bluuebunny/crossref_metadata_2025 huggingface dataset:
Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults
Authors: Wyatt Lauren H. , Devlin Robert B. , Rappold Ana G. , Case Martin W. , Diaz-Sanchez David
Published: November 2020

Background

Fine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies.

Methods

To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8 μg/m3, SD 6.5), and filtered air (mean: 2.1 μg/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure.

Results

Low-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8 μg/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure.

Conclusions

This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard.

Clinical trial registration information

clinicaltrials.gov; Identifier: NCT03232086. The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.
Characterization of the cytokinin sensor TCSv2 in arabidopsis and tomato
Authors: Steiner Evyatar , Israeli Alon , Gupta Rupali , Shwartz Ido , Nir Ido , Leibman-Markus Meirav , Tal Lior , Farber Mika , Amsalem Ziva , Ori Naomi , Müller Bruno , Bar Maya
Published: November 2020

Background

Hormones are crucial to plant life and development. Being able to follow the plants hormonal response to various stimuli and throughout developmental processes is an important and increasingly widespread tool. The phytohormone cytokinin (CK) has crucial roles in the regulation of plant growth and development.

Results

Here we describe a version of the CK sensorTwo Component signaling Sensor(TCS), referred to asTCSv2.TCSv2has a different arrangement of binding motifs when compared to previousTCSversions, resulting in increased sensitivity in some examined tissues. Here, we examine the CK responsiveness and distribution pattern ofTCSv2in arabidopsis and tomato.

Conclusions

The increased sensitivity and reported expression pattern ofTCSv2make it an idealTCSversion to study CK response in particular hosts, such as tomato, and particular tissues, such as leaves and flowers.
Large and non-specific somatic disease burdens among ageing, long-term opioid maintenance treatment patients
Authors: Medved David , Clausen Thomas , Bukten Anne , Bjørnestad Ronny , Muller Ashley Elizabeth
Published: November 2020

Objectives

To describe and explore somatic disease burdens of ageing long-term patients in opioid maintenance treatment (OMT), a unique population emerging in countries offering OMT as a long-term treatment.

Methods

We used data from the Norwegian Cohort of Patient in Opioid Maintenance Treatment and Other Drug Treatment Study (NorComt). 156 patients enrolled for at least three of the past five years provided data during structured interviews, including on chronic conditions, somatic treatment received, mental distress (SCL-25), and treatment satisfaction. A somatic disease burden was calculated from a list measuring the recent severity of 16 somatic complaints. A hierarchical multiple linear regression analysis identified correlates of somatic disease burden.

Results

Over half of patients reported at least seven somatic complaints. Reported somatic disease burden was associated with higher mental distress, more chronic conditions, fewer years in OMT, and treatment dissatisfaction. Age was unrelated, and there were few gender differences. These five variables explained 43.6% of the variance in disease burden.

Conclusion

Long-term OMT patients experience a large range of somatic complaints, and at non-acute levels. As OMT secures longevity for opioid-dependent persons, the clinical focus must be adjusted from acute to chronic care. Providers must address how to optimize health and quality of life while in treatment, as treatment may last for many years.
Exploring the mental health and psychosocial problems of Congolese refugees living in refugee settings in Rwanda and Uganda: a rapid qualitative study
Authors: Chiumento Anna , Rutayisire Theoneste , Sarabwe Emmanuel , Hasan M. Tasdik , Kasujja Rosco , Nabirinde Rachel , Mugarura Joseph , Kagabo Daniel M. , Bangirana Paul , Jansen Stefan , Ventevogel Peter , Robinson Jude , White Ross G.
Published: November 2020

Background

Refugees fleeing conflict often experience poor mental health due to experiences in their country of origin, during displacement, and in new host environments. Conditions in refugee camps and settlements, and the wider socio-political and economic context of refugees’ lives, create structural conditions that compound the effects of previous adversity. Mental health and psychosocial support services must address the daily stressors and adversities refugees face by being grounded in the lived reality of refugee’s lives and addressing issues relevant to them.

Methods

We undertook a rapid qualitative study between March and May 2019 to understand the local prioritisation of problems facing Congolese refugees living in two refugee settings in Uganda and Rwanda. Thirty free list interviews were conducted in each setting, followed by 11 key informant interviews in Uganda and 12 in Rwanda.

Results

Results from all interviews were thematically analysed following a deductive process by the in-country research teams. Free list interview findings highlight priority problems of basic needs such as food, shelter, and healthcare access; alongside contextual social problems including discrimination/inequity and a lack of gender equality. Priority problems relating to mental and psychosocial health explored in key informant interviews include discrimination and inequity; alcohol and substance abuse; and violence and gender-based violence.

