bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota: closely tied to the regulation of circadian clock in the development of type 2 diabetes mellitus
Authors: Ding Lu , Xiao Xin-Hua 
Published: February 2020

Abstract
Type 2 diabetes mellitus (T2DM), a worldwide epidemic disease, has caused tremendous economic and social burden, but the pathogenesis remains uncertain. Nowadays, the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has be increasingly studied. However, the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored. It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism. Considering all these above, we reviewed the literature related to the gut microbiota, circadian clock, and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM, which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.
Breast cancer immunology and immunotherapy: targeting the programmed cell death protein-1/programmed cell death protein ligand-1
Authors: Zhao Jing , Huang Jian 
Published: February 2020

Abstract
Historically, breast cancer has been regarded as an immunogenic “cold” tumor. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy, which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. Collectively, the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going.
Creating a Safe Space for Nursing Students' Spiritual Reflection
Authors: Briggs Crista L. , Lartey Grace , Eagle Susan 
Published: February 2020

ABSTRACT:In an effort to improve students' comfort level and confidence with spiritual care, nursing faculty initiated a classroom activity to encourage students to think about and reflect upon 10 questions. Students responded by answering whether they had ever thought about the question being asked, then writing a short narrative response. Topics included issues about life, death, afterlife, spiritual well-being, truth, and God. Although 88.8% of participants (n = 107) considered themselves to be religious or spiritual, results revealed many had never thought about the questions being asked. Based on these findings, nurse educators should consider including a similar classroom reflection exercise to better prepare students for providing spiritual care prior to beginning clinical rotations.
Clinical Evaluation of 225 Sub-SMAS Facelifts with No Temporal Incision
Authors: Swanson Eric 
Published: February 2020

Background:
Despite their name, “short scar” procedures leave scars in the temples and the postauricular scar often requires extension. Redraping the orbicularis muscle for periorbital rejuvenation increases the risk of facial nerve injury. This retrospective cohort study was undertaken to clinically evaluate a surgical approach that eliminates the temporal incision.

Methods:
A sub-superficial musculoaponeurotic system (SMAS) facelift was used, incorporating a triple-vector platysmaplasty and fat injection for periorbital rejuvenation. From 2009 to 2019, 225 consecutive outpatients underwent a sub-SMAS facelift with a triple-vector (superior, lateral, medial) platysmaplasty, either alone or in combination with fat injection, laser resurfacing, blepharoplasties, endoscopic forehead lift, and other cosmetic procedures. Release of the retaining ligaments optimized SMAS mobilization. A temporal incision was not used. Fat (mean volume 32 ml) was injected into the undissected subcutaneous tissue plane. The mean follow-up time was 28 months.

Results:
The most frequent complication was a neuropraxia (7.6%), usually affecting a frontal nerve branch, and always temporary. Two deep venous thromboses were detected by ultrasound surveillance. No significant correlation was detected between complications and age, sex, body mass index, smoking history, or a previous facelift. Sixteen patients (7%) returned for a secondary facelift (mean interval, 3.5 years).

Conclusions:
A sub-SMAS facelift and triple-vector platysmaplasty with fat injection combine effective neckline rejuvenation with facial volume restoration. Avoiding a temporal incision eliminates a telltale scar. Orbicularis preservation avoids additional dissection, possibly reducing the risk of neuropraxia. Fat injection provides a net increase in facial volume. Long-term measurement studies are recommended.
TOXICITY AND EFFICACY OF INTRAVITREAL MELPHALAN FOR RETINOBLASTOMA
Authors: Liao Albert , Hsieh Terry , Francis Jasmine H. , Lavery Jessica A. , Mauguen Audrey , Brodie Scott E. , Abramson David H. 
Published: February 2020

Purpose:
To compare retinal toxicity as measured by electroretinogram, ocular, and patient survival in retinoblastoma treated with intravitreal melphalan at two concentrations (25 vs. 30 µg).

Methods:
Single-center, retrospective analysis of retinoblastoma eyes receiving 25-µg or 30-µg intravitreal melphalan from September 2012 to January 2019. Ocular toxicity was measured by electroretinogram of evaluable injections in 449 injections in 136 eyes. A repeated-measures linear mixed model with a random intercept and slope was applied to account for repeated measures for each eye.

Results:
Average decline in electroretinogram after each additional injection was −4.9 µV (95% confidence interval −6.3 to −3.4); electroretinogram declined by −4.6 µV (95% confidence interval −7.0 to −2.2) after 25-µg injections and −5.2 µV (95% confidence interval −6.6 to −3.8) after 30-µg injections (P = 0.66). Injection at a new clock site hour was associated with a −3.91-µV lower average (95% confidence interval −7.8 to −0.04).

Conclusion:
Electroretinogram-measured toxicity in retinoblastoma eyes treated with intravitreal injections was not found to be different across 25-µg and 30-µg injections. There were no cases of extraocular extension or metastatic deaths in our patient population.
A cohort-based comprehensive characterization of different patterns of very short-term, within-visit, blood pressure variability
Authors: Papaioannou Theodore G. , Protogerou Athanase D. , Stamatelopoulos Kimon S. , Alexandraki Krystallenia I. , Vrachatis Dimitrios , Argyris Antonios , Papaioannou Vasilios , Vavuranakis Manolis , Stefanadis Christodoulos , Tousoulis Dimitrios 
Published: February 2020

Aim
To characterize different patterns of variability of three repeated within-visit blood pressure (BP) readings and to determine the prevalence of specific variation trends in systolic (SBP), diastolic (DBP) blood pressure and pulse pressure (PP).

Methods
Data from 53 737 subjects from the National Health and Nutrition Examination Survey were analyzed. In each subject, three consecutive BP measurements were performed with a minimum time-interval of at least 30 s. We propose three patterns of within-visit BP variability (separately for SBP, DBP and PP): (1) increasing trend (BP3 > BP2 > BP1); (2) decreasing trend (BP1 > BP2 > BP3) and (3) no trend (BP3 ≈ BP2 ≈ BP1). A threshold of minimum change (ΔP > 3 mmHg) between BP1-BP2 and BP2-BP3 was also applied as a prerequisite for the definition of these trends.

Results
An increasing trend was observed among three consecutive measurements of SBP, DBP and PP in 7.4, 10.4 and 10.2%, respectively. When a minimum threshold of 3 mmHg was set the respective increasing trends were observed in 1.8, 2.9 and 4.4%, respectively. There was a higher prevalence of decreasing trend within three consecutive SBP, DBP and PP readings: 17, 13.1 and 16.2%, respectively, whereas using a threshold of ΔP >3 mmHg the respective prevalence was 6.3, 4.1 and 7.7%. A maximum absolute difference >10 mmHg within triplicate of SBP/DBP/PP readings was observed in 12.9, 13 and 29.4%, respectively. In the era of personalized medicine, these patterns are well worth further investigation concerning their pathophysiologic and clinical relevance.
TWIRLS, an automated topic-wise inference method based on massive literature, suggests a possible mechanism via ACE2 for the pathological changes in the human host after coronavirus infection
Authors: Ji Xiaoyang , Zhang Chunming , Zhai Yubo , Zhang Zhonghai , Zhang Chunli , Xue Yiqing , Tan Guangming , Niu Gang 
Published: February 2020

AbstractFaced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the “coronavirus” should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying the viruses and the hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly when the scientific understanding may be limited, which can further lower the information processing efficiency. We present TWIRLS, a method that can automatically acquire, organize, and classify information. Additionally, independent functional data sources can be added to build an inference system using a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. TWIRLS can automatically analyze more than three million words in more than 14,000 literature articles in only 4 hours. Combining with generalized gene interaction databases creates a data interface that can help researchers to further analyze the information. Using the TWIRLS system, we found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in the host pathological changes on binding to the coronavirus after infection. After triggering functional changes in ACE2/AT2R, an imbalance in the steady-state cytokine regulatory axis involving the Renin-Angiotensin System and IP-10 leads to a cytokine storm.
Machine Learning Assisted Intraoperative Assessment of Brain Tumor Margins Using HRMAS NMR Spectroscopy
Authors: Cakmakci Doruk , Karakaslar Emin Onur , Ruhland Elisa , Chenard Marie-Pierre , Proust Francois , Piotto Martial , Namer Izzie Jacques , Cicek A. Ercument 
Published: February 2020

AbstractComplete resection of the tumor is important for survival in glioma patients. Even if the gross total resection was achieved, left-over micro-scale tissue in the excision cavity risks recurrence. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) technique can distinguish healthy and malign tissue efficiently using peak intensities of biomarker metabolites. The method is fast, sensitive and can work with small and unprocessed samples, which makes it a good fit for real-time analysis during surgery. However, only a targeted analysis for the existence of known tumor biomarkers can be made and this requires a technician with chemistry background, and a pathologist with knowledge on tumor metabolism to be present during surgery. Here, we show that we can accurately perform this analysis in real-time and can analyze the full spectrum in an untargeted fashion using machine learning. We work on a new and large HRMAS NMR dataset of glioma and control samples (n = 568), which are also labeled with a quantitative pathology analysis. Our results show that a random forest based approach can distinguish samples with tumor cells and controls accurately and effectively with a mean AUC of 85.6% and AUPR of 93.4%. We also show that we can further distinguish benign and malignant samples with a mean AUC of 87.1% and AUPR of 96.1%. We analyze the feature (peak) importance for classification to interpret the results of the classifier. We validate that known malignancy biomarkers such as creatine and 2-hydroxyglutarate play an important role in distinguish tumor and normal cells and suggest new biomarker regions. The code is released at http://github.com/ciceklab/HRMAS_NC.
Oxytocin Acts on Astrocytes in the Central Amygdala to Promote a Positive Emotional State
Authors: Wahis Jérôme , Kerspern Damien , Althammer Ferdinand , Baudon Angel , Goyon Stéphanie , Hagiwara Daisuke , Lefèvre Arthur , Boury-Jamot Benjamin , Bellanger Benjamin , Abatis Marios , da Gouveia Miriam Silva , Benusiglio Diego , Eliava Marina , Rozov Andrej , Weinsanto Ivan , Knobloch-Bollmann Hanna Sophie , Wang Hong , Pertin Marie , Inquimbert Perrine , Pitzer Claudia , Siemens Jan , Goumon Yannick , Boutrel Benjamin , Darbon Pascal , Lamy Christophe Maurice , Stern Javier E. , Décosterd Isabelle , Chatton Jean-Yves , Young W. Scott , Stoop Ron , Poisbeau Pierrick , Grinevich Valery , Charlet Alexandre 
Published: February 2020

SUMMARYOxytocin orchestrates social and emotional behaviors through modulation of neural circuits in brain structures such as the central amygdala (CeA). The long-standing dogma is that oxytocin signaling in the central nervous system occurs exclusively via direct actions on neurons. However, several findings over the last decades showed that astrocytes actively participate in the modulation of neuronal circuits. Here, we investigate the degree of astrocytes’ involvement in oxytocin functions. Using astrocyte’ specific gain and loss of function approaches, we demonstrate that CeA astrocytes not only directly respond to oxytocin, but are actually necessary for its effects on neuronal circuits and ultimately behavior. Our work identifies astrocytes as a crucial cellular substrate underlying the promotion of a positive emotional state by oxytocin. These results further corroborate that astrocytes are key regulators of neuronal circuits activity by responding to specific neuropeptidergic inputs, and opens up new perspectives to understand how neuromodulators gate brain functions.
Creative destruction: Sparse activity emerges on the mammal connectome under a simulated communication strategy with collisions and redundancy
Authors: Hao Yan , Graham Daniel 
Published: February 2020

ABSTRACTSignal interactions in brain network communication have been little studied. We describe how nonlinear collision rules on simulated mammal brain networks can result in sparse activity dynamics characteristic of mammalian neural systems. We tested the effects of collisions in “information spreading” (IS) routing models and in standard random walk (RW) routing models. Simulations employed synchronous agents on tracer-based mesoscale mammal connectomes at a range of signal loads. We find that RW models have high average activity that increases with load. Activity in RW models is also densely distributed over nodes: a substantial fraction is highly active in a given time window, and this fraction increases with load. Surprisingly, while IS models make many more attempts to pass signals, they show lower net activity due to collisions compared to RW, and activity in IS increases little as function of load. Activity in IS also shows greater sparseness than RW, and sparseness decreases slowly with load. Results hold on two networks of the monkey cortex and one of the mouse whole-brain. We also find evidence that activity is lower and more sparse for empirical networks compared to degree-matched randomized networks under IS, suggesting that brain network topology supports IS-like routing strategies.
Modular biomaterials vaccine technology protects against multiple pathogens and septic shock
Authors: Super Michael , Doherty Edward J. , Cartwright Mark J. , Seiler Benjamin T. , White Des A. , Langellotto Fernanda , Stafford Alexander G. , Dimitrakakis Nikolaos , Karkada Mohan , Graveline Amanda R. , Horgan Caitlin L. , Lightbown Kayla R. , Urena Frank R. , Yeager Chyenne D. , Rifai Sami A. , Dellacherie Maxence O. , Li Aileen W. , Jiang Amanda R. , Chandrasekhar Vasanth , Scott Justin M. , Lightbown Shanda L. , Ingber Donald E. , Mooney David J. 
Published: February 2020

AbstractBroad spectrum vaccines could provide a solution to the emergence of antibiotic resistant microbes, pandemics and engineered biothreat agents. Here, we describe a modular vaccine (composite infection vaccine technology (ciVAX)) which can be rapidly assembled and in which 4 of the 5 components are already approved for human use. ciVAX consists of an injectable biomaterial scaffold with factors to recruit and activate dendritic cells (DC)in vivoand microbeads conjugated with the broad-spectrum opsonin Fc-Mannose-binding Lectin (FcMBL) that is pre-bound to polysaccharide-rich cell wall antigens, such as the pathogen-associated molecular patterns (PAMPs) fractions, captured from whole inactivated bacteria. Vaccination of mice and rabbits with ciVAX generates potent humoral and T cell responses to PAMPs isolated from native antibiotic-resistantE. coliandS. aureus, and ciVAX protects mice and pigs against lethalE colichallenge in sepsis and septic shock models. In addition to the efficacy of ciVAX against homologous challenge, PAMPS isolated from an infected animal protects other animals against infection by heterologous challenge using differentE. coliserotypes – demonstrating the potential for use of ciVAX in controlling pandemics. The advantage of the ciVAX technology is the strong immunogenicity with limited reactogenicity, the use of inactivated pathogens, and the modular manufacture using cGMP approved products which can be stockpiled ready for the next pandemic.One Sentence SummaryBiomaterial vaccine induces strong immunogenicity, weak reactogenicity, and protects fromE. colisepsis in rodents and pigs, and MRSA skin abscess.
TheDrosophila FUSorthologcabezapromotes adult founder myoblast selection by Xrp1-dependent regulation of FGF signaling
Authors: Catinozzi Marica , Mallik Moushami , Frickenhaus Marie , Been Marije , Sijlmans Céline , Kulshrestha Divita , Alexopoulos Ioannis , Weitkunat Manuela , Schnorrer Frank , Storkebaum Erik 
Published: February 2020

AbstractThe number of adult myofibers inDrosophilais determined by the number of founder myoblasts selected from a myoblast pool, a process governed by fibroblast growth factor (FGF) signaling. Here, we show that loss ofcabeza(caz) function results in a reduced number of adult founder myoblasts, leading to a reduced number and misorientation of adult dorsal abdominal muscles. Genetic experiments revealed that loss ofcazfunction in both adult myoblasts and neurons contributes tocazmutant muscle phenotypes. Selective overexpression of the FGF receptor Htl or the FGF receptor-specific signaling molecule Stumps in adult myoblasts partially rescuedcazmutant muscle phenotypes, and Stumps levels were reduced incazmutant founder myoblasts, indicating FGF pathway deregulation. In both adult myoblasts and neurons,cazmutant muscle phenotypes were mediated by increased expression levels of Xrp1, a DNA-binding protein involved in gene expression regulation. Xrp1-induced phenotypes were dependent on the DNA-binding capacity of its AT-hook motif, and increased Xrp1 levels in founder myoblasts reduced Stumps expression. Thus, control of Xrp1 expression by Caz is required for regulation of Stumps expression in founder myoblasts, resulting in correct founder myoblast selection.Author SummarySkeletal muscles mediate movement, and therefore, proper structure and function of skeletal muscles is required for respiration, locomotion, and posture. Adult muscles arise from fusion of muscle precursor cells during development. In the fruit flyDrosophila melanogaster, muscle precursor cells come in two flavors: founder cells and fusion-competent cells. The number of founder cells selected during development corresponds to the number of adult muscles formed. Here, we report that inactivation of theDrosophila cazgene results in muscle developmental defects. Loss ofcazfunction in both muscle precursor cells and the nerve cells that innervate muscles contributes to the muscle developmental defect. At the molecular level, loss ofcazfunction leads to increased levels of Xrp1. Xrp1 regulates the expression of many other genes, including genes that produce components of the FGF signaling pathway, which is known to be involved in founder cell selection. In all, we uncovered a novel molecular mechanism that regulates founder cell selection during muscle development.
Immune reactivity to neurofilaments and dipeptide repeats in ALS progression
Authors: Puentes Fabiola , Lombardi Vittoria , Lu Ching-Hua , Yildiz Ozlem , Kang Angray , Nissim Ahuva , Fratta Pietro , Isaacs Adrian , Bobeva Yoana , Malaspina Andrea 
Published: February 2020

AbstractObjectiveTo test antibody response and formation of immune-complexes to neurofilaments and dipeptide-repeats, the translational products of the mutated C9orf72 gene, as potential biomarkers for clinical stratification of amyotrophic lateral sclerosis (ALS).MethodsUsing neurofilament protein isoforms plasma expression as reference, antibodies and immune-complexes against neurofilament-light, medium and heavy chain and poly-(GP)-GR dipeptide-repeats were tested in blood from 105 fast and slow progressing ALS patients, 26 C9orf72 mutation carriers (C9+ve) ALS patients and 77 healthy controls (HC) using single-molecule and immune-capture assays. Longitudinal antibody/immune-complex responses were measured in serial blood samples from 37 (including 11 C9+ve) patients.ResultsAntibodies and immune-complex reactivity was higher in ALS patients than HC, particularly in C9+ve ALS patients, and modestly correlated with total neurofilament protein isoforms (r:0.24p=0.002; r:0.18p=0.02 respectively). Neurofilament-light immune-complexes and neurofilament-heavy antibodies had the best diagnostic performances distinguishing ALS subtypes from HC (AUC=0.68p<0.01; AUC=0.68p<0.001 respectively). Neurofilament-light immune-complexes (AUC=0.69p<0.01) and poly-(GP) dipeptide-repeats antibodies (AUC=0.71p<0.001) separated C9+ve from C9-ve patients. Multivariate mortality hazard ratio and Kaplan-Meier analyses showed low neurofilament-heavy antibody levels associated with increased survival. Longitudinal analysis identified raising levels of antibodies against neurofilaments in fast progressing ALS and of neurofilament-light immune-complexes in C9+ve patients.InterpretationC9+ve and fast progressing ALS patients have a distinct neurofilament and dipeptide-repeat immuno-phenotype, with increasing levels of blood neurofilament-light immune-complexes and neurofilament antibodies with disease progression. The study of the expression of these biomarkers in the natural history of ALS may shed light on disease initiation and progression and provide novel pharmacodynamic biomarkers in emerging C9orf72 gene silencing therapies.