bluuebunny/crossref_metadata_2025 huggingface dataset:
Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review
Authors: Lozano F. , Raventos C. X. , Carrion A. , Trilla E. , Morote J.
Published: July 2020

Background

Genetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques.

Methods

Following PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported.

Results

There are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers.

Conclusions

Although cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.
Necrotizing sialometaplasia: a malignant masquerade but questionable precancerous lesion, report of four cases
Authors: Shin Sun Ah. , Na Hee Young , Choe Ji Young , Hong Seung-No , Lee Ho , Park Sunwon , Kim Ji Eun
Published: July 2020

Background

Necrotizing sialometaplasia (NSM) is an extremely rare benign lesion with an uncertain pathogenesis. The differential diagnosis of this lesion is challenging due to little familiarity with this entity and histologic similarity with carcinomas, especially mucoepidermoid carcinoma (MEC). The purpose of this study is to raise awareness about NSM, which is often overlooked or misdiagnosed as malignancy in a small biopsy.

Methods

We reviewed all biopsy materials taken from the oral cavity in a single institution in Korea from 2012 to 2018 and found 4 cases of NSM out of 726. Clinicopathologic characteristics and comparison with other lesions were discussed.

Results

Unlike previous reports, patients in our series were relatively young, and NSM was not related to smoking and not associated with malignancies, although one patient was misdiagnosed with MEC on the basis of the initial biopsy. High-grade squamous dysplasia was observed in one patient; however, all four patients showed excellent prognoses without further management.

Conclusions

A conservative approach is recommendable for necrotizing lesions of the palate in young adults to avoid unnecessary treatment. However, careful monitoring is also required due to uncertainty of premalignant potential.
Outcome of revascularization therapy in traumatized immature incisors
Authors: Mittmann Carolina W. , Kostka Eckehard , Ballout Husam , Preus Mareike , Preissner Robert , Karaman Murat , Preissner Saskia
Published: July 2020

Background

The aim of this retrospective analysis was to evaluate the clinical and radiological outcome of revascularization therapy in traumatized permanent incisors to determine whether this approach could be implemented into clinical routine.

Methods

A total of 16 traumatized incisors (either avulsion or severe luxation/intrusion) with open apices (> 1 mm) that underwent revascularization following a standardized protocol were analyzed with a mean follow-up of 22 months. Radiographs and clinical parameters (such as root length, pulp space, dentin wall width, apical foramen, alveolar bone loss, ankylosis/mobility, supra−/infraposition, discoloration, probing depth) were compared pre- and postoperatively and statistically analyzed.

Results

Over the follow-up period, 81.3% of the teeth survived revascularization and regained sensitivity, while 18.7% failed, as they had to be extracted due to serious root resorption. Regarding radiographic outcomes a significant difference could only be found in the decrease of apical foramina (p = 0.04). The other parameters showed no significant difference between pre- and postoperative measurements. More than half of the teeth (56.3%) developed root resorptions and 31.3% displayed signs of ankylosis and 92.9% developed discolorations during follow-up. However, 85.7% of the teeth maintained the bone level and outcomes of mobility showed a significant solidification.

Conclusions

Revascularization is a promising approach for the treatment of immature incisors to regain sensitivity and to enhance apical closure and at least to maintain alveolar bone in terms of a socket preservation. Further studies have to be performed to determine ideal conditions (type of trauma, age, width of apical foramen) for a revascularization.
Systems all the way down: embracing complexity in mental health research
Authors: Fried Eiko I. , Robinaugh Donald J.
Published: July 2020

In this editorial for the collection on complexity in mental health research, we introduce and summarize the inaugural contributions to this collection: a series of theoretical, methodological, and empirical papers that aim to chart a path forward for investigating mental health in all its complexity. A central theme emerges from these contributions: if we are to make genuine progress in explaining, predicting, and treating mental illness, we must study the systems from which psychopathology emerges. As the articles in this collection make clear, the systems that give rise to psychopathology encompass a host of components across biological, psychological, and social levels of analysis, intertwined in a web of complex interactions. The task of advancing our understanding of these systems will be a challenging one. Yet, this challenge presents a unique opportunity. From physics to ecology, there is a rapidly evolving body of interdisciplinary research dedicated to investigating complex systems. This work provides clear guidance for psychiatric research, opportunities for collaboration, and a set of tools and concepts from which we can draw in our efforts to understand mental health, helping us move toward our ultimate aim of improving the prevention and treatment of psychopathology.
Correction to: Novel sulphamoylated 2-methoxy estradiol derivatives inhibit breast cancer migration by disrupting microtubule turnover and organization
Authors: van Vuuren Rustelle Janse , Botes Mandie , Jurgens Tamarin , Joubert Anna Margaretha , van den Bout Iman
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Weight and head circumference at birth in function of placental paraben load in Belgium: an ENVIRONAGE birth cohort study
Authors: Vrijens Karen , Van Overmeire Ilse , De Cremer Koen , Neven Kristof Y. , Carollo Riccardo M. , Vleminckx Christiane , Van Loco Joris , Nawrot Tim S.
Published: July 2020