Conclusions

Our findings strongly resonate with models of mental health and psychosocial wellbeing that emphasise their socially determined and contextually embedded nature. Specifically, findings foreground the structural conditions of refugees’ lives such as the physical organisation of camp spaces or refugee policies that are stigmatising through restricting the right to work or pursue education. This structural environment can lead to disruptions in social relationships at the familial and community levels, giving rise to discrimination/inequity and gender-based violence. Therefore, our findings foreground that one consequence of living in situations of pervasive adversity caused by experiences of discrimination, inequity, and violence is poor mental health and psychosocial wellbeing. This understanding reinforces the relevance of feasible and acceptable intervention approaches that aim to strengthening familial and community-level social relationships, building upon existing community resources to promote positive mental health and psychosocial wellbeing among Congolese refugees in these settings.
Assessing effectiveness and implementation of a perioperative enhanced recovery protocol for children undergoing surgery: study protocol for a prospective, stepped-wedge, cluster, randomized, controlled clinical trial
Authors: Raval Mehul V. , Wymore Erin , Ingram Martha-Conley E. , Tian Yao , Johnson Julie K. , Holl Jane L.
Published: November 2020

Background

Perioperative enhanced recovery protocols (ERPs) have been found to decrease hospital length of stay, in-hospital costs, and complications among adult surgical populations but evidence for pediatric populations is lacking. The study is designed to evaluate the adoption, effectiveness, and generalizability of a 21-element ERP, adapted for pediatric surgery.

Methods

The multicenter study is a stepped-wedge, cluster-randomized, pragmatic clinical trial that will evaluate the effectiveness of the ENhanced Recovery In CHildren Undergoing Surgery (ENRICH-US) intervention while also assessing site-specific adaptations, implementation fidelity, and sustainability. The target patient population is pediatric patients, between 10 and 18 years old, who undergo elective gastrointestinal surgery. Eighteen (N = 18) participating sites will be randomly assigned to one of three clusters with each cluster, in turn, being randomly assigned to an intervention start period (stepped-wedge). Each cluster will participate in a Learning Collaborative, using the National Implementation Research Network’s five Active Implementation Frameworks (AIFs) (competency, organization, and leadership), as drivers of facilitation of rapid-cycle adaptations and implementation. The primary study outcome is hospital length of stay, with implementation metrics being used to evaluate adoption, fidelity, and sustainability. Additional clinical outcomes include opioid use, post-surgical complications, and post-discharge healthcare utilization (clinic/emergency room visits, telephone calls to clinic, and re-hospitalizations), as well as, assess patient- and parent-reported health-related quality of life outcomes. The protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.

Discussion

The study provides a unique opportunity to accelerate the adoption of ERPs across 18 US pediatric surgical centers and to evaluate, for the first time, the effect of a pediatric-specific ENRICH-US intervention on clinical and implementation outcomes. The study design and methods can serve as a model for future pediatric surgical quality improvement implementation efforts.

Trial registration

ClinicalTrials.gov NCT04060303. Registered on 07 August 2019.
PathoSPOT genomic epidemiology reveals under-the-radar nosocomial outbreaks
Authors: Berbel Caban Ana , Pak Theodore R. , Obla Ajay , Dupper Amy C. , Chacko Kieran I. , Fox Lindsey , Mills Alexandra , Ciferri Brianne , Oussenko Irina , Beckford Colleen , Chung Marilyn , Sebra Robert , Smith Melissa , Conolly Sarah , Patel Gopi , Kasarskis Andrew , Sullivan Mitchell J. , Altman Deena R. , van Bakel Harm
Published: November 2020

Background

Whole-genome sequencing (WGS) is increasingly used to map the spread of bacterial and viral pathogens in nosocomial settings. A limiting factor for more widespread adoption of WGS for hospital infection prevention practices is the availability of standardized tools for genomic epidemiology.

Methods

We developed the Pathogen Sequencing Phylogenomic Outbreak Toolkit (PathoSPOT) to automate integration of genomic and medical record data for rapid detection and tracing of nosocomial outbreaks. To demonstrate its capabilities, we applied PathoSPOT to complete genome surveillance data of 197 MRSA bacteremia cases from two hospitals during a 2-year period.

Results

PathoSPOT identified 8 clonal clusters encompassing 33 patients (16.8% of cases), none of which had been recognized by standard practices. The largest cluster corresponded to a prolonged outbreak of a hospital-associated MRSA clone among 16 adults, spanning 9 wards over a period of 21 months. Analysis of precise timeline and location data with our toolkit suggested that an initial exposure event in a single ward led to infection and long-term colonization of multiple patients, followed by transmissions to other patients during recurrent hospitalizations.

