bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular vesicles: novel communicators in lung diseases
Authors: Mohan Aradhana , Agarwal Stuti , Clauss Matthias , Britt Nicholas S. , Dhillon Navneet K. 
Published: July 2020

AbstractThe lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.
A social ecological approach to understanding service utilization barriers among male survivors of sexual violence in three refugee settings: a qualitative exploratory study
Authors: Chynoweth Sarah K. , Buscher Dale , Martin Sarah , Zwi Anthony B. 
Published: July 2020

Abstract
Background
Post-sexual violence service utilization is often poor in humanitarian settings. Little is known about the service uptake barriers facing male survivors specifically.

Methods
To gain insights into this knowledge gap, we undertook a qualitative exploratory study to better understand the barriers to service utilization among male survivors in three refugee-hosting countries. The study sites and populations included refugees who had travelled the central Mediterranean migration route through Libya living in Rome and Sicily, Italy; Rohingya refugees in Cox’s Bazar, Bangladesh; and refugees from eastern Democratic Republic of the Congo, Somalia, and South Sudan residing in urban areas of Kenya. Methods included document review, 55 semi-structured focus group discussions with 310 refugees, semi-structured key informant interviews with 148 aid workers and human rights experts, and observation of service delivery points. Data were thematically analyzed using NVivo 12.

Results
We identified eleven key barriers and situated them within a social ecological framework to describe impediments at the policy, community (inter-organizational), organizational, interpersonal, and individual levels. Barriers entailed: 1) restrictions to accessing legal protection, 2) legislative barriers such as the criminalization of same-sex sexual relations, 3) few designated entry points, 4) poor or nonexistent referral systems, 5) lack of community awareness-raising and engagement, 6) limited staff capacity, 7) negative provider attitudes and practices, 8) social stigma, 9) limited knowledge (at the individual level), 10) self-stigma, and 11) low formal help-seeking behaviors.

Conclusion
The social ecological framework allowed us to better understand the multifaceted ways that the barriers facing male survivors operate and reinforce one another, and may be useful to inform efforts promoting service uptake. Additional research is warranted in other refugee settings.
One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case “for” and “against”
Authors: Montero-Odasso Manuel , Ismail Zahinoor , Livingston Gill 
Published: July 2020

Abstract
Background
Recently, it has been suggested that up to a third of the dementia cases might be preventable. While prevention is always better than cure, this is particularly important in the field of dementia, as current interventions are not able to modify the disease. This article revises the evidence “for” and “against” dementia primary prevention.

Discussion
Evidence “for” is sustained by the Lancet Commission on Dementia Prevention, Intervention and Care that noted a reduction of age-related incidence of dementia in high-income countries. Based on results from large cohort studies and using population attributable risk, the commission concluded that up to 35% of dementia cases could be prevented by modifying nine risk factors: low education, midlife hearing loss, obesity, hypertension, late-life depression, smoking, physical inactivity, diabetes, and social isolation. In this life course conceptual framework, modifications of risk factors can influence dementia decades before clinical disease onset. However, evidence “against” is supported by large randomized controlled trials (RCT, > 250 participants per arm, minimum of 6 months follow-up), primarily set to prevent dementia using lifestyle interventions that have shown modest or negative results. The 2017 National Academy of Medicine report concluded that the current evidence is limited and there are no specific interventions to warrant a public health recommendation for dementia prevention.

Summary
Multiple pathological pathways are involved in the development of dementia which are theoretically treatable by managing midlife hearing loss and hypertension, and with physical exercise and education, as suggested by robust observational studies. However, evidence from large clinical trials is not conclusive to support that a third of dementia cases might be prevented. Current initiatives testing the effect of lifestyle interventions in larger clinical trials may help to settle this debate.
Complete genome sequence of butenyl-spinosyn-producing Saccharopolyspora strain ASAGF58
Authors: Guo Chao , Guo Weiqun , Liu Yuchun , Wang Chao 
Published: July 2020

Abstract
Purpose
This study aimed to analyze the complete genome sequence of the butenyl-spinosyn-producing strain Saccharopolyspora sp. ASAGF58, isolated from Zhejiang province.

Methods
PacBio RS II sequencing platform with single-molecule real-time technology was used to obtain the complete genome sequence of Saccharopolyspora sp. ASAGF58. Gene prediction and annotation analysis were carried out through several software and databases. The antiSMASH online server was used to evaluate the secondary metabolite potential of strain ASAGF58.

