bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Local Anesthesia Depth on Procedural Pain During Fluoroscopically Guided Lumbar Transforaminal Epidural Injections
Authors: Baek In Chan , Choi Su Youn , Suh Jiwoo , Kim Shin Hyung 
Published: August 2018

Objectives
The aim of the study was to evaluate the influence of the depth of local anesthesia application on procedural pain during lumbar transforaminal epidural steroid injection.

Design
Sixty-eight patients were enrolled who were scheduled for single-level, unilateral fluoroscopically guided lumbar transforaminal epidural steroid injection. Patients were randomly allocated to receive either subcutaneous local anesthesia (group S) or deep local anesthesia (group D) for transforaminal epidural steroid injection. The data related to pain and technical performance during the procedure was compared. In addition, the incidence of injection site soreness was assessed 2 wks after transforaminal epidural steroid injection.

Results
Sixty-seven patients completed all assessments (group S, n = 33; group D, n = 34). There was no significant difference in procedural pain and discomfort level between the groups (P = 0.151, P = 0.183, respectively). Patients in group D showed lower behavioral pain scores (P = 0.017). There was no significant difference in the numbers of needle manipulations, fluoroscopy time, and radiation dose during the procedure between the groups. Two patients in group S and three in group D complained of injection site soreness after transforaminal epidural steroid injection for a few days, but there was no significant difference in its incidence (P = 0.667).

Conclusions
Deep local anesthesia to reduce procedural pain during transforaminal epidural steroid injection seems to have no significant clinical benefit compared with conventional subcutaneous local anesthesia.

To Claim CME Credits
Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME

CME Objectives
Reduce procedural pain by considering clinical factors of the patient during fluoroscopically guided lumbar transforaminal epidural injections.
Upon completion of this article, the reader should be able to: (1) Understand the potential impact of procedural pain on the performance of transforaminal epidural steroid injections; (2) Distinguish cutaneous nociceptive afferents from nociceptive afferents in muscle; and (3) Explain the factors to reduce procedural pain during fluoroscopically guided lumbar transforaminal epidural injections.

Level
Advanced

Accreditation
The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Muscle Strength and Aerobic Capacity in HIV-Infected Patients: A Systematic Review and Meta-Analysis
Authors: Gomes-Neto Mansueto , Rodriguez Indira , Lédo Ana P. , Vieira João P. B. , Brites Carlos 
Published: August 2018

Background:
Physical impairment is highly prevalent in HIV-infected patients. We conducted a systematic review of published studies that included studies comparing muscle function in HIV-infected patients to matched healthy controls, and studies comparing aerobic capacity in HIV-infected patients with that observed in matched healthy controls.

Design:
Systematic review and meta-analysis.

Methods:
We searched for references on MEDLINE, SciELO, Cumulative Index to Nursing and Allied Health (CINAHL), and Scopus up to December 2017. Weighted mean differences and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test.

Results:
A total of 30 studies, covering 2148 healthy controls and 2161 HIV-infected patients, fulfilled the inclusion criteria. The average muscle strength and aerobic capacity were significantly lower in HIV-infected patients. Meta-analysis revealed moderate-quality evidence of weaker muscle strength and aerobic capacity in HIV-infected patients. A significant difference in lower-body strength of 1.07 (95% CI: 0.29 to 1.84) was found for participants in the healthy control group compared with HIV group. A significant difference in aerobic capacity (peak VO2) of 8.4 (95% CI: 4.8 to 12.0) was found for participants in the healthy control group compared with HIV group.

