bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTMonoclonal 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.ImportanceCarbapenem-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

ABSTRACTPathological 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

AbstractRecent 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

AbstractThis 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

AbstractCholera 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

PurposeThis 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/approachThis 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.FindingsThe 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 implicationsWith 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/valueTo 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

PurposeThe 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/approachThe 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).FindingsThe 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 implicationsThe 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/valueThe 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

SummaryBackgroundMortality for patients with acute‐on‐chronic liver failure (ACLF) may be underestimated by the model for end‐stage liver disease‐sodium (MELD‐Na) score.AimTo 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.MethodsWe analysed the United Network for Organ Sharing (UNOS) database, years 2010‐2017. Waitlist outcomes were evaluated using Fine and Gray's competing risks regression.ResultsWe 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).ConclusionsThe 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

AbstractA 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

AbstractBackgroundThe 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.MethodsWe 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.ResultsThirty‐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.ConclusionsThe 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

AbstractAdvanced 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

AbstractABO‐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.