Results
The whole genome of Saccharopolyspora sp. ASAGF58 is 8,190,340 bp divided into one chromosome of 8,044,361 bp with a GC content of 68.1% and a plasmid of 145,979 bp with a GC content of 64.6%. A total of 7486 coding sequences, 15 rRNA genes, 61 tRNA genes, 41 miscRNA genes, and 1 tmRNA gene were predicted. The domains encoded by one of the type I polyketide synthase (T1PKS) gene clusters have 91% similarity with those encoded by a spinosad biosynthetic gene cluster from Saccharopolyspora spinosa. In addition, antiSMASH results predicted that the strain also contains the biosynthetic gene clusters for the synthesis of ectoine, geosmin, and erythreapeptin.

Conclusions
Our data revealed the complete genome sequence of a new isolated butenyl-spinosyn-producing strain. This work will provide some methods, from genetics to biotechnology and biochemistry, aimed at the production improvement of butenyl-spinosyns.
Optimized method for extraction of exosomes from human primary muscle cells
Authors: Le Gall Laura , Ouandaogo Zamalou Gisele , Anakor Ekene , Connolly Owen , Butler Browne Gillian , Laine Jeanne , Duddy William , Duguez Stephanie 
Published: July 2020

AbstractSkeletal muscle is increasingly considered an endocrine organ secreting myokines and extracellular vesicles (exosomes and microvesicles), which can affect physiological changes with an impact on different pathological conditions, including regenerative processes, aging, and myopathies. Primary human myoblasts are an essential tool to study the muscle vesicle secretome. Since their differentiation in conditioned media does not induce any signs of cell death or cell stress, artefactual effects from those processes are unlikely. However, adult human primary myoblasts senesce in long-term tissue culture, so a major technical challenge is posed by the need to avoid artefactual effects resulting from pre-senescent changes. Since these cells should be studied within a strictly controlled pre-senescent division count (<21 divisions), and yields of myoblasts per muscle biopsy are low, it is difficult or impossible to amplify sufficiently large cell numbers (some 250 × 106 myoblasts) to obtain sufficient conditioned medium for the standard ultracentrifugation approach to exosome isolation.Thus, an optimized strategy to extract and study secretory muscle vesicles is needed. In this study, conditions are optimized for the in vitro cultivation of human myoblasts, and the quality and yield of exosomes extracted using an ultracentrifugation protocol are compared with a modified polymer-based precipitation strategy combined with extra washing steps. Both vesicle extraction methods successfully enriched exosomes, as vesicles were positive for CD63, CD82, CD81, floated at identical density (1.15-1.27 g.ml−1), and exhibited similar size and cup-shape using electron microscopy and NanoSight tracking. However, the modified polymer-based precipitation was a more efficient strategy to extract exosomes, allowing their extraction in sufficient quantities to explore their content or to isolate a specific subpopulation, while requiring >30 times fewer differentiated myoblasts than what is required for the ultracentrifugation method. In addition, exosomes could still be integrated into recipient cells such as human myotubes or iPSC-derived motor neurons.Modified polymer-based precipitation combined with extra washing steps optimizes exosome yield from a lower number of differentiated myoblasts and less conditioned medium, avoiding senescence and allowing the execution of multiple experiments without exhausting the proliferative capacity of the myoblasts.
Selective serotonin reuptake inhibitors (SSRIs) prevent meta-iodobenzylguanidine (MIBG) uptake in platelets without affecting neuroblastoma tumor uptake
Authors: Blom Thomas , Meinsma Rutger , Rutgers Marja , Buitenhuis Corine , Dekken-Van den Burg Marieke , van Kuilenburg André B. P. , Tytgat Godelieve A. M. 
Published: July 2020

Abstract
Background
The therapeutic use of [131I]meta-iodobenzylguanidine ([131I]MIBG) is often accompanied by hematological toxicity, mainly consisting of persistent and severe thrombocytopenia. While MIBG accumulates in neuroblastoma cells via selective uptake by the norepinephrine transporter (NET), the serotonin transporter (SERT) is responsible for cellular uptake of MIBG in platelets. In this study, we have investigated whether pharmacological intervention with selective serotonin reuptake inhibitors (SSRIs) may prevent radiotoxic MIBG uptake in platelets without affecting neuroblastoma tumor uptake.

Methods
To determine the transport kinetics of SERT for [125I]MIBG, HEK293 cells were transfected with SERT and uptake assays were conducted. Next, a panel of seven SSRIs was tested in vitro for their inhibitory potency on the uptake of [125I]MIBG in isolated human platelets and in cultured neuroblastoma cells. We investigated in vivo the efficacy of the four best performing SSRIs on the accumulation of [125I]MIBG in nude mice bearing subcutaneous neuroblastoma xenografts. In ex vivo experiments, the diluted plasma of mice treated with SSRIs was added to isolated human platelets to assess the effect on [125I]MIBG uptake.

Results
SERT performed as a low-affinity transporter of [125I]MIBG in comparison with NET (Km = 9.7 μM and 0.49 μM, respectively). Paroxetine was the most potent uptake inhibitor of both serotonin (IC50 = 0.6 nM) and MIBG (IC50 = 0.2 nM) in platelets. Citalopram was the most selective SERT inhibitor of [125I]MIBG uptake, with high SERT affinity in platelets (IC50 = 7.8 nM) and low NET affinity in neuroblastoma cells (IC50 = 11.940 nM). The in vivo tested SSRIs (citalopram, fluvoxamine, sertraline, and paroxetine) had no effect on [125I]MIBG uptake levels in neuroblastoma xenografts. In contrast, treatment with desipramine, a NET selective inhibitor, resulted in profoundly decreased xenograft [125I]MIBG levels (p < 0.0001). In ex vivo [125I]MIBG uptake experiments, 100- and 34-fold diluted murine plasma of mice treated with citalopram added to isolated human platelets led to a decrease in MIBG uptake of 54–76%, respectively.

Conclusion
Our study demonstrates for the first time that SSRIs selectively inhibit MIBG uptake in platelets without affecting MIBG accumulation in an in vivo neuroblastoma model. The concomitant application of citalopram during [131I]MIBG therapy seems a promising strategy to prevent thrombocytopenia in neuroblastoma patients.
Kinfitr — an open-source tool for reproducible PET modelling: validation and evaluation of test-retest reliability
Authors: Tjerkaski Jonathan , Cervenka Simon , Farde Lars , Matheson Granville James 
Published: July 2020

AbstractBackgroundIn positron emission tomography (PET) imaging, binding is typically estimated by fitting pharmacokinetic models to the series of measurements of radioactivity in the target tissue following intravenous injection of a radioligand. However, there are multiple different models to choose from and numerous analytical decisions that must be made when modelling PET data. Therefore, it is important that analysis tools be adapted to the specific circumstances, and that analyses be documented in a transparent manner.Kinfitr, written in the open-source programming language R, is a tool developed for flexible and reproducible kinetic modelling of PET data, i.e. performing all steps using code which can be publicly shared in analysis notebooks. In this study, we compared outcomes obtained usingkinfitrwith those obtained using PMOD: a widely used commercial tool.ResultsUsing previously collected test-retest data obtained with four different radioligands, a total of six different kinetic models were fitted to time-activity curves derived from different brain regions. We observed good correspondence between the two kinetic modelling tools both for binding estimates and for microparameters. Likewise, no substantial differences were observed in the test-retest reliability estimates between the two tools.ConclusionsIn summary, we showed excellent agreement between the open-source R packagekinfitr, and the widely used commercial application PMOD. We, therefore, conclude thatkinfitris a valid and reliable tool for kinetic modelling of PET data.
A review of animal health and drug use practices in India, and their possible link to antimicrobial resistance
Authors: Mutua Florence , Sharma Garima , Grace Delia , Bandyopadhyay Samiran , Shome Bibek , Lindahl Johanna 
Published: July 2020

Abstract
Background
Livestock production, particularly the dairy sector, is important for food and nutritional wellbeing of communities in India, it supports livelihoods of many farmers, and contributes to the economy of the country. India is a high consumer of antibiotics and antimicrobial resistant (AMR) bacteria are a major public health concern.

Objectives
Our objectives were to identify animal health and drug use practices that may contribute to emergence and spread of AMR in the country, review previous AMR- mitigation strategies, and discuss “theory of change” as an approach to informing the choice of interventions.

Methods
We undertook a desk review of literature to identify practices with potential to contribute to emergence and spread of antimicrobial resistance in India. Searches were done in PubMed, Google scholar, and Google. Data were synthesized and discussed by themes.

Results
Animal disease surveillance is less developed and infrastructure to support delivery of services is inadequate. Several groups are known to offer animal health services. The untrained “animal health workers” and para-veterinarians are more popular with farmers as they charge less for consultations (compared to veterinarians who are few and charge more). Over-the-counter access of antibiotics, without prescription, and direct marketing of drugs to farmers are common. Because of this, farmers are able to treat their animals and only consult when cases become non- responsive to treatment. Antibiotics are mostly used in management of mastitis cases. Drug withdrawal periods are rarely observed and occurrence of antibiotic- contaminated milk has been reported. Awareness on AMR is low and antimicrobial stewardship in livestock is yet to be developed. Initiatives such as the National programme for containment of AMR, National Action Plan on AMR, and the National Health policy point to government’s commitment in addressing the problem of AMR in the country.