Conclusions

We demonstrate that PathoSPOT genomic surveillance enables the detection of complex transmission chains that are not readily apparent from epidemiological data and that contribute significantly to morbidity and mortality, enabling more effective intervention strategies.
Therapeutic efficacy of umbilical cord-derived stem cells for diabetes mellitus: a meta-analysis study
Authors: Kassem Dina H. , Kamal Mohamed M.
Published: November 2020

Background

Stem cell therapy provides great hope for patients with diabetes mellitus (DM). DM is a seriously alarming metabolic disease characterized by hyperglycemia and β cell dysfunction. Efficient novel therapeutic modalities to treat DM are indeed warranted. Stem cells (SC) derived from the umbilical cord specifically provide several advantages and unique characteristics being a readily available non-invasive source, with an additional credit for their banking potential. This meta-analysis study aims to provide a focused assessment for therapeutic efficacy of umbilical cord (UC)-derived SC-transplantation, namely Wharton’s jelly mesenchymal stem cells (WJ-MSCs) and umbilical cord blood (UCB) for DM.

Methods

The clinical efficacy was evaluated based on glycemic control status (reflected on HbA1c%) and β cell function (reflected on C-peptide levels), as well as the daily insulin requirement in diabetic patients after receiving UC-derived SC-transplantation compared to baseline values. Moreover, we assessed these outcome measures in patients who received such intervention compared to those who did not receive it in randomized/non-randomized controlled clinical trials. We employed a random-effects model and standardized mean difference for this meta-analysis.

Results

Eleven eligible clinical studies were included; WJ-MSCs (6 studies; 172 patients including 71 controls) and UCB (5 studies; 74 patients including 15 controls). WJ-MSCs significantly improved HbA1c% (pooled-estimate − 1.085; 95%CI (− 1.513, − 0.657); p < 0.001) and C-peptide levels (pooled-estimate 1.008; 95%CI (0.475, 1.541); p < 0.001), as well as the daily insulin-requirement (pooled-estimate − 2.027; 95%CI (− 3.32, − 0.733); p = 0.002). On the contrary, UCB was found to be uniformly ineffective; HbA1c% (pooled-estimate − 0.091, 95%CI (− 0.454, 0.271); p = 0.622), significantly deteriorated C-peptide levels (pooled-estimate − 0.789; 95%CI (− 1.252, − 0.325); p < 0.001) and daily insulin-requirement (pooled-estimate 0.916; 95%CI (0.247, 1.585); p = 0.007). All these observations remained consistent when we carried out sub-group meta-analysis for T1DM and T2DM and also when we compared patients who received WJ-MSCs or UCB to controls.

Conclusions

The results of our meta-analysis provide a clear evidence for the superior efficacy of WJ-MSCs over UCB in DM. This sheds lights on the importance to consider banking of WJ-MSCs together with the well-established routine UCB-banking, especially for those with family history of DM. Additionally, further clinical studies are required to investigate therapeutic efficacy of selected/enriched UCB-derived cell populations with immunomodulatory/regenerative potential in DM.
Newly evolving pastoral and post-pastoral rangelands of Eastern Africa
Authors: Lind Jeremy , Sabates-Wheeler Rachel , Caravani Matteo , Kuol Luka Biong Deng , Nightingale Deborah Manzolillo
Published: November 2020

Over the past two decades, the rangelands of Eastern Africa have experienced sweeping changes associated with growing human populations, shifting land use, expanding livestock marketing and trade, and greater investment by domestic and global capital. These trends have coincided with several large shocks that were turning points for how rangeland inhabitants make a living. As livelihoods in the region’s rangelands transform in seemingly paradoxical directions, away from customary pastoralist production systems, greater insight is required of how these transformations might affect poverty and vulnerability. This article reviews the state of what is known regarding directions of livelihood change in the rangelands of Eastern Africa, drawing on case studies of structural change in five settings in the region. It considers the implications of long-term change, as well as the emergence of very different livelihood mixes in pastoral rangelands, for efforts to reduce poverty and vulnerability in these places.
Social determinants and other aspects associated with rheumatic diseases in the Brazilian population: a cross-sectional study based on the National Health Survey (PNS2013)
Authors: Souza Clécio Gabriel , Souza Marcelo Cardoso , Silva Hugo Jario , Assis Sanderson José Costa , Dantas Diego Sousa
Published: November 2020

Background

Rheumatic diseases are increasingly present in the world population, represented by chronic joint and musculoskeletal pain. Among them, osteoarthritis (OA) is the most prevalent. It is considered the third most prevalent chronic non-communicable disease in the Brazilian population, being responsible for a high rate of physical disability and reduced quality of life. Little has been discussed about the social factors associated with this health condition. This study aimed to analyze the social factors associated with arthritis in the Brazilian population.

