bluuebunny/crossref_metadata_2025 huggingface dataset:
How perceptions of a successful physician-scientist varies with gender and academic rank: toward defining physician-scientist's success
Authors: Gotian Ruth , Andersen Olaf S.
Published: February 2020

Background

Physician-scientists (the physician-scientist workforce) are aging, and there are too few physician-scientists in the pipeline to replace those who retire. Moreover, the pipeline is leaky because some trainees and junior physician-scientists choose other career paths. Significant attention has been directed toward patching the leaking pipeline, thereby increasing the quantity of physician-scientists. Less attention has been devoted to identifying and training more successful physician-scientists, thereby increasing the quality of the pool and making up for the attrition. Though all training programs strive to develop more successful graduates, there is no clear understanding of what constitutes predictors of future success. Identifying characteristics of success would enable those who recruit trainees—and later hire and fund physician-scientists—to make more informed decisions. It also could impact on the training, as it would be possible to focus on competencies that foster success. Predictors of success are therefore important. Prior to taking on this task, however, we must first define success for physician-scientists.

Methods

To identify likely characteristics of success, we undertook a qualitative case study where 21 physician-scientists were interviewed to determine their perceptions of what constitutes a successful physician-scientist. Sixteen interviewees were selected based on convenience sampling, while the remaining five were selected based on the snowball effect. Interviews were transcribed and coded in Dedoose® and a qualitative analysis was conducted using an inductive approach to content analysis.

Results

There was considerable variation in their perceptions based on seniority and gender. Junior physician-scientists focused on metrics on which their promotion is based, e.g., publications and grants; senior physician-scientists focused on their legacy, e.g., contribution to the field and mentoring. Women were more likely to emphasize objective measures of success, like publications, while concurrently concentrating on relational skills, like networking, collaboration and public recognition. Men emphasized the impact of science and subjective characteristics like boldness, confidence and critical thinking.

Conclusion

Clearly, physician-scientists are not working off of a uniform metric of success, thereby making their evaluation and remuneration a convoluted process, especially if those evaluating the physician-scientists are not of the same mind as to the definition of success.
Production of riboflavin and related cofactors by biotechnological processes
Authors: Liu Shuang , Hu Wenya , Wang Zhiwen , Chen Tao
Published: February 2020

Riboflavin (RF) and its active forms, the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have been extensively used in the food, feed and pharmaceutical industries. Modern commercial production of riboflavin is based on microbial fermentation, but the established genetically engineered production strains are facing new challenges due to safety concerns in the food and feed additives industry. High yields of flavin mononucleotide and flavin adenine dinucleotide have been obtained using whole-cell biocatalysis processes. However, the necessity of adding expensive precursors results in high production costs. Consequently, developing microbial cell factories that are capable of efficiently producing flavin nucleotides at low cost is an increasingly attractive approach. The biotechnological processes for the production of RF and its cognate cofactors are reviewed in this article.
Optimal process design space to ensure maximum viability and productivity in Penicillium chrysogenum pellets during fed-batch cultivations through morphological and physiological control
Authors: Veiter Lukas , Kager Julian , Herwig Christoph
Published: February 2020

Background

Biomass growth of Pencillium chrysogenum is characterised by a distinct pellet morphology consisting of compact hyphal agglomerates. Fungal pellets are advantageous in industrial process control due to rheological advantages but lead to biomass degradation due to diffusional limitations of oxygen and substrate in the pellet’s core. Several fermentation parameters are known to affect key pellet characteristics regarding morphology, viability and productivity. Pellet morphology and size are affected by agitation. Biomass viability and productivity are tightly interlinked with substrate uptake and dissolved oxygen concentration.

Results

The goal of this study was to study the impact of the fermentation parameters power input, dissolved oxygen content and specific substrate uptake rate on morphology, biomass viability and productivity. A design of experiments (DoE) approach was conducted and corresponding responses were analysed using novel morphological descriptors analysed by a previously established flow cytometry method. Results clearly display inverse correlations between power input and pellet size, specific morphological parameters related to pellet density can be increased in direct proportion to power input. Biomass viability and productivity are negatively affected by high specific substrate uptake rates.

Conclusions

Based upon multiple linear regression, it was possible to obtain an optimal design space for enhanced viability and productivity at beneficial morphological conditions. We could maintain a high number of pellets with favourable morphology at a power input of 1500 W/m3. A sound compromise between viability and high productivity is possible at a specific glucose uptake rate of 0.043 g/g/h at dissolved oxygen levels of 40% minimum.
Downregulation of Siah1 promotes colorectal cancer cell proliferation and migration by regulating AKT and YAP ubiquitylation and proteasome degradation
Authors: Xiao Zhiyuan , Wei Zhigang , Deng Danling , Zheng Zhe , Zhao Yali , Jiang Shenglu , Zhang Dan , Zhang Ling-Jie , Fan Mingmei , Chen Siqi , Wang ShuYang , Ding Yanqing , Ye Yaping , Jiao Hongli
Published: February 2020

Background

Colorectal cancer (CRC) is one of the most common malignant tumors in the world. Siah E3 ubiquitin protein ligase 1 (Siah1) has been identified as a tumor suppressor gene and plays an important role in the development of malignant tumors. However, the potential role and molecular mechanism of Siah1 in the development and progression of CRC is still unclear.

Methods

To explore the role and molecular mechanism of Siah1 in the development and progression of CRC, we examined the expression of Siah1 in CRC tissue samples and analyzed its association with progression and prognosis in CRC. In addition, overexpression and knockdown of Siah1 was used to investigate its activity in CRC cells. We also use bioinformatics to analyze and verify the significant roles of Siah1 in critical signaling pathways of CRC.

Results

We found that the expression of Siah1 was significantly downregulated in CRC tissues, and low expression of Siah1 was associated with aggressive TNM staging and poor survival of CRC patients. Moreover, we revealed that overexpression of Siah1 in CRC cells markedly inhibited CRC cell proliferation and invasion in vitro and in vivo, while knockdown of Siah1 enhanced CRC cell proliferation and invasion. Furthermore, we found that Siah1 prohibited cell proliferation and invasion in CRC partially through promoting AKT (the serine-threonine protein kinase) and YAP (yes associated protein) ubiquitylation and proteasome degradation to regulate the activity of MAPK(mitogen-activated protein kinase 1), PI3K-AKT (phosphatidylinositol 3-kinase-the serine-threonine protein kinase) and Hippo signaling pathways.

Conclusions

These findings suggested that Siah1 is a novel potential prognostic biomarker and plays a tumor suppressor role in the development and progression of CRC.
Key to the females of Afrotropical Anopheles mosquitoes (Diptera: Culicidae)
Authors: Coetzee Maureen
Published: February 2020

Background

In 1987, Gillies and Coetzee published a pictorial key for the morphological identification of adult female mosquitoes. Since then, several new species of anopheline mosquitoes have been described.

Methods

The 1987 key to adult female mosquitoes was used as the template for the current key.

Results

New species described in the literature over the past 32 years have been included. A list of all currently known Afrotropical species is provided.Anopheles stephensiis included for the first time as occurring on the African continent.

Conclusions

An updated key for the morphological identification of Afrotropical anopheline species is presented.
Increasing venoarterial extracorporeal membrane oxygenation flow puts higher demands on left ventricular work in a porcine model of chronic heart failure
Authors: Hála Pavel , Mlček Mikuláš , Ošťádal Petr , Popková Michaela , Janák David , Bouček Tomáš , Lacko Stanislav , Kudlička Jaroslav , Neužil Petr , Kittnar Otomar
Published: February 2020

Background

Venoarterial extracorporeal membrane oxygenation (VA ECMO) is widely used in the treatment of circulatory failure, but repeatedly, its negative effects on the left ventricle (LV) have been observed. The purpose of this study is to assess the influence of increasing extracorporeal blood flow (EBF) on LV performance during VA ECMO therapy of decompensated chronic heart failure.

Methods

A porcine model of low-output chronic heart failure was developed by long-term fast cardiac pacing. Subsequently, under total anesthesia and artificial ventilation, VA ECMO was introduced to a total of five swine with profound signs of chronic cardiac decompensation. LV performance and organ specific parameters were recorded at different levels of EBF using a pulmonary artery catheter, a pressure–volume loop catheter positioned in the LV, and arterial flow probes on systemic arteries.

Results

Tachycardia-induced cardiomyopathy led to decompensated chronic heart failure with mean cardiac output of 2.9 ± 0.4 L/min, severe LV dilation, and systemic hypoperfusion. By increasing the EBF from minimal flow to 5 L/min, we observed a gradual increase of LV peak pressure from 49 ± 15 to 73 ± 11 mmHg (P = 0.001) and an improvement in organ perfusion. On the other hand, cardiac performance parameters revealed higher demands put on LV function: LV end-diastolic pressure increased from 7 ± 2 to 15 ± 3 mmHg, end-diastolic volume increased from 189 ± 26 to 218 ± 30 mL, end-systolic volume increased from 139 ± 17 to 167 ± 15 mL (all P < 0.001), and stroke work increased from 1434 ± 941 to 1892 ± 1036 mmHg*mL (P < 0.05). LV ejection fraction and isovolumetric contractility index did not change significantly.

Conclusions

In decompensated chronic heart failure, excessive VA ECMO flow increases demands and has negative effects on the workload of LV. To protect the myocardium from harm, VA ECMO flow should be adjusted with respect to not only systemic perfusion, but also to LV parameters.
Assessment of a multiplex PCR and Nanopore-based method for dengue virus sequencing in Indonesia
Authors: Stubbs Samuel C. B. , Blacklaws Barbara A. , Yohan Benediktus , Yudhaputri Frilasita A. , Hayati Rahma F. , Schwem Brian , Salvaña Edsel M. , Destura Raul V. , Lester James S. , Myint Khin S. , Sasmono R. Tedjo , Frost Simon D. W.
Published: February 2020

Background

Dengue virus (DENV) infects hundreds of thousands of people annually in Indonesia. However, DENV sequence data from the country are limited, as samples from outbreaks must be shipped across long-distances to suitably equipped laboratories to be sequenced. This approach is time-consuming, expensive, and frequently results in failure due to low viral load or degradation of the RNA genome.

Methods

We evaluated a method designed to address this challenge, using the ‘Primal Scheme’ multiplex PCR tiling approach to rapidly generate short, overlapping amplicons covering the complete DENV coding-region, and sequencing the amplicons on the portable Nanopore MinION device. The resulting sequence data was assessed in terms of genome coverage, consensus sequence accuracy and by phylogenetic analysis.

Results

The multiplex approach proved capable of producing near complete coding-region coverage from all samples tested ($$ \overline{x} $$x¯ = 99.96%, n = 18), 61% of which could not be fully amplified using the current, long-amplicon PCR, approach. Nanopore-generated consensus sequences were found to be between 99.17–99.92% identical to those produced by high-coverage Illumina sequencing. Consensus accuracy could be improved by masking regions below 20X coverage depth (99.69–99.92%). However, coding-region coverage was reduced at this depth ($$ \overline{x} $$x¯ = 93.48%). Nanopore and Illumina consensus sequences generated from the same samples formed monophyletic clades on phylogenetic analysis, and Indonesian consensus sequences accurately clustered by geographical origin.

Conclusion

The multiplex, short-amplicon approach proved superior for amplifying DENV genomes from clinical samples, particularly when the virus was present at low concentrations. The accuracy of Nanopore-generated consensus sequences from these amplicons was sufficient for identifying the geographic origin of the samples, demonstrating that the approach can be a useful tool for identifying and monitoring DENV clades circulating in low-resource settings across Indonesia. However, the inaccuracies in Nanopore-generated consensus sequences mean that the approach may not be appropriate for higher resolution transmission studies, particularly when more accurate sequencing technologies are available.
A priority oriented nutrition education program to improve nutritional and cardiometabolic status in the workplace: a randomized field trial
Authors: Hassani Bahar , Amani Reza , Haghighizadeh Mohammad Hussein , Araban Marzieh
Published: February 2020

Background

Workplace nutrition has been identified as a priority setting that can significantly reduce cardiovascular diseases (CVD) risk factors. This study was conducted as a part of the workplace education program to improve nutritional practices and cardiometabolic status in industrial personnel.

Methods

The present research was a randomized controlled field trial conducted on employees of a regional petrochemical company. The health-related priorities of the program were defined and addressed in the study in which 104 employees with dyslipidemia were randomly divided into two groups of education and control. Data were collected pre- and post-intervention, using valid and reliable multi-session questionnaires on demographic data, nutritional knowledge, and nutritional intake. Anthropometric measures, serum FBS, HbA1C, hs-CRP and homocysteine (Hcy) were assessed in both groups. In the education group, the nutrition program included five educational workshops about healthy nutrition and regular exercise along with educational messages over a 3-month period. The controls did not receive any education during the study.

Results

There were no statistically significant differences between the two groups regarding the baseline variables. The education group significantly improved their nutritional knowledge (p < 0.001), dietary intakes (p < 0.005), serum FBS (p < 0.001) and Hcy levels (p < 0.001) and anthropometric indices.

Conclusion

Workplace nutrition education programs can improve knowledge and reduce important CVD risk factors.
Heart in art: cardiovascular diseases in novels, films, and paintings
Authors: Kaptein Ad A. , van der Meer Pim B. , Florijn Barend W. , Hilt Alexander D. , Murray Michael , Schalij Martin J.
Published: February 2020

Background

Understanding representations of disease in various art genres provides insights into how patients and health care providers view the diseases. It can also be used to enhance patient care and stimulate patient self-management.

Methods

This paper reviews how cardiovascular diseases are represented in novels, films, and paintings: myocardial infarction, aneurysm, hypertension, stroke, heart transplantation, Marfan’s disease, congestive heart failure. Various search systems and definitions were used to help identify sources of representations of different cardiovascular diseases. The representations of the different diseases were considered separately. The Common Sense Model was used a theoretical model to outline illness perceptions and self-management in the various identified novels, films, and paintings.

Results

Myocardial infarction followed by stroke were the most frequently detailed diseases in all three art genres. This reflects their higher prevalence. Representations ranged from biomedical details through to social and psychological consequences of the diseases.

Conclusions

Artistic representations of cardiovascular diseases reflect cognitions, emotions, and images of prevalent disease. These representations shape views and behaviour of ill and healthy persons regarding heart diseases. As these representations are amenable to change, they deserve further research, which may be instrumental in improving the quality of life of persons struck by cardiovascular diseases. Changing illness perceptions appears to be a method to improve self-management and thereby quality of life in patients with various cardiovascular diseases.
Correlation of dosimetric factors with the development of symptomatic radiation pneumonitis in stereotactic body radiotherapy
Authors: Ryckman Jeffrey M. , Baine Michael , Carmicheal Joseph , Osayande Ferdinand , Sleightholm Richard , Samson Kaeli , Zheng Dandan , Zhen Weining , Lin Chi , Zhang Chi
Published: February 2020

Background

The development of radiation pneumonitis (RP) after Stereotactic Body Radiotherapy (SBRT) is known to be associated with many different factors, although historical analyses of RP have commonly utilized heterogeneous fractionation schemes and methods of reporting. This study aims to correlate dosimetric values and their association with the development of Symptomatic RP according to recent reporting standards as recommended by the American Association of Physicists in Medicine.

Methods

We performed a single-institution retrospective review for patients who received SBRT to the lung from 2010 to 2017. Inclusion criteria required near-homogeneous tumoricidal (α/β = 10 Gy) biological effective dose (BED10) of 100–105 Gy (e.g., 50/5, 48/4, 60/8), one or two synchronously treated lesions, and at least 6 months of follow up or documented evidence of pneumonitis. Symptomatic RP was determined clinically by treating radiation oncologists, requiring radiographic evidence and the administration of steroids. Dosimetric parameters and patient factors were recorded. Lung volumes subtracted gross tumor volume(s). Wilcoxon Rank Sums tests were used for nonparametric comparison of dosimetric data between patients with and without RP; p-values were Bonferroni adjusted when applicable. Logistic regressions were conducted to predict probabilities of symptomatic RP using univariable models for each radiation dosimetric parameter.

Results

The final cohort included 103 treated lesions in 93 patients, eight of whom developed symptomatic RP (n = 8; 8.6%). The use of total mean lung dose (MLD) > 6 Gy alone captured five of the eight patients who developed symptomatic RP, while V20 > 10% captured two patients, both of whom demonstrated a MLD > 6 Gy. The remaining three patients who developed symptomatic RP without exceeding either metric were noted to have imaging evidence of moderate interstitial lung disease, inflammation of the lungs from recent concurrent chemoradiation therapy to the contralateral lung, or unique peri-tumoral inflammatory appearance at baseline before treatment.

Conclusions

This study is the largest dosimetric analysis of symptomatic RP in the literature, of which we are aware, that utilizes near-homogenous tumoricidal BED fractionation schemes. Mean lung dose and V20 are the most consistently reported of the various dosimetric parameters associated with symptomatic RP. MLD should be considered alongside V20 in the treatment planning process.

Trial registration

Retrospectively registered on IRB 398–17-EP.
Adverse events during oral colchicine use: a systematic review and meta-analysis of randomised controlled trials
Authors: Stewart Sarah , Yang Kevin Chih Kai , Atkins Kate , Dalbeth Nicola , Robinson Philip C.
Published: February 2020

Background

Colchicine is a widely used drug to treat inflammatory diseases. Due to its long historical use in medicine, controlled clinical trials have been small and there remains some caution with the use of this drug in patients with co-morbidities. The aim of the study is to systematically examine the side effect profile of colchicine in controlled clinical trials across all published indications.

Methods

A systematic review was conducted in accordance with PRISMA methodology. The Cochrane Library, MEDLINE and EMBASE were searched for double-blind controlled trials of oral colchicine in adult patients that reported adverse event data. Meta-analyses were used to determine the relative risk (RR) of adverse events in colchicine users compared to comparator groups.

Results

A total of 4915 studies were initially identified and after exclusions, 35 randomised controlled trials with placebo (n = 30) or active comparators (n = 5) were included. The most common diseases studied were gout, liver cirrhosis and pericarditis. There were a total of 8659 pooled participants, 4225 participants were randomised to receive colchicine, 3956 to placebo and 411 to an active comparator. Diarrhoea was reported in 17.9% of colchicine users versus 13.1% in comparator groups (RR 2.4, 95% confidence interval (CI) 1.6, 3.7). Any gastrointestinal event was reported in 17.6% of colchicine users and 13.1% of comparators (RR 1.7, 95% CI 1.3, 2.3). Adverse liver events were reported in 1.9% of colchicine users versus 1.1% in the comparator groups (RR 1.6, 95% CI 0.9, 3.0). Muscle events were reported in 4.2% of colchicine users and 3.3% in the comparator groups (RR 1.3, 95% CI 0.8, 1.9). Haematology events were reported in 0.6% of colchicine users and 0.4% of comparator groups (RR 1.34 (0.64, 2.82). No study reported neuropathy events. Other sensory events were reported in 1.1% of colchicine users and 1.5% of comparator groups (RR 1.4, 95% CI 0.3, 6.7). Infectious events were reported in 0.4% of colchicine users and 2.1% of comparator groups (RR 1.0, 95% CI 0.7, 1.5). No study reported death as an adverse event.

Conclusion

Colchicine increases the rate of diarrhoea and gastrointestinal adverse events but does not increase the rate of liver, sensory, muscle, infectious or haematology adverse events or death.
Association between periodontitis and anti-citrullinated protein antibodies in rheumatoid arthritis patients: a cross-sectional study
Authors: González-Febles Jerián , Rodríguez-Lozano Beatriz , Sánchez-Piedra Carlos , Garnier-Rodríguez Jorge , Bustabad Sagrario , Hernández-González Martina , González-Dávila Enrique , Sanz Mariano , Díaz-González Federico
Published: February 2020

Aim

The aim of this study was to evaluate the association between periodontal parameters related with the periodontal disease severity and the presence and levels of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients.

Materials and methods

This cross-sectional study included 164 RA patients. Socio-demographics and RA disease characteristics, including ELISA-detected ACPA (anti-CCP-2), were recorded. Exposure was assessed by periodontal parameters: plaque index (PI), bleeding on probing (BoP), probing pocket depth, and clinical attachment levels (CAL). Presence and levels of ACPAs (outcome) and exposure variables were compared by both parametric and non-parametric tests and associations were evaluated by adjusted odds ratio (OR).

Results

A significant association was observed between the presence of anti-CCP antibodies and severity of periodontal outcomes such as the mean CAL (OR 1.483, p = 0.036), mean PI (OR 1.029, p = 0.012), and the number of pockets ≥ 5 mm (OR 1.021, p = 0.08). High anti-CCP antibodies levels were associated with mean CAL, mean PI, and number of pockets ≥ 5 mm with an OR of 1.593 (p = 0.043), 1.060 (p <  0.001), and 1.031 (p = 0.031), respectively. Furthermore, a significant increase of 4.45 U/mL in anti-CCP antibodies levels (p = 0.002) in RA patients was found for each pocket ≥ 5 mm after adjusting for age, gender, smoking, time of disease evolution, and RA activity.

Conclusions

In RA patients, the severity of periodontal conditions such as mean CAL, mean PI, and the number of pockets ≥ 5 mm were linearly associated with both the presence and levels of anti-CCP antibodies.
Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia
Authors: Huo Jiali , Zhang Leisheng , Ren Xiang , Li Chengwen , Li Xingxin , Dong Peiyuan , Zheng Xuan , Huang Jinbo , Shao Yingqi , Ge Meili , Zhang Jing , Wang Min , Nie Neng , Jin Peng , Zheng Yizhou
Published: February 2020

Background

Longitudinal studies have verified the pivotal role of mesenchymal stem/stromal cells (MSCs) in the bone marrow microenvironment for hematopoiesis and coordinate contribution to leukemia pathogenesis. However, the precise characteristics and alternation of MSCs during acquired aplastic anemia (AA) remain obscure.

Methods

In this study, we originally collected samples from both healthy donors (HD) and AA patients to dissect the hematological changes. To systematically evaluate the biological defects of AA-derived MSCs (AA-MSCs), we analyzed alterations in cellular morphology, immunophenotype, multi-lineage differentiation, cell migration, cellular apoptosis, and chromosome karyocyte, together with the immunosuppressive effect on the activation and differentiation of lymphocytes. With the aid of whole genome sequencing and bioinformatic analysis, we try to compare the differences between AA-MSCs and HD-derived MSCs (HD-MSCs) upon the molecular genetics, especially the immune-associated gene expression pattern. In addition, the efficacy of umbilical cord-derived MSC (UC-MSC) transplantation on AA mice was evaluated by utilizing survivorship curve, histologic sections, and blood cell analyses.

Results

In coincidence with the current reports, AA patients showed abnormal subsets of lymphocytes and higher contents of proinflammatory cytokines. Although with similar immunophenotype and chromosome karyotype to HD-MSCs, AA-MSCs showed distinguishable morphology and multiple distinct characteristics including genetic properties. In addition, the immunosuppressive effect on lymphocytes was significantly impaired in AA-MSCs. What is more, the cardinal symptoms of AA mice were largely rescued by systemic transplantation of UC-MSCs.

Conclusions

Herein, we systematically investigated the signatures and efficacy of MSCs to dissect the alterations occurred in AA both at the cellular and molecular levels. Different from HD-MSCs, AA-MSCs exhibited multifaceted defects in biological characteristics and alterative molecular genetics in the whole genome. Our findings have provided systematic and overwhelming new evidence for the defects of AA-MSCs, together with effectiveness assessments of UC-MSCs on AA as well.
Allogeneic umbilical cord-derived mesenchymal stem cell transplantation for treating chronic obstructive pulmonary disease: a pilot clinical study
Authors: Le Thi Bich Phuong , Nguyen Thi Ha , Dang Ngo Chau Hoang , Phan Van Tien , Do Quyet , Dong Khac Hung , Le Van Dong , Nguyen Huy Luc , Mai Cong Khan , Ta Ba Thang , Do Minh Trung , Vu Bich Ngoc , Truong Chau Nhat , Van Pham Phuc
Published: February 2020

Introduction

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD.

Methods

Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up.

Results

No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment.

Conclusion

Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations.

Trial registration

ISRCTN, ISRCTN70443938. Registered 06 July 2019
Evaluating sustainability in the Childhood Obesity Research Demonstration project: the model and process
Authors: Lee Rebecca E. , Kao Dennis , Parker Nathan H. , Hallett Allen M. , Kochi Camila Y. , Modelska Maria J. , Rifai Hanadi S. , O’Connor Daniel P.
Published: February 2020

Background

In the context of health-related interventions, sustainability is the capacity to maintain the changes resulting from the intervention. These can be improved policies, practices or trends intended to improve population health. The Childhood Obesity Research Demonstration (CORD) project was a multi-site, multi-intervention collaboration testing the Obesity Chronic Care Model with interventions for childhood obesity prevention and management. We present the model, definitions and methodology used for the cross-site sustainability evaluation of CORD.

Methods

We applied the Ecologic Model of Obesity to childhood obesity interventions to operationalize four sustainability constructs: replicability, continuation of benefits, institutionalization, and community capacity. We used a triangulation approach and employed mixed methods to assess sustainability constructs at each level of the Ecologic Model of Obesity: Micro, Meso, Exo and Macro. We constructed checklists to count and code intervention activities, use of evidence-based practices among providers, and environmental factors and policies hypothesized to influence intervention sustainability. We developed in-depth interviews for principal investigators and project leads. We applied the Wilder Collaboration Factors Inventory with key stakeholders.

Results

Lessons learned suggested that sustainability constructs should be clearly identified and operationalized a priori. Constructs must be flexible to account for differences between intervention plans and implementation to obtain robust and informative data.

Conclusion

Strong links are needed among researchers, program implementers and communities to accomplish consistent, robust and valuable data collection efforts to assure sustainable and healthy communities.
The novel llama‐human chimeric antibody has potent effect in lowering LDL‐c levels in hPCSK9 transgenic rats
Authors: Li Xinyang , Wang Meiniang , Zhang Xinhua , Liu Chuxin , Xiang Haitao , Huang Mi , Ma Yingying , Gao Xiaoyan , Jiang Lin , Liu Xiaopan , Li Bo , Hou Yong , Zhang Xiuqing , Yang Shuang , Yang Naibo
Published: February 2020

Background

The advent of proprotein convertase subtilisin/kexin type 9 (PCSK9)–inhibiting drugs have provided an effective, but extremely expensive treatment for the management of low density lipoprotein (LDL). Our aim was to explore a cost‐effective application of camelid anti‐PCSK9 single domain antibodies (sdAbs), which are high variable regions of the camelid heavy chain antibodies (VHHs), as a human PCSK9 (hPCSK9) inhibitor. One female llama was immunized with hPCSK9. Screening of high affinity anti‐PCSK9 VHHs was carried out based on surface plasmon resonance (SPR) technology. We reported a lysate kinetic analysis method improving the screening efficiency. To increase the serum half‐life and targeting properties, the constant region fragment of the human immunoglobulin gamma sub‐type 4 (IgG4 Fc) was incorporated to form a novel llama‐human chimeric molecule (VHH‐hFc).

Results

The PCSK9 inhibiting effects of the VHH proteins were analyzed in two human liver hepatocellular cells (HepG2 and Huh7) and in the hPCSK9 transgenic Sprague–Dawley (SD) rat model. The hPCSK9 antagonistic potency of the bivalent VHH‐hFc exceeded the monovalent VHH (P < 0.001) in hepatocarcinoma cells. Furthermore, the llama‐human chimeric VHH‐Fc protein had a similar reduction (~ 40%) of the LDL‐c and total cholesterol when compared to the approved evolocumab in transgenic SD rat model, but with low cost. More surprisingly, the chimeric heavy chain antibodies could be persevered for 3 months at room temperature with little loss of the affinity.

Conclusions

Due to the high yield and low cost of Pichia pastoris, lipid‐lowering effect and strong stability, the llama‐human chimeric antibody (VHH‐Fc) offers a potent therapeutic candidate for the control of the serum lipid level.
Does physiological arousal lead to increased catastrophic misinterpretation? An experiment based on the concept of a fear memory
Authors: Ohst Barnabas , Tuschen-Caffier Brunna
Published: February 2020

Background

While there has been research on catastrophic misinterpretation of ambiguous situations and on the effects of the induction of physiological arousal, there has been no experimental research on the relationship between them. Based on the concept of a fear memory, we aimed to investigate if the induction of physiological arousal leads to catastrophic misinterpretations.

Methods

Participants were shown either a suspenseful film clip to induce physiological arousal (EG, n = 43) or a calm film clip with no specific effect on arousal levels (CG, n = 40) before completing a measure of catastrophic misinterpretation (BSIQ-FR). To assess the specific predictive value of physiological arousal, measurements of other known predictors were included (BSI, BDI-II, ACQ, BSQ, STAI-T, ASI-3).

Results

The film manipulation led to a significant increase in physiological arousal in the EG but not in the CG. The EG did not report more catastrophic misinterpretations than the CG – however, more participants in the EG reported at least one catastrophic misinterpretation. The increase in physiological arousal due to the film manipulation predicted catastrophic misinterpretation in the open response format in the EG, but not in the CG, even when controlling for other known predictors.

Conclusions

Our study provides evidence that experimentally induced physiological arousal can predict catastrophic misinterpretation. The findings support the concept of a fear memory. With the BSIQ-FR, a German questionnaire measuring catastrophic misinterpretation was introduced. Further research on the relationship between physiological arousal and catastrophic misinterpretation with clinical samples is recommended.
A new model for calculating the maximum trust in Online Social Networks and solving by Artificial Bee Colony algorithm
Authors: Saeidi Shahram
Published: February 2020

The social networks are widely used by millions of people worldwide. The trust concept is one of the most important issues in Social Network Analysis (SNA) which highly affects the quantity and quality of the inter-connections, decisions, and interactions among the users in e-commerce or recommendation systems. Many normative algorithms are developed to calculate the trust which most of them are complicated, depend on the network structure, and need lots of critical information that makes them hard to use. The aim of this paper is proposing a descriptive, simple and effective method for calculating the maximal trust and the trust route between any two users of an Online Social Network (OSN). For this purpose, four new models for estimating the trust mechanism of the users are proposed and analyzed using Kolmogorov–Smirnov and Anderson–Darling statistical hypothesis tests to identify and validate the best-fitted model based on 20,613 empirical results gathered from 4552 social network volunteers. Due to the time–complexity of the problem, a meta-heuristic algorithm based on the Artificial Bee Colony (ABC) optimization method is also developed for solving the best-fitted model. The proposed algorithm is simulated in Matlab®over six larger test cases adopted from the Facebook dataset. In order to evaluate the performance of the developed algorithm, the Ant Colony Optimization (ACO) and Genetic Algorithm (GA) based meta-heuristics are also simulated on the same test cases. The comparison of the computational results shows that the ABC approach performs better than the ACO and GA as the size of the network increases.
Multiple liver metastases originating from synchronous double cancer of neuroendocrine tumor and rectal cancer: a case report
Authors: Omori Sachie , Harada Noboru , Toshima Takeo , Takeishi Kazuki , Itoh Shinji , Ikegami Toru , Yoshizumi Tomoharu , Mori Masaki
Published: February 2020

Background

Neuroendocrine tumor (NET) is a relatively rare tumor and can develop in almost any organ, but primary mesenteric NETs are extremely rare. In addition, liver metastases from synchronous double cancer of neuroendocrine tumor graded as G1 and second primary malignancies (SPMs) have never been reported before. We herein report a case of multiple liver metastases from synchronous double cancer of NET (G1) at the ileal mesentery and rectal cancer.

Case presentation

A 66-year-old man was identified as having tumors in the rectum and the ileal mesentery by computed tomography (CT). He underwent laparoscopic low anterior resection for rectal cancer and biopsy of the ileal mesentery lymph node and was diagnosed with rectal cancer as pT3 pN1 cM0 (stage IIIB) and NET (G1) of the ileal mesentery. He received oxaliplatin and capecitabine (XELOX) for 3 months as adjuvant chemotherapy for rectal cancer. The NET (G1) of the ileal mesentery was low grade and had not expanded at follow-up. A CT scan performed 4 years after the surgery indicated multiple liver metastases. All the metastases had the same findings on CT and magnetic resonance imaging (MRI). Thus, the patient underwent the first stage of modified associating liver partition and portal vein ligation for staged hepatectomy (modified ALPPS), comprising partial hepatectomies of segments 3 and 4, ligation of the right branch of portal vein, and hepatic partition on the demarcation line, followed by the second stage of modified ALPPS (right lobectomy). Histopathological findings revealed that the 14 nodules were metastatic liver tumors of rectal cancer and the 2 nodules were liver metastases of the NET (G1).

Conclusions

Our findings suggest that synchronous double cancer of NET and gastrointestinal cancer may be indistinguishable in preoperative images. However, curative resection, precise pathological diagnosis, and adequately adjusted treatment may result in a better prognosis.
Standard care informed by the result of a placental growth factor blood test versus standard care alone in women with reduced fetal movement at or after 36+0 weeks’ gestation: a pilot randomised controlled trial
Authors: Armstrong-Buisseret Lindsay , Godolphin Peter J. , Bradshaw Lucy , Mitchell Eleanor , Ratcliffe Sam , Storey Claire , Heazell Alexander E. P.
Published: February 2020

Background

Biomarkers of placental function can potentially aid the diagnosis and prediction of pregnancy complications. This randomised controlled pilot trial assessed whether for women with reduced fetal movement (RFM), intervention directed by the measurement of a placental biomarker in addition to standard care was feasible and improved pregnancy outcome compared with standard care alone.

Methods

Women aged 16–50 years presenting at eight UK maternity units with RFM between 36+0 and 41+0 weeks’ gestation with a viable singleton pregnancy and no indication for immediate delivery were eligible. Participants were randomised 1:1 in an unblinded manner to standard care and a biomarker blood test result revealed and acted on (intervention arm) or standard care where the biomarker result was not available (control arm). The objectives were to determine the feasibility of a main trial by recruiting 175–225 participants over 9 months and to provide proof of concept that informing care by measurement of placental biomarkers may improve outcome. Feasibility was assessed via the number of potentially eligible women, number recruited, reasons for non-recruitment and compliance. Proof of concept outcomes included the rates of the induction of labour and caesarean birth, and a composite adverse pregnancy outcome.

Results

Overall, 2917 women presented with RFM ≥ 36 weeks, 352 were approached to participate and 216 (61%) were randomised (intervention n = 109, control n = 107). The main reason for not approaching women was resource/staff issues (n = 1510). Ninety-seven women declined the trial, mainly due to not liking blood tests (n = 24) or not wanting to be in a trial (n = 21). Compliance with the trial interventions was 100% in both arms. Labour was induced in 97 (45%) participants (intervention n = 49, control n = 48), while 17 (9%) had planned caesarean sections (intervention n = 9, control n = 8). Overall, 9 (8%) babies in the intervention arm had the composite adverse pregnancy outcome versus 4 (4%) in the control arm.

Conclusions

A main trial using a placental biomarker in combination with delivery, as indicated by the biomarker, in women with RFM is feasible. The frequency of adverse outcomes in this population is low, hence, a large sample size would be required along with consideration of the most appropriate outcome measures.

Trial registration

ISRCTN, ISRCTN12067514; registered 8 September 2017.
Sputum and plasma adiponectin levels in clinically stable adult cystic fibrosis patients with CFTR I1234V mutation
Authors: AbdulWahab Atqah , Allangawi Mona , Thomas Merlin , Bettahi Ilham , Sivaraman Siveen K. , Jerobin Jayakumar , Chandra Prem , Abou-Samra Abdul-Badi , Ramanjaneya Manjunath
Published: February 2020

Background

Cystic fibrosis (CF) lung disease is associated with chronic inflammation leading to progress in lung function. Adiponectin is a predominantly anti-inflammatory adipokine that may have a role in CF lung. This study aims to determine total sputum and total plasma adiponectin levels in clinically stable adults CF patients with CFTR I1234V mutation, compared to plasma adiponectin levels in healthy controls and to investigate their correlations with body mass index (BMI) and spirometry in patients with CF.

Methods

A cross-sectional study comprises 17 CF patients and 18 healthy controls. Adiponectin levels were measured by magnetic bead-based multiplex assay.

Results

The mean age of adult CF patients was 22.9 years±3.8 (18–30) and 76.5% CF patients had pancreatic sufficiency. The mean BMI in healthy controls was slightly higher than CF patients. The mean sputum adiponectin level was significantly lower than plasma adiponectin levels in CF patients and healthy controls (p < 0.001), whereas no significant difference in plasma adiponectin levels between CF patients and healthy controls. The mean sputum adiponectin level was observed to be higher in CF patients with pancreatic insufficiency. Sputum adiponectin level was correlated positively with plasma adiponectin level in CF patients (r = 0.47, p = 0.06). Sputum and plasma adiponectin levels in CF patients were correlated negatively with BMI and percentage predicted forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC).

Conclusions

Sputum adiponectin may provide a minimally invasive tool in the assessment of inflammatory status in CF patients. A further larger study to address any difference in sputum and plasma adiponectin levels among CF patients with pancreatic sufficiency versus pancreatic insufficiency.
Highlights from the previous volumes
Authors: Holgate J. T. , Negro G. , Shvetsov O. O. , Bertolami O. , Francisco F.
Published: February 2020

Spontaneous rapid rotation and breakup of metal droplets in tokamak edge plasmas Contraction-based motility in a compressible active fluid Multiple magnon modes in a magnetic Weyl semimetal Understanding the dynamics of the Earth System
Serum Anti-Müllerian Hormone in the Prediction of Response to hCG Stimulation in Children With DSD
Authors: Lucas-Herald Angela K , Kyriakou Andreas , Alimussina Malika , Guaragna-Filho Guilherme , Diver Louise A , McGowan Ruth , Smith Karen , McNeilly Jane D , Ahmed S Faisal
Published: February 2020

Introduction

The relationship between serum anti-Müllerian hormone (AMH) and the testosterone response to human chorionic gonadotropin (hCG) stimulation test is unclear.

Methods

Children who had hCG stimulation tests in one tertiary centre from 2001 to 2018 were included (n = 138). Serum testosterone was measured before (day 1 [D1]) and after 3 days (D4) of hCG stimulation. Sixty-one of these children also had prolonged hCG stimulation for 2 more weeks and serum testosterone measured after 21 days (D22). All children had a serum AMH measured on D1.

Results

Of the 138 children, D4 testosterone was normal in 104 (75%). AMH was low in 24/138 (17%) children, and 16 (67%) of these had a low D4 testosterone. Median AMH in those who had a normal vs low D4 testosterone was 850 pmol/L (24, 2280) and 54 pmol/L (0.4, 1664), respectively (P < 0.0001). An AMH > 5th centile was associated with a low D4 testosterone in 18/118 (13%; P < 0.0001). Of the 61 children who had prolonged hCG stimulation, D22 testosterone was normal in 39 (64%). AMH was low in 10/61(16%) children and 9 (90%) of these had a low D22 testosterone. Median AMH in children who responded and did not respond by D22 was 639 pmol/L (107, 2280) and 261 pmol/L (15, 1034) (P < 0.0001).

Conclusion

A normal AMH may provide valuable information on overall testicular function. However, a low AMH does not necessarily predict a suboptimal testosterone response to hCG stimulation.