bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Checkpoint Inhibitor Nivolumab and Radiotherapy in Pretreated Lung Cancer Patients
Authors: Fiorica Francesco , Belluomini Lorenzo , Stefanelli Antonio , Santini Alessandra , Urbini Benedetta , Giorgi Carlotta , Frassoldati Antonio 
Published: January 2018

Background:In the last decade, the discovery of immune checkpoint inhibitors such as thePD-1inhibitor, nivolumab, has revolutionized the treatment of advanced non–small cell lung cancer (NSCLC). Concurrent radiotherapy (RT) is of particular interest in showing the potential role of the combination.Objective:The purpose of this study was to retrospectively evaluate the addition of RT to an immune checkpoint inhibitor, nivolumab, with regard to activity and feasibility in pretreated, advanced, or metastatic lung cancer patients at our center.Patients and Methods:We retrospectively identified 35 consecutive patients (30 men and 5 women), who received nivolumab for pretreated NSCLC, between March 2015 to December 2016. Fifteen received hypofractionated RT as a palliative measure, and, in these patients, nivolumab was administered at an interval of at least 1 week from the end of RT.Results:The median age was 69 years, and 23 patients (65.7%) had an Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. All patients had previously received at least 1 systemic regimen, and, for only 3 (8.6%), nivolumab was a third-line treatment. The 2 treatment arms, RT-nivolumab and only-nivolumab, were well matched for baseline characteristics. At a median follow-up of 7.4 months, the 1-year overall survival rates were 57.8% for patients treated with RT-nivolumab and 27.4% for patients treated with only-nivolumab (P=0.043). The 1-year progression-free survival in the RT-nivolumab group was 57.8% and 20.6% in the only-nivolumab group (P=0.040). No difference in adverse events was detected.Conclusions:In conclusion, RT and nivolumab can be combined, obtaining a benefit in overall survival and progression-free survival, without an increase in acute toxicities in pretreated advanced NSCLC patients. Prospective studies are needed to confirm these results.
Accuracy of Corneal Thickness by Swept-Source Optical Coherence Tomography and Scheimpflug Camera in Virgin and Treated Fuchs Endothelial Dystrophy
Authors: Arnalich-Montiel Francisco , Ortiz-Toquero Sara , Auladell Clara , Couceiro Ana 
Published: January 2018

Purpose:
To assess intraobserver repeatability, intersession reproducibility, and agreement of swept-source Fourier-domain optical coherence tomography (SS-OCT) and the Scheimpflug camera in measuring corneal thickness in virgin and grafted eyes with Fuchs endothelial corneal dystrophy (FECD).

Methods:
Thirty-six control eyes, 35 FECD eyes, 30 FECD with corneal edema eyes, 25 Descemet stripping automated endothelial keratoplasty (DSAEK) eyes, and 29 Descemet membrane endothelial keratoplasty (DMEK) eyes were included. The apical center, pupillary center, and thinnest corneal thickness were determined in 3 consecutive images and repeated 2 weeks later. Repeatability and reproducibility coefficients, intraclass correlation coefficients, and 95% limits of agreement (LOA) between measurements were calculated. Agreement between devices was assessed using Bland–Altman analysis.

Results:
Corneal thickness measurements were highly reproducible and repeatable with both systems. SS-OCT showed better repeatability in all corneal locations in the normal, FECD, FECD with edema, DSAEK, and DMEK groups (coefficient of variation ≤0.60%, ≤0.36%, ≤0.43%, ≤1.09%, and ≤0.48%, respectively) than the Scheimpflug (coefficient of variation ≤1.15%, ≤0.92%, ≤1.10%, ≤1.25%, and ≤1.14%, respectively). Between-session 95% LOA for SS-OCT was less than 3% for all groups except for the FECD with edema group, being almost double using the Scheimpflug camera. Differences between instruments were statistically significant in all groups and locations (P < 0.01) except in the DSAEK group (P ≤ 0.51); however, SS-OCT underestimated all measurements.

Conclusions:
SS-OCT provides better reproducible and repeatable measurements of corneal thickness than those obtained with the Scheimpflug camera in patients with FECD or an endothelial transplant. Variations between examinations higher than the 95% LOA observed in our study should raise awareness of changes in the endothelial function.
Reduction in Histone H3 Acetylation and Chromatin Remodeling in Corneas of Alloxan-Induced Diabetic Rats
Authors: Herencia-Bueno Karina E. , Aldrovani Marcela , Crivelaro Roberta M. , Thiesen Roberto , Barros-Sobrinho Alexandre A. F. , Claros-Chacaltana Flor D. Y. , Padua Ivan R. M. , Santos Daniela M. , Laus José L. 
Published: January 2018

Purpose:
To evaluate acetylation of histone H3, chromatin remodeling, nuclear size and shape, DNA ploidy, and distribution of nucleolus organizing regions (NORs) in corneal epithelial and stromal cells of diabetic and nondiabetic rats.

