bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospect on the use of antiviral drugs to control local outbreaks of COVID-19
Authors: Torneri Andrea , Libin Pieter , Vanderlocht Joris , Vandamme Anne-Mieke , Neyts Johan , Hens Niel 
Published: June 2020

AbstractBackgroundCurrent outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic.MethodsUsing a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process.ResultsFor an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out.ConclusionIn all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.
Ab locks for improving the selectivity and safety of antibody drugs
Authors: Lin Wen-Wei , Lu Yun-Chi , Chuang Chih-Hung , Cheng Tian-Lu 
Published: June 2020

AbstractMonoclonal antibodies (mAbs) are a major targeted therapy for malignancies, infectious diseases, autoimmune diseases, transplant rejection and chronic inflammatory diseases due to their antigen specificity and longer half-life than conventional drugs. However, long-term systemic antigen neutralization by mAbs may cause severe adverse events. Improving the selectivity of mAbs to distinguish target antigens at the disease site from normal healthy tissue and reducing severe adverse events caused by the mechanisms-of-action of mAbs is still a pressing need. Development of pro-antibodies (pro-Abs) by installing a protease-cleavable Ab lock is a novel and advanced recombinant Ab-based strategy that efficiently masks the antigen binding ability of mAbs in the normal state and selectively “turns on” the mAb activity when the pro-Ab reaches the proteolytic protease-overexpressed diseased tissue. In this review, we discuss the design and advantages/disadvantages of different Ab lock strategies, focusing particularly on spatial-hindrance-based and affinity peptide-based approaches. We expect that the development of different masking strategies for mAbs will benefit the local reactivity of mAbs at the disease site, increase the therapeutic efficacy and safety of long-term treatment with mAbs in chronic diseases and even permit scientists to develop Ab drugs for formerly undruggable targets and satisfy the unmet medical needs of mAb therapy.
Dietary inflammatory index, risk of incident hypertension, and effect modification from BMI
Authors: MacDonald Conor-James , Laouali Nasser , Madika Anne-Laure , Mancini Francesca Romana , Boutron-Ruault Marie-Christine 
Published: June 2020

AbstractIntroductionPrevious studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI.MethodsData from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship.ResultsDuring 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII >  3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5–21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed.ConclusionEvidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women.
ERNICA guidelines for the management of rectosigmoid Hirschsprung’s disease
Authors: Kyrklund Kristiina , Sloots Cornelius E. J. , de Blaauw Ivo , Bjørnland Kristin , Rolle Udo , Cavalieri Duccio , Francalanci Paola , Fusaro Fabio , Lemli Annette , Schwarzer Nicole , Fascetti-Leon Francesco , Thapar Nikhil , Johansen Lars Søndergaard , Berrebi Dominique , Hugot Jean-Pierre , Crétolle Célia , Brooks Alice S. , Hofstra Robert M. , Wester Tomas , Pakarinen Mikko P. 
Published: June 2020

Abstract
Background
Hirschsprung’s disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management.

Aims
This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders.

Methods
Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted.

Results
Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion.

Conclusion
In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.
Core outcome sets through the healthcare ecosystem: the case of type 2 diabetes mellitus
Authors: Dodd Susanna , Harman Nicola , Taske Nichole , Minchin Mark , Tan Toni , Williamson Paula R. 
Published: June 2020

Abstract
Background
It is increasingly accepted that insufficient attention has been given to the patient health outcomes that are important to measure in comparative effectiveness research that will inform decision-making. The relationship between outcomes chosen for comparative effectiveness research, outcomes used in decision-making in routine care, and outcome data recorded in electronic health records (EHR) is also poorly understood. The COMET Initiative (http://www.comet-initiative.org/. Accessed 3 Apr 2020) supports and encourages the development and use of ‘core outcome sets’ (COS), which represent the minimum set of patient health outcomes that should be measured and reported for a specific condition. There is growing interest in identifying how COS might fit into the different stages of the healthcare research and delivery ecosystem, and whether inclusion in the EHR might facilitate this.

Methods
We sought to determine the degree of overlap between outcomes within COS for research and routine care, EMA, FDA and NICE guidelines, NICE quality statements/indicators, EHR and a point-of-care randomised clinical trial, using type 2 diabetes (T2D) as a case study.

Results
There is substantial agreement about important patient outcomes for T2D for research and healthcare, with associated coverage within the UK general practice EHR.

