bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of new β-lactamase inhibitors in gram-negative infections
Authors: Vena Antonio , Castaldo Nadia , Bassetti Matteo 
Published: October 2019

Purpose of review
In recent years, traditional β-lactams have dramatically reduced their effectiveness against gram-negative bacteria mainly because of their ability to express multiple β-lactamase or carabapenemases that are not hydrolyzed by the old β-lactam inhibitors (BLIs) such as clavulanic acid, tazobactam, and sulbactam. New BLIs molecules have been developed to face the need of compounds that are active against multidrug or pandrug resistant gram-negative pathogens. The aim of this review is to summarize the new generation of BLIs and β-lactams combinations.

Recent findings
A number of new molecules with activity against Ambler class A (e.g., extended-spectrum β-lactamases, serine carbapenemases), class C (e.g., AmpC), or class D (e.g., oxacillinase-48) have been recently approved in combination with old β-lactams for the treatment of multidrug-resistant bacteria, and other agents are under investigation. These new compounds include diazabicyclooctanones non-β-lactam inhibitors (e.g., avibactam, relebactam, nacubactam) and boronic acid inhibitors (e.g., vaborbactam).

Summary
Newly approved and investigational new BLIs are expected to offer many advantages for the management of patients with multidrug-resistant gram-negative pathogens. Promising characteristics of new compounds include high activity against multi drug resistance gram-negative bacteria and a favorable safety profile.
In Vivo Assessment of Tau Deposition in Alzheimer Disease and Assessing Its Relationship to Regional Brain Glucose Metabolism and Cognition
Authors: Baghel Vivek , Tripathi Madhavi , Parida Girish , Gupta Ravikant , Yadav Saroj , Kumar Praveen , Dey A.B. , Damle Nishikant Avinash , Kumar Rajeev , Bal Chandrasekhar 
Published: October 2019

Aim
In this study, we investigated the relationship of cerebral tau deposition (18F-tau-AD-ML 104 PET/CT) with glucose metabolism (18F-FDG PET/CT) and cognitive function in patients with Alzheimer disease (AD).

Patients and Methods
Seventy subjects (Mini Mental State Examination [MMSE] score <18 = 37 [AD]; MMSE score, 18–24 = 16 [early AD]) and 17 controls were included in this study. All participants underwent detailed neurological and neuropsychological evaluation, followed by 18F-tau-AD-ML 104 and 18F-FDG PET/CT imaging. Region-wise SUVmax ratios at 50 to 60 minutes postinjection were calculated for 18F-tau-AD-ML 104 and 18F-FDG, using the cerebellar cortex as the reference region. Linear models were used to investigate the association of regional 18F-tau-AD-ML 104 retention with 18F-FDG uptake and cognition (MMSE scores).

Results

18F-Tau-AD-ML 104 retention was observed in the parietal lobe, temporal lobe, hippocampus, parahippocampus, frontal lobe, anterior and posterior cingulate, and precuneus in advanced and early AD patient as compared with normal controls with regional hypometabolism in overlapping regions on 18F-FDG PET. Significant negative association was found between 18F-tau-AD-ML 104 regional retention and glucose metabolism in the parietal lobe, temporal lobe, hippocampus, parahippocampus, frontal lobe, anterior and posterior cingulate, and precuneus among patients with advanced and early AD. In advanced and early AD patients, a negative association was found between 18F-tau-AD-ML 104 regional retention (precuneus) and cognition (MMSE score), whereas a positive association was observed between 18F-FDG regional uptake (precuneus) and cognition (MMSE score).

Conclusions
Tau pathology overlapped with areas of hypometabolism on FDG PET in the brains of AD patients. Tau deposition was found to have negative association with cognitive scores in these patients.
Dual-Energy Computed Tomography in Thoracic Imaging—Current Practices and Utility
Authors: Rajiah Prabhakar 
Published: October 2019

Purpose:
The purpose of this study was to determine the current practice patterns of utilization of dual-energy computed tomography (DECT) in thoracic imaging.