Methods:
Diabetes was induced by a single intraperitoneal injection of alloxan. All diabetic rats (n = 20) included in the study had 4 weeks of moderate-to-severe hyperglycemia (plasma glucose levels >400 mg/dL). Acetylated histone H3 levels were quantified in corneal tissue using a colorimetric assay. Chromatin remodeling, nuclear sizes (area/perimeter) and shapes (circularity), and DNA ploidies were evaluated from Feulgen-stained tissue sections using video image analysis. Distributions of NORs were studied in tissue sections impregnated with silver ions. Ophthalmic clinical parameters, including corneal sensitivity, were investigated. Twenty nondiabetic rats were used as controls.

Results:
Acetylation of histone H3 was reduced in the corneas of the diabetic rats. Nuclei in corneal epithelial cells of diabetic rats compacted chromatin, increased in size, modified their shapes, and elevated DNA ploidy. The only nuclear change observed in the corneal stromal cells of diabetic rats was chromatin decompaction. The size of the silver-stained NOR did not differ between the study samples. The corneal sensitivity in diabetic rats was 51.8% lower than that in nondiabetic rats.

Conclusions:
The results of this study show that alloxan-induced diabetes altered the histone H3 acetylation pattern and compromised the chromatin supraorganization in corneal tissue/cells. Continued research is needed to understand the clinical and morphofunctional significance of changes in corneal cell nuclei of diabetic individuals.
DNA methylation in human lipid metabolism and related diseases
Authors: Mittelstraß Kirstin , Waldenberger Melanie 
Published: January 2018

Purpose of review
It is becoming increasingly evident that epigenetic mechanisms, particularly DNA methylation, play a role in the regulation of blood lipid levels and lipid metabolism-linked phenotypes and diseases.

Recent findings
Recent genome-wide methylation and candidate gene studies of blood lipids have highlighted several robustly replicated methylation markers across different ethnicities. Furthermore, many of these lipid-related CpG sites associated with blood lipids are also linked to lipid-related phenotypes and diseases. Integrating epigenome-wide association studies (EWAS) data with other layers of molecular data such as genetics or the transcriptome, accompanied by relevant statistical methods (e.g. Mendelian randomization), provides evidence for causal relationships. Recent data suggest that epigenetic changes can be consequences rather than causes of dyslipidemia. There is sparse information on many lipid classes and disorders of lipid metabolism, and also on the interplay of DNA methylation with other epigenetic layers such as histone modifications and regulatory RNAs.

Summary
The current review provides a literature overview of epigenetic modifications in lipid metabolism and other lipid-related phenotypes and diseases focusing on EWAS of DNA methylation from January 2016 to September 2017. Recent studies strongly support the importance of epigenetic modifications, such as DNA methylation, in lipid metabolism and related diseases for relevant biological insights, reliable biomarkers, and even future therapeutics.
A Systemic Review of Transoral Thyroidectomy
Authors: Shan Liqun , Liu Jianing 
Published: January 2018

Background:
Transoral thyroidectomy is a kind of “natural orifice transluminal endoscopic surgery (NOTES)” which is now being performed in increasing frequency. However, the safety and feasibility have not been concluded yet.

Materials and Methods:
A systemic literature search was performed in Pubmed, Cochrane, and Embase databases to identify all studies written in English and published up to April 2017. The keywords used were “transoral endoscopic,” “transoral robotic,” “oral vestibular endoscopic,” and “oral vestibular robotic” combined with “thyroidectomy” or “thyroid surgery.”

Results:
Ten articles containing 211 cases matched the review criteria. The weighted average operative time was 119.9 minutes with an average intraoperative blood loss of 35.5 mL while the weighted average length of hospital stay was 4.0 days. The overall conversion rate to open surgery was 1.9%. An overall incidence rate of temporary hypoparathyroidism was 7.1%, temporary recurrent laryngeal nerve injury was 4.3%, whereas of mental nerve palsy was 4.3%.

Conclusions:
According to those reviewed literatures, we can conclude that transoral thyroidectomy is safe and feasible in well-selected patients and offers good perioperative and postoperative outcomes.
Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart
Authors: Sánchez-Iranzo Héctor , Galardi-Castilla María , Sanz-Morejón Andrés , González-Rosa Juan Manuel , Costa Ricardo , Ernst Alexander , Sainz de Aja Julio , Langa Javier , Mercader Nadia 
Published: January 2018

ABSTRACTIn the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b- and collagen 1alpha2 (col1a2)-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated, but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells impaired cardiomyocyte proliferation. We conclude that ECM-producing cells are key players in the regenerative process and suggest that anti-fibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.SCIENTIFIC STATEMENTAfter myocardial infarction in the mammalian heart, millions of cardiomyocytes are lost and replaced by fibrotic scar tissue. While fibrosis is persistent in adult mammals, there are some vertebrates, including zebrafish, with the capacity for regeneration. This process does not occur in the absence of fibrosis. Here we studied subpopulations of collagen producing cells and analyzed their fate after complete regeneration of the zebrafish myocardium. Our data show that fibroblasts persisted in the regenerated heart, but shut down the profibrotic program. While fibrosis could be considered as detrimental to the regeneration process, our study reveals a positive effect on cardiomyocyte proliferation. Accordingly, a fibrotic response can be beneficial for heart regeneration.
Intrinsic noise modulation in closed oligomerization-type systems⋆
Authors: Rooman Marianne , Pucci Fabrizio 
Published: January 2018

AbstractHow random fluctuations impact on biological systems and what is their relationship with complexity and energetic cooperativity are challenging questions that are far from being elucidated. Using the stochastic differential equation formalism, we studied analytically the effect of fluctuations on a series of oligomerization processes, in which several molecules of the same or different species interact to form complexes, without interaction with the environment. The conservation of the total number of molecules within the systems imposes constraints on the stochastic quantities, among which the negativity of the covariances and the vanishing of the determinant of the covariance matrix. The intrinsic noise on the number of molecules of each species is represented by the Fano factor, defined as the variance to mean ratio. At the equilibrium steady states, the sum of the Fano factors of all molecular species is equal to the rank of the system, independently of the parameters. The Fano factors of the individual molecular species are, however, parameter dependent. We found that when the free energy cooperativity of the reactions increases, the intrinsic noise on the oligomeric product decreases, and is compensated by a higher noise on the monomeric reactants and/or intermediate states. The noise reduction is moreover more pronounced for higher complexity systems, involving oligomers of higher degrees.
High-throughput automatic training system for odor-based cognitive behaviors in head-fixed mice
Authors: Han Zhe , Zhang Xiaoxing , Zhu Jia , Chen Yulei , Li Chengyu T. 
Published: January 2018

AbstractUnderstanding neuronal mechanisms of cognitive behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS) for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping, and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS), delayed paired association (DPA), Go/No-go (GNG), and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making, and cognitive flexibility. Mice reached stable levels of performance within several days in the tasks. HATS enabled an experimenter to train eight mice simultaneously, therefore greatly enhanced the experimental efficiency. Combined with causal perturbation and activity recording techniques, HATS can greatly facilitate our understanding of the neural-circuitry mechanisms underlying cognitive behaviors.
Estimating variance components in population scale family trees
Authors: Shor Tal , Geiger Dan , Erlich Yaniv , Weissbrod Omer 
Published: January 2018

AbstractThe rapid digitization of genealogical and medical records enables the assembly of extremely large pedigree records spanning millions of individuals and trillions of pairs of relatives. Such pedigrees provide the opportunity to investigate the sociological and epidemiological history of human populations in scales much larger than previously possible. Linear mixed models (LMMs) are routinely used to analyze extremely large animal and plant pedigrees for the purposes of selective breeding. However, LMMs have not been previously applied to analyze population-scale human family trees. Here, we presentSparseCholesky factorIzation LMM (Sci-LMM), a modeling framework for studying population-scale family trees that combines techniques from the animal and plant breeding literature and from human genetics literature. The proposed framework can construct a matrix of relationships between trillions of pairs of individuals and fit the corresponding LMM in several hours. We demonstrate the capabilities of Sci-LMM via simulation studies and by estimating the heritability of longevity and of reproductive fitness (quantified via number of children) in a large pedigree spanning millions of individuals and over five centuries of human history. Sci-LMM provides a unified framework for investigating the epidemiological history of human populations via genealogical records.Author SummaryThe advent of online genealogy services allows the assembly of population-scale family trees, spanning millions of individuals and centuries of human history. Such datasets enable answering genetic epidemiology questions on unprecedented scales. Here we present Sci-LMM, a pedigree analysis framework that combines techniques from animal and plant breeding research and from human genetics research for large-scale pedigree analysis. We apply Sci-LMM to analyze population-scale human genealogical records, spanning trillions of relationships. We have made both Sci-LMM and an anonymized dataset of millions of individuals freely available to download, making the analysis of population-scale human family trees widely accessible to the research community. Together, these resources allow researchers to investigate genetic and epidemiological questions on an unprecedented scale.
Computational modelling of atherosclerosis: developing a community resource
Authors: Parton Andrew , McGilligan Victoria , O’Kane Maurice , Watterson Steven 
Published: January 2018