Conclusions
This case study has demonstrated the potential for efficient research and value-based healthcare when the EHR can include COS for both research and care, where the COS comprises outcomes of importance to all relevant stakeholders. However, this concordance may not hold more generally, as the focus on patient-centred outcomes may well be greater in T2D than in other conditions. Work is ongoing to examine other clinical areas, in order to highlight any current inefficiencies when health outcomes in research and healthcare do not agree with core outcomes identified by patients, clinicians and other key stakeholders.
FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial
Authors: Poinas Alexandra , Lemoigne Marie , Le Naour Sarah , Nguyen Jean-Michel , Schirr-Bonnans Solène , Riche Valery-Pierre , Vrignaud Florence , Machet Laurent , Claudel Jean-Paul , Leccia Marie-Thérèse , Hainaut Ewa , Beneton Nathalie , Dert Cécile , Boisrobert Aurélie , Flet Laurent , Chiffoleau Anne , Corvec Stéphane , Khammari Amir , Dréno Brigitte 
Published: June 2020

Abstract
Background
Acne vulgaris has increased in women over the past 10 years; it currently affects 20–30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone’s efficacy in order to establish it as an alternative to cyclines.

Methods
Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months.

Discussion
The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage.

Trial registration
ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.
Multiplex PCR for simultaneous genotyping of kdr mutations V410L, V1016I and F1534C in Aedes aegypti (L.)
Authors: Villanueva-Segura Karina , Ponce-Garcia Gustavo , Lopez-Monroy Beatriz , Mora-Jasso Esteban , Perales Lucia , Gonzalez-Santillan Francisco J. , Ontiveros-Zapata Kevin , Davila-Barboza Jesus A. , Flores Adriana E. 
Published: June 2020

Abstract
Background
Knockdown resistance (kdr) is the main mechanism that confers resistance to pyrethroids and DDT. This is a product of non-synonymous mutations in the voltage-gated sodium channel (vgsc) gene, and these mutations produce a change of a single amino acid which reduces the affinity of the target site for the insecticide molecule. In Mexico, V410L, V1016I and F1534C mutations are common in pyrethroid-resistant Aedes aegypti (L.) populations.

Methods
A multiplex PCR was developed to detect the V410L, V1016I and F1534C mutations in Ae. aegypti. The validation of the technique was carried out by DNA sequencing using field populations previously characterized for the three mutations through allele-specific PCR (AS-PCR) and with different levels of genotypic frequencies.

Results
The standardized protocol for multiplex end-point PCR was highly effective in detecting 15 genotypes considering the three mutations V410L, V1106I and F1534C, in 12 field populations of Ae. aegypti from Mexico. A complete concordance with AS-PCR and DNA sequencing was found for the simultaneous detection of the three kdr mutations.

Conclusions
Our diagnostic method is highly effective for the simultaneous detection of V410L, V1016I and F1534C, when they co-occur. This technique represents a viable alternative to complement and strengthen current monitoring and resistance management strategies against Ae. aegypti.
Epigenome-wide DNA methylation analysis of small cell lung cancer cell lines suggests potential chemotherapy targets
Authors: Krushkal Julia , Silvers Thomas , Reinhold William C. , Sonkin Dmitriy , Vural Suleyman , Connelly John , Varma Sudhir , Meltzer Paul S. , Kunkel Mark , Rapisarda Annamaria , Evans David , Pommier Yves , Teicher Beverly A. 
Published: June 2020

Abstract
Background
Small cell lung cancer (SCLC) is an aggressive neuroendocrine lung cancer. SCLC progression and treatment resistance involve epigenetic processes. However, links between SCLC DNA methylation and drug response remain unclear. We performed an epigenome-wide study of 66 human SCLC cell lines using the Illumina Infinium MethylationEPIC BeadChip array. Correlations of SCLC DNA methylation and gene expression with in vitro response to 526 antitumor agents were examined.

Results
We found multiple significant correlations between DNA methylation and chemosensitivity. A potentially important association was observed for TREX1, which encodes the 3′ exonuclease I that serves as a STING antagonist in the regulation of a cytosolic DNA-sensing pathway. Increased methylation and low expression of TREX1 were associated with the sensitivity to Aurora kinase inhibitors AZD-1152, SCH-1473759, SNS-314, and TAK-901; the CDK inhibitor R-547; the Vertex ATR inhibitor Cpd 45; and the mitotic spindle disruptor vinorelbine. Compared with cell lines of other cancer types, TREX1 had low mRNA expression and increased upstream region methylation in SCLC, suggesting a possible relationship with SCLC sensitivity to Aurora kinase inhibitors.
We also identified multiple additional correlations indicative of potential mechanisms of chemosensitivity. Methylation of the 3′UTR of CEP350 and MLPH, involved in centrosome machinery and microtubule tracking, respectively, was associated with response to Aurora kinase inhibitors and other agents. EPAS1 methylation was associated with response to Aurora kinase inhibitors, a PLK-1 inhibitor and a Bcl-2 inhibitor. KDM1A methylation was associated with PLK-1 inhibitors and a KSP inhibitor. Increased promoter methylation of SLFN11 was correlated with resistance to DNA damaging agents, as a result of low or no SLFN11 expression. The 5′ UTR of the epigenetic modifier EZH2 was associated with response to Aurora kinase inhibitors and a FGFR inhibitor. Methylation and expression of YAP1 were correlated with response to an mTOR inhibitor. Among non-neuroendocrine markers, EPHA2 was associated with response to Aurora kinase inhibitors and a PLK-1 inhibitor and CD151 with Bcl-2 inhibitors.