Materials and Methods:
In this IRB-approved study, the URL link for an anonymous 26-question survey was sent by email to all the members of the Society of Thoracic Radiology (STR). Survey questions focused on the practice type, case volume, DECT scanner availability, common indications, image types, and perceived utility of DECT. Study data were collected and managed using SurveyMonkey tools and analyzed with χ2 tests.

Results:
The survey response rate was 11% (104/962). DECT was available in 75% of respondents’ institutions, with 90% of these having 1 to 5 DECT scanners (P<0.001). Seventy percent performed 1 to 500 DECT chest CTs per month (P<0.001). Dual-source was the most common DECT scanner (81%) (P=0.239). DECT was opted depending on the clinical indication in 89% (P=0.433). The technologist reconstructs the additional DECT images in 75% of instances (P<0.001). Acute pulmonary embolism (PE) was the most common indication of DECT (53%) (P=0.006), while chronic PE was considered the most valuable use of DECT (33%) (P<0.001). Iodine map was the most commonly used DECT image (53%) (P<0.001) followed by low-energy virtual monoenergetic image (VMI) (29%). For VMI, 50 keV was the most commonly used energy level for improving vascular contrast (43%) (P=0.048), whereas 120 keV was the most commonly used energy in VMI for decreasing artifacts (25%) (P=0.027).

Conclusions:
There is wide variability on the utilization of DECT in thoracic imaging. PE is perceived to be the most valuable utility of DECT, and iodine map is considered the most valuable DECT image.
Modified Bilateral Pi Craniectomy Technique for Reduction Cranioplasty: Novel Technique
Authors: Abuzayed Bashar , Alawneh Khaled , Qawasmeh Majdi A.L. , Raffee Liqaa 
Published: October 2019

Objective:
Severe hydrocephalic macrocephaly can cause significant morbidity in infants due to positioning difficulties, skin breakdown, and poor cosmesis. Many surgeons over the past decades have described a variety of surgical techniques of reduction cranioplasty. In this article, the authors describe a novel technique for skull reduction cranioplasty with modified bilateral Pi craniectomy.

Methods:
Anterior coronal and posterior lambdoid bone cuts are performed to extend inferiorly toward the sqamous bone. Last bone cuts are made connecting the parasagittal burr holes bilaterally, thus isolating and de-roofing of the sagittal suture. Bilateral peninsular bone flaps are reduced medially aiming to approximate the upper borders of both flaps. Edges of frontal and occipital bone can be resected and shaved to achieve smooth round contour of the reconstruct. The final reconstruct can be fixated with metal meshes.

Results:
In our technique, modified bilateral Pi craniectomy is simple and effective reduction cranioplasty technique, as the technique does not require bone graft resection and reconstruction of the grafts making the time of the surgery short with decreased possible complications. Also, the amount of bone resection, bone bending, and shaving of the bone edges can be controlled and adjusted during the. An important issue is that this technique avoids posterior skull reconstruction which is more risky, as many patients are bed ridden with secondary compressed and flat occiput.

Conclusions:
Modified bilateral Pi craniectomy is a simple and effective technique for cranial vault reduction, especially in flat-occiput cases. Good understanding of the structural abnormality and the pathophysiological mechanisms of the possible complications is very important for performing proper surgical reconstruction.
Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data
Authors: Chen Xiao , Sanchis-Juan Alba , French Courtney E , Connell Andrew J , Delon Isabelle , Kingsbury Zoya , Chawla Aditi , Halpern Aaron L , Taft Ryan J ,   NIHR BioResource, Bentley David R , Butchbach Matthew ER , Raymond F Lucy , Eberle Michael A 
Published: October 2019