Methods

This is a cross-sectional study based on data from the 2013 National Health Survey in Brazil with arthritis as its main outcome. Sex, age, body weight, usual activities, physical activity, self-perceived health and diagnosis of depression were analyzed as independent variables. Descriptive and inferential statistics were used. Poisson multiple regression was performed, and the prevalence ratio (PR) and confidence interval (CI) of 95% were calculated using a significance level of 5% (p ≤ 0.05).

Results

A total of 60,202 individuals of both sexes took part in this study and the rheumatic diseases or arthrtitis prevalence was 6.4%. The individual factors associated with a higher prevalence of arthritis were female (PR = 2.09; CI = 1.95–2.25), age over 35 years (PR = 2.88; CI = 2.57–3.24) and excess body weight (PR = 1.61; CI = 1.25–2.07). The presence of rhemautic diseases showed an association with lower performance of usual activities (PR = 1.61; CI = 1.50–1.73) and self-perceived health as very poor (PR = 3.96; CI = 3.31–4.72). In addition, it was associated with a higher prevalence of mental illnesses such as depression (PR = 1.77; CI = 1.64–1.90).

Conclusion

Social and modifiable factors which are associated with a higher prevalence of arthritis can be controlled through incentive measures such as social participation and physical activity.
Evaluation of the nutritional status of rural children living in Zambia
Authors: Mitsunaga Arimi , Yamauchi Taro
Published: November 2020

Background

Growth references (growth charts) are used to assess the nutritional and growth status of children. In developed countries, there are growth charts based on the country’s national surveys. However, many developing countries do not have their own growth references, so they usually use WHO and US CDC references. In such cases, it is known that the growth statuses of the subject are underestimated or overestimated. This study sought to accurately assess the growth status of children by developing a local growth chart for children living in the Southern Province of Zambia.

Methods

Anthropometric measurements were conducted on 1135 children aged 2–19 years in the target area. The height and weight data for each sex and age were smoothed using the LMS method, and a percentile curve of height and weight was developed. Based on the US CDC reference, three indicators of undernutrition (stunting, underweight, and thinness) were calculated to determine the proportion of those who are undernourished (z-score < − 2).

Results

The 50th percentile curve of height and weight in the growth chart of the target population was equivalent to the 5–25th percentile curve of the US reference, and the children of Zambia were both small and of low weight. Conversely, although many subjects are small and of low weight, it was found that there were few poor nutritional statuses as judged by BMI. Through comparison with a previous study in the Southern Province of Zambia, a secular change in the growth of children over 20 years was found. Although there was no significant increase in height and weight in the older age group, there was a significant increase in height and weight at an earlier age. This is thought to be due to an increase in the growth rate of children due to improved socioeconomic conditions, women’s education level, and improvement in health care standards.

Conclusions

The subjects were small and of low weight compared to the US population, but the nutritional status was not poor by BMI. The height and weight at an earlier age increased compared to 20 years ago.
The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats
Authors: Darweesh Ruba S. , El-Elimat Tamam , Zayed Aref , Khamis Tareq N. , Babaresh Wahby M. , Arafat Tawfiq , Al Sharie Ahmed H.
Published: November 2020

Background

Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, withN-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite,N-desmethyl imatinib, in SD-rats.

Methods

Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib andN-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined.

Results

h-GS dose significantly decreased imatinib’s Cmaxand the$$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞by 61.1 and 72.2%, respectively. Similar effects onN-desmethyl imatinib’s exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold.l-GT caused a significant decrease in imatinib’s Cmaxand$$ {\mathrm{AUC}}_0^{\infty } $$AUC0∞by 53.6 and 63.5%, respectively, with more significant effects onN-desmethyl imatinib’s exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively.h-GT showed similar effects as those ofl-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in CmaxofN-desmethyl imatinib by 71.5%.

Conclusions

These results demonstrated that the pharmacokinetics of imatinib andN-desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized.

Graphical abstract
Open access in vocational education and training research: results from four structured group discussions
Authors: Getz Laura , Langenkamp Karin , Rödel Bodo , Taufenbach Kerstin , Weiland Meike
Published: November 2020

Aim

Open Access fosters the exchange of academic research information by making publications free of charge and, wherever possible, available through open licences and without any technical barriers. Although the Open Access publication model is already well established in the natural sciences, there seems to be more resistance towards Open Access in the social sciences, including the field of vocational education and training research. The research project “Open Access in Vocational Education and Training Research” aims to uncover the conditions influencing the acceptance, dissemination and use of Open Access in vocational education and training research. The project is grounded in a sociology of knowledge approach and in media theory. It comprises of two parts. First, four structured group discussions are conducted as focus groups and analysed using a qualitative content analysis. This paper focusses on this first part of the research project, the implementation and analysis of the group discussions as well as the results thereof. The second part of the research project will be based on an online questionnaire built upon these results. The questionnaire will be sent out to authors involved in vocational education and training research in the second part of the research project.

Findings

The analysis of the group discussions reveals several thematic clusters. According to group discussion participants, the scope of their publications as well as transparent quality assurance procedures in publishing are particularly relevant. The reputation of their chosen publication medium is another central aspect. It also becomes clear that in some cases an information deficit regarding the financing of Open Access publications or accompanying licensing models exists. Finally, participants discuss changing literature research strategies and changes of work and reading practices. The latter being clearly discernible in an increasingly digitalised daily work routine of vocational education and training researchers, while academic research communication is also an important topic discussed.
Does tertiary vocational education beat academic education? A matching analysis of young men’s earnings developments
Authors: Lukesch Veronika , Zwick Thomas
Published: November 2020

This paper shows that young men who completed an apprenticeship education plus a tertiary vocational education have considerably higher earnings during the first half of their career than those who obtained an academic education in addition to their apprenticeship education. We match employees with a tertiary vocational and an academic education based on their labour market experience and their individual and employer characteristics during their formative apprenticeship training years in which they presumably decided on their further education track. Then we compare the earnings developments in both groups of the matched sample during their tertiary education phase and after its completion for maximally 16 years after apprenticeship completion. We use linked employer-employee data of the IAB (LIAB9310).
Phylogenetic positions of “pico-sized” radiolarians from middle layer waters of the tropical Pacific
Authors: Li Luyan , Endo Kazuyoshi
Published: November 2020

In order to determine whether truly pico-sized adult radiolarians exist, we compared spumellarian sequences from individual adult samples collected in the central Pacific, with filtered sea water samples of juvenile (5–42 μm) and gamete (0.2–5 μm) sized fractions to see whether the gene sequences are similar or different. Environmental spumellarian-affiliated sequences we sampled were mostly concentrated in samples from 250 to 400 m depth and only appeared in the RAD-III clade, which corresponds to the family Astrosphaeridae (including Arachnosphaera, Astrosphaera, and Cladococcus). None of the same ITS (internal transcribed spacer) sequences were found in both filter membranes of the same sea water samples. Pairwise distances among these environmental spumellarian-affiliated sequences are within or slightly above the range of intra-morphospecific variations. We propose a model to explain our observations based on the hypothesis that the “pico-sized radiolarians” represent gametes of radiolarians of normal size, assuming different sinking speeds of parents and offspring.
Fully automated radiosynthesis of [18F]LBT999 on TRACERlab FXFN and AllinOne modules, a PET radiopharmaceutical for imaging the dopamine transporter in human brain
Authors: Vala Christine , Mothes Céline , Chicheri Gabrielle , Magadur Pauline , Viot Gilles , Deloye Jean-Bernard , Maia Serge , Bouvet Yann , Dupont Anne-Claire , Arlicot Nicolas , Guilloteau Denis , Emond Patrick , Vercouillie Johnny
Published: November 2020

Background

Fluorine labelled 8-((E)-4-fluoro-but-2-enyl)-3β-p-tolyl-8-aza-bicyclo[3.2.1]octane-2β-carboxylic acid methyl ester ([18F]LBT999) is a selective radioligand for the in vivo neuroimaging and quantification of the dopamine transporter by Positron Emission Tomography (PET). [18F]LBT999 was produced on a TRACERlab FXFN for the Phase I study but for Phase III and a potent industrial production transfer, production was also implemented on an AllinOne (AIO) system requiring a single use cassette. Both production methods are reported herein.

Results

Automation of [18F]LBT999 radiosynthesis on FXFN was carried out in 35% yield (decay-corrected) in 65 min (n = 16), with a radiochemical purity higher than 99% and a molar activity of 158 GBq/μmol at the end of synthesis. The transfer to the AIO platform followed by optimizations allowed the production of [18F]LBT999 in 32.7% yield (decay-corrected) within 48 min (n = 5), with a radiochemical purity better than 98% and a molar activity above 154 GBq/μmol on average at the end of synthesis. Quality controls of both methods met the specification for clinical application.

Conclusion

Both modules allow efficient and reproducible radiosynthesis of [18F]LBT999 with good radiochemical yields and a reasonable synthesis time. The developments made on AIO, such as its ability to meet pharmaceutical criteria and to more easily comply with GMP requirements, make it an optimal approach for the potent industrial production of [18F]LBT999 and future wider use.
Prevalence of incidental thyroid malignancy on routine 18F-fluorodeoxyglucose PET-CT in a large teaching hospital
Authors: Roddy Shea , Biggans Thomas , Raofi Ahmad K. , Kanodia Avinash , Sudarshan Thiru , Guntur Ramkumar Prasad
Published: November 2020

Purpose

To quantify incidental thyroid pathology including malignancy on routine 18F-FDG PET-CT scans

To compare standardised uptake values (SUVmax) in thyroid malignancy subtypes

Methods and materials

This is a retrospective study of all 18F-FDG PET-CT scans (n = 6179) performed in a teaching hospital between June 2010 and May 2019. RIS database search of reports for the word “thyroid” was performed. Studies with evidence of thyroid uptake were included. Patient age and gender, primary indication for PET scan (malignant or non-malignant), thyroid result on PET (diffuse or focal tracer uptake, SUVmax), ultrasound and FNAC results were recorded.

Results

Incidental abnormal thyroid tracer uptake as a proportion of all 18F-FDG PET-CT scans was 4.37% (n = 270). Out of region patients (n = 87) whose records could not be obtained were excluded leaving a study group of n = 183. Ninety-four in this group had focal uptake, and 89 had diffuse uptake. Fifty-five patients in the focal group had undergone further investigations. Of these, 30 were thought to be benign on USS alone, and 25 patients underwent USS/FNAC. Thirteen (24%) malignancies were identified (5 papillary, 6 follicular, 1 poorly differentiated thyroid cancer, 1 metastatic malignancy). Mean SUVmax for papillary carcinoma was noted to be 8.2 g/ml, and follicular carcinoma was 12.6 g/ml.

Conclusion

Incidental abnormal thyroid 18F-FDG PET-CT uptake in PET-CT scans of 4.37% is in keeping with the known limited literature. Rather similar number of patients was noted in the focal and diffuse tracer uptake categories in the final study group. Around quarter of the focal lesions were identified to be malignant, implying focal lesions should always be further investigated.
A deep learning model to predict recurrence of atrial fibrillation after pulmonary vein isolation
Authors: Kim Ju Youn , Kim Younghoon , Oh Gil-Hwan , Kim Sun Hwa , Choi Young , Hwang Youmi , Kim Tae-Seok , Kim Sung-Hwan , Kim Ji-Hoon , Jang Sung-Won , Oh Yong-Seog , Lee Man Young
Published: November 2020

Background and Objectives

The efficacy of radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) is well established. The standard approach to RFCA in AF is pulmonary vein isolation (PVI). However, a large proportion of patients experiences recurrence of atrial tachyarrhythmia. The purpose of this study is to find out whether the AI model can assess AF recurrence in patients who underwent PVI.

Materials and methods

This study was a retrospective cohort study that enrolled consecutive patients who underwent catheter ablation for symptomatic, drug-refractory AF and PVI. We developed an AI algorithm to predict recurrence of AF after PVI using patient demographics and three-dimensional (3D) reconstructed left atrium (LA) images.

Results

We included 527 consecutive patients in the study. The overall mean LA diameter was 42.0 ± 6.8 mm, and the mean LA volume calculated using 3D reconstructed images was 151.1 ± 46.7 ml. During the follow-up period, atrial tachyarrhythmia recurred in 158 patients. The area under the curve (AUC) of the AI model based on a convolutional neural network (including 3D reconstruction images) was 0.61 (95% confidence interval [CI] 0.53–0.74) using the test dataset. The total test accuracy was 66.3% (57.0–75.6), and the sensitivity was 53.3% (34.8–71.9). The specificity was 73.2% (51.8–75.0), and the F1 score was 52.5% 34.5–66.7).

Conclusion

In this study, we developed an AI algorithm to predict recurrence of AF after catheter ablation of PVI using individual reconstructed LA images. This AI model was unable to predict recurrence of AF overwhelmingly; therefore, further large-scale study is needed.
Helping to heal nature and ourselves through human-rights-based and gender-responsive One Health
Authors: Garnier Julie , Savic Sara , Boriani Elena , Bagnol Brigitte , Häsler Barbara , Kock Richard
Published: November 2020

The health of our planet and humanity is threatened by biodiversity loss, disease and climate crises that are unprecedented in human history, driven by our insatiable consumption and unsustainable production patterns, particularly food systems. The One Health approach is a pathway to synergistically addressing outcomes in term of health and sustainability, but gender issues at the One Health and biodiversity nexus are largely ignored.

By examining the roles and responsibilities of Indigenous and Local People, and especially women, in conserving natural resources, and the social costs of living at the Human-Animal-Environment interface under current conservation strategies, we show that women bear a disproportionate health, poverty and climate burden, despite having pivotal roles in conserving biodiversity. To mitigate risks of emerging infectious diseases, food insecurity and climate change impacts, a gender perspective has previously been proposed, but implementation lags behind. Endemic zoonotic diseases, human-wildlife conflict and environmental pollution lack gender-sensitive frameworks. We demonstrate that women can be powerful agents for change at all levels of society, from communities to businesses, and policy-making institutions, but gender inequalities still persist.

We develop a framework for mainstreaming a gender-responsive and rights-based One Health approach, in order to heal ourselves and nature. Using a leverage-points perspective, we suggest a change of paradigm, from the pursuit of GDP and over-consumption, to a focus on human well-being and their reconnection with healthy environments, using a One Health understanding of nature and health. We recommend learning from Indigenous People to re-position ourselves within nature and to better conserve biodiversity. We also propose integration of gender equity in leadership, the respect of human rights, women’s rights (access to health care, healthy food, land tenure, natural resources, education, and economic opportunities), and the rights of nature, through the implementation of gender-responsive and rights-based One Health Action Plans, at policy-making level, in the private sector and the civil society. As the COVID-19 pandemic continues to unveil deep socio-economic inequities in the wealthiest economies and the vital role of nature in supporting our health, we argue to seize this opportunity to build back better and improve resilience and sustainability by using a gender-responsive and rights-based One Health approach.
Educational attainment inequalities in depressive symptoms in more than 100,000 individuals in Europe
Authors: Chlapecka Adam , Kagstrom Anna , Cermakova Pavla
Published: November 2020

Background

Increasing educational attainment (EA) could decrease the occurrence of depression. We investigated the relationship between EA and depressive symptoms in older individuals across four European regions.

Methods

We studied 108,315 Europeans (54% women, median age 63 years old) from the Survey on Health, Ageing and Retirement in Europe assessing EA (seven educational levels based on International Standard Classification of Education [ISCED] classification) and depressive symptoms (≥4 points on EURO-D scale). Logistic regression estimated the association between EA and depressive symptoms, adjusting for sociodemographic and health-related factors, testing for sex/age/region and education interactions.

Results

Higher EA was associated with lower odds of depressive symptoms, independent of sociodemographic and health-related factors. A threshold of the lowest odds of depressive symptoms was detected at the first stage of tertiary education (OR 0.60; 95% confidence interval [CI] 0.55–0.65;p < 0.001; relative to no education). Central and Eastern Europe showed the strongest association (OR for high vs. low education 0.37; 95% CI 0.33–0.40;p < 0.001) and Scandinavia the weakest (OR for high vs. low education 0.69; 95% CI 0.60–0.80;p < 0.001). The association was strongest among younger individuals. There was a sex and education interaction only within Central and Eastern Europe.

Conclusions

Level of EA is reflected in later-life depressive symptoms, suggesting that supporting individuals in achieving EA, and considering those with lower EA at increased risk for depression, could lead to decreased burden of depression across the life course. Further educational support in Central and Eastern Europe may decrease the higher burden of depressive symptoms in women.
Comparison of the ELISA and ECL Assay for Vedolizumab Anti-drug Antibodies: Assessing the Impact on Pharmacokinetics and Safety Outcomes of the Phase 3 GEMINI Trials
Authors: Wyant Timothy , Yang Lili , Rosario Maria
Published: November 2020

Vedolizumab immunogenicity has been assessed using an enzyme-linked immunosorbent assay (ELISA) with a ~ 0.5 μg/mL drug interference, which may underestimate on-drug immunogenicity. We aimed to compare immunogenicity results between ELISA and the new drug-tolerant electrochemiluminescence (ECL) assay (and the two versions of neutralizing assays, drug-sensitive versus drug-tolerant). The ECL assay drug tolerance is ~ 100 times higher than that of the ELISA (≥ 50 μg/mL vs. 0.5 μg/mL with a 500 ng/mL positive control), and assay sensitivity is < 5 ng/mL for both assays. Vedolizumab immunogenicity was assessed in 2000 GEMINI 1 and 2 patients originally tested by ELISA and retested by ECL assay. Anti-drug antibody (ADA) impact on infusion-related reactions and pharmacokinetics (PK) was examined using descriptive statistics and population PK analyses. By ECL assay, 6% (86/1427) of patients treated with vedolizumab as induction and maintenance therapy tested ADA-positive. Of these, 20 patients were persistently positive and 56 had neutralizing antibodies. By ELISA, 4% (56/1434) of these patients were ADA-positive, 9 were persistently positive, and 33 had neutralizing antibodies. Among 61 patients with infusion-related reactions, 6 (10%) were ADA-positive (2 persistently positive) by ECL assay. By ELISA, 3 (5%) patients were both ADA-positive and persistently positive. Most results (96%) were similar with both assays. In the updated population PK model, ADA-positive status was estimated to increase vedolizumab linear clearance by a factor of 1.10 (95% credible interval 1.03–1.17), which is consistent with previous reports. The impact of ADA on safety and PK modeling remained generally consistent using either ELISA or ECL assay. ClinicalTrials.gov: NCT00783718 and NCT00783692
Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers
Authors: Acosta Maria F. , Abrahamson Michael D. , Encinas-Basurto David , Fineman Jeffrey R. , Black Stephen M. , Mansour Heidi M.
Published: November 2020