Background

Parabens are a group of esters of para-hydroxybenzoic acid utilized as antimicrobial preservatives in many personal care products. Epidemiological studies regarding the adverse effects of parabens on fetuses are limited. The aim of this study was to determine the association between placental paraben exposure and birth outcomes. We assessed paraben concentrations in placental tissue, which potentially gives a better understanding of fetal exposure than the maternal urinary concentrations which are the current golden standard.

Methods

Placental tissue was collected immediately after birth from 142 mother-child pairs from the ENVIRONAGE birth cohort. The placental concentrations of four parabens (methyl (MeP), ethyl (EtP), propyl (PrP), and butyl (BuP)) were determined by ultra-performance liquid chromatography coupled with tandem mass-spectrometry. Generalized linear regression models were used to determine the association between paraben exposure levels and birth outcomes.

Results

The geometric means of placental MeP, EtP, PrP, and BuP were 1.84, 2.16, 1.68 and 0.05 ng/g tissue, respectively. The sum of parabens (∑ parabens, including MeP, EtP and PrP) was negatively associated with birth weight in newborn girls (− 166 g, 95% CI: − 322, − 8.6, p = 0.04) after adjustment for a priori selected covariates. The sum of parabens was negatively associated with head circumference (− 0.6 cm, 95% CI: − 1.1, − 0.2, p = 0.008) and borderline associated with birth length (− 0.6 cm, 95% CI:-1.3, 0.1, p = 0.08). In newborn girls the placental concentration of EtP was negatively associated with head circumference (− 0.6 cm, 95% CI:-1.1, − 0.1, p = 0.01) and borderline significantly associated with birth weight and birth length. Lastly, placental EtP and ∑parabens were negatively associated with placental weight in newborn girls but not in newborn boys (− 45.3 g, 95% CI:-86.2, − 4.4, p = 0.03).

Conclusion

The negative association between maternal paraben exposure and birth outcomes warrants further research and follow-up over time to determine long term effects of gestational exposure to parabens.
“Apple does not fall far from the tree” – subclinical atherosclerosis in children with familial hypercholesterolemia
Authors: Podgórski Michał , Szatko Katarzyna , Stańczyk Małgorzata , Pawlak-Bratkowska Monika , Konopka Agnieszka , Starostecka Ewa , Tkaczyk Marcin , Góreczny Sebastian , Rutkowska Lena , Gach Agnieszka , Łukaszewski Maciej , Grzelak Piotr , Banach Maciej
Published: July 2020

Background

Familial hypercholesterolemia (FH) increases the risk of atherosclerosis in children and adults. Atherosclerotic cardiovascular disease in young patients FH is usually subclinical but recognition of children with more pronounced changes is crucial for adjusting effective management. Aim of this research was to use ultrasonography with two-dimensional speckle tracking (2DST) and tonometry to evaluate atherosclerotic changes in patients with FH (parents and their offspring).

Methods

Applanation tonometry and carotid arteries sonography with evaluation of the intima-media complex thickness (IMCT) and application of the 2DST were performed in 20 families with FH (20 parents and 29 children). The same size control group (age and sex matched) was included. Results were compared between peers and between generations together with the correlation analysis.

Results

Adults with FH, in comparison with healthy peers, presented significantly more atherosclerotic plaques (9 vs. 2, p = 0.0230), had significantly thicker IMC (0.84 ± 0.19 vs. 0.56 ± 0.06 mm, p < 0.0001) and had stiffer arterial wall (for stain: 6.25 ± 2.3 vs. 8.15 ± 2.46, p = 0.0103). In children from both groups there were no atherosclerotic plaques and IMCT did not differ significantly (0.42 ± 0.07 vs. 0.39 ± 0.04, p = 0.1722). However, children with FH had significantly stiffer arterial wall according to 2DST (for strain: 9.22 ± 3.4 vs. 11.93 ± 3.11, p = 0.0057) and tonometry (for the pulse wave velocity: 4.5 ± 0.64 vs.3.96 ± 0.62, p = 0.0047). These parameters correlated with atherosclerosis surrogates in their parents (p < 0.001) but were not significantly affected by presence of presumed pathogenic gene variant.