AbstractPurposeSpinal muscular atrophy (SMA), caused by loss of the SMN1 gene, is a leading cause of early childhood death. Due to the near identical sequences of SMN1 and SMN2, analysis of this region is challenging. Population-wide SMA screening to quantify the SMN1 copy number (CN) is recommended by the American College of Medical Genetics.MethodsWe developed a method that accurately identifies the CN of SMN1 and SMN2 using genome sequencing (GS) data by analyzing read depth and eight informative reference genome differences between SMN1/2.ResultsWe characterized SMN1/2 in 12,747 genomes, identified 1568 samples with SMN1 gains or losses and 6615 samples with SMN2 gains or losses and calculated a pan-ethnic carrier frequency of 2%, consistent with previous studies. Additionally, 99.8% of our SMN1 and 99.7% of SMN2 CN calls agreed with orthogonal methods, with a recall of 100% for SMA and 97.8% for carriers, and a precision of 100% for both SMA and carriers.ConclusionThis SMN copy number caller can be used to identify both carrier and affected status of SMA, enabling SMA testing to be offered as a comprehensive test in neonatal care and an accurate carrier screening tool in GS sequencing projects.
Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development
Authors: Lu Yufeng , Shiau Fion , Yi Wenyang , Lu Suying , Wu Qian , Pearson Joel D. , Kallman Alyssa , Zhong Suijuan , Hoang Thanh , Zuo Zhentao , Zhao Fangqi , Zhang Mei , Tsai Nicole , Zhuo Yan , He Sheng , Zhang Jun , Stein-O’Brien Genevieve L. , Sherman Thomas D. , Duan Xin , Fertig Elana J. , Goff Loyal A. , Zack Donald J. , Handa James T. , Xue Tian , Bremner Rod , Blackshaw Seth , Wang Xiaoqun , Clark Brian S. 
Published: October 2019

SummaryThe development of single-cell RNA-Sequencing (scRNA-Seq) has allowed high resolution analysis of cell type diversity and transcriptional networks controlling cell fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-Seq over retinal organoid andin vivoretinal development, across 20 timepoints. Using both pseudotemporal and cross-species analyses, we examined the conservation of gene expression across retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we examined gene expression differences between developing macula and periphery and between two distinct populations of horizontal cells. We also identify both shared and species-specific patterns of gene expression during human and mouse retinal development. Finally, we identify an unexpected role forATOH7expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development, and may help guide the design of cell-based therapies for treating retinal dystrophies.
Impaired Efflux of the Siderophore Enterobactin Induces Envelope Stress inEscherichia coli
Authors: Guest Randi L. , Court Emily A. , Waldon Jayne L. , Schock Kiersten A. , Raivio Tracy L. 
Published: October 2019

AbstractThe Cpx response is one of several envelope stress responses that monitor and maintain the integrity of the gram-negative bacterial envelope. While several conditions that are known or predicted to generate misfolded inner membrane proteins activate the Cpx response, the molecular nature of the Cpx inducing cue is not yet known. Studies have demonstrated that mutation of multidrug efflux pumps activates the Cpx response in many gram-negative bacteria. InVibrio cholerae, pathway activation is due to accumulation of the catechol siderophore vibriobactin. However, the mechanism by which the Cpx response is activated by mutation of efflux pumps inEscherichia coliremains unknown. Here we show that inhibition of efflux by deletion oftolC, the outer membrane channel of several multidrug efflux pumps, activates the Cpx response inE. colias a result of impaired efflux of the siderophore enterobactin. Enterobactin accumulation in thetolCmutant reduces activity of the NADH oxidation arm of the aerobic respiratory chain. However, NADH dehydrogenase I, NADH dehydrogenase II, and cytochromebo3do not contribute to Cpx pathway activation in theE. coli tolCmutant. We show that the Cpx response down-regulates transcription of the enterobactin biosynthesis operon. These results suggest that the Cpx response promotes adaptation to envelope stress in enteric bacteria that are exposed to iron-limited environments, which are rich in envelope-damaging compounds and conditions.
G-OnRamp: Generating genome browsers to facilitate undergraduate-driven collaborative genome annotation
Authors: Sargent Luke , Liu Yating , Leung Wilson , Mortimer Nathan T. , Lopatto David , Goecks Jeremy , Elgin Sarah C. R. 
Published: October 2019

AbstractScientists are sequencing new genomes at an increasing rate with the goal of associating genome contents with phenotypic traits. After a new genome is sequenced and assembled, structural gene annotation is often the first step in analysis. Despite advances in computational gene prediction algorithms, most eukaryotic genomes still benefit from manual gene annotation. Undergraduates can become skilled annotators, and in the process learn both about genes/genomes and about how to utilize large datasets. Data visualizations provided by a genome browser are essential for manual gene annotation, enabling annotators to quickly evaluate multiple lines of evidence (e.g., sequence similarity, RNA-Seq, gene predictions, repeats). However, creating genome browsers requires extensive computational skills; lack of the expertise required remains a major barrier for many biomedical researchers and educators.To address these challenges, the Genomics Education Partnership (GEP;https://gep.wustl.edu/) has partnered with the Galaxy Project (https://galaxyproject.org) to develop G-OnRamp (http://g-onramp.org), a web-based platform for creating UCSC Assembly Hubs and JBrowse genome browsers. G-OnRamp can also convert a JBrowse instance into an Apollo instance for collaborative genome annotations in research and educational settings. G-OnRamp enables researchers to easily visualize their experimental results, educators to create Course-based Undergraduate Research Experiences (CUREs) centered on genome annotation, and students to participate in genomics research.Development of G-OnRamp was guided by extensive user feedback from in-person workshops. Sixty-five researchers and educators from over 40 institutions participated in these workshops, which produced over 20 genome browsers now available for research and education. For example, genome browsers for four parasitoid wasp species were used in a CURE engaging 142 students taught by 13 faculty members — producing a total of 192 gene models. G-OnRamp can be deployed on a personal computer or on cloud computing platforms, and the genome browsers produced can be transferred to the CyVerse Data Store for long-term access.
No genetic evidence for involvement of alcohol dehydrogenase genes in risk for Parkinson’s disease
Authors: Kim Jonggeol Jeffrey , Bandres-Ciga Sara , Blauwendraat Cornelis ,   International Parkinson’s Disease Genomics Consortium, Gan-Or Ziv 
Published: October 2019

AbstractMultiple genes have been implicated in Parkinson’s disease (PD), including causal gene variants and risk variants typically identified using genome-wide association studies (GWAS). Variants in the alcohol dehydrogenase genes ADH1C and ADH1B are among the genes that have been associated with PD, suggesting that this family of genes may be important in PD. As part of the International Parkinson’s Disease Genomics Consortium’s (IPDGC) efforts to scrutinize previously reported risk factors for PD, we explored genetic variation in the alcohol dehydrogenase genes ADH1A, ADH1B, ADH1C, ADH4, ADH5, ADH6, and ADH7 using imputed GWAS data from 15,097 cases and 17,337 healthy controls. Rare-variant association tests and single-variant score tests did not show any statistically significant association of alcohol dehydrogenase genetic variation with the risk for PD.
Natural image reconstruction from brain waves: a novel visual BCI system with native feedback
Authors: Rashkov Grigory , Bobe Anatoly , Fastovets Dmitry , Komarova Maria 
Published: October 2019

AbstractHere we hypothesize that observing the visual stimuli of different categories trigger distinct brain states that can be decoded from noninvasive EEG recordings. We introduce an effective closed-loop BCI system that reconstructs the observed or imagined stimuli images from the co-occurring brain wave parameters. The reconstructed images are presented to the subject as a visual feedback. The developed system is applicable to training BCI-naïve subjects because of the user-friendly and intuitive way the visual patterns are employed to modify the brain states.
Comprehensive palmitoyl-proteomic analysis identifies distinct protein signatures for large and small cancer-derived extracellular vesicles
Authors: Mariscal Javier , Vagner Tatyana , Kim Minhyung , Zhou Bo , Chin Andrew , Zandian Mandana , Freeman Michael R. , You Sungyong , Zijlstra Andries , Yang Wei , Vizio Dolores Di 
Published: October 2019

AbstractExtracellular vesicles (EVs) are membrane-enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. ProteinS-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L- and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.
A pair of esterases from a commensal gut bacterium remove acetylations from all positions on complex β-mannans
Authors: Michalak Leszek , La Rosa Sabina Leanti , Leivers Shaun Allan , Lindstad Lars Jordhøy , Kjendseth Åsmund Røhr , Aachmann Finn Lillelund , Westereng Bjørge 
Published: October 2019

Abstractβ-Mannans and xylans are important components of the plant cell wall and they are acetylated to be protected from degradation by glycoside hydrolases. β-Mannans are widely present in human and animal diets as fiber from leguminous plants and as thickeners and stabilizers in processed foods. There are many fully characterized acetylxylan esterases (AcXEs), however, the enzymes deacetylating mannans are less understood. Here we present two carbohydrate esterases, RiCE2 and RiCEX, from the Firmicute Roseburia intestinalis, which together deacetylate complex galactoglucomannan (GGM). The 3D-structure of RiCEX with a mannopentaose in the active site shows that the CBM35 domain of RiCEX forms a confined complex, where the axially oriented C2-hydroxyl of a mannose residue points towards the Ser41 of the catalytic triad. Cavities on the RiCEX surface may accept galactosylations at the C6 positions of mannose adjacent to the mannose residue being deacetylated (subsite −1 and +1). In depth characterization of the two enzymes using time-resolved NMR, HPLC and mass spectrometry demonstrates that they work in a complementary manner. RiCEX exclusively removes the axially oriented 2-O-acetylations on any mannose residue in an oligosaccharide, including double acetylated mannoses, while the RiCE2 is active on 3-O-, 4-O- and 6-O-acetylations. Activity of RiCE2 is dependent on RiCEX removing 2-O-acetylations from double acetylated mannose. Furthermore, transacetylation of oligosaccharides with the 2-O specific RiCEX provided new insight to how temperature and pH affects acetyl migration on mannooligosaccharides.Significance statementAcetylations are an important feature of hemicellulose, altering the physical properties of the plant cell wall, and limiting enzyme accessibility. Removal of acetyl groups from beta-mannan is a key step towards efficient utilization of mannans as a carbon source for gut microbiota and in biorefineries. We present detailed insight into mannan deacetylation by two highly substrate-specific acetyl-mannan esterases (AcMEs) from a prevalent gut commensal Firmicute, which cooperatively deacetylate complex galactoglucomannan. The 3D structure of RiCEX with mannopentaose in the active site has a unique two-domain architecture including a CBM35 and an SGNH superfamily hydrolytic domain. Discovery of mannan specific esterases improves the understanding of an important step in dietary fiber utilization by gut commensal Firmicutes.
Toxoplasmainduces stripping of perisomatic inhibitory synapses
Authors: Carrillo Gabriela L. , Ballard Valerie A. , Glausen Taylor , Boone Zack , Teamer Joseph , Hinkson Cyrus L. , Wohlfert Elizabeth A. , Blader Ira J. , Fox Michael A. 
Published: October 2019

ABSTRACTInfection and inflammation within the brain induces changes in neuronal connectivity and function. The intracellular protozoan parasite,Toxoplasma gondii, is one pathogen that infects the brain and can cause encephalitis and seizures. Persistent infection by this parasite is also associated with behavioral alterations and an increased risk for developing psychiatric illness, including schizophrenia. Current evidence from studies in humans and mouse models suggest that both seizures and schizophrenia result from a loss or dysfunction of inhibitory synapses. In line with this, we recently reported that persistentToxoplasma gondiiinfection alters the distribution of glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes GABA synthesis in inhibitory synapses. These changes could reflect a redistribution of presynaptic machinery in inhibitory neurons or a loss of inhibitory nerve terminals. To directly assess the latter possibility, we employed serial block face scanning electron microscopy (SBFSEM) and quantified inhibitory perisomatic synapses in neocortex and hippocampus following parasitic infection. Not only did persistent infection lead to a significant loss of perisomatic synapses, it induced the ensheathment of neuronal somata by phagocytic cells. Immunohistochemical, genetic, and ultrastructural analyses revealed that these phagocytic cells included reactive microglia. Finally, ultrastructural analysis identified phagocytic cells enveloping perisomatic nerve terminals, suggesting they may participate in synaptic stripping. Thus, these results suggest that microglia contribute to perisomatic inhibitory synapse loss following parasitic infection and offer a novel mechanism as to how persistentToxoplasma gondiiinfection may contribute to both seizures and psychiatric illness.MAIN POINTSToxoplasma-infection leads the loss of perisomatic inhibitory synapsesPhagocytic microglia ensheath neuronal somata followingToxoplasma-infectionMicroglia contact and envelop perisomatic nerve terminals, suggesting thatToxoplasmainduces synaptic stripping