bluuebunny/crossref_metadata_2025 huggingface dataset:
Noninvasive model for predicting future ischemic strokes in patients with silent lacunar infarction using radiomics
Authors: Su Jie-hua , Meng Ling-wei , Dong Di , Zhuo Wen-yan , Wang Jian-ming , Liu Li-bin , Qin Yi , Tian Ye , Tian Jie , Li Zhao-hui
Published: July 2020

Background

This study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI).

Methods

Radiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)–Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan–Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation.

Results

Radiomic signature (p < 0.01), age (p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score < 0.17 had higher probabilities of stroke-free survival. The prognostic nomogram and calibration curves of the training and validation cohorts showed acceptable discrimination and calibration capabilities (concordance index [95% confidence interval]: 0.7864 [0.70–0.86]; 0.7140 [0.59–0.83], respectively).

Conclusions

Radiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.
Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi Migraine Disease Specific Programme
Authors: Hirata Koichi , Ueda Kaname , Ye Wenyu , Kim Yongin , Komori Mika , Jackson James , Cotton Sarah , Rajan Narayan , Treuer Tamas
Published: July 2020

Background

Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan.

Methods

This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression.

Results

Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4,p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16,p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29–2.88;p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05–2.60;p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02–1.06;p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28–0.98;p = 0.044).

Conclusions

Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life.
Influence of pacifier use on the association between duration of breastfeeding and anterior open bite in primary dentition
Authors: de Deus Vanessa Felipe , Gomes Erissandra , da Silva Fernanda Caramez , Giugliani Elsa Regina Justo
Published: July 2020

Background

The literature is controversial with regard to the association between longer breastfeeding duration and lower prevalence of anterior open bite. Pacifier use may be involved in this controversy. Thus, the objective of the study was to assess the influence of pacifier use and its duration on the association between longer breastfeeding duration and lower prevalence of anterior open bite in children with primary dentition.

Methods

This was a cross-sectional study nested in a cohort study involving 153 infants recruited at a maternity hospital in the municipality of Porto Alegre, southern Brazil. The study outcome (anterior open bite) was assessed when the children were between 3 and 5 years old. Data on breastfeeding and pacifier use were collected at 7, 30, 60, 120, and 180 days of life and on the date of the evaluation here described. Poisson regression with robust variance was used to analyze the association between the prevalence of anterior open bite and breastfeeding duration, expressed in months.

Results

The univariate analysis showed a protective effect of breastfeeding against anterior open bite (prevalence ratio [PR] 0.96; 95% confidence interval [95%CI] 0.95–0.98). This effect remained significant after adjustment for pacifier use at any time between birth and the date of dental assessment (PR0.98; 95%CI; 0.96–0.99), i.e., there was a reduction of 2% in the prevalence of anterior open bite for each month of breastfeeding. However, this effect lost significance when pacifier use duration was included in the multivariate analysis (PR1.00; 95%CI; 0.99–1.01).

Conclusions

Pacifier use duration influences the association between longer breastfeeding duration and lower prevalence of anterior open bite. It is likely that prolonged pacifier use reduces the magnitude of this association.
CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway
Authors: Jiang Xiao , Huang Zhijie , Sun Xiang , Zheng Xianghuai , Liu Jingpeng , Shen Jun , Jia Bo , Luo Haiyun , Mai Zhaoyi , Chen Guodong , Zhao Jianjiang
Published: July 2020

Background

Chemokine (C-C motif) ligand 18 (CCL18) affects the malignant progression of varying cancers by activating chemokine receptors. Our previous work has shown that CCL18 promotes hyperplasia and invasiveness of oral cancer cells; however, the cognate receptors of CCL18 involved in the pathogenesis of oral squamous cell carcinoma (OSCC) have not yet been identified. This study aimed to investigate the molecular mechanisms which underlie promotive effects of CCL18 on OSCC progression by binding to functional receptors.

Methods

The expression of CCL18 receptor-NIR1 in OSCC was determined by conducting western blot, immunofluorescence, and immunocytochemistry assays. Chi square test was applied to analyze the relationship between expression levels of NIR1 and clinicopathological variables. Recombinant CCL18 (rCCL18), receptor siRNA and JAK specific inhibitor (AG490) were used in experiments investigating the effects of the CCL18-NIR1 axis on growth of cancer cells (i.e., proliferation, and metastasis), epithelial-mesenchymal transition (EMT) and the activation of the JAK2/STAT3 signaling pathway.

Results

NIR1 as functional receptor of CCL18 in OSCC, was found to be significantly upregulated in OSCC and positively related to the TNM stage of OSCC patients. rCCL18 induced the phenotypical alterations in oral cancer cells including cell growth, metastasis and EMT. The JAK2/STAT3 signaling pathway was confirmed to be a downstream pathway mediating the effects of CCL18 in OSCC. AG490 and knockdown of NIR1 could block the effects of rCCL18-induced OSCC.

Conclusion

CCL18 can promote the progression of OSCC by binding NIR1, and the CCL18-NIR1 axis can activate JAK2/STAT3 signaling pathway. The identification of the mechanisms underlying CCL18-mediated promotion of OSCC progression could highlight potential therapeutic targets for treating oral cancer.
Cone beam computed tomography (CBCT) in periodontal diseases: a Systematic review based on the efficacy model
Authors: Assiri Hassan , Dawasaz Ali Azhar , Alahmari Ahmad , Asiri Zuhair
Published: July 2020

Background

Periodontal diseases are prevalent among adult populations. Its diagnosis depends mainly on clinical findings supported by radiographic examinations. In previous decades, cone beam computed tomography has been introduced to the dental field. The aim of this study was to address the diagnostic efficacy of cone-beam computed tomographic (CBCT) imaging in periodontics based on a systematic search and analysis of the literature using the hierarchical efficacy model.

Methods

A systematic search of electronic databases such as PubMed, Scopus, Web of Science, and Cochrane was conducted in February 2019 to identify studies addressing the efficacy of CBCT imaging in Periodontics. The identified studies were subjected to pre-identified inclusion criteria followed by an analysis using a hierarchical model of efficacy (model) designed for an appraisal of the literature on diagnostic imaging modality. Four examiners performed the eligibility and quality assessment of relevant studies and consensus was reached in cases where disagreement occurred.

Results

The search resulted in 64 studies. Of these, 34 publications were allocated to the relevant level of efficacy and quality assessments wherever applicable. The overall diagnostic accuracy of the included studies showed a low or moderate risk of bias and applicability concerns in the use of CBCT. In addition, CBCT is accurate in identifying periodontal defects when compared to other modalities. The studies on the level of patient outcomes agreed that CBCT is a reliable tool for the assessment of outcomes after the treatment of periodontal defects.

Conclusion

CBCT was found to be beneficial and accurate in cases of infra-bony defects and furcation involvements.
Developments in oral health care in the Netherlands between 1995 and 2018
Authors: den Boer Joost C. L. , van der Sanden Wil J. M. , Bruers Josef J. M.
Published: July 2020

Background

Over the past several decades, changes in legislation and regulations have been implemented in oral health care in the Netherlands. In 1995, for example, a major transformation in the funding of oral health care was implemented, after which most oral health care for adults was no longer covered by national insurance. In 1997, the Individual Healthcare Professions Act, in which the authorizations of care providers were described, was established. The Healthcare Quality, Complaints and Disputes Act, established in 2016, concerns the accountability of professional behavior. Regulations concerning employment have changed several times since 1995. These changes have affected the work and practice situation of oral health care providers.

Methods

Data from many publicly available sources were gathered and combined with internal reports mainly derived from the Data Stations project of the Royal Dutch Dental Association. This project was established in 1995 and, since its initiation, 6716 dentists have participated an average of 6.7 times.

Results

Between 1995 and 2018, nearly all professional groups in oral health care increased, particularly those of dental hygienists and prevention assistants. The number of dental practices decreased, but practices got larger in terms of dental units, number of patients, and personnel. The percentage of inhabitants visiting oral health care professionals remained unchanged, but the type of care provided moved towards more prevention. Oral health care providers exploited new opportunities to enhance and express their professional behavior.

Conclusions

Oral health care in the Netherlands has evolved in recent years toward more collaboration in teams, and professions have established institutions to promote the quality and safety of care. Greater emphasis has been placed on prevention of dental diseases. These processes were influenced by new legislation and regulations, demographic changes within professional groups, and other social developments.
Utilization of denture adhesives and the factors associated with its use: a cross-sectional survey
Authors: Bo Tun Min , Hama Yohei , Akiba Norihisa , Minakuchi Shunsuke
Published: July 2020

Background

An increase in the number of elderly edentulous patients likely leads to a greater demand for dentures and denture adhesives. As denture adhesives have both positive and negative features, dentists need to know the types of denture adhesive users to be able to provide instruction to denture wearers on how to use denture adhesives effectively. This study aims to examine the utilization of denture adhesives and associated factors.

Methods

Seven closed-ended questionnaires were developed for a web-based survey. After that, Fisher’s exact tests were performed to determine the difference in the denture adhesive usage rate by gender, type of denture, last dental visit, and smoking status. A multivariate-adjusted logistic regression analysis was performed with denture adhesive use or non-use as the dependent variable and the other items as independent variables. Next, Fisher’s exact tests and a multivariate-adjusted logistic regression analysis were performed with the type of denture adhesives as the dependent variable in the same way. Statistical analyses were performed for all denture wearers, complete denture wearers, and partial denture wearers. The level of statistical significance was set at p = 0.05.

Results

A total of 1470 denture wearers in Japan participated in this study. Of these, 318 used denture adhesives, while 212 (66.7%) used cream; 74 (23.3%) used home liner; 25 (7.9%) used powder; four (1.3%) used sheets; and three (0.9%) used several types. The Fisher’s exact tests revealed that the ratios of using denture adhesives were significantly higher for complete denture wearers (p < 0.001), last dental visit over 1 year (p = 0.005), and smokers (p = 0.005). For partial denture wearers, the ratio was significantly higher in smokers (p = 0.262). The multivariate adjusted logistic regression revealed that denture adhesive use or non-use were significantly associated with the type of denture and smoking status in all denture wearers, and just smoking status in partial denture wearers. There were no significant results about the type of denture adhesive selection.

Conclusions

From all denture wearers, complete denture wearers and smokers are more likely to use denture adhesives. In addition, smokers significantly use denture adhesives if they are partial denture wearers.
Pre-implantological treatment routines for alveolar ridge atrophy – an investigation among maxillofacial and oral surgeons in southern Germany
Authors: Korsch Michael , Walther Winfried , Robra Bernt-Peter , Sahin Aynur , Hannig Matthias , Bartols Andreas
Published: July 2020

Background

It is not well-known which pre-implantological procedures are preferred by maxillofacial (MFS) and oral surgeons (OS) for the narrow atrophic alveolar ridge under practice based conditions and, if different training paths in surgery lead to other pre-implantological techniques being preferred. This study aims to identify which procedures are preferred by the respective specialists in which indication.

Methods

A questionnaire was sent to a total of 300 MFS and OS in southern Germany. The questionnaire examined pre-implantological procedures (bone block, bone grafting material and/or particulate autogenous bone, titanium mesh, bone split, resection) in the edentulous severely atrophic mandible and in the severely atrophic single-tooth gap. Kendall’s Tau-b test was used for statistical analyses.

Results

One hundred seventeen participants returned the questionnaire. 68 (58%) were OS and 49 (42%) were MFS. In the edentulous mandible, bone substitute material and resection were most preferred by both specialists. Bone blocks were statistically significantly more frequently associated with MFS and bone substitute materials with OS. Bone split was more frequently used in the atrophic single tooth gap than in the edentulous mandible. OS preferred bone blocks in the single tooth gap more often than in the edentulous mandible. MFS and OS preferred resection in the edentulous mandible significantly more frequently than in the single tooth gap.

Conclusions

MFS in general prefer more invasive pre-implantological therapies with the same initial diagnosis than OS, which seems to be attributed to different training paths.
Inspecting teams’ and organisations’ expectations regarding external inspections in health care: a qualitative study
Authors: Hovlid Einar , Teig Inger Lise , Halvorsen Kjersti , Frich Jan C.
Published: July 2020

Background

There is a gap in the literature regarding what takes place between the announcement of a regulatory intervention, such as an external inspection of a health care organisation, and the inspecting body’s site visit. This study aimed to explore inspecting bodies’ expectations of how inspected organisations should prepare before an external inspection and to elucidate how inspected health care organisations prepare before site visits.

Methods

This qualitative study was based on data from 17 group interviews with a total of 75 participants representing inspection teams, organisation leaders and clinicians in inspected health care organisations. The data were analysed using a qualitative content analysis method.

Results

We identified two approaches to how the inspection teams expected that the inspected organisations should prepare before site visits. In the first approach the inspection teams did not expect any improvement activities to be initiated during this period and focused on identifying inadequacies that the inspected organisations should subsequently improve. In the second approach the inspection teams expected organisations to review their own practices and begin improvement activities if necessary. The inspected organisations responded in different ways to an upcoming site visit, and the organisations’ leaders were important in determining which activities would be initiated. Organisations in which leaders involved clinicians in assessing care delivery tended to initiate action to improve and expected inspection teams to assess their ongoing improvement work and provide guidance on further improvements. Leaders who did not involve clinicians in assessing the quality of care tended to perceive the current quality of care as adequate on the basis of reviewing written guidelines. They did not initiate action to improve care delivery apart from updating written guidelines describing how care should be delivered, and they expected the inspection team to confirm that their current practices were in line with the guidelines and external standards.

Conclusions

To promote anticipatory effects in inspected organisations, inspecting bodies should stress the importance of assessing clinical practice and involving frontline clinical staff and leaders in the assessment and in improvement work before the site visit.
Extracellular vesicles: novel communicators in lung diseases
Authors: Mohan Aradhana , Agarwal Stuti , Clauss Matthias , Britt Nicholas S. , Dhillon Navneet K.
Published: July 2020

The 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.
Correction to: Response to Juberg et al
Authors: Mie Axel , Rudén Christina , Grandjean Philippe
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

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.

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

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

Skeletal 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

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

Background

In 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.

Results

Using 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.

Conclusions

In 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

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

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

This 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

The 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.
Clinical characteristics of different subtypes and risk factors for the severity of illness in patients with COVID-19 in Zhejiang, China
Authors: Zhang Shan-Yan , Lian Jiang-Shan , Hu Jian-Hua , Zhang Xiao-Li , Lu Ying-Feng , Cai Huan , Gu Jue-Qing , Ye Chan-Yuan , Jin Ci-Liang , Yu Guo-Dong , Jia Hong-Yu , Zhang Yi-Min , Sheng Ji-Fang , Li Lan-Juan , Yang Yi-Da
Published: July 2020

Background

The outbreak of coronavirus disease 2019 (COVID-19) is now becoming an enormous threat to public health. The clinical spectrum of COVID-19 is extensive, of which critical cases are with rapid disease progression and high mortality. The aim of our study is to summarize the characteristics of different subtypes and explore risk factors of illness severity for early identification and prompt treatment.

Methods

In this retrospective study, we collected data of patients confirmed COVID-19 in Zhejiang Province from 17 January to 12 February 2020. According to the definition of clinical classification, we divided confirmed cases into four types, and summarize epidemiological and clinical characteristics, laboratory and radiograph findings, treatments, and outcomes, respectively. Moreover, we used univariate and multivariate ordinal logistic regression models to explore risk factors for the severity of illness in patients with COVID-19.

Results

A total of 788 patients were enrolled in our study, of whom 52 cases (6.6%) were mild type, 658 cases (83.5%) were common type, 61 cases (7.2%) were severe type, and 17 cases (2.2%) were critical type. Multivariate ordinal logistic regression demonstrated increasing odds of the severity of illness in patients with COVID-19 associated with male (odds ratio [OR] = 1.7, 95% confidence interval [CI]: 1.2–2.6 P = 0.008), fever (OR = 3.6, 95% CI: 2.1–6.3, P <  0.001), cough (OR = 1.7, 95% CI: 1.0–2.9, P = 0.041), hemoptysis (OR = 3.4, 95% CI: 1.1–10.3, P = 0.032), gastrointestinal symptoms (OR = 1.9, 95% CI: 1.0–3.5, P = 0.047), hypertension (OR = 2.6, 95% CI: 1.2–5.6, P = 0.013). With the increase of age-grading, risk for the severity of illness was gradually higher (≤ 18 years [OR = 1.0], 19–40 years [OR = 12.7, 95% CI: 4.5–36.0, P < 0.001], 41–65 years [OR = 14.8, 95% CI: 5.2–42.1, P <  0.001], ≥ 66 years [OR = 56.5, 95% CI: 17.1–186.5, P < 0.001]).

Conclusions

Clinicians should pay close attention to these features in patients with COVID-19 including older age, male, fever, cough, hemoptysis, gastrointestinal symptoms and hypertension to identify the severity of illness as early as possible.
Reply to the comment by Osuka et al.
Authors: Endo Akira , Shiraishi Atsushi , Fushimi Kiyohide , Otomo Yasuhiro
Published: July 2020

Patient transfer between hospitals can be one of the biases when evaluating the hospital performance in severe burn care. Optimal handling of such a population is challenging in the analysis of an inpatient database not specialized for burn due to the lack of detailed information.
Platelet-rich plasma (PRP) accelerates murine patellar tendon healing through enhancement of angiogenesis and collagen synthesis
Authors: Kobayashi Yohei , Saita Yoshitomo , Takaku Tomoiku , Yokomizo Tomomasa , Nishio Hirofumi , Ikeda Hiroshi , Takazawa Yuji , Nagao Masashi , Kaneko Kazuo , Komatsu Norio
Published: July 2020

Purpose

Although platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes.

Methods

Full-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation.

Results

The total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks.

Conclusions

We have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.