AbstractRationaleAtherosclerosis is a dynamical process that emerges from the interplay between lipid metabolism, inflammation and innate immunity. The arterial location of atherosclerosis makes it logistically and ethically difficult to study in vivo. To improve our understanding of the disease, we must find alternative ways to investigate its progression. There is currently no computational model of atherosclerosis openly available to the research community for use in future studies and for refinement and development.ObjectiveHere we develop the first predictive computational model to be made openly available and demonstrate its use for therapeutic hypothesis generation.Methods and ResultsWe compiled a dataset of relevant interactions from the literature along with available parameters. These were used to build a network model describing atherosclerotic plaque development. A visual map of the network model was produced using the Systems Biology Graphical Notation (SBGN) and a dynamic mathematical description of the network model that enables us to simulate plaque growth was developed and is made available using the Systems Biology Markup Language (SBML). We used this model to investigate whether multi-drug therapeutic interventions could be identified that stimulate plaque regression. The model produced comprised 20 cell types and 41 proteins with 89 species in total. The visual map is available for reuse and refinement using the SBGN Markup Language standard format and the mathematical model is available using the SBML standard format. We used a genetic algorithm to identify a multi-drug intervention hypothesis comprising five drugs that comprehensively reverse plaque growth within the model.ConclusionsWe have produced the first predictive mathematical and computational model of atherosclerosis that can be reused and refined by the cardiovascular research community. We demonstrated its potential as a tool for future studies of cardiovascular disease by using it to identify multi-drug intervention hypotheses.Subject CodesAtherosclerosis, Computational Biology, Lipids and Cholesterol, Cell Signaling/Signal Transduction, Cardiovascular Disease
Social behavior and anxiety contribute to nicotine self-administration in adolescent outbred rats
Authors: Wang Tengfei , Han Wenyan , Chitre Apurva , Polesskaya Oksana , Solberg Woods Leah C. , Palmer Abraham A. , Chen Hao 
Published: January 2018

ABSTRACTBoth emotional and social traits interact with genetic factors to influence smoking behavior. We previously established a socially acquired nicotine intravenous self-administration model where social learning of a nicotine-associated odor cue reversed conditioned flavor aversion and promoted nicotine intake. In this study, we first phenotyped ~ 800 adolescent heterogeneous stock rats in open field, novel object interaction, social interaction, elevated plus maze, and marble bury behaviors. These rats were then phenotyped on socially acquired nicotine self-administration. We found 243 significant correlations between different behavioral tests. Principal component regression analysis found that ~ 10–20% of the variance in nicotine-related measures, such as intake during the first or the last three fixed-ratio sessions, the progressive ratio session, and reinstatement behavior, can be explained by variations in behavioral traits. Factors corresponding to social behavior and anxiety were among the strongest predictors of nicotine intake and reinstatement of nicotine-seeking behavior. We also found many sex differences in behavioral measures. These data indicated that the genetic diversity of this population, in combination with social behavior and anxiety, are significant contributors to the divergent nicotine self-administration behavior and indicated a high probability of discovering sex-specific genetic mechanisms for nicotine intake in future genome-wide association studies.
Relationship between money lenders and farmers
Authors: Balachandran Rakhe P. , Dhal Sarat Chandra 
Published: January 2018

Purpose
The dependence of farmers on money lenders for agricultural credit despite the penetration of the formal financial sector with subsidized interest rates remains an economic puzzle. The purpose of this paper is to revisit the relationship between money lenders and farmers in the presence of trade-loan nexus.

Design/methodology/approach
The study provides a theoretical framework supported by empirical evidence. It uses primary survey data of farmers in a major potato producing district of West Bengal, India. For the empirical analysis, apart from descriptive statistics, the authors use a logit regression model to derive insights from some testable hypotheses.

Findings
The study finds that trade-loan nexus increases defaults on agricultural loans through two channels: first, by increasing loan requirement and repayment obligations through high input prices and interest rates, respectively; and second, by reducing income of farmers by setting low prices for the output.

Research limitations/implications
The functioning of money lenders in rural areas, including their sources of finance and political control over local economy, and the existing social hierarchies in the rural context will have to be studied in detail to understand the complexities of the issue.

Practical implications
The findings of the study underline the need for policy initiatives to break the trade-loan nexus to reduce the dependence of farmers on money lenders.

Social implications
The higher defaults help the money lender to sustain in the rural agricultural loan market as the formal sector becomes reluctant to lend in the presence of pervasive defaults.

Originality/value
The study is entirely original based on primary survey data of seven blocks of a major potato producing district in West Bengal, India. It could be the first such study on the subject. The findings are fresh and expected to contribute to development economics and agriculture finance literature and policy making.