Conclusions

Children with FH presented subclinical atherosclerosis manifested as decreased arterial wall elasticity. Degree of stiffening was associated with advancement of atherosclerosis in their parents but did not present significant association with gene variants. Sonography with application of 2DST seems to be a good candidate for comprehensive evaluation of atherosclerosis in families with FH.
Potential use of 3D-printed graphene oxide scaffold for construction of the cartilage layer
Authors: Cheng Zhong , Xigong Li , Weiyi Diao , Jingen Hu , Shuo Wang , Xiangjin Lin , Junsong Wu
Published: July 2020

Background

Three-dimensional (3D) printing involves the layering of seed cells, biologically compatible scaffolds, and biological activity factors to precisely recapitulate a biological tissue. Graphene oxide (GO), a type of micro material, has been utilized as a small molecule-transport vehicle. With the proliferation of GO, the biocompatibility of chondrocytes in a microenvironment constructed by 3D printed scaffolds and GO is innovative. Accordingly, we speculate that, as a type of micro material, GO can be used with 3D scaffolds for a uniform distribution in the cartilage layer.

Results

A qualitative analysis of the chondrocyte-proliferation potential revealed that the culture of 3D printing with a 10% GO scaffold was higher than that of the other groups. Meanwhile, the progress of cell apoptosis was activated. Through scanning electron microscopy, immunofluorescence, and in vivo research, we observed that the newborn cartilage matrix extended along the border of the cartilage and scaffold and matured. After an analysis with immunohistochemical staining with aggrecan and collagen I, the cartilage following the 3D-printed scaffold was thinner than that of the 3D-printed GO scaffold. Furthermore, the collagen I of the cartilage expression in treatment with the GO scaffold was significant from week 2 to 6.

Conclusions

The findings indicate that a 3D-printed GO scaffold can potentially be utilized for the construction of a cartilage matrix. However, the optimum concentration of GO requires further research and discussion.
Impact of changes in perceived attentional function on postsurgical health-related quality of life in breast cancer patients awaiting adjuvant treatment
Authors: Jung Mi Sook , Visovatti Moira A. , Sohn Eun Hee , Yoo Hwa-Seung , Kim Mijung , Kim Je Ryong , Lee Jin Sun
Published: July 2020

Purpose

Few studies have assessed pre-surgery cognitive impairment or the impact of pre-surgery cognitive impairment on quality of life. The purpose of this study was to assess changes in perceived cognitive function from pre-surgery to 1 month post-surgery and to determine whether cognitive function predicted health-related quality of life in women who awaited adjuvant treatment for breast cancer.

Methods

This study used a descriptive pre-post design to assess women newly diagnosed with breast cancer prior to any treatment (N = 132). Cognition was assessed using the Attentional Function Index (AFI) and health-related quality of life was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G). Statistical methods included descriptive, comparative and regression analyses. Covariates assessed and controlled for in analyses included depressed mood, fatigue, disturbed sleep, surgery-related symptoms (lymphedema/decreased mobility), and cultural tendency.

Results

Perceived attention and memory function decreased from pre-surgery to 1 month post-surgery alongside alterations in arm function and a decrease in depressed mood (p < 0.05). Regression analysis indicated that, after controlling for covariates, poorer perceived attention and memory function, surgery-specific symptoms, and a greater tendency toward collectivism predicted poorer quality of life.

Conclusion

Perceived function on tasks requiring attention and working memory 1 month post-surgery was poorer compared to pre-surgery suggesting that the mental and physical demands of a new diagnosis of breast cancer and surgery may effect cognitive function. Additionally, changes in perceived cognitive function significantly predicted perceived quality of life in women awaiting adjuvant treatment for breast cancer. Findings suggest that breast cancer patients are at risk for an early decline in cognitive function and that interventions aimed at supporting and optimizing function may improve quality of life early in the disease trajectory.
Comparison of resilience and quality of life between adolescent blood cancer survivors and those with congenital heart disease: a cross sectional study.
Authors: Lee Sunhee , Chung Nack-Gyun , Choi Jae Young
Published: July 2020

Background

The resilience and Quality of Life (QOL) of adolescent cancer survivors was compared with those of children with other diseases to identify the patterns and factors that affect resilience and QOL The purpose of the present study was to compare the resilience and QOL between adolescent blood cancer survivors and adolescents with Congenital Heart Disease (CHD).

Methods

A cross-sectional study was conducted in two hospitals. Ninety-four adolescent blood cancer survivors and 81 adolescents with CHD completed a self-reported questionnaire regarding resilience, QOL, and general characteristics. Independent t-test and ANCOVA were used to compare the resilience and QOL between adolescent blood cancer survivors and adolescents with CHD.

Results

The resilience of adolescent blood cancer survivors was significantly lower than that of adolescents with CHD, and the QOL of adolescent blood cancer survivors was not different from that of adolescents with CHD.

Conclusions

The experiences of adolescent blood cancer survivors were different from those of adolescents with CHD even though they are of the same ages. Adolescents with chronic disease have a different level of illness controllability and self-regulation according to their disease and situation. Therefore, health-providers need to develop the specific programs for improving resilience and QOL of adolescents with chronic illness with focusing their characteristics and situations.
Short- and long-term outcomes of surgery for colorectal and non-colorectal liver metastasis: a report from a single center in the Baltic country
Authors: Račkauskas Rokas , Baušys Augustinas , Sokolovas Vitalijus , Paškonis Marius , Strupas Kęstutis
Published: July 2020

Background

The liver is a major target organ for metastases of various types of cancers. Surgery is a well-established option for colorectal liver metastases (CRLM). Regarding the improved surgical and anesthetic techniques, the safety of liver resection has increased. Consequently, the interest in the surgical management of non-colorectal liver metastases (non-CRLM) has gained significant attention. Therefore, this study was designed to investigate the surgical treatment outcomes for non-CRLM and to compare it with an outcome of CRLM in a tertiary care center in the Baltic country—Lithuania.

Methods

We retrospectively analyzed data from all patients who underwent liver resection for CRLM or non-CRLM between 2010 and 2017 in a tertiary care center—Vilnius University hospital Santaros Clinics. Demographic and metastasis characteristics, as well as disease-free and overall survival, were compared between the study groups.

Results

In total, 149 patients were included in the study. Patients in the CRLM group were older (63.2 ± 1.01 vs 54.1 ± 1.8 years, p < 0.001) and mainly predominant by males. Overall postoperative morbidity rate (16.3% vs 9.8%, p = 0.402) and major complications rate (10% vs 7.8%, p = 0.704) after liver resection for CRLM and non-CRLM was similar. Kaplan-Meier analysis showed higher disease-free survival in the CRLM group with 89.4% vs 76.5% and 64.9% vs 31.4% survival rates at 1 and 3 years, respectively (p = 0.042), although overall survival was not different between the CRLM and non-CRLM groups with 89.4% vs 78.4% and 72.0% vs 46.1% survival rates at 1 and 3 years, respectively (p = 0.300).

Conclusions

In this study, we confirmed comparable short- and long-term outcomes after liver resection for CRLM and non-CRLM. Surgical resection should be encouraged as an option in well-selected patients with non-CRLM.
Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response
Authors: Kringos D. , Carinci F. , Barbazza E. , Bos V. , Gilmore K. , Groene O. , Gulácsi L. , Ivankovic D. , Jansen T. , Johnsen S. P. , de Lusignan S. , Mainz J. , Nuti S. , Klazinga N. ,   on behalf of the HealthPros Network, Baji P. , Brito Fernandes O. , Kara P. , Larrain N. , Meza B. , Murante A. , Pentek M. , Poldrugovac M. , Wang S. , Willmington C. , Yang Y.
Published: July 2020

Background

The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems’ decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic.

Discussion

A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance.

Conclusion

Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.
Microglia induce the transformation of A1/A2 reactive astrocytes via the CXCR7/PI3K/Akt pathway in chronic post-surgical pain
Authors: Li Ting , Liu Tongtong , Chen Xuhui , Li Li , Feng Miaomiao , Zhang Yue , Wan Li , Zhang Chuanhan , Yao Wenlong
Published: July 2020

Background

Activated astrocytes play important roles in chronic post-surgical pain (CPSP). Recent studies have shown reactive astrocytes are classified into A1 and A2 phenotypes, but their precise roles in CPSP remain unknown. In this study, we investigated the roles of spinal cord A1 and A2 astrocytes and related mechanisms in CPSP.

Methods

We used a skin/muscle incision and retraction (SMIR) model to establish a rat CPSP model. Microglia, CXCR7, and the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways were regulated by intrathecal injections of minocycline (a non-specific microglial inhibitor), AMD3100 (a CXCR7 agonist), and LY294002 (a specific PI3K inhibitor), respectively. Mechanical allodynia was detected with von Frey filaments. The changes in microglia, A1 astrocytes, A2 astrocytes, CXCR7, and PI3K/Akt signaling pathways were examined by enzyme-linked immunosorbent assay (ELISA), western blot, and immunofluorescence.

Results

Microglia were found to be activated, with an increase in interleukin-1 alpha (IL-1α), tumor necrosis factor alpha (TNFα), and complement component 1q (C1q) in the spinal cord at an early stage after SMIR. On day 14 after SMIR, spinal cord astrocytes were also activated; these were mainly of the A1 phenotype and less of the A2 phenotype. Intrathecal injection of minocycline relieved SMIR-induced mechanical allodynia and reverted the ratio of A1/A2 reactive astrocytes. The expression of CXCR7 and PI3K/Akt signaling was decreased after SMIR, while they were increased after treatment with minocycline. Furthermore, intrathecal injection of AMD3100 also relieved SMIR-induced mechanical allodynia, reverted the ratio of A1/A2 reactive astrocytes, and activated the PI3K/Akt signaling pathway, similar to the effects produced by minocycline. However, intrathecal injection of AMD3100 did not increase the analgesic effect of minocycline. Last, LY294002 inhibited the analgesic effect and A1/A2 transformation induced by minocycline and AMD3100 after SMIR.

Conclusion

Our results indicated that microglia induce the transformation of astrocytes to the A1 phenotype in the spinal cord via downregulation of the CXCR7/PI3K/Akt signaling pathway during CPSP. Reverting A1 reactive astrocytes to A2 may represent a new strategy for preventing CPSP.
Vitamin D status affects the relationship between lipid profile and high-sensitivity C-reactive protein
Authors: Jin Dan , Zhu Dao-Min , Hu Hong-Lin , Yao Meng-Nan , Yin Wan-Jun , Tao Rui-Xue , Zhu Peng
Published: July 2020

Background

The biological pathways through which vitamin D is involved in the regulation of systemic inflammation remain largely unknown.

Objective

The objective of this study was to evaluate the role of vitamin D status on the relationship between lipid profile and high-sensitivity C-reactive protein (hs-CRP) in pregnant women.

Design

Serum 25-hydroxyvitamin D (25(OH)D), hs-CRP, and indicators of lipid profiles (total cholesterol, TC; triglyceride, TG; high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C), were measured in 2479 pregnant women during the second trimester. Potential confounding including maternal sociodemographic characteristics, perinatal health status, diet, and lifestyle was prospectively collected. Multiple regression models and cubic models were used to evaluate the associations.

Results

There was a significant non-linear relationship between lipid profile (TC, TG, HDL-C, LDL-C) and hs-CRP (P < 0.05). Increased serum 25(OH)D was significantly associated with decreasing TC, TG, HDL-C, LDL-C, and hs-CRP levels. Compared with medium levels of lipids group, pregnant women with higher levels of TC or TG have higher levels of hs-CRP, and pregnant women with lower levels of TC, HDL-C or LDL-C also have higher levels of hs-CRP in the vitamin D deficient group, and there was a significant correlation between low levels of TG and decreased hs-CRP (adjusted β for TG: -0.063, 95%CI: − 0.120,-0.007) in the non-vitamin D deficient group. Mediators that had appreciable shares of the associations between 25(OH)D and hs-CRP was TG (10.2% of the association; β = − 0.011; total indirect effect: 95% CI: − 0.019, − 0.002). The cubic model suggested that a steep increase in the adjusted regression coefficient of lipid with hs-CRP up to 50 nmol/L of 25(OH)D, and the highest adjusted regression coefficients were observed in pregnant women with 25(OH)D above 50 nmol/L.

Conclusion

Our findings suggest that high levels of vitamin D during pregnancy may improve lipid profile levels and inhibit elevated hs-CRP induced by high lipid metabolism.
Multicenter evaluation of a syndromic rapid multiplex PCR test for early adaptation of antimicrobial therapy in adult patients with pneumonia
Authors: Monard Céline , Pehlivan Jonathan , Auger Gabriel , Alviset Sophie , Tran Dinh Alexy , Duquaire Paul , Gastli Nabil , d’Humières Camille , Maamar Adel , Boibieux André , Baldeyrou Marion , Loubinoux Julien , Dauwalder Olivier , Cattoir Vincent , Armand-Lefèvre Laurence , Kernéis Solen ,   the ADAPT study group, Becker Agathe , Charpentier Julien , Textoris Julien , Gustave Claude-Alexandre , Destras Grégory , Vandenesch François , Lina Bruno , Casalegno Jean Sebastien , Lejeune Manon , Montravers Philippe , Poyart Claire , Tête Hugo , Timsit Jean-François , Uberti Thomas
Published: July 2020

Background

Improving timeliness of pathogen identification is crucial to allow early adaptation of antibiotic therapy and improve prognosis in patients with pneumonia. We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP).

Methods

This retrospective multicenter study was conducted in four French university hospitals. Respiratory samples were obtained from patients with clinical and radiological signs of pneumonia and simultaneously tested using conventional microbiological methods and the rm-PCR. A committee composed of an intensivist, a microbiologist, and an infectious diseases specialist retrospectively assessed all medical files and agreed on the most appropriate antimicrobial therapy for each pneumonia episode, according to the results of rm-PCR and blinded to the culture results. The rm-PCR-guided antimicrobial regimen was compared to the empirical treatment routinely administered to the patient in standard care.

Results

We included 159 pneumonia episodes. Most patients were hospitalized in intensive care units (n = 129, 81%), and episodes were HAP (n = 68, 43%), CAP (n = 54, 34%), and VAP (n = 37, 23%). Conventional culture isolated ≥ 1 microorganism(s) at significant level in 95 (60%) patients. The syndromic rm-PCR detected at least one bacteria in 132 (83%) episodes. Based on the results of the rm-PCR, the multidisciplinary committee proposed a modification of the empirical therapy in 123 (77%) pneumonia episodes. The modification was a de-escalation in 63 (40%), an escalation in 35 (22%), and undetermined in 25 (16%) patients. In microbiologically documented episodes (n = 95), the rm-PCR increased appropriateness of the empirical therapy to 83 (87%), as compared to 73 (77%) in routine care.

Conclusions

Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia.
Impact of intracellular toxic advanced glycation end-products (TAGE) on murine myoblast cell death
Authors: Takata Takanobu , Sakasai-Sakai Akiko , Takeuchi Masayoshi
Published: July 2020

Background

Sarcopenia is a progressive condition that is characterized by decreases in skeletal muscle mass and function. Although sarcopenia is associated with lifestyle-related diseases (LSRD), the mechanisms underlying cell death in myoblasts, which differentiate to myotubes, remain unclear. We previously designated glyceraldehyde (an intermediate of glucose/fructose metabolism)-derived advanced glycation end-products (AGEs) as toxic AGEs (TAGE) because of their cytotoxicity and involvement in LSRD, and hypothesized that TAGE contribute to cell death in myoblasts.

Methods

C2C12 cells, which are murine myoblasts, were treated with 0, 0.5, 1, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE were then assessed using 5-[2,4,-bis(sodioxysulfonyl)phenyl]-3-(2-methoxy-4-nitrophenyl)-2-(4-nitrophenyl)-2H-tetrazole-3-ium (WST-8) and slot blot assays. Cells were pretreated with 8 mM aminoguanidine, an inhibitor of AGE production, for 2 h, followed by 0, 1.5, and 2 mM glyceraldehyde for 24 h. Cell viability and intracellular TAGE levels were then assessed. Serum TAGE levels in STAM mice, in which there were four stages (no steatosis, simple steatosis, steatohepatitis, and fibrosis), were measured using a competitive enzyme-linked immunosorbent assay. Results were expressed as TAGE units (U) per milliliter of serum, with 1 U corresponding to 1.0 μg of glyceraldehyde-derived AGE-bovine serum albumin (BSA) (TAGE-BSA). The viability of cells treated with 20, 50, and 100 μg/mL non-glycated BSA and TAGE-BSA for 24 h was assessed using the WST-8 assay.

Results

In C2C12 cells treated with 1.5 and 2 mM glyceraldehyde, cell viability decreased to 47.7% (p = 0.0021) and 5.0% (p = 0.0001) and intracellular TAGE levels increased to 6.0 and 15.9 μg/mg protein, respectively. Changes in cell viability and TAGE production were completely inhibited by 8 mM aminoguanidine. Serum TAGE levels at the steatohepatitis and fibrosis stages were 10.51 ± 1.16 and 10.44 ± 0.95 U/mL, respectively, and were higher than those at the no steatosis stage (7.27 ± 0.18 U/mL). Cell death was not induced by 20 or 50 μg/mL TAGE-BSA. The viabilities of C2C12 cells treated with 100 μg/mL non-glycated BSA and TAGE-BSA were 105.0% (p = 0.2890) and 85.3% (p = 0.0217), respectively.

Conclusion

Intracellular TAGE strongly induced cell death in C2C12 cells and may also induce myoblast cell death in LSRD model mice.
Changes in excessive alcohol use among older women across the menopausal transition: a longitudinal analysis of the Study of Women’s Health Across the Nation
Authors: Peltier MacKenzie R. , Verplaetse Terril L. , Roberts Walter , Moore Kelly , Burke Catherine , Marotta Phillip L. , Phillips Sarah , Smith Philip H. , McKee Sherry A.
Published: July 2020

Background

Recent data suggest that excessive alcohol use is increasing among women and older adults. Such trends are concerning, as women are more vulnerable to alcohol-related health consequences, and such health problems may be exacerbated with age. Furthermore, there are sex-specific factors that may influence alcohol consumption among women, including the hormonal changes associated with the menopausal transition and negative affect. The present study sought to investigate transitions in excessive drinking among women across the menopausal transition and included exploration of sex hormones (estradiol; testosterone) and depression.

Methods

The present study utilized publicly available data from the Study of Women Across the Nation (SWAN) and included 3302 women (42–52 years old at baseline), who completed 10 years of annual assessments. National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria were used as guidance when defining excessive drinking within the present dataset. At year 1, 170 women were identified as drinking excessively. Random-effect logistic regressions were used to examine transitions in excessive drinking.

Results

Women identified as excessive drinkers were more likely to transition to non-excessive drinking across all menopausal transition stages (ORs range = 3.71–5.11), while women were more likely to transition from non-excessive to excessive drinking during the early peri- and postmenopausal stages (OR = 1.52 and 1.98, respectively). Higher testosterone levels were associated with a decreased likelihood of transitioning to non-excessive drinking (OR = 0.59). Depression and estradiol levels were not related to transitions in drinking.

Conclusions

The present study demonstrates that the menopausal transition marks a period of instability in alcohol use among women. Further research is warranted to understand factors related to transitioning in and out of excessive drinking.
Detection limit of 89Zr-labeled T cells for cellular tracking: an in vitro imaging approach using clinical PET/CT and PET/MRI
Authors: Lechermann Laura M. , Manavaki Roido , Attili Bala , Lau Doreen , Jarvis Lorna B. , Fryer Tim D. , Bird Nick , Aloj Luigi , Patel Neel , Basu Bristi , Cleveland Matthew , Aigbirhio Franklin I. , Jones Joanne L. , Gallagher Ferdia A.
Published: July 2020

Purpose

Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI.

Methods

Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection.

Results

Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells.

Conclusion

The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require detection of low cell numbers while minimizing radiation dose per cell.
Securing communication by attribute-based authentication in HetNet used for medical applications
Authors: Lone Tufail A. , Rashid Aabid , Gupta Sumeet , Gupta Sachin Kumar , Rao Duggirala Srinivasa , Najim Mohd , Srivastava Ashutosh , Kumar Abhishek , Umrao Lokendra Singh , Singhal Achintya
Published: July 2020

One of the major applications of the Heterogeneous Network (HetNet) is in the healthcare system. Deploying HetNet in healthcare systems enables patients, physicians, and other stakeholders to communicate easily with each other. Due to the large growth in the network’s subscribers, the security of the stored health data became one of the major concerns because unauthorized access to this data may lead to very serious complications, and unreliable transmission of data may lead to fatal risks to the patient’s life. Therefore, taking data integrity into consideration, user authentication has become one of the main factors. However, significant research work has been performed at HetNet’s physical layer to secure communication, but the result of this leads to an increase in hardware components. The increasing hardware components not only costs money but also power consumption. Therefore, this paper presents an alternate way of securing communication in HetNet at the network layer. However, resolving security problems at the network layer increases computational complexity. Nevertheless, earlier, some encryption techniques like identity-based encryption (IBE), symmetric key encryption (SKE), and public-key encryption (PKE) have been utilized for securing data. Due to their own disadvantages, this paper utilizes an attribute-based encryption (ABE) authentication scheme for securing health data in medical applications. With the help of this method, access to the intruders is denied which results in reduced communication overhead. This authentication scheme helps protect the essential information against attacks by the intruders. It includes a third party server that helps to authenticate and store patient’s information. The whole security technique has been written in the form of HLPSL (high-level protocol specification language) codes, and the results are then validated with the help of AVISPA (automated validation of Internet security protocols and applications) tool.
Asymptotic behavior and threshold of a stochastic SIQS epidemic model with vertical transmission and Beddington–DeAngelis incidence
Authors: Chen Yang , Zhao Wencai
Published: July 2020

This paper investigates a deterministic and stochastic SIQS epidemic model with vertical transmission and Beddington–DeAngelis incidence. Firstly, for the corresponding deterministic system, the global asymptotic stability of disease-free equilibrium and the endemic equilibrium is proved through the stability theory. Secondly, for the stochastic system, the threshold conditions which decide the extinction or permanence of the disease are derived. By constructing suitable Lyapunov functions, we investigate the oscillation behavior of the stochastic system solution near the endemic equilibrium. The results of this paper show that there exists a great difference between the deterministic and stochastic systems, which implies that the large stochastic noise contributes to inhibiting the spread of disease. Finally, in order to validate the theoretical results, a series of numerical simulations are presented.
Modeling equatorial ionospheric vertical plasma drifts using machine learning
Authors: Shidler S. A. , Rodrigues F. S.
Published: July 2020

We present the results of an effort to model quiet-time vertical plasma drifts in the low-latitude F-region ionosphere using the random forest machine learning technique. The model is capable of describing the climatological variation of the drifts as a function of universal time, day of the year, solar flux, and altitude (200–600 km). The model has been trained using measurements of the vertical plasma drifts made by the incoherent scatter radar of the Jicamarca Radio Observatory ($$11.95^\circ \hbox { S}$$

11
.

95
∘

S

, $$76.87^\circ$$

76
.

87
∘

W, $$\sim 1^\circ$$

∼

1
∘

dip lat). In our analysis, we compare our machine learning model results with the Scherliess and Fejer (J Geophys Res 104:6829–6842, 1999) model (SF99 model), a widely used empirical model of the vertical drifts developed using a different set of Jicamarca measurements. We find that the machine learning model is able to capture the overall features of the diurnal variation of the equatorial drifts for different seasonal and solar flux conditions. The model is also capable of capturing the mean height variation of the drifts, particularly the height gradient enhancements that have been observed near sunrise and sunset. Finally, the model can easily be expanded and improved as more drift measurements are made and become available for training.
Correction to: Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner
Authors: Mackewn J. E. , Stirling J. , Jeljeli S. , Gould S-M , Johnstone R. I. , Merida I. , Pike L. C. , McGinnity C. J. , Beck K. , Howes O. , Hammers A. , Marsden P. K.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Evaluation of a Questionnaire Measuring University Students’ Sense of Belonging to and Involvement in a Biology Department
Authors: Knekta Eva , Chatzikyriakidou Kyriaki , McCartney Melissa
Published: July 2020

The article presents an instrument measuring university students’ sense of belonging to and involvement in their "home" department (biology), as well as initial validity evidence supporting the proposed use of the instrument.
The ASPET Mentoring Network: Enhancing Diversity and Inclusion through Career Coaching Groups within a Scientific Society
Authors: Womack Veronica Y. , Thakore Bhoomi K. , Wood Christine V. , Jewett David C. , Jones Remi F. , Ingram Susan L. , Clark Janet A. , Fry Catherine L. , Wecker Lynn , McGee Richard
Published: July 2020

The American Society for Pharmacology and Experimental Therapeutics (ASPET) Mentoring Network, career mentoring groups of six PhD students and postdocs, begin with an in-person meeting the day before the ASPET annual meeting. Led by an experienced ASPET member, each group then meets virtually for a year. Evaluation data from the first three cohorts provide strong evidence of perceived and real benefits of the groups.
Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer
Authors: Brunt Adrian Murray , Haviland Joanne S. , Sydenham Mark , Agrawal Rajiv K. , Algurafi Hafiz , Alhasso Abdulla , Barrett-Lee Peter , Bliss Peter , Bloomfield David , Bowen Joanna , Donovan Ellen , Goodman Andy , Harnett Adrian , Hogg Martin , Kumar Sri , Passant Helen , Quigley Mary , Sherwin Liz , Stewart Alan , Syndikus Isabel , Tremlett Jean , Tsang Yat , Venables Karen , Wheatley Duncan , Bliss Judith M. , Yarnold John R.
Published: July 2020

PURPOSE

Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented.

METHODS

Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens.

RESULTS

A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/β estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred.

CONCLUSION

At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.