Conclusions:
Muscle strength and aerobic capacity of HIV-infected patients are reduced in comparison with healthy controls. Additional studies are needed to define the best interventions to improve the physical function in HIV-infected patients.
EBADIMEX: An empirical Bayes approach to detect joint differential expression and methylation and to classify samples
Authors: Madsen Tobias , Świtnicki Michał , Juul Malene , Pedersen Jakob Skou 
Published: August 2018

1AbstractDNA methylation and gene expression are interdependent and both implicated in cancer development and progression, with many individual biomarkers discovered. A joint analysis of the two data types can potentially lead to biological insights that are not discoverable with separate analyses. To optimally leverage the joint data for identifying perturbed genes and classifying clinical cancer samples, it is important to accurately model the interactions between the two data types.Here, we present EBADIMEX for jointly identifying differential expression and methylation and classifying samples. The moderated t-test widely used with empirical Bayes priors in current differential expression methods is generalised to a multivariate setting by developing: (1) a moderated Welch t-test for equality of means with unequal variances; (2) a moderated F-test for equality of variances; and (3) a multivariate test for equality of means with equal variances. This leads to parametric models with prior distributions for the parameters, which allow fast evaluation and robust analysis of small data sets.EBADIMEX is demonstrated on simulated data as well as a large breast cancer (BRCA) cohort from TCGA. We show that the use of empirical Bayes priors and moderated tests works particularly well on small data sets.
Repurposing of drugs as novel influenza inhibitors from clinical gene expression infection signatures
Authors: Pizzorno Andrés , Terrier Olivier , de Lamballerie Claire Nicolas , Julien Thomas , Padey Blandine , Traversier Aurélien , Roche Magali , Hamelin Marie-Eve , Rhéaume Chantal , Croze Séverine , Escuret Vanessa , Poissy Julien , Lina Bruno , Legras-Lachuer Catherine , Textoris Julien , Boivin Guy , Rosa-Calatrava Manuel 
Published: August 2018

AbstractBackground:Influenza virus infections remain a major and recurrent public health burden. The intrinsic ever-evolving nature of this virus, the suboptimal efficacy of current influenza inactivated vaccines, as well as the emergence of resistance against a limited antiviral arsenal, highlight the critical need for novel therapeutic approaches. In this context, the aim of this study was to develop and validate an innovative strategy for drug repurposing as host-targeted inhibitors of influenza viruses and the rapid evaluation of the most promising candidates in Phase II clinical trials.Methods:We exploitedin vivoglobal transcriptomic signatures of infection directly obtained from a patient cohort to determine a shortlist of already marketed drugs with newly identified, host-targeted inhibitory properties against influenza virus. The antiviral potential of selected repurposing candidates was further evaluatedin vitro, in vivoandex vivo.Results:Our strategy allowed the selection of a shortlist of 35 high potential candidates out of a rationalized computational screening of 1,309 FDA-approved bioactive molecules, 31 of which were validated for their significantin vitroantiviral activity. Ourin vivoandex vivoresults highlight diltiazem, a calcium channel blocker currently used in the treatment of hypertension, as a promising option for the treatment of influenza infections. Additionally, transcriptomic signature analysis further revealed the so far undescribed capacity of diltiazem to modulate the expression of specific genes related to the host antiviral response and cholesterol metabolism. Finally, combination treatment with diltiazem and virus-targeted oseltamivir neuraminidase inhibitor further increased antiviral efficacy, prompting rapid authorization for the initiation of a Phase II clinical trial.Conclusions:This original, host-targeted, drug repurposing strategy constitutes an effective and highly reactive process for the rapid identification of novel anti-infectious drugs, with potential major implications for the management of antimicrobial resistance and the rapid response to future epidemic or pandemic (re)emerging diseases for which we are still disarmed.
A unified model for microtubule rescue
Authors: Fees Colby P. , Moore Jeffrey K. 
Published: August 2018

AbstractHow microtubules transition from depolymerization to polymerization, known as rescue, is poorly understood. Here we examine two models for rescue: 1) an ‘end-driven’ model in which the depolymerizing end stochastically switches to a stable state; and 2) a ‘lattice-driven’ model in which rescue-sites are integrated into the microtubule prior to depolymerization. We test these models using a combination of computational simulations andin vitroexperiments with purified tubulin. Our findings support the ‘lattice-driven’ model by identifying repeated rescue sites in microtubules. In addition, we discover an important role for divalent cations in determining the frequency and location of rescue sites. We use ‘wash-in’ experiments to show that divalent cations inhibit rescue during depolymerization, but not during the polymerization. We propose a unified model in which rescues are driven by embedded rescue sites in microtubules, but the activity of these sites is influenced by changes in the depolymerizing ends.
The Emotional Glue of the Senses: Affective Certainty and Congruency in the Rubber Hand Illusion
Authors: Filippetti Maria Laura , Kirsch Louise P. , Crucianelli Laura , Fotopoulou Aikaterini 
Published: August 2018