Metformin is an activator of the AMPK and Nrf2 pathways which are important in the pathology of several complex pulmonary diseases with unmet medical needs. Organic solution advanced spray drying in the absence of water in closed-mode was used to design and develop respirable dry powders. Following comprehensive characterization, the influence of physicochemical properties was correlated with performance as aerosols using inertial impaction and three different human dry powder inhaler (DPI) devices varying in device properties.In vitrocell assays were conducted to test safety in 2D human pulmonary cell lines and in 3D small airway epithelia comprising primary cells at the air-liquid interface (ALI). In addition,in vitrotransepithelial electrical resistance (TEER) was carried out. Metformin remained crystalline following advanced spray drying under these conditions. All SD powders consisted of nanoparticles/microparticles in the solid state.In vitroaerosol dispersion performance showed high aerosolization for all SD metformin powders with all DPI devices tested. High emitted dose for all powders with all three DPI devices was measured. Differences in other aerosol performance parameters and the interplay between the properties of different formulations produced at specific pump rates and the three different DPI devices were correlated with spray drying pump rate and device properties. Safety over a wide metformin dose range was also demonstratedin vitro. Aerosol delivery of metformin nanoparticles/microparticles has the potential to be a new “first-in-class” therapeutic for the treatment of a number of pulmonary diseases including pulmonary vascular diseases such as pulmonary hypertension.
Germán Bernácer’s Analysis of the Great Depression
Authors: Zabalza Juan
Published: November 2020

The self-made Spanish economist Germán Bernácer (1833–1865) drew up a coherent theory of economic fluctuations—the theory of disposable funds—during the 1920s that has recently drawn the attention of historians of economic thought who appreciate its original approach and have weighted his possible influence on the Cambridge economists. This article analyses how Bernácer updated the model to the new formal rhetoric of the 1930s in light of the publication of Keynes’s A Treatise on Money. On the other hand, the article also analyzes how Bernácer, as a member of the Research Department of the Bank of Spain, applied the theory of disposable funds to interpret a wide range of economic, monetary, and financial events in a series of reports that he drafted for advising the board of the bank during the period 1932–36, in the midst of the Great Depression.
The State of Exception Goes Viral
Authors: Chatterjee Partha
Published: November 2020

The recent protests against the Citizenship Amendment Act have been widespread, spontaneous, and without the active sponsorship of political parties. They have brought out on the streets thousands of students and women who have never before participated in political rallies. What is the significance of this movement as a point of resistance against authoritarian Hindu nationalism? What does it mean for the future of Indian democracy?
Dark Ages and Bright Futures
Authors: Misri Deepti
Published: November 2020

This article examines the shape of time for those living in Indian-occupied Kashmir, focusing particularly on two calendars that became embroiled in a “calendar war” in Indian-occupied Kashmir in the year 2017. The first was the annual calendar of the Jammu and Kashmir Bank, which proudly featured twelve “talented youth[s]” of the state. The second was a “countercalendar” circulated online by the anonymously run pro-azadi (self-determination) Facebook group Aalaw, featuring a rather different image of Kashmiri youth. Situating these calendars against a larger backdrop of visual representations of time in occupied Kashmir, this article examines how each calendar mobilized narratives about the past, present, and future in Kashmir, narratives that were negotiated through competing gendered images of youth via rhetorics of ability and disability. The article takes up the tensions between two strands of disability studies: liberal approaches that emphasize the celebration of disability and biopolitical critiques that foreground the violent production of debilitation, to consider how Kashmiri visual production suggests a vision of crip futures for those now living with disabilities in Kashmir.
Dinuclear Triple-Stranded Helicates Comprising Al(III), Ga(III), or In(III) and a Hydrazine-Linked Bisiminopyrrolyl Ligand: Synthesis, Structure, Optical Resolution, and Chiroptical Properties
Authors: Ishihama Kohei , Ono Toshikazu , Okawara Toru , Harada Takunori , Furusho Kiyonao , Hasegawa Masashi , Nojima Yuki , Koide Taro , Abe Masaaki , Hisaeda Yoshio
Published: November 2020

The synthesis of helical complexes is attracting increased attention because their chiral properties lead to a variety of functional applications. In this work, a series of neutral, dinuclear M(III) (M = Al, Ga, or In) triple-stranded helicates were prepared using a tetradentate bisiminopyrrole ligand (H2L). An X-ray crystallographic analysis revealed that both right- (P) and left-handed (M) helical structures exist in the solid state for Al2L3, Ga2L3, and In2L3. The enantiomers were successfully resolved by chiral column chromatography, and the chiroptical properties of the complexes were characterized by circular dichroism, circularly polarized emission spectroscopy, and time-dependent density functional theory calculations.