Wirkstoffen sowie gegebenenfalls deren Dosierung abhängen. Attenuierte Lebendimpfstoffe dürfen unter einer bereits laufenden Immunsuppression nur unter bestimmten Bedingungen eingesetzt werden. Innerhalb von sechs Monaten nach der Gabe von Rituximab ist die Ausbildung einer protektiven Immunantwort so stark reduziert, dass – mit Ausnahme der Grippeimpfung – auch die Gabe von Totimpfstoffen aufgrund eingeschränkter Wirksamkeit nicht angeraten wird.

Der vorliegende Weiterbildungsartikel fasst gültige Impfempfehlungen für immunsupprimierte Personen mit einem Schwerpunkt auf dermatologische Erkrankungen und die hier eingesetzten Wirkstoffe zusammen, um Leserinnen und Lesern eine gezielte Beratung und Veranlassung notwendiger Impfungen für diese vulnerable Personengruppe zu ermöglichen.
Understanding the Value of Delayed Discounts in Retail Rewards Programs
Authors: Jalili Monire , Pangburn Michael S.
Published: July 2020

In practice, it is not uncommon for a retailer to incentivize consumers to purchase its products by instituting a standing “rewards program” across its product line. These rewards often take the form of earned credit, calculated based on current spending, applicable toward a future purchase. In this article, we show that despite their euphemistic “rewards” label, the future‐credit promotion structure is often advantageous for the retailer, even given customers who behave rationally. By analyzing a retailer who sells distinct products to heterogeneous consumers with stochastic demands, we find that a time‐lagged discount increases the number of resulting net‐price states, thus expanding the set of rational shopping behaviors and segmentation. We also prove that even while delayed rewards generally yield higher discount levels (relative to immediate discounts), they can generate higher expected profits. We also consider the impact of imposing a spending‐level threshold for customers to earn rewards, and analyze the impact of the distinct shopping behaviors, which then emerge. By proving the efficacy of such delayed‐reward promotion structures, relative to the alternative of immediate discounts, we establish a theoretical basis for explaining why rewards programs are common in retail practice.
Patents and invention in Jamaica and the British Atlantic before 1857 †
Authors: Graham Aaron
Published: July 2020

Before 1852 the English patent system operated at both a domestic and a global level, allowing inventors to extend its operation beyond England to the colonies, where it interacted in territories such as Jamaica with a colonial system of patents and grants. It therefore provides one of the few examples of a workable global patent system, and an important case study of the structures that supported the development and circulation of technology within the British Atlantic during the early stages of the industrial revolution. Providing a framework of ‘tiered’ rather than ‘parallel’ powers and jurisdictions, the imperial patent system was a flexible instrument that inventors could use strategically to promote transnational technological innovation, in which people, ideas, and skills moved back and forth between Britain and colonies such as Jamaica. Patenting, which was concentrated in wealthy plantation colonies that sought greater productivity, was therefore a key part of the economic development of empire.
Hippocampal blood–brain barrier of methamphetamine self‐administering HIV‐1 transgenic rats
Authors: Ohene‐Nyako Michael , Persons Amanda L. , Napier T. Celeste
Published: July 2020

Combined antiretroviral therapy for HIV infection reduces plasma viral load and prolongs life. However, the brain is a viral reservoir, and pathologies such as cognitive decline and blood–brain barrier (BBB) disruption persist. Methamphetamine abuse is prevalent among HIV‐infected individuals. Methamphetamine and HIV toxic proteins can disrupt the BBB, but it is unclear if there exists a common pathway by which HIV proteins and methamphetamine induce BBB damage. Also unknown are the BBB effects imposed by chronic exposure to HIV proteins in the comorbid context of chronic methamphetamine abuse. To evaluate these scenarios, we trained HIV‐1 transgenic (Tg) and non‐Tg rats to self‐administer methamphetamine using a 21‐day paradigm that produced an equivalency dose range at the low end of the amounts self‐titrated by humans. Markers of BBB integrity were measured for the hippocampus, a brain region involved in cognitive function. Outcomes revealed that tight junction proteins, claudin‐5 and occludin, were reduced in Tg rats independent of methamphetamine, and this co‐occurred with increased levels of lipopolysaccharide, albumin (indicating barrier breakdown) and matrix metalloproteinase‐9 (MMP‐9; indicating barrier matrix disruption); reductions in GFAP (indicating astrocytic dysfunction); and microglial activation (indicating inflammation). Evaluations of markers for two signaling pathways that regulate MMP‐9 transcription, NF‐κB and ERK/∆FosB revealed an overall genotype effect for NF‐κB. Methamphetamine did not alter measurements from Tg rats, but in non‐Tg rats, methamphetamine reduced occludin and GFAP, and increased MMP‐9 and NF‐κB. Study outcomes suggest that BBB dysregulation resulting from chronic exposure to HIV‐1 proteins or methamphetamine both involve NF‐κB/MMP‐9.