bluuebunny/crossref_metadata_2025 huggingface dataset:
How French general practitioners adapt their care to patients with social difficulties?
Authors: De Oliveira Annie , Chavannes Barbara , Steinecker Magali , Denantes Mady , Chastang Julie , Ibanez Gladys
Published: January 2020

Objective

Several studies have shown the role of the primary care system in access to care and in reducing social inequalities in health. The objective of this study was to describe the practices of general practitioners (GPs) in taking into account the social environment of their patient, and the ways they adapted to social difficulties.

Design

Qualitative study comprising interviews and focus groups.

Setting

French primary care settings.

Participants

Twenty semistructured interviews and two focus groups were conducted with 33 GPs. Sessions were audio recorded, transcribed verbatim and analysed using thematic analysis. The reporting of findings was guided by consolidated criteria for reporting qualitative research.

Result

This study identified adaptations at three levels: in the individual management of patients (alert system, full involvement in prevention, better communication, prioritised additional examinations, financial facilities, help in administrative tasks), in the collective management of patients in an office (consultation without appointment, pay-for-performance indicators, medical staffs, multidisciplinary protocols, medical practice in group, medical student), and in the community management (patients description, cooperation with associations, public health sector and politics).

Conclusion

In France, GPs can take into account the social determinants of health in practice through simple or more complex actions.
Curriculum development: a how to primer
Authors: Schneiderhan Jill , Guetterman Timothy C , Dobson Margaret L
Published: January 2020

Curriculum development is a topic everyone in the field of medical education will encounter. Due to the breadth of ages and types of care provided in Family Medicine, family medicine faculty in particular need to be facile in developing effective curricula for medical students, residents, fellows and for faculty development. In the area of medical education, changing and evolving learning environments, as well as changing requirements necessitate new and innovative curricula to address these evolving needs. The process of developing a medical education curriculum can seem daunting but when broken down into smaller components can become very straightforward and easy to accomplish. This paper focuses on the curriculum development process using a six-step approach: performing a needs assessment, determining content, writing goals and objectives, selecting the educational strategies, implementing the curriculum and, finally, evaluating the curriculum. This process may serve as a template for Family Medicine educators, and all medical educators looking to design (or redesign) their own medical education curriculum.
Basics of statistics for primary care research
Authors: Guetterman Timothy C
Published: January 2020

The purpose of this article is to provide an accessible introduction to foundational statistical procedures and present the steps of data analysis to address research questions and meet standards for scientific rigour. It is aimed at individuals new to research with less familiarity with statistics, or anyone interested in reviewing basic statistics. After examining a brief overview of foundational statistical techniques, for example, differences between descriptive and inferential statistics, the article illustrates 10 steps in conducting statistical analysis with examples of each. The following are the general steps for statistical analysis: (1) formulate a hypothesis, (2) select an appropriate statistical test, (3) conduct a power analysis, (4) prepare data for analysis, (5) start with descriptive statistics, (6) check assumptions of tests, (7) run the analysis, (8) examine the statistical model, (9) report the results and (10) evaluate threats to validity of the statistical analysis. Researchers in family medicine and community health can follow specific steps to ensure a systematic and rigorous analysis.
Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning
Authors: Hedman Åsa K , Hage Camilla , Sharma Anil , Brosnan Mary Julia , Buckbinder Leonard , Gan Li-Ming , Shah Sanjiv J , Linde Cecilia M , Donal Erwan , Daubert Jean-Claude , Mälarstig Anders , Ziemek Daniel , Lund Lars
Published: January 2020

Objective

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. We aimed to derive HFpEF phenotype-based groups ('phenogroups') based on clinical and echocardiogram data using machine learning, and to compare clinical characteristics, proteomics and outcomes across the phenogroups.

Methods

We applied model-based clustering to 32 echocardiogram and 11 clinical and laboratory variables collected in stable condition from 320 HFpEF outpatients in the Karolinska-Rennes cohort study (56% female, median 78 years (IQR: 71–83)). Baseline proteomics and the composite end point of all-cause mortality or heart failure (HF) hospitalisation were used in secondary analyses.

Results

We identified six phenogroups, for which significant differences in the prevalence of concomitant atrial fibrillation (AF), anaemia and kidney disease were observed (p<0.05). Fifteen out of 86 plasma proteins differed between phenogroups (false discovery rate, FDR<0.05), including biomarkers of HF, AF and kidney function. The composite end point was significantly different between phenogroups (log-rank p<0.001), at short-term (100 days), mid-term (18 months) and longer-term follow-up (1000 days). Phenogroup 2 was older, with poorer diastolic and right ventricular function and higher burden of risk factors as AF (85%), hypertension (83%) and chronic obstructive pulmonary disease (30%). In this group a third experienced the primary outcome to 100 days, and two-thirds to 18 months (HR (95% CI) versus phenogroups 1, 3, 4, 5, 6: 1.5 (0.8–2.9); 5.7 (2.6–12.8); 2.9 (1.5–5.6); 2.7 (1.6–4.6); 2.1 (1.2–3.9)).

Conclusions

Using machine learning we identified distinct HFpEF phenogroups with differential characteristics and outcomes, as well as differential levels of inflammatory and cardiovascular proteins.
Mechanism of action of the erector spinae plane block: distribution of dye in a porcine model
Authors: Otero Pablo E , Fuensalida Santiago E , Russo Pedro C , Verdier Natali , Blanco Carlos , Portela Diego A
Published: January 2020

This study aimed to describe the anatomical distribution of dye injected in the erector spinae plane (ESP) in a porcine living model, which could aid to reveal factors potentially relevant to the unexplained clinical effects of the ESP block. Six pigs received 0.6 mL/kg of 0.25% new methylene blue at the level of the sixth thoracic vertebra through either a cranial-to-caudal or a caudal-to-cranial in-plane ultrasound-guided bilateral ESP injection 20 min before euthanasia.

Spread of dye evaluated through transverse cryosections (four injections) extended from T5 to T10 and from T5 to T8 when a cranial-to-caudal direction of injection was used, and from T5 to T9 and from T5 to T8 when the opposite direction of injection was used. A median of 4.5 medial and lateral branches of the dorsal rami was observed stained through anatomical dissection (eight injections), regardless of the direction of injection. No evidence of dye was found in the thoracic paravertebral or epidural spaces, where the dorsal root ganglia, ventral rami and rami communicantes are located. In all the cases, dye solution was found in the prevertebral thoracic lymph nodes.

In this study, ESP injection resulted in a median spread over five spinal segments (12 injections), staining the lateral and medial branches of the dorsal rami of the spinal nerves, regardless of the direction of the needle used.
Holomorphic Jacobi manifolds
Authors: Vitagliano Luca , Wade Aïssa
Published: January 2020

In this paper, we develop holomorphic Jacobi structures. Holomorphic Jacobi manifolds are in one-to-one correspondence with certain homogeneous holomorphic Poisson manifolds. Furthermore, holomorphic Poisson manifolds can be looked at as special cases of holomorphic Jacobi manifolds. We show that holomorphic Jacobi structures yield a much richer framework than that of holomorphic Poisson structures. We also discuss the relationship between holomorphic Jacobi structures, generalized contact bundles and Jacobi–Nijenhuis structures.
Aspects of gravitational wave/particle duality: Bulk torsion ↔boundary gravity correspondence
Authors: Gupta Rohit K. , Kar Supriya , Nitish R.
Published: January 2020

A geometric torsion (GT) underlying a [Formula: see text]-form in a [Formula: see text]-dimensional [Formula: see text] gauge theory is revisited with a renewed perspective for a nonperturbation (NP) gravity in [Formula: see text]. In this context, we provide evidences to a holographic correspondence between a bulk GT and a boundary NP gravity. Interestingly the Killing symmetries in General Relativity (GR) are shown to provide a subtle clue to the quantum gravity. The NP gravity is shown to incorporate a [Formula: see text] coupling, sourced by a non-Newtonian potential, to an exact geometry in GR. Remarkably the NP correction is identified as a mass dipole and is shown to be sourced by a propagating GT. A detailed analysis is performed in a bulk GT to show a modification to the precession of perihelion in a boundary NP gravity. The perspective of an electromagnetic (EM) wave in the bulk is investigated to reveal a spin [Formula: see text] (mass-less) quantum sourced by an apparent 2-form. A Goldstone scalar is absorbed by the apparent 2-form to describe a massive [Formula: see text]-form in the coulomb gauge. Alternately a Goldstone scalar together with a local degree of GT and 2-form is argued to govern a composite (mass-less) spin [Formula: see text] particle in Lorentz gauge. Both the scenarios, further ensure a graviton in a boundary NP gravity. A qualitative analysis reveals a (noninteracting) graviton underlying a plausible gravitational wave/particle duality in NP gravity.
High spin states of Zr isotopes around A = 80 mass region — A study on cold and hot rotating nuclei
Authors: Aggarwal Mamta , Kaushik M. , Saxena G.
Published: January 2020

High spin structure of Zr isotopes, in particular, around [Formula: see text] has been studied in yrast and nonyrast regions. Spin dependence of shapes for the yrast levels are investigated by employing Cranked Hartree–Fock–Bogoliubov (CHFB) theory using a [Formula: see text] model interaction and the calculations are in good accord with the experimental data. The nonyrast states are treated by incorporating temperature degree of freedom using the statistical theory (ST). Highly deformed prolate shapes dominate the nonrotating proton rich region at low temperatures (T) with coexisting oblate and prolate shapes in [Formula: see text]Zr. Hot rotating nuclei show highest deformation around [Formula: see text] among all the other Zr isotopes even at high temperatures. [Formula: see text]Zr exhibits interesting structural transitions, hence studied in detail in yrast and non yrast regions. Triaxiality predominates in both yrast and nearly yrast (low temperature) regions at low spins with transition to elongated shapes at mid spin values 30–38[Formula: see text] to highly deformed oblate shapes at higher spins. CHFB predicts a strong backbending effect at 32[Formula: see text] and 40[Formula: see text]. A shape coexistence between the rare shape phase of noncollective prolate and oblate is reported in [Formula: see text]Zr at low temperature and [Formula: see text]. Prolate shape phase disappears with increasing temperature and spin but the nucleus remains highly deformed (with [Formula: see text] at spin [Formula: see text]40[Formula: see text]) even at high temperatures of the order of 3–3.5[Formula: see text]MeV, hence a very promising candidate for GDR probes of nuclear shapes.
Buckling Behavior of Horizontal Hydraulic Cylinder Articulated at Both Supports
Authors: Zhou Ji , Shi Duanwei , Di Chengyun , Zhang Yang , Cheng Xionghao
Published: January 2020

The existing critical buckling load calculation methods of horizontal hydraulic cylinder failed to fully reflect the initial boundary conditions and some critical influence factors, resulting in an unjustified critical buckling load. A new method to analyze the buckling behavior of the horizontal hydraulic cylinder articulated at both supports is developed on basis of large deflection theory and Timoshenko beam theory. Friction at supports, self-weight and initial misalignment by clearances are taken into account. Friction moments of supports are built according to Hertz contact theory. Bending stiffness of cylinder-rod junction is figured out in terms of elastic deformation theory. Runge–Kutta and Newton–Raphson method are used in numerical calculation for the critical buckling load. Practical calculation and stability test are carried out to verify the necessity of considering large deflection and shear effect in the proposed method. Experimental work shows the critical buckling load by the proposed method can well match to that by stability test with 0.55% deviation. Moreover, the numerical calculation results demonstrate that the friction moment of the support at piston rod end is crucial for the buckling behavior. The critical buckling load rises increasingly as the friction coefficient [Formula: see text] rises. As the friction coefficients [Formula: see text] increases from 0 to 0.020, the rise rate of critical buckling load increases from 1.782% to 8.055% per 0.001. And the clearance at cylinder-rod junction is a minor factor on the critical buckling load. As the clearances increase by 10 times, the critical buckling load decreases by 3.542%.
An efficient technique for two-dimensional fractional order biological population model
Authors: Veeresha P. , Prakasha D. G.
Published: January 2020

In this paper, we find the solutions for two-dimensional biological population model having fractional order using fractional natural decomposition method (FNDM). The proposed method is a graceful blend of decomposition scheme with natural transform, and three examples are considered to validate and illustrate its efficiency. The nature of FNDM solution has been captured for distinct arbitrary order. In order to illustrate the proficiency and reliability of the considered scheme, the numerical simulation has been presented. The obtained results illuminate that the considered method is easy to apply and more effective to examine the nature of multi-dimensional differential equations of fractional order arisen in connected areas of science and technology.
Recent advances in the application of mineral chemistry to exploration for porphyry copper–gold–molybdenum deposits: detecting the geochemical fingerprints and footprints of hypogene mineralization and alteration
Authors: Cooke David R. , Agnew Paul , Hollings Pete , Baker Michael , Chang Zhaoshan , Wilkinson Jamie J. , Ahmed Ayesha , White Noel C. , Zhang Lejun , Thompson Jennifer , Gemmell J. Bruce , Danyushevsky Leonid , Chen Huayong
Published: January 2020

In the past decade, significant research efforts have been devoted to mineral chemistry studies to assist porphyry exploration. These activities can be divided into two major fields of research: (1) porphyry indicator minerals (PIMs), which are used to identify the presence of, or potential for, porphyry-style mineralization based on the chemistry of magmatic minerals such as zircon, plagioclase and apatite, or resistate hydrothermal minerals such as magnetite; and (2) porphyry vectoring and fertility tools (PVFTs), which use the chemical compositions of hydrothermal minerals such as epidote, chlorite and alunite to predict the likely direction and distance to mineralized centres, and the potential metal endowment of a mineral district. This new generation of exploration tools has been enabled by advances in and increased access to laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), short-wave length infrared (SWIR), visible near-infrared (VNIR) and hyperspectral technologies. PIMs and PVFTs show considerable promise for exploration and are starting to be applied to the diversity of environments that host porphyry and epithermal deposits globally. Industry has consistently supported development of these tools, and in the case of PVFTs encouraged by several successful blind tests where deposit centres have successfully been predicted from distal propylitic settings. Industry adoption is steadily increasing but is restrained by a lack of the necessary analytical equipment and expertise in commercial laboratories, and also by the ongoing reliance on well-established geochemical exploration techniques (e.g. sediment, soil and rock chip sampling) that have aided the discovery of near-surface resources over many decades, but are now proving less effective in the search for deeply buried mineral resources and for those concealed under cover.

Thematic collection:
This article is part of the Exploration 17 collection available at:
https://www.lyellcollection.org/cc/exploration-17
Enhancing scientific and societal understanding of geohazards in Sri Lanka
Authors: Weththasinghe D. S. M. , Ratnayake N. P. , Hemalal P. V. A. , Dushyantha N. P.
Published: January 2020

After the Indian Ocean tsunami in 2004, the possibility of the occurrence of catastrophic disasters was realized, although Sri Lanka is not close to a plate boundary. This catastrophic event has emphasized that Sri Lanka as a country may not be able to cope with these major natural disasters, in addition to localized and frequently occurring disasters such as landslides and floods, without a proper disaster management plan (DMP). In the aftermath of the 2004 tsunami, the Government of Sri Lanka developed a comprehensive DMP with the consultation of international expertise. This study reviews the DMP in Sri Lanka and examines the effectiveness of the existing management structure by revisiting the affected areas and communities in selected case studies of a tsunami-struck coastal strip in 2004 and a recent catastrophic landslide. Questionnaire surveys and field observations were used to collect data on preparedness, the availability of evacuation plans and pre-disaster warning systems. The results show the necessity for further improvements in the management of geohazards.
Effect of acute and short-term dietary fat ingestion on postprandial skeletal muscle protein synthesis rates in middle-aged, overweight, and obese men
Authors: Tsintzas Kostas , Jones Robert , Pabla Pardeep , Mallinson Joanne , Barrett David A. , Kim Dong-Hyun , Cooper Scott , Davies Amanda , Taylor Tariq , Chee Carolyn , Gaffney Christopher , van Loon Luc J. C. , Stephens Francis B.
Published: January 2020

Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese men [46.4 ± 1.4 yr, body mass index (BMI) 32.3 ± 5.4 kg/m2] participated in the acute feeding study, which consisted of two randomized crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion), 4 h before the coingestion of milk protein, intrinsically labeled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese men (44.0 ± 1.7 yr, BMI 30.1 ± 1.1 kg/m2) participated in the chronic study, which consisted of a baseline, 1-wk isocaloric diet, followed by a 2-wk high-fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was twofold higher ( P < 0.05) in the lipid trial compared with control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, pyruvate dehydrogenase complex activity, and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle diacylglycerol C16:0 ( P = 0.06) and ceramide C16:0 ( P < 0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on the skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting that dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.
Sociodemographic and Lifestyle Factors in relation to Overweight Defined by BMI and “Normal-Weight Obesity”
Authors: Ohlsson Bodil , Manjer Jonas
Published: January 2020

Sociodemographic factors and lifestyle habits affect body weight and body composition. A new syndrome, called normal-weight obesity (NWO), is found in individuals with normal weight and excess body fat in contrast to lean and overweight individuals. The aim of the present study was to explore the associations between sociodemographic factors and smoking and alcohol habits and lower versus higher BMI (≥25 kg/m2) and to examine whether categorization into lean, NWO, and overweight leads to further information about sociodemographic and lifestyle associations, compared with the common categorization defined by BMI. A cohort of 17,724 participants (9,936 females, 56.1%) from the EpiHealth study, with a median age of 61 (53–67) years, was examined. The participants answered a questionnaire about lifestyle, and weight and fat percentage were measured. Associations between sociodemographic factors and lifestyle habits and lower versus higher BMI, and lean versus NWO or lean and NWO versus overweight were calculated by binary logistic regression. Male sex, age, sick leave/disability, married/cohabitating, divorced/widowed, former smoking, and a high alcohol consumption were associated with higher BMI, whereas higher education and frequent alcohol consumption were inversely associated (all p<0.001). The associations were similar to associations with lean versus overweight and NWO versus overweight, except for age in the latter case. Associations with lean versus NWO differed from those of lower versus higher BMI, with an association with retirement, an inverse association with male sex (OR, 0.664; 95% confidence interval, 0.591–0.746), and no associations with marital status, smoking, and alcohol consumption frequency. Associations with age and occupation were sex dependent, in contrast to other variables examined. Thus, sociodemographic and lifestyle habits showed similar associations with lower versus higher BMI as with lean and NWO versus overweight, whereas lean versus NWO showed different directions of associations regarding sex, marital status, occupation, smoking, and frequency of alcohol consumption.
In Situ Stress Effects on Smooth Blasting: Model Test and Analysis
Authors: Yang Renshu , Fang Shizheng , Yang Aiyun , Xie Huanzhen , Yang Liyun
Published: January 2020

Most of the roadway excavation is completed by the drilling and blasting method. With the increase of buried depth, the existence of ground stress will generate a significant impact on the rock blasting, especially on the smooth blasting. In this study, self-made homogeneous similar materials and digital image correlation methods were used to determine influence of ground stress on the smooth blasting under uniform explosive charge parameters and various in situ stress conditions. The results show that the crack outline after blasting changes from zigzag to straight in shape, and multifractal calculation results of the rupture section between blastholes show that the fracture surface becomes flatter as ground stress increases, which is conducive to roadway formation. The strain and equivalent strain rate obviously decrease as the distance between the blasthole and measuring points increases. The same trend occurs as the confining pressure goes up. Meanwhile, a postexplosion acoustic wave test indicates that confining pressure inhibits damage of the retained rock, which is consistent with strain and equivalent strain rate results. Finally, we discussed the crack propagation mechanism of rock in smooth blasting.
Driver’s Anticipation and Memory Driving Car-Following Model
Authors: Jafaripournimchahi Ammar , Sun Lu , Hu Wusheng
Published: January 2020

We developed a new car-following model to investigate the effects of driver anticipation and driver memory on traffic flow. The changes of headway, relative velocity, and driver memory to the vehicle in front are introduced as factors of driver’s anticipation behavior. Linear and nonlinear stability analyses are both applied to study the linear and nonlinear stability conditions of the new model. Through nonlinear analysis a modified Korteweg-de Vries (mKdV) equation was constructed to describe traffic flow near the traffic near the critical point. Numerical simulation shows that the stability of traffic flow can be effectively enhanced by the effect of driver anticipation and memory. The starting and breaking process of vehicles passing through the signalized intersection considering anticipation and driver memory are presented. All results demonstrate that the AMD model exhibit a greater stability as compared to existing car-following models.
Rapid Microwave Synthesis of Tunable Cadmium Selenide (CdSe) Quantum Dots for Optoelectronic Applications
Authors: Thomas Donovan , Lee Harold O. , Santiago Kevin C. , Pelzer Marvin , Kuti Ayodeji , Jenrette Erin , Bahoura Messaoud
Published: January 2020

Quantum dots (QDs) are a hot topic in optoelectronic device research, due to tailorable absorption and emission properties. Unfortunately, the conventional methods of QD synthesis are hazardous and time-consuming. In this work, we present an alternative method of fabricating cadmium selenide (CdSe) QDs (via rapid microwave synthesis). This novel fabrication method provides a quick and efficient way to synthesize QDs that are almost identical to those commercially available. We also demonstrate the tuning of QD sizes by varying time and temperature during the growth process. Optical spectroscopy was used to measure the emission profile of QDs of various sizes. With ease repeatability, tunability, and scalability, this QD synthesis method can be integrated into a wide range of applications and optoelectronic devices.
Nonadherence in Home-Based Pulmonary Rehabilitation Program for COPD Patients
Authors: Li Yi , Qian Hongyu , Yu Kewei , Huang Ying
Published: January 2020

Background. The pulmonary rehabilitation (PR) is beneficial for COPD patients. Due to the poor rate of adherence, we evaluate the factors which will predict the nonadherence of PR.Method. We analyzed the data from a retrospective study of COPD patients who were enrolled to attend the PR program. Patients were classified as the adherence group and the nonadherence group according to completion of over 50% sessions during the 8-week PR program. Demographic characteristics, 6-minute walking distance (6MWD), COPD assessment test (CAT), modified Medical Research Council scale (mMRC), and emotional function were compared between two groups. Univariate and multivariable analyses were performed to determine the factors of poor adherence of PR.Results. Among 418 patients, 170 patients (40.7%) who completed less than 50% sessions of the PR program were categorized as “nonadherence.” Compared to completers, “nonadherence” patients had more cigarette consumption, higher emotional score, less 6MWD, more exacerbation, using nebulizer frequently, and higher rate of smoking at enrollment. On multivariate analysis, more exacerbation frequency (odds ratio (OR) = 1.434, 95% confidence interval (CI): 1.191∼1.796,P=0.046) and smoking at enrollment (OR = 3.349, 95% CI: 1.194∼6.302,P=0.012) were predict factors associated with nonadherence of PR.Conclusion. COPD patients with frequent exacerbation and smoking currently were more likely to be nonadherence during PR.
Therapeutic Efficacy of Alpha-Lipoic Acid against Acute Myocardial Infarction and Chronic Left Ventricular Remodeling in Mice
Authors: Yang Zequan , Tian Yikui , Berr Stuart S. , French Brent A.
Published: January 2020

Background. We hypothesized that daily administration of a potent antioxidant (α-lipoic acid: ALA) would protect the heart against both acute myocardial infarction (AMI) and left ventricular remodeling (LVR) post-AMI. Methods and Results. Two separate studies were conducted. In the AMI study, C57Bl/6 mice were fed ALA daily for 7 d prior to a 45-minute occlusion of the left coronary artery (LCA). Mean infarct size in control mice (fed water) was 60 ± 2%. Mean infarct size in ALA-treated mice was 42 ± 3% in the 15 mg/kg·d group and 39 ± 3% in the 75 mg/kg·d group (both P<0.05 vs. control). In the LVR study, AMI increased LV end-systolic volume (LVESV) and reduced LV ejection fraction (LVEF) to a similar extent in both groups when assessed by cardiac MRI 1 day after a 2-hour LCA occlusion. Treatment with ALA (75 mg/kg·d) or H2O was initiated 1 day post-AMI and continued until study’s end. Both LVESV and LVEF in ALA-treated mice were significantly improved over control when assessed 28 or 56 days post-AMI. Furthermore, the survival rate in ALA-treated mice was 63% better than in control mice by 56 days post-AMI. Conclusions. Daily oral ingestion of ALA not only protects mice against AMI but also attenuates LVR and preserves contractile function in the months that follow.
The Immunosuppressant Fingolimod (FTY720) for the Treatment of Mechanical Force-Induced Abnormal Scars
Authors: Aoki Masayo , Kondo Akatsuki , Matsunaga Noriko , Honda Azusa , Okubo Yuri , Takabe Kazuaki , Ogawa Rei
Published: January 2020

Aim. Abnormal scars such as hypertrophic scars (HSs) and keloids are excessively growing scars that exhibit chronic inflammation and capillary vasculogenesis. The lipid mediator sphingosine-1-phosphate (S1P) is important in inflammatory cell recruitment and angiogenesis. Fingolimod (FTY720) is an analog of S1P and thus functionally antagonizes S1P receptors and inhibits the enzyme that produces S1P. We examined the effects of topical FTY720 injections on mechanical force-induced HS progression. Methods. Mechanical force-induced HSs were generated in C57BL6/J mice by suturing a dorsal incision and applying a stretching device on Days 6, 8, 10, and 12. On Days 8, 10, and 12, intracutaneous FTY720 (10 μM) or control vehicle injections were performed. On Day 14, scar tissues and blood were procured and subjected to histology and flow cytometry. Results. Flow cytometry showed that FTY720 decreased the frequencies of macrophages with M2 predominance in the scars but had no effect on total, CD4+, or CD8a+ T cell frequencies. FTY720 also decreased the vascular endothelial cell frequencies in the scar along with the microvessels, as determined by immunohistochemistry. Compared to the vehicles, FTY720 treatment significantly reduced the gross scar area and the cross-sectional scar area on histology. On the other hand, FTY720 tended to reduce white blood cells and significantly reduced the lymphocyte frequencies in the blood. Conclusion. Topical FTY720 induces M2 predominance and impairs angiogenesis. Therefore, its local immunosuppressive mechanisms differ from those of conventional immunosuppressive agents. Topical FTY720 can be a novel therapeutic option for abnormal scars that are difficult to control with corticosteroids. Its lymphocytopenic effects may be limited by careful optimization of the treatment regimen.
Radiomics and Machine Learning Differentiate Soft-Tissue Lipoma and Liposarcoma Better than Musculoskeletal Radiologists
Authors: Malinauskaite Ieva , Hofmeister Jeremy , Burgermeister Simon , Neroladaki Angeliki , Hamard Marion , Montet Xavier , Boudabbous Sana
Published: January 2020

Distinguishing lipoma from liposarcoma is challenging on conventional MRI examination. In case of uncertain diagnosis following MRI, further invasive procedure (percutaneous biopsy or surgery) is often required to allow for diagnosis based on histopathological examination. Radiomics and machine learning allow for several types of pathologies encountered on radiological images to be automatically and reliably distinguished. The aim of the study was to assess the contribution of radiomics and machine learning in the differentiation between soft-tissue lipoma and liposarcoma on preoperative MRI and to assess the diagnostic accuracy of a machine-learning model compared to musculoskeletal radiologists. 86 radiomics features were retrospectively extracted from volume-of-interest on T1-weighted spin-echo 1.5 and 3.0 Tesla MRI of 38 soft-tissue tumors (24 lipomas and 14 liposarcomas, based on histopathological diagnosis). These radiomics features were then used to train a machine-learning classifier to distinguish lipoma and liposarcoma. The generalization performance of the machine-learning model was assessed using Monte-Carlo cross-validation and receiver operating characteristic curve analysis (ROC-AUC). Finally, the performance of the machine-learning model was compared to the accuracy of three specialized musculoskeletal radiologists using the McNemar test. Machine-learning classifier accurately distinguished lipoma and liposarcoma, with a ROC-AUC of 0.926. Notably, it performed better than the three specialized musculoskeletal radiologists reviewing the same patients, who achieved ROC-AUC of 0.685, 0.805, and 0.785. Despite being developed on few cases, the trained machine-learning classifier accurately distinguishes lipoma and liposarcoma on preoperative MRI, with better performance than specialized musculoskeletal radiologists.
Profile of Endothelin-1, Nitric Oxide, and Prostacyclin Levels in Pulmonary Arterial Hypertension Related to Uncorrected Atrial Septal Defect: Results from a Single Center Study in Indonesia
Authors: Dinarti Lucia Kris , Hartopo Anggoro Budi , Anggrahini Dyah Wulan , Sadewa Ahmad Hamim , Setianto Budi Yuli , Wahab Abdus Samik
Published: January 2020

Background and Objectives. Pulmonary arterial hypertension (PAH) pathomechanism involves an increased plasma level of endothelin-1 and a reduced plasma level of prostacyclin and nitric oxide. Whether similar mechanisms prevail in PAH associated with atrial septal defect (ASD) is unclear. This study aimed to investigate the relationship of endothelin-1, prostacyclin, and nitric oxide with PAH in uncorrected ASD in Indonesian population. Methods. The study design was cross-sectional. The subjects were adult uncorrected secundum ASD with PAH. Pulmonary artery pressure was measured with right heart catheterization. Pulmonary venous blood was obtained during catheterization for measuring endothelin-1, prostacyclin, and nitric oxide. Correlation tests were performed to determine any association between biomarkers and mean pulmonary artery pressure (mPAP). The levels of biomarkers were compared based on the severity of PAH. Statistical significance was determined at p<0.05. Results. Forty-four subjects were enrolled in this study. Endothelin-1 level and mPAP had significant moderate positive correlation (r = 0.423 and p value = 0.004). However, no significant correlation was observed between prostacyclin, nitric oxide levels, and mPAP. The pattern of endothelin-1, prostacyclin, and nitric oxide was distinctive. Levels of endothelin-1 were incrementally increased from mild, moderate, to severe PAH. The levels of prostacyclin and nitric oxide had similar pattern in association with the severity of PAH, which was increased in mild-to-moderate PAH but decreased in severe PAH. Conclusions. There was a distinctive pattern of endothelin-1, prostacyclin, and nitric oxide based on severity of PAH in adult uncorrected ASD. Significant correlations existed between endothelin-1 and the severity of PAH and mPAP.
Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers
Authors: Hedbrant Alexander , Andersson Lena , Bryngelsson Ing-Liss , Eklund Daniel , Westberg Håkan , Särndahl Eva , Persson Alexander
Published: January 2020

Purpose. To study the association between inhalation of particulate matter or quartz in Swedish iron foundries and the effects on NLRP3 inflammasome activation.Methods. Particle exposure measurements were performed during an eight-hour work day for 85 foundry workers at three Swedish iron foundries. Personal sampling was used for measurement of respirable quartz and dust and stationary measurements to obtain exposure measurements for inhalable dust and PM10. The NLRP3 inflammasome markers, interleukin- (IL-) 1βand IL-18, and inhibitors IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP) were measured in plasma. Inflammasome activation was measured by caspase-1 enzymatic activity in monocytes in whole blood by flow cytometry, and expression of inflammasome-related genes was quantified using real-time PCR. Multiple linear regression analysis was used to investigate associations between PM exposures and inflammatory markers. Sex, age, smoking, current infection, BMI, and single nucleotide polymorphism in the inflammasome regulating genesCARD8(C10X) andNLRP3(Q705K) were included as covariates.Results. The average exposure levels of respirable dust and quartz were 0.85 and 0.052 mg/m3, respectively. A significant exposure-response was found for respirable dust and IL-18 and for inhalable dust and IL-1Ra. Whole blood, drawn from study participants, was stimulatedex vivowith inflammasome priming stimuli LPS or Pam3CSK4, resulting in a 47% and 49% increase in caspase-1 enzymatic activity in monocytes. This increase in caspase-1 activity was significantly attenuated in the higher exposure groups for most PM exposure measures.Conclusions. The results indicate that exposure levels of PM in the iron foundry environment can affect the NLRP3 inflammasome and systemic inflammation.
Emergency Evacuation Simulation and Optimization for a Complex Rail Transit Station: A Perspective of Promoting Transportation Safety
Authors: Xu Hui , Tian Cheng , Li Yang
Published: January 2020

Rail transit stations with multifloor structures have been built in many cities to intensively utilize land resources and facilitate lives of community. However, being overcrowded with passengers results in high risks during daily operation. In response, this study conducted an emergency evacuation simulation and optimization in the three-dimensional (3D) space of “complex rail transit stations” (CRTSs). The aim of the paper is to provide a methodology to determine effective emergency evacuation strategies for CRTSs. The Lianglukou Rail Transit Station in Chongqing, China, was used as a case study and the AnyLogic simulation platform employed for simulating emergency evacuations. An emergency evacuation theoretical framework was established. The emergency evacuation strategies, including evacuation routes and evacuation times, were determined based on the theoretical demonstration. Simulation and optimization of emergency evacuation in the Lianglukou station were conducted. Accordingly, four main simulation results were obtained: (1) Escalators/stairs and turnstiles are key facilities in the evacuation; (2) Effective guidance for the evacuation is necessary in the public space of the station; (3) Passenger aggregation nodes should be guided for balanced evacuation; (4) Removing metal barriers is a useful evacuation optimization measure. The proposed research method and framework can be used by other CRTSs in the establishment of emergency evacuation strategies and effective optimization strategies to promote safety of transportation system. The research findings are beneficial to passengers in helping them provide valuable emergency evacuation guidance.
Inflammatory Fibroid Polyp in a 48-Year-Old Male: A Rare Cause of Intussusception
Authors: Karuhanga Theresia , Ngimba Caroline , Yahaya James J.
Published: January 2020

Inflammatory fibroid polyp is a neoplastic condition affecting the gastrointestinal tract and particularly the gastric antrum. It is virtually a benign submucosal mass comprising mesenchymal cells and numerous small blood vessels with inflammatory cells and commonly eosinophils. Patients with inflammatory fibroid polyps usually present clinically with mechanical intestinal obstruction with or without intussusception. Herein, we present a case of a 48-year-old male with a known history of schizophrenia who presented with mechanical intestinal obstruction following intussusception due to inflammatory fibroid polyp involving the proximal jejunojejunal part of the jejunum.
The Immunosuppressive Microenvironment in BRCA1-IRIS–Overexpressing TNBC Tumors Is Induced by Bidirectional Interaction with Tumor-Associated Macrophages
Authors: Sami Eman , Paul Bibbin T. , Koziol James A. , ElShamy Wael M.
Published: January 2020

Tumor-associated macrophages (TAM) promote triple-negative breast cancer (TNBC) progression. Here, we report BRCA1-IRIS–overexpressing (IRISOE) TNBC cells secrete high levels of GM-CSF in a hypoxia-inducible factor-1α (HIF1α)- and a NF-κB–dependent manner to recruit macrophages to IRISOE cells and polarize them to protumor M2 TAMs. GM-CSF triggered TGFβ1 expression by M2 TAMs by activating STAT5, NF-κB, and/or ERK signaling. Despite expressing high levels of TGFβ1 receptors on their surface, IRISOE TNBC cells channeled TGFβ1/TβRI/II signaling toward AKT, not SMAD, which activated stemness/EMT phenotypes. In orthotopic and syngeneic mouse models, silencing or inactivating IRIS in TNBC cells lowered the levels of circulating GM-CSF, suppressed TAM recruitment, and decreased the levels of circulating TGFβ1. Coinjecting macrophages with IRISOE TNBC cells induced earlier metastasis in athymic mice accompanied by high levels of circulating GM-CSF and TGFβ1. IRISOE TNBC cells expressed low levels of calreticulin (the “eat me” signal for macrophages) and high levels of CD47 (the “do not eat me” signal for macrophages) and PD-L1 (a T-cell inactivator) on their surface. Accordingly, IRISOE TNBC tumors had significantly few CD8+/PD-1+ cytotoxic T cells and more CD25+/FOXP3+ regulatory T cells. These data show that the bidirectional interaction between IRISOE cells and macrophages triggers an immunosuppressive microenvironment within TNBC tumors that is favorable for the generation of immune-evading/stem-like/IRISOE TNBC metastatic precursors. Inhibiting this interaction may inhibit disease progression and enhance patients' overall survival.

Significance:

The BRCA1-IRIS oncogene promotes breast cancer aggressiveness by recruiting macrophages and promoting their M2 polarization.
Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis
Authors: Zhang Yaqing , Lazarus Jenny , Steele Nina G. , Yan Wei , Lee Ho-Joon , Nwosu Zeribe C. , Halbrook Christopher J. , Menjivar Rosa E. , Kemp Samantha B. , Sirihorachai Veerin R. , Velez-Delgado Ashley , Donahue Katelyn , Carpenter Eileen S. , Brown Kristee L. , Irizarry-Negron Valerie , Nevison Anna C. , Vinta Alekya , Anderson Michelle A. , Crawford Howard C. , Lyssiotis Costas A. , Frankel Timothy L. , Bednar Filip , Pasca di Magliano Marina
Published: January 2020

Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin–expressing fibroblasts. Conversely, we observed an increase in chemokines Ccl3, Ccl6, and Ccl8 leading to increased myeloid cell recruitment, restoration of immune suppression, and promotion of carcinogenesis, an effect that was inhibited by blockade of the common CCL3/6/8 receptor CCR1. Further, Treg depletion unleashed pathologic CD4+ T-cell responses. Our data point to new mechanisms regulating fibroblast differentiation in pancreatic cancer and support the notion that fibroblasts are a heterogeneous population with different and opposing functions in pancreatic carcinogenesis.

Significance:

Here, we describe an unexpected cross-talk between Tregs and fibroblasts in pancreatic cancer. Treg depletion resulted in differentiation of inflammatory fibroblast subsets, in turn driving infiltration of myeloid cells through CCR1, thus uncovering a potentially new therapeutic approach to relieve immunosuppression in pancreatic cancer.

See related commentary by Aykut et al., p. 345.

This article is highlighted in the In This Issue feature, p. 327
How to Intervene in the Caries Process: Early Childhood Caries – A Systematic Review
Authors: Schmoeckel Julian , Gorseta Kristina , Splieth Christian H. , Juric Hrvoje
Published: January 2020

For an Organisation for Caries Research/European Federation of Conservative Dentistry consensus, this systematic review is aimed to assess the question of how to manage the caries process in the case of early childhood caries (ECC). Medline via PubMed was searched systematically regarding management of ECC. First priority was existing systematic reviews or randomized clinical trials otherwise cohort studies dealing with management of ECC, primarily with carious anterior teeth. After data extraction, the potential risk of bias was estimated depending on the study types, and the level of evidence was evaluated. Regarding management of ECC, results are presented for silver diamine fluoride (SDF, n = 5), nonoperative caries management (NOCM, n = 10), and restorative approaches (RA, n = 8) separately, as different kinds of studies with different levels of evidence were found for the different aspects in the management of ECC. The 5 systematic reviews on SDF showed a high potential for arrest of ECC on a high level of evidence. In NOCM, a low level of evidence for a moderate effect of fluoride varnish in arresting or remineralizing, especially non-cavitated lesions, was assessed. For RA in carious anterior upper primary teeth, a low level of evidence was found for higher failure rates of glass ionomer cement and composite fillings than composite strip crowns even if placed under general anaesthesia and especially compared to other crowns (stainless steel and zirconia). In conclusions, ECC may be managed successfully with nonoperative (SDF, regular fluoride application) and moderately well with operative approaches, but the decision is affected by many other variables such as pulpal involvement, the child’s cooperation, or a general anaesthesia setting.
The Role of Diet as an Adjuvant Treatment in Scarring and Nonscarring Alopecia
Authors: Pham Christine T. , Romero Karina , Almohanna Hind M. , Griggs Jacob , Ahmed Azhar , Tosti Antonella
Published: January 2020

Background: Diet is known to affect a wide range of health disorders. Many patients with hair and scalp diseases often inquire about special diets that may improve their symptoms. Objective: To evaluate nutrition and diet as adjunct treatments in nonscarring and scarring alopecia. Methods: A primary literature search using PRISMA guidelines was conducted using the PubMed database in October 2019. Results: Twenty-four articles with 1,787 patients were included. The Mediterranean diet, which is rich in raw vegetables and fresh herbs, and isoflavone-rich soy contain anti-inflammatory nutrients that may promote hair health and growth in androgenetic alopecia (AGA). The gluten-free diet was shown to stimulate hair growth in alopecia areata (AA) patients with concomitant celiac disease, though no effect was seen with a lactose-free diet. Sufficient protein was found to be necessary for hair health. The human chorionic gonadotropin diet, hypocaloric diet, and increased fish, buckwheat, and millet groats consumption were possible triggers of alopecias such as AGA, AA, telogen effluvium, or frontal fibrosing alopecia. Limitations: This review was limited by the lack of studies and controls. Conclusion: The Mediterranean diet as well as diets rich in protein and soy may be potential adjunct therapeutics for the treatment of nonscarring alopecias. The use of diets in alopecia treatment regimens warrants further exploration.