bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic signatures for liver tissue and cecum contents in high-fat diet-induced obese mice based on UHPLC-Q-TOF/MS
Authors: Cai Hongying , Wen Zhiguo , Meng Kun , Yang Peilong 
Published: June 2021

Abstract
Background
The incidence of obesity is increasing worldwide, and it is a risk factor for diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Our previous study had demonstrated that high-fat diet induced increased weight gain, fat weight, serum cholesterol, triglyceride, and ATL levels in liver, and influenced the diversity and composition of cecal microbiota in mice. Hence, this study aimed to investigate the roles of the gut microbially derived metabolites and liver metabolites between the obese and lean mice, focusing on their association with the progression of obesity induced by high-fat diet (HFD).

Methods
An obesity model in mice was established with HFD for 16 weeks. Cecal contents and liver tissues metabolomics based on ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry and orthogonal partial least squares discriminant analyses (OPLS-DA) was performed to identify the alterations in metabolites associated with obese mice.

Results
Obese and lean groups were clearly discriminated from each other on OPLS-DA score plot and major metabolites contributing to the discrimination were mainly involved in glycerophospholipid metabolism, primary bile acid biosynthesis, and biosynthesis of unsaturated fatty acids pathways. HFD-induced alterations of 19 metabolites in liver and 43 metabolites in cecum contents were identified as potential biomarkers related to obesity. Specifically, chenodeoxycholic acid, taurochenodeoxycholate, and tauroursodeoxycholic acid in liver were elevated 35.94, 24.36, and 18.71-fold, respectively. PI(P-16:0/18:1(9Z)), PG(19:0/16:0), PS(P-16:0/20:2(11Z,14Z)), PI(22:1(11Z)/12:0), and PE(21:0/0:0) in cecum were enhanced 884, 640.96, 226.63, 210.10, 45.13-fold in comparison with the lean mice. These metabolites were the most important biomarkers for discriminating between the obese and lean mice. In addition, cecum contents metabolites were strongly correlated with hepatic metabolites through gut-liver axis analysis.

Conclusions
HFD increased lipid profiles (i.e. glycerophospholipids, PC, PE, PI, PG, and PS) and total bile acid (primary and secondary bile acid) in liver and cecum, suggesting that they may play an important role in the progression of obesity. These metabolites can be used to better understand obesity and related disease induced by HFD. Furthermore, the level alterations of these metabolites can be used to assess the risk of obesity and the therapeutic effect of obesity management.
On the arts and humanities in medical education
Authors: Rabinowitz Danielle G. 
Published: June 2021

AbstractThis paper aims to position the birth of the Medical Humanities movement in a greater historical context of twentieth century American medical education and to paint a picture of the current landscape of the Medical Humanities in medical training. It first sheds light on the model of medical education put forth by Abraham Flexner through the publishing of the 1910 Flexner Report, which set the stage for defining physicians as experimentalists and rooting the profession in research institutions. While this paved the way for medical advancements, it came at the cost of producing a patriarchal approach to medical practice. By the late 1960s, the public persona of the profession was thus devoid of humanism. This catalyzed the birth of the Medical Humanities movement that helped lay the framework for what has perpetuated as the ongoing incorporation of humanistic subjects into medical training. As we enter a time in medicine in which rates of burnout are ever-increasing and there are growing concerns about a concomitant reduction in empathy among trainees, the need for instilling humanism remains important. We must consequently continue to consider how to ensure the place of the Medical Humanities in medical education moving forward.
Insufficient blood supply of fovea capitis femoris, a risk factor of femoral head osteonecrosis
Authors: Zhao Keyang , Zhang Fangfang , Quan Kun , Zhu Bin , Li Guangyi , Mei Jiong 
Published: June 2021

AbstractBackgroundA defective nutrient foramen in the fovea capitis femoris was hypothesized to reflect the blood circulation pattern of the femoral head, leading to insufficient blood supply and causing osteonecrosis of the femoral head.MethodsNormal and necrotic femoral head specimens were collected. The necrotic femoral head group was divided into a non-traumatic and traumatic subgroup. 3D scanning was applied to read the number, the diameter, and the total cross-sectional area of the nutrient foramina in the fovea capitis femoris. Chi-squared tests and independent t-tests were used to detect any differences in the categorical and continuous demographic variables. Logistic regression models were used to estimate the odds ratio (OR) for non-traumatic and traumatic osteonecrosis in different characteristic comparisons.ResultsA total of 249 femoral head specimens were collected, including 100 normal femoral heads and 149 necrotic femoral heads. The necrotic femoral head group revealed a significantly higher percentage of no nutrient foramen (p < 0.001), a smaller total area of nutrient foramina (p < 0.001), a smaller mean area of nutrient foramina (p = 0.014), a lower maximum diameter of the nutrient foramen (p < 0.001), and a lower minimum diameter of the nutrient foramen (p < 0.001) than the normal femoral head group. The logistic regression model demonstrated an increasing number of nutrient foramina (crude OR, 0.51; p < 0.001), a larger total area of nutrient foramina (crude OR, 0.58; p < 0.001), a larger mean area of nutrient foramina (crude OR, 0.52; p = 0.023), a greater maximum diameter of the nutrient foramen (crude OR, 0.26; p < 0.001), and greater minimum diameter of the nutrient foramen (crude OR, 0.20; p < 0.001) significantly associated with reduced odds of osteonecrosis of the femoral head (ONFH). The necrotic femoral head group was further divided into 118 non-traumatic and 31 traumatic necrotic subgroups, and no significant difference was observed in any characteristics between them.ConclusionsCharacteristics of the nutrient foramen in the fovea capitis femoris showed a significant defect of necrotic than normal femoral heads, and significantly reduced odds were associated with the higher abundance of the nutrient foramen in ONFH. Therefore, the condition of the nutrient foramen might be the indicator of ONFH.
Interplay between Epstein-Barr virus infection and environmental xenobiotic exposure in cancer
Authors: Aguayo Francisco , Boccardo Enrique , Corvalán Alejandro , Calaf Gloria M. , Blanco Rancés 
Published: June 2021

AbstractEpstein-Barr virus (EBV) is a herpesvirus associated with lymphoid and epithelial malignancies. Both B cells and epithelial cells are susceptible and permissive to EBV infection. However, considering that 90% of the human population is persistently EBV-infected, with a minority of them developing cancer, additional factors are necessary for tumor development. Xenobiotics such as tobacco smoke (TS) components, pollutants, pesticides, and food chemicals have been suggested as cofactors involved in EBV-associated cancers. In this review, the suggested mechanisms by which xenobiotics cooperate with EBV for carcinogenesis are discussed. Additionally, a model is proposed in which xenobiotics, which promote oxidative stress (OS) and DNA damage, regulate EBV replication, promoting either the maintenance of viral genomes or lytic activation, ultimately leading to cancer. Interactions between EBV and xenobiotics represent an opportunity to identify mechanisms by which this virus is involved in carcinogenesis and may, in turn, suggest both prevention and control strategies for EBV-associated cancers.
Aversive emotion rapidly activates orexin neurons and increases heart rate in freely moving mice
Authors: Yamashita Akira , Moriya Shunpei , Nishi Ryusei , Kaminosono Jun , Yamanaka Akihiro , Kuwaki Tomoyuki 
Published: June 2021

AbstractThe perifornical area of the hypothalamus has been known as the center for the defense response, or fight-or-flight response, which is characterized by a concomitant rise in arterial blood pressure, heart rate, and respiratory frequency. It is well established that orexin neurons, which are located in this region, play a critical role in this response. In this study, we further examined this role by recording orexin neuronal activity and heart rate in freely moving mice using an original dual-channel fiber photometry system in vivo. Analysis of orexin neuron activity in relation to autonomic responses to aversive stimuli revealed a rapid increase in neuronal activity just prior to changes in heart rate. In addition, we examined whether orexin neurons would be activated by a conditioned neutral sound that was previously associated with aversive stimulus. We show that the memory of the aversive stimulus activated orexin neurons and increased heart rate. Our data suggest that orexin neurons are a key component linking aversive emotions to autonomic defense response. Our data also suggest that targeting orexin neurons may enable treatment of psychiatric disorders associated with chronic stress and traumatic memories.
Evolving therapeutic landscape in follicular lymphoma: a look at emerging and investigational therapies
Authors: Hanel Walter , Epperla Narendranath 
Published: June 2021

AbstractFollicular Lymphoma (FL) is the most common subtype of indolent B cell non-Hodgkin lymphoma. The clinical course can be very heterogeneous with some patients being safely observed over many years without ever requiring treatment to other patients having more rapidly progressive disease requiring multiple lines of treatment for disease control. Front-line treatment of advanced FL has historically consisted of chemoimmunotherapy but has extended to immunomodulatory agents such as lenalidomide. In the relapsed setting, several exciting therapies that target the underlying biology and immune microenvironment have emerged, most notable among them include targeted therapies such as phosphoinositide-3 kinase and Enhancer of Zeste 2 Polycomb Repressive Complex 2 inhibitors and cellular therapies including chimeric antigen receptor T cells and bispecific T cell engagers. There are several combination therapies currently in clinical trials that appear promising. These therapies will likely reshape the treatment approach for patients with relapsed and refractory FL in the coming years. In this article, we provide a comprehensive review of the emerging and investigational therapies in FL and discuss how these agents will impact the therapeutic landscape in FL.
Molecular pathogenesis of the myeloproliferative neoplasms
Authors: Greenfield Graeme , McMullin Mary Frances , Mills Ken 
Published: June 2021

AbstractThe Philadelphia negative myeloproliferative neoplasms (MPN) compromise a heterogeneous group of clonal myeloid stem cell disorders comprising polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Despite distinct clinical entities, these disorders are linked by morphological similarities and propensity to thrombotic complications and leukaemic transformation. Current therapeutic options are limited in disease-modifying activity with a focus on the prevention of thrombus formation. Constitutive activation of the JAK/STAT signalling pathway is a hallmark of pathogenesis across the disease spectrum with driving mutations in JAK2, CALR and MPL identified in the majority of patients. Co-occurring somatic mutations in genes associated with epigenetic regulation, transcriptional control and splicing of RNA are variably but recurrently identified across the MPN disease spectrum, whilst epigenetic contributors to disease are increasingly recognised. The prognostic implications of one MPN diagnosis may significantly limit life expectancy, whilst another may have limited impact depending on the disease phenotype, genotype and other external factors. The genetic and clinical similarities and differences in these disorders have provided a unique opportunity to understand the relative contributions to MPN, myeloid and cancer biology generally from specific genetic and epigenetic changes. This review provides a comprehensive overview of the molecular pathophysiology of MPN exploring the role of driver mutations, co-occurring mutations, dysregulation of intrinsic cell signalling, epigenetic regulation and genetic predisposing factors highlighting important areas for future consideration.
Evolution of inspiratory muscle function in children during mechanical ventilation
Authors: Crulli Benjamin , Kawaguchi Atsushi , Praud Jean-Paul , Petrof Basil J. , Harrington Karen , Emeriaud Guillaume 
Published: June 2021

Abstract
Background
There is no universally accepted method to assess the pressure-generating capacity of inspiratory muscles in children on mechanical ventilation (MV), and no study describing its evolution over time in this population.

Methods
In this prospective observational study, we have assessed the function of the inspiratory muscles in children on various modes of MV. During brief airway occlusion maneuvers, we simultaneously recorded airway pressure depression at the endotracheal tube (ΔPaw, force generation) and electrical activity of the diaphragm (EAdi, central respiratory drive) over five consecutive inspiratory efforts. The neuro-mechanical efficiency ratio (NME, ΔPaw/EAdimax) was also computed. The evolution over time of these indices in a group of children in the pediatric intensive care unit (PICU) was primarily described. As a secondary objective, we compared these values to those measured in a group of children in the operating room (OR).

Results
In the PICU group, although median NMEoccl decreased over time during MV (regression coefficient − 0.016, p = 0.03), maximum ΔPawmax remained unchanged (regression coefficient 0.109, p = 0.50). Median NMEoccl at the first measurement in the PICU group (after 21 h of MV) was significantly lower than at the only measurement in the OR group (1.8 cmH2O/µV, Q1–Q3 1.3–2.4 vs. 3.7 cmH2O/µV, Q1–Q3 3.5–4.2; p = 0.015). Maximum ΔPawmax in the PICU group was, however, not significantly different from the OR group (35.1 cmH2O, Q1–Q3 21–58 vs. 31.3 cmH2O, Q1–Q3 28.5–35.5; p = 0.982).

Conclusions
The function of inspiratory muscles can be monitored at the bedside of children on MV using brief airway occlusions. Inspiratory muscle efficiency was significantly lower in critically ill children than in children undergoing elective surgery, and it decreased over time during MV in critically ill children. This suggests that both critical illness and MV may have an impact on inspiratory muscle efficiency.
Plasticity engineering of plant monoterpene synthases and application for microbial production of monoterpenoids
Authors: Lei Dengwei , Qiu Zetian , Qiao Jianjun , Zhao Guang-Rong 
Published: June 2021

AbstractPlant monoterpenoids with structural diversities have extensive applications in food, cosmetics, pharmaceuticals, and biofuels. Due to the strong dependence on the geographical locations and seasonal annual growth of plants, agricultural production for monoterpenoids is less effective. Chemical synthesis is also uneconomic because of its high cost and pollution. Recently, emerging synthetic biology enables engineered microbes to possess great potential for the production of plant monoterpenoids. Both acyclic and cyclic monoterpenoids have been synthesized from fermentative sugars through heterologously reconstructing monoterpenoid biosynthetic pathways in microbes. Acting as catalytic templates, plant monoterpene synthases (MTPSs) take elaborate control of the monoterpenoids production. Most plant MTPSs have broad substrate or product properties, and show functional plasticity. Thus, the substrate selectivity, product outcomes, or enzymatic activities can be achieved by the active site mutations and domain swapping of plant MTPSs. This makes plasticity engineering a promising way to engineer MTPSs for efficient production of natural and non-natural monoterpenoids in microbial cell factories. Here, this review summarizes the key advances in plasticity engineering of plant MTPSs, including the fundamental aspects of functional plasticity, the utilization of natural and non-natural substrates, and the outcomes from product isomers to complexity-divergent monoterpenoids. Furthermore, the applications of plasticity engineering for improving monoterpenoids production in microbes are addressed.
Screening and characterization of cellulolytic molds from empty fruit bunches and soils in palm oil plantation area in Indonesia
Authors: Miller Tracy , Waturangi Diana Elizabeth , Purwadaria Tresnawati 
Published: June 2021

Abstract
Objective
This research was aimed to isolate cellulolytic molds in empty fruit bunches of oil palm (EFBOP) and soils from palm oil plantation area and identify their enzyme activities to digest EFBOP.

Results
A total of seven molds were successfully isolated and screened for their enzyme activities from EFBOP and the soils. The enzymes from each isolate were produced in submerged culture using Mineral Mandels and 3% of alkali pretreated pollard in triplicates. The results indicated that all of the isolates were able to hydrolyze Carboxymethyl Cellulose (CMC), Whatmann No. 1 filter paper, and also EFBOP to sugars with reducing ends that reacted to 3,5-Dinitrosalicylic acid (DNS). The CMCase activity of isolate X showed the highest while the lowest was found for isolate MT8. Filter paperase (FPase) activity of isolate X performed the highest wile the lowest were found from isolate MT3 and MT6. The saccharification activity of isolate P showed the highest while MT6 performed the lowest activity
Structure and function of capsid protein in flavivirus infection and its applications in the development of vaccines and therapeutics
Authors: Zhang Xingcui , Zhang Yanting , Jia Renyong , Wang Mingshu , Yin Zhongqiong , Cheng Anchun 
Published: June 2021

AbstractFlaviviruses are enveloped single positive-stranded RNA viruses. The capsid (C), a structural protein of flavivirus, is dimeric and alpha-helical, with several special structural and functional features. The functions of the C protein go far beyond a structural role in virions. It is not only responsible for encapsidation to protect the viral RNA but also able to interact with various host proteins to promote virus proliferation. Therefore, the C protein plays an important role in infected host cells and the viral life cycle. Flaviviruses have been shown to affect the health of humans and animals. Thus, there is an urgent need to effectively control flavivirus infections. The structure of the flavivirus virion has been determined, but there is relatively little information about the function of the C protein. Hence, a greater understanding of the role of the C protein in viral infections will help to discover novel antiviral strategies and provide a promising starting point for the further development of flavivirus vaccines or therapeutics.
Smoking cessation using preference-based tools: a mixed method pilot study of a novel intervention among smokers with low socioeconomic position
Authors: Héron Mégane , Le Faou Anne-Laurence , Ibanez Gladys , Métadieu Brigitte , Melchior Maria , El-Khoury Lesueur Fabienne 
Published: June 2021

Abstract
Background
Compared to smokers with favorable socio-economic position (SEP), those with low SEP are less likely to have a successful smoking cessation attempt. Tailored approaches are therefore needed, and general practitioners could help reaching and assisting usually hard-to-reach population.

Method
STOP (Sevrage Tabagique à l’aide d’Outils dédiés selon la Préférence) is a pilot study, examining the feasibility, acceptability and potentiality of a smoking cessation intervention centered on smoker’s preference. Smokers with low SEP, wishing to quit, were recruited in six healthcare centers in the Greater Paris area. They were asked to choose between different types of nicotine replacement therapy (NRT) products and/or e-cigarette with liquids delivered free of charge to aid their smoking cessation attempt. We describe the characteristics of recruited participants, their perception of smoking cessation aids, and the evolution of their smoking status 4 to 6 weeks after recruitment.

Results
We recruited 49 participants, of which 29% chose an e-cigarette, 29% chose NRT and 42% chose both an e-cigarette and NRT. The intervention was shown to be acceptable by participants and health professionals. Among the 24 participants followed for at least one month, 14 (28% of all participants) stopped smoking, and 9 (18%) considerably reduced their consumption.

Conclusion
The STOP intervention is feasible and acceptable, even if more efforts should be made to limit lost-to-follow-up. This preference-based intervention also shows interesting prospect in helping smokers with low SEP quit smoking. We will test the efficacy of this preference-based intervention in a randomized controlled trial.
Transcription factor 7-like 2 gene- smoking interaction on the risk of diabetic nephropathy in Chinese Han population
Authors: Xue Peng , Cao Haihong , Ma Zhimin , Zhou Ying , Wang Nian 
Published: June 2021

Abstract
Objectives
To evaluate the relationship between transcription factor 7-like 2 (TCF7L2) gene polymorphism and diabetic nephropathy (DN) risk, as well as the effect of gene-environment interactions on DN risk in Chinese Han population.

Methods
The Hardy-Weinberg equilibrium (HWE) and the relationship between TCF7L2 gene single nucleotide polymorphism (SNPs) and DN susceptibility were evaluated by SNPStats. The interaction among four SNPs and environmental factors were tested by generalized multifactor dimensionality reduction (GMDR). The consistency of cross validation, accuracy of test balance and sign test were calculated to evaluate the interaction of each selection. The logistic regression was used to test the interaction between rs7903146 and current smoking by stratified analysis.

Results
Logistic regression analysis indicated that the DN risk of rs7903146-T allele carriers were obviously higher than that in CC genotype carriers (CT + TT versus CC), adjusted OR (95 %CI) = 1.64 (1.24–2.06). However, we also discovered that people with rs12255372, rs11196205 and rs290487 minor allele had non-significant difference risk of DN compared with people with major allele. The GMDR model found a significant two-locus model (p = 0.0100) including rs7903146 and current smoking, suggesting a potential gene–environment interaction between rs7903146 and current smoking. Compared with never smokers with rs7903146- CC genotype, current smokers with rs7903146- CT or TT genotype had the highest DN risk. After covariate adjustment, OR (95 %CI) was 2.15 (1.58–2.78).

Conclusions
We found a significant relationship of rs7903146-T alleles, and the interaction between rs7903146-T and current smoking with increased DN risk.
Assessment about Luneberg integrals and application to digital in-line holography
Authors: Coëtmellec S. , Lebrun D. , Brunel M. , E. M. Janssen A. J. 
Published: June 2021

AbstractIn this publication, the Luneberg integrals are revisited and the conditions of the using of such integrals have been recalled. Additivity law of Luneberg’s integrals and the link with the Frenel kernel for the propagation are discussed. By means of the definition of the Luneberg’s integrals, the propagation of a vectorial electromagnetic field (Hertz potentials) is developed and a new approach of the computation have been proposed based on Zernike polynomials. With this new approach simulations of holograms is illustrated in the case of the digital in-line holography with an opaque disk.