Conclusions
Multiple associations indicate potential epigenetic mechanisms affecting SCLC response to chemotherapy and suggest targets for combination therapies. While many correlations were not specific to SCLC lineages, several lineage markers were associated with specific agents.
Anaerobic methane-oxidizing bacterial communities in sediments of a drinking reservoir, Beijing, China
Authors: Liu Yang , Wang Xiaoyan , Chen Yongjuan , Zhang Lingrong , Xu Kangli , Du Yi 
Published: June 2020

Abstract
Purpose
Nitrate/nitrite-dependent anaerobic methane oxidation (N-DAMO) connects the global cycle of carbon and nitrogen in aquatic ecosystems. The aims of this study were to investigate the spatiotemporal variation of N-DAMO bacteria and its driving factors in a drinking reservoir which are strongly affected by human consumption.

Methods
Cloning analyses were used to study the pmoA and 16S rRNA genes of N-DAMO bacteria. Sequencing and phylogenetic analyses were used to investigate the bacterial composition and structure. Redundancy analyses (RDA) and spearman’s correlations analyses were applied to analyze the relationships between bacterial distribution and environmental factors.

Result
There were remarkable spatial variations of N-DAMO bacteria in winter. Shannon biodiversity of 16S rRNA genes was higher in winter than that in summer. Compared with other freshwater ecosystems, there was higher diversity of N-DAMO bacteria in Miyun Reservoir. The N-DAMO bacterial communities (16S rRNA and pmoA genes) in sampling sites near to dam were different from the bacterial communities in other sampling sites. The N-DAMO bacterial community structure in dam areas may be associated with the water column depth in front of the dam. Moreover, Spearman’s correlations revealed that DO, NO3− -N, NO2−-N, and NH4+-N in interstitial water and sediment were potential determinant factors influencing the diversity of N-DAMO bacteria (16S rRNA and pmoA genes).

Conclusion
There were distinct seasonal variations in 16S rRNA and spatial variations in pmoA genes. N-DAMO bacterial communities contained novel Methylomirabilis oxyfera-like pmoA genes in Miyun Reservoir. Nitrogen (NO2−-N, NO3−-N, and NH4+-N) were the dominant factor influencing the N-DAMO bacterial community structure in the drinking reservoir. N-DAMO bacterial community structure in dam areas indicates that water depth and DO might be the dominant factor influencing the N-DAMO bacterial communities in the reservoir.
A depthwise separable convolutional neural network for keyword spotting on an embedded system
Authors: Sørensen Peter Mølgaard , Epp Bastian , May Tobias 
Published: June 2020

AbstractA keyword spotting algorithm implemented on an embedded system using a depthwise separable convolutional neural network classifier is reported. The proposed system was derived from a high-complexity system with the goal to reduce complexity and to increase efficiency. In order to meet the requirements set by hardware resource constraints, a limited hyper-parameter grid search was performed, which showed that network complexity could be drastically reduced with little effect on classification accuracy. It was furthermore found that quantization of pre-trained networks using mixed and dynamic fixed point principles could reduce the memory footprint and computational requirements without lowering classification accuracy. Data augmentation techniques were used to increase network robustness in unseen acoustic conditions by mixing training data with realistic noise recordings. Finally, the system’s ability to detect keywords in a continuous audio stream was successfully demonstrated.
Integrating pharmaceutical systems strengthening in the current global health scenario: three ‘uncomfortable truths’
Authors: Hafner Tamara , Banda Marlon , Kohler Jillian , Babar Zaheer-Ud-Din , Lumpkin Murray , Adeyeye Mojisola Christianah , Nfor Emmanuel , Aboagye-Nyame Francis , Guzman Javier 
Published: June 2020

AbstractThe response to emergency public health challenges such as HIV, TB, and malaria has been successful in mobilising resources and scaling up treatment for communicable diseases. However, many of the remaining challenges in improving access to and appropriate use of medicines and services require pharmaceutical systems strengthening. Incorporating pharmaceutical systems strengthening into global health programmes requires recognition of a few ‘truths’. Systems strengthening is a lengthy and resource-intensive process that requires sustained engagement, which may not align with the short time frame for achieving targets in vertical-oriented programmes. Further, there is a lack of clarity on what key metrics associated with population and patient level outcomes should be tracked for systems strengthening interventions. This can hinder advocacy and communication with decision makers regarding health systems investments. Moving forward, it is important to find ways to balance the inherent tensions between the short-term focus on the efficiency of vertical programmes and broader, longer-term health and development objectives. Global health programme design should also shift away from a narrow view of medicines primarily as an input commodity to a more comprehensive view that recognizes the various structures and processes and their interactions within the broader health system that help ensure access to and appropriate use of medicines and related services.