Conclusion
Several animal health and drug use practices, with potential to cause AMR, have been described, and their contribution can be discussed further by engaging stakeholders in a “theory of change” exercise. Interventions that address AMR from the animal health perspective should be promoted, and incentives to increase their adoption explored.
Effect of dietary near ideal amino acid profile on heat production of lactating sows exposed to thermal neutral and heat stress conditions
Authors: Zhang S. , Johnson J. S. , Trottier N. L. 
Published: July 2020

Abstract
Background
Reduced protein diet manifested potential to mitigate heat production based on the concept of ideal amino acid profile. The hypothesis of this study was that lactating sows fed a low crude protein (LCP) diet with supplemental amino acid produce less heat compared to those fed a high crude protein (HCP) diet under both thermal neutral (TN) and heat stress (HS) conditions.

Methods
Thirty-two lactating sows were allotted to HCP (193 g CP/kg) and LCP (140 g CP/kg) diets under thermal neutral (TN, 21 ± 1.5 °C) or cycling heat stress (HS, 32 ± 1.5 °C daytime and 24 ± 1.5 °C nighttime) conditions. Diets contained 0.90% SID lysine and 10.8 MJ/kg net energy. Positive pressure indirect calorimeters were used to measure gas exchange in individual sows with litters, and individual piglets on days 4, 8, 14 and 18. Sow and litter weights were recorded on days 1, 10 and 21.

Results
Sow total heat production (THP) was calculated by subtracting litter THP from sow + litter THP based on BW0.75. Sow BW and body protein (BP) loss was greater for LCP diet compared to HCP diet in peak lactation (P < 0.05 and P < 0.01, respectively) and throughout the entire lactation period (P < 0.05 and P = 0.056, respectively) under HS conditions. Heat-stressed sows fed HCP diet had higher (P < 0.05) rectal temperature at 13:00 (P < 0.05) and 19:00 (P < 0.01), and higher respiration rate at 07:00 (P <  0.05), 13:00 (P < 0.05) and 19:00 (P < 0.05) compared to TN sows fed HCP diet. In sows fed LCP diet, those under HS tended to have higher (P = 0.098) rectal temperature at 13:00 and had higher (P <  0.05) respiration rate at 07:00, 13:00 and 19:00 compared to TN sows. The relationship between daily THP and days in lactation of sows fed LCP diet was quadratic (P < 0.05), with an ascending trend until day 14 and a descending trend from days 14 to 18. Sows fed LCP diet had lower daily THP at day 18 (P < 0.001) compared to those fed the HCP diet under HS conditions.

Conclusion
Reduction in THP in sows fed LCP diet was largely associated with THP on day 18 of lactation under HS conditions. Feeding LCP diets alleviated the increased body temperature in sows under HS conditions throughout lactation, which was accompanied by a reduction in respiration rate. Total heat production is associated with days in lactation, in particular under HS conditions with THP appearing to peak between days 14 and 18.
Built environment attributes and crime: an automated machine learning approach
Authors: Dakin Kyle , Xie Weizhi , Parkinson Simon , Khan Saad , Monchuk Leanne , Pease Ken 
Published: July 2020

AbstractThis paper presents the development of an automated machine learning approach to gain an understanding of the built environment and its relationship to crime. This involves the automatic capture of street-level photographs using Google Street View (GSV), followed by the use of supervised machine learning techniques (specifically image feature recognition) to recognise features of the built environment. In this exploratory proof-of-concept work, 8 key features (building, door, fence, streetlight, tree, window, hedge, and garage) are considered and a worked case-study is demonstrated for a small geographical area (8300 square kilometres) in Northern England. A total of 60,100 images were automatically collected and analysed across the area where 5288 crime incidents were reported over a twelve-month period. Dependency between features and crime incidents are measured; however, no strong correlation has been identified. This is unsurprisingly considering the high number of crime incidents in a small geographic region (8300 square kilometres), resulting in an overlap between specific features and multiple crime incidents. Furthermore, due to the unknown precise location of crime instances, an approximation technique is developed to survey a crime’s local proximity. Despite the absence of a strong correlation, this paper presents a first-of-a-kind cross-discipline approach to attempt and use computation techniques to produce new empirical knowledge. There are many avenues of future research in this fertile and important area.
Human genetics and genomics meetings going virtual: practical lessons learned from two international meetings in early 2020
Authors: Forrest Alistair R. R. , Repetto Gabriela M. , Reichardt Juergen K. V. 
Published: July 2020

AbstractThe recent coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disruption which also extends to the arena of scientific meetings around the world. Here, we explore the lessons learned from moving two human genetics and genomics meetings quickly to an online format in early 2020. The tips presented herein may be useful not only for future virtual meetings but may also enrich future physical if not hybrid meetings once they resume.