AbstractOur sense of body ownership relies on integrating different sensations according to their temporal and spatial congruency. Nevertheless, there is ongoing controversy about the role ofaffective congruencyduring multisensory integration, i.e. whether the stimuli to be perceived by the different sensory channels are congruent or incongruent in terms of their affective quality. In the present study, we applied a widely used multisensory integration paradigm, the Rubber Hand Illusion, to investigate the role of affective, top-down aspects of sensory congruency between visual and tactile modalities in the sense of body ownership. In Experiment 1 (N = 36), we touched participants with either soft or rough fabrics in their unseen hand, while they watched a rubber hand been touched synchronously with the same fabric or with a ‘hidden’ fabric of ‘uncertain roughness’. In Experiment 2 (N = 50), we used the same paradigm as in Experiment 1, but replaced the ‘uncertainty’ condition with an ‘incongruent’ one, in which participants saw the rubber hand being touched with a fabric of incongruent roughness and hence opposite valence. We found that certainty (Experiment 1) and congruency (Experiment 2) between the felt and vicariously perceived tactile affectivity led to higher subjective embodiment compared to uncertainty and incongruency, respectively, irrespective of any valence effect. Our results suggest that congruency in the affective top-down aspects of sensory stimulation is important to the multisensory integration process leading to embodiment, over and above temporal and spatial properties.
A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites
Authors: Tang Yong , Meister Thomas R. , Walczak Marta , Pulkoski-Gross Michael J. , Hari Sanjay B. , Sauer Robert T. , Amberg-Johnson Katherine , Yeh Ellen 
Published: August 2018

SummaryEndosymbiosis has driven major molecular and cellular innovations.Plasmodiumspp. parasites that cause malaria contain an essential, non-photosynthetic plastid, the apicoplast, which originated from a secondary (eukaryote-eukaryote) endosymbiosis. To discover organellar pathways with evolutionary and biomedical significance, we performed a mutagenesis screen for essential genes required for apicoplast biogenesis inP. falciparum.Apicoplast-minusmutants were isolated using a chemical rescue that permits conditional disruption of the apicoplast and a new fluorescent reporter for organelle loss. Five candidate genes were validated (out of 12 identified), including a TIM-barrel protein that likely derived from a core metabolic enzyme but evolved a new activity. Our results demonstrate the first forward genetic screen to assign essential cellular functions to unannotatedP. falciparumgenes. A putative TIM-barrel enzyme and other newly-identified apicoplast biogenesis proteins open opportunities to discover new mechanisms of organelle biogenesis, molecular evolution underlying eukaryotic diversity, and drug targets against multiple parasitic diseases.
Aurora A inhibition limits centrosome clustering and promotes mitotic catastrophe in cells with supernumerary centrosomes
Authors: Navarro-Serer Bernat , Childers Eva P , Hermance Nicole M , Mercadante Dayna , Manning Amity L 
Published: August 2018

AbstractThe presence of supernumerary centrosomes is prevalent in cancer, where they promote the formation of transient multipolar mitotic spindles. Active clustering of supernumerary centrosomes enables the formation of a functional bipolar spindle that is competent to complete a bipolar division. Disruption of spindle pole clustering in cancer cells promotes multipolar division and generation of non-proliferative daughter cells with compromised viability. Hence molecular pathways required for spindle pole clustering in cells with supernumerary centrosomes, but dispensable in normal cells, are promising therapeutic targets. Here we demonstrate that Aurora A kinase activity is required for spindle pole clustering in cells with extra centrosomes. While cells with two centrosomes are ultimately able to build a bipolar spindle and proceed through a normal cell division in the presence of Aurora A inhibition, cells with supernumerary centrosomes form multipolