bluuebunny/crossref_metadata_2025_split huggingface dataset:
Encephalocraniocutaneous Lipomatosis (Haberland Syndrome or Fishman Syndrome)
Authors: Garozzo Maria , Attardo Daniele , Smilari Pierluigi , Greco Filippo , Fiumara Agata , Polizzi Agata , Pirrone Concetta , Zanghì Antonio , Schepis Carmelo , Lacarrubba Francesco , Micali Giuseppe , Ruggieri Martino , Praticò Andrea , Mazzurco Marina 
Published: August 2018

AbstractEncephalocraniocutaneous lipomatosis is a sporadic, congenital neurocutaneous disorder characterized by the involvement of skin, central nervous system, and eye. A non-hereditary, autosomal mutation that may survive only in a mosaic state may be the cause of the clinical picture of the syndrome. Less than 80 patients have been so far reported and their clinical manifestations consisted of unilateral lipomatous hamartoma of the scalp or eyelid, epibulbar choristomas, and ipsilateral brain malformations. There is no clinical correlation between the severity of brain malformations and the clinical manifestations, and many patients with extremely extensive cerebral abnormalities are only minimal symptomatic. Seizures and mental retardation may also occur. The natural history is often favorable, without drug-resistant seizures and normal intelligence in most of the cases.
The Future of the Lecture in Neurology Education
Authors: Schaefer Sara , Dominguez Moises , Moeller Jeremy 
Published: August 2018

AbstractThe lecture has been a core pedagogical method since the early days of formal medical education. Although approaches to formal lectures have evolved over the years, there has been ongoing debate about the role that lectures should play in modern medical education. Arguably, traditional lectures do not align well with modern learning theory, and do not take full advantage of our current knowledge of how people learn. In many modern medical curricula, lectures have been replaced by self-study activities, including video-based lectures, computer-based learning modules, and other self-directed learning. We argue that scheduled “together time” is still important, particularly in neurology education, where there is a strong emphasis on clinical reasoning. We outline alternative teaching methods that effectively use this time, including the flipped classroom, just-in-time teaching, problem-based learning, and team-based learning. We discuss ways in which these approaches may be particularly conducive to components of neurology education.
Complications of Nasoseptal Flap Reconstruction: A Systematic Review
Authors: Lavigne Philippe , Faden Daniel , Wang Eric , Snyderman Carl 
Published: August 2018

Objective The nasoseptal flap (NSF) is considered the primary vascularized flap for reconstruction of dural defects with endoscopic endonasal surgery (EES) of the skull base. However, the complications and morbidities associated with this reconstructive flap are poorly understood. This article presents a systematic review of the complications and morbidities related to the use of the NSF in skull base surgery.
Method A systematic review of the literature based on published guidelines was performed to identify potential complications and morbidities related to the NSF. The MEDLINE and Embase databases were searched from January 1, 1950 to February 5, 2018.
Results Twenty-seven articles were identified. Reported complications were as follows: NSF necrosis (4 studies; [0–1.3%]), mucocele formation (5 studies; [0–3.6%]), septal perforation (6 studies, [0–14.4%]), nasal dorsum collapse (2 studies, [0.7–5.8%]), effects on quality of life (QoL) (8 studies), and olfactory loss (11 studies).
Conclusion Although complications associated with the NSF may be underreported in the literature, the NSF appears to be a safe and reliable reconstructive flap in EES of the skull base.
Identification of a multipotent Twist2-expressing cell population in the adult heart
Authors: Min Yi-Li , Jaichander Priscilla , Sanchez-Ortiz Efrain , Bezprozvannaya Svetlana , Malladi Venkat S. , Cui Miao , Wang Zhaoning , Bassel-Duby Rhonda , Olson Eric N. , Liu Ning 
Published: August 2018

Significance
Adult mammalian hearts have limited self-renewal capacity. Although mounting evidence indicates that new cardiomyocytes are derived from dedifferentiation and proliferation of existing cardiomyocytes, the contribution of adult cardiac progenitors to cardiomyocyte renewal during homeostasis and upon injury remains under debate. The basic helix–loop–helix transcription factor Twist2 is expressed in interstitial cells in the adult myocardium. Using genetic lineage tracing, we identified a Twist2-expressing cell population that gives rise to a small number of adult cardiomyocytes in vivo. These Twist2-expressing cells can differentiate into cardiomyocytes, endothelial cells, and fibroblasts in culture and contribute to cardiac renewal through cell fusion and de novo differentiation. Our findings add Twist2-expressing cells to the cellular constituents involved in adult cardiac maintenance and remodeling.
Auto-fatty acylation of transcription factor RFX3 regulates ciliogenesis
Authors: Chen Baoen , Niu Jixiao , Kreuzer Johannes , Zheng Baohui , Jarugumilli Gopala K. , Haas Wilhelm , Wu Xu 
Published: August 2018

SignificanceRegulatory Factor X 3 (RFX3) is one of the key transcription factors involved in cilia formation and functions. Our study reveals that auto-fatty acylation is a critical regulatory mechanism for RFX3 transcriptional activities. Fatty acylation of RFX3 is required for its dimerization, leading to transcription of cilia-associated genes. More importantly, fatty acylation of RFX3 regulates ciliogenesis and Hedgehog signaling pathways, which are associated with developmental and degenerative disorders known as ciliopathies. Our results indicate a major role of auto-fatty acylation in the regulation of RFX3 function and ciliogenesis, providing a potential link between deregulation of fatty acid metabolism to ciliopathies and diabetes.
Transfer RNA genes experience exceptionally elevated mutation rates
Authors: Thornlow Bryan P. , Hough Josh , Roger Jacquelyn M. , Gong Henry , Lowe Todd M. , Corbett-Detig Russell B. 
Published: August 2018

Significance
While transcription-associated mutagenesis (TAM) has been demonstrated for protein-coding genes, its implications in shaping genome structure at transfer RNA (tRNA) loci in metazoans have not been fully appreciated. We show that cytosolic tRNAs are a striking example of TAM because of their variable rates of transcription, well-defined boundaries, and internal promoter sequences. tRNA loci have a mutation rate approximately 7- to 10-fold greater than the genome-wide average, and these mutations are consistent with signatures of TAM. These observations indicate that tRNA loci are disproportionately large contributors to mutational load in the human genome. Furthermore, the correlations between tRNA locus variation and transcription indicate that prediction of tRNA gene expression based on sequence variation data is possible.
Bistable emergence of oscillations in growing
Bacillus subtilis
biofilms
Authors: Martinez-Corral Rosa , Liu Jintao , Süel Gürol M. , Garcia-Ojalvo Jordi 
Published: August 2018

Significance
Cell communities can become resilient to stress by undergoing collective growth oscillations, which provide periodic stress relief and are collective in the sense that they arise only for large enough numbers of cells. Collective oscillatory phenomena usually emerge continuously as the system size increases, with oscillations starting with small amplitude and slowly growing as the cells proliferate. This behavior, however, is not appropriate in situations in which the population needs to implement a full-sized response quickly. Our combined theoretical and experimental study shows that collective oscillations in bacterial biofilm communities emerge via a discontinuous transition as their size increases. This behavior may provide an evolutionary advantage to cell communities, by allowing them to quickly alter qualitatively their dynamics in response to variations in external conditions such as stress.
Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector
Authors: Cideciyan Artur V. , Sudharsan Raghavi , Dufour Valérie L. , Massengill Michael T. , Iwabe Simone , Swider Malgorzata , Lisi Brianna , Sumaroka Alexander , Marinho Luis Felipe , Appelbaum Tatyana , Rossmiller Brian , Hauswirth William W. , Jacobson Samuel G. , Lewin Alfred S. , Aguirre Gustavo D. , Beltran William A. 
Published: August 2018

Significance
A number of gene-augmentation strategies are entering clinical trials for the treatment of inherited retinal blindness. Gene therapy for autosomal dominant diseases faces significant obstacles that include allelic heterogeneity and the potential need to silence the mutated gene. Here we show that a single-gene therapy vector that combines knockdown of the causative gene with its replacement by a resistant wild-type copy can prevent photoreceptor cell death and vision loss in a canine model of autosomal dominant retinitis pigmentosa.
Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa
Authors: Vonaesch Pascale , Morien Evan , Andrianonimiadana Lova , Sanke Hugues , Mbecko Jean-Robert , Huus Kelsey E. , Naharimanananirina Tanteliniaina , Gondje Bolmbaye Privat , Nigatoloum Synthia Nazita , Vondo Sonia Sandrine , Kaleb Kandou Jepthé Estimé , Randremanana Rindra , Rakotondrainipiana Maheninasy , Mazel Florent , Djorie Serge Ghislain , Gody Jean-Chrysostome , Finlay B. Brett , Rubbo Pierre-Alain , Wegener Parfrey Laura , Collard Jean-Marc , Sansonetti Philippe J. ,   The Afribiota Investigators, Andriatahirintsoa Emilson Jean , Barbot-Trystram Laurence , Barouki Robert , Bastaraud Alexandra , Collard Jean-Marc , Doria Maria , Duffy Darragh , Etienne Aurélie , Finlay B. Brett , Djorie Serge Ghislain , Giles-Vernick Tamara , Gody Jean-Chrysostome , Hasan Milena , Héraud Jean-Michel , Huetz François , Hunald Francis Allan , Kapel Nathalie , Lombart Jean-Pierre , Manirakiza Alexandre , Nigatoloum Synthia Nazita , Novault Sophie , Wegener-Parfrey Laura , Raharimalala Lisette , Rakotondrainipiana Maheninasy , Randremanana Rindra , Randriamizao Harifetra Mamy Richard , Randrianirina Frédérique , Robinson Annick , Rubbo Pierre-Alain , Sansonetti Philippe , Schaeffer Laura , Gouandjika-Vassilache Ionela , Vonaesch Pascale , Vondo Sonia Sandrine , Vigan-Womas Inès 
Published: August 2018

Significance
Stunting globally affects an estimated 155 million children under 5 years of age, representing about 25% of children worldwide. Due to poor understanding of the underlying pathophysiology, therapeutic interventions to efficiently correct for linear growth delay or associated pathophysiological disturbances are still lacking. Here, we describe the microbial composition of duodenal fluids from stunted children. We show that these children are affected by small intestinal bacterial overgrowth and harbor a characteristic microbial community composed mainly of oropharyngeal bacteria. This microbial signature is also reflected in their feces and conserved between countries. Stunting is traditionally considered to arise from recurrent enteric infections. This study shows that oropharyngeal taxa are associated with stunting, suggesting that alternative pathophysiological mechanisms are involved.
Gelation of plasmonic metal oxide nanocrystals by polymer-induced depletion attractions
Authors: Saez Cabezas Camila A. , Ong Gary K. , Jadrich Ryan B. , Lindquist Beth A. , Agrawal Ankit , Truskett Thomas M. , Milliron Delia J. 
Published: August 2018

Significance
Self-supported gelation of optically active nanocrystals offers a modular pathway to harness optoelectronic functionality in multiscale materials by directly controlling volume fraction, bonding, and structure during assembly. We combine depletion attractions that emerge from the incorporation of small polymer chains and electrostatic repulsions to induce the gelation of isotropic metal oxide nanocrystals. We develop a theoretical model to assess our experimental fluid-to-gel-phase progression observations. By preventing nanocrystal fusion during network assembly, we achieve gels with a strong near-infrared absorption, reminiscent of the inherent near-infrared localized surface plasmon resonance of the nanocrystal building blocks.
Selective permeability of mouse blood-aqueous barrier as determined by
15
N-heavy isotope tracing and mass spectrometry
Authors: Liu Pan , Thomson Benjamin R. , Khalatyan Natalia , Feng Liang , Liu Xiaorong , Savas Jeffrey N. , Quaggin Susan E. , Jin Jing 
Published: August 2018

Significance
The aqueous fluid of the eye is composed of proteins from both blood circulation and ocular production. The main filter between the blood bed and the intraocular fluid is referred to as the blood-aqueous barrier. Here we devised an approach to address the selectivity of the barrier using nitrogen-15–labeled serum proteins as tracers. Following systemic injection of the labeled serum to normal nitrogen-14 mice, the labeled proteins subsequently entered the aqueous fluid and were measured by mass spectrometry. This new quantitative method captured the dynamic redistribution patterns of approximately 500 serum proteins entering normal eye and the eye recovering from injury. We discovered inhibitory complement proteins crossed the blood-ocular barrier of the wounded eye but not of the normal eye.
Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles
Authors: Guo Shang‐Chun , Tao Shi‐Cong , Dawn Helen 
Published: August 2018

ABSTRACTExtracellular vesicles (EVs), which can be found in almost all body fluids, consist of a lipid bilayer enclosing proteins and nucleic acids from their cells of origin. EVs can transport their cargo to target cells and have therefore emerged as key players in intercellular communication. Their potential as either diagnostic and prognostic biomarkers or therapeutic drug delivery systems (DDSs) has generated considerable interest in recent years. However, conventional methods used to study EVs still have significant limitations including the time‐consuming and low throughput techniques required, while at the same time the demand for better research tools is getting stronger and stronger. In the past few years, microfluidics‐based technologies have gradually emerged and have come to play an essential role in the isolation, detection and analysis of EVs. Such technologies have several advantages, including low cost, low sample volumes, high throughput and precision. This review summarizes recent advances in microfluidics‐based technologies, compares conventional and microfluidics‐based technologies, and includes a brief survey of recent progress towards integrated “on‐a‐chip” systems. In addition, this review also discusses the potential clinical applications of “on‐a‐chip” systems, including both “liquid biopsies” for personalized medicine and DDS devices for precision medicine, and then anticipates the possible future participation of cloud‐based portable disease diagnosis and monitoring systems, possibly with the participation of artificial intelligence (AI).
Preclinical development of anti-BCMA immunotoxins targeting multiple myeloma
Authors: Shancer Zoe , Williams Matthew , Igelman Austin , Nagata Satoshi , Ise Tomoko , Pastan Ira , Bera Tapan K 
Published: August 2018

ABSTRACT

Background
Multiple myeloma (MM) is a B-cell malignancy that is incurable for the majority of patients. New treatments are urgently needed. Recombinant immunotoxins (RITs) are chimeric proteins that are composed of the Fv or Fab portion of an antibody fused to a bacterial toxin. B-cell maturation antigen (BCMA) is a lineage-restricted differentiation protein and an ideal target for antibody-based treatments for MM.

Methods
RITs were produced by expressing plasmids encoding the components of the anti-BCMA RITs in Escherichia coli followed by inclusion body preparation, solubilization, renaturation, and purification by column chromatography. The cytotoxic activity of RITs was tested in vitro by WST-8 assays. We also measured their binding to human and mouse serum albumins and to BCMA and measured their serum half-life in mice.

Results
Using Fvs from different anti-BCMA antibodies, we produced RITs that specifically kill BCMA-expressing MM cells in vitro. To increase the serum half-life in vivo, we generated RITs that are fused with albumin-binding domains (ABDs). All RITs with ABDs have some decreased activity compared to the parent RIT, which is not due to decreased binding to BCMA.

Conclusions
Various new anti-BCMA immunotoxins were produced and evaluated. None of these were better than LMB-75 (anti-BCMA BM306-disulfide-stabilized Fv-LRggs) supporting the further preclinical development of LMB-75.
Bystander inhibition of humoral immune responses by Epstein–Barr virus LMP1
Authors: Tsai Chao-Yuan , Sakakibara Shuhei , Yasui Teruhito , Minamitani Takeharu , Okuzaki Daisuke , Kikutani Hitoshi 
Published: August 2018

Abstract
Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (LMP1), which mimics a constitutively active receptor, is required for viral transformation of primary B cells. LMP1 is expressed in EBV-infected germinal center (GC) B cells of immunocompetent individuals, suggesting that it may contribute to persistent EBV infection. In this study, we generated and analyzed mice that expressed LMP1 under the control of the CD19 or activation-induced cytidine deaminase (AID) promoter. Expression of LMP1 induced activation of B cells but severely inhibited their differentiation into antibody-secreting cells (ASCs) in vitro and GC B cells in vivo. LMP1-expressing (LMP1+) B cells not only suppressed the functions of wild-type (WT) B cells in in vitro co-culture, but also blocked differentiation of WT B cells into GC B cells and ASCs in immunized bone marrow chimeric mice. Microarray analysis revealed that the gene encoding indoleamine 2,3-dioxygenase 1 (IDO1), a major enzyme involved in the tryptophan metabolic process, was highly induced by LMP1. Either inhibition of IDO1 activity by methyl-l-tryptophan or knockout of Ido1 in LMP1+ B cells could rescue WT B cells from such suppression. IDO1-induced tryptophan consumption and production of tryptophan metabolites appeared to be responsible for inhibition of B-cell function. We conclude that LMP1 expression in antigen-committed B cells not only directly impairs GC B-cell differentiation, but also indirectly inhibits the functions of neighboring B cells, resulting in suppression of humoral immune responses. Such bystander inhibition by LMP1+ B cells may contribute to immune evasion by EBV.
Neurological paraneoplastic syndromes: an update
Authors: Berzero Giulia , Psimaras Dimitri 
Published: August 2018

Purpose of review
To describe recent advances in the diagnosis and treatment of paraneoplastic neurological syndromes (PNS).

Recent findings
PNS are rare complications of cancer caused by an immune cross-reaction between antigens expressed by tumor cells and neurons. The target of the immune attack can be an intracellular antigen or a cell-surface antigen. Although both types of autoimmunity are ‘paraneoplastic’, as indirectly triggered by the presence of a tumor, they profoundly differ in terms of clinical profile, pathogenesis and outcome. PNS associated with antibodies to intracellular antigens (icPNS) are characterized by relentless progression and poor response to treatment, because of rapid and permanent neuronal loss. PNS associated with antibodies to cell-surface antigens (csPNS) generally show favorable response to immune therapy and good functional outcome, as they result from reversible neuronal dysfunction.

Summary
The spectrum of paraneoplastic autoimmunity has dramatically expanded following the discovery of cell-surface antibodies. Novel antibodies are incessantly discovered, some of which have a solid association with cancer. As csPNS usually respond to immune therapy, the optimization of current treatment strategies should have high priority to improve therapeutic results and prevent relapses.
Congenital Myasthenic Syndrome: Spectrum of Mutations in an Indian Cohort
Authors: Selvam Pavalan , Arunachal Gautham , Danda Sumita , Chapla Aaron , Sivadasan Ajith , Alexander Mathew , Thomas Maya Mary , Thomas Nihal J. 
Published: August 2018

Objectives:
To investigate the mutational spectrum and genotype–phenotype correlation in Indian patients with congenital myasthenic syndrome (CMS), using next-generation sequencing of 5 genes.

Methods:

CHRNE, COLQ, DOK7, RAPSN, and GFPT1 were sequenced in 25 affected patients.

Results:
We found clinically significant variants in 18 patients, of which variants in CHRNE were the most common, and 9 were novel. A common pathogenic COLQ variant was also detected in 4 patients with isolated limb-girdle congenital myasthenia.

Conclusions:
Targeted screening of 5 genes is an effective alternate test for CMS, and an affordable one even in a developing country such as India. In addition, we recommend that patients with isolated limb-girdle congenital myasthenia be screened initially for the common COLQ pathogenic variant. This study throws the first light on the genetic landscape of CMSs in India.
Evaluation of Anterior and Posterior Corneal Irregularity After Descemet Membrane Endothelial Keratoplasty
Authors: Oyakawa Itaru , Hayashi Takahiko , Kobashigawa Yuji , Matsuzawa Akiko , Takahashi Hidenori , Kato Naoko 
Published: August 2018

Purpose:
To investigate the changes in anterior and posterior corneal irregularity after Descemet membrane endothelial keratoplasty (DMEK).

Methods:
This retrospective study included 27 eyes of 23 patients who underwent DMEK and 27 eyes of age-matched healthy controls. Corneal irregularity indexes, surface regularity of height (SR_H), and higher-order aberrations were evaluated in 4- and 6-mm diameters of the cornea, preoperatively and postoperatively, using anterior segment optical coherence tomography.

Results:
The best spectacle-corrected visual acuity (logarithm of the minimum angle of resolution) improved from 1.01 ± 0.54 preoperatively to 0.08 ± 0.11 at 6 months postoperatively. Anterior SR_H was significantly lower at 6 months postoperatively [from 1.86 ± 0.73 to 1.20 ± 0.34 (P < 0.01) (4-mm) and from 2.29 ± 0.62 to 1.64 ± 0.42 (P < 0.01) (6-mm)]. Posterior SR_H showed a significant decrease from 6.87 ± 4.19 to 2.18 ± 0.51 (4-mm) and from 5.21 ± 2.60 to 2.44 ± 0.38 (6-mm) at 6 months postoperatively (P < 0.001). The SR_H was positively correlated with best spectacle-corrected visual acuity (anterior 4 mm: R = 0.524; anterior 6 mm: R = 0.477; posterior 4 mm: R = 0.655; posterior 6 mm: R = 0.655, P < 0.001) and with higher-order aberrations for 4-mm and 6-mm diameters (R = 0.511 and R = 0.325, P < 0.001, respectively).

Conclusions:
The SR_H reflects corneal irregularity and is correlated with the visual outcome after DMEK, which may be very helpful to corneal surgeons as an index indicating the severity before DMEK, and the quality of visual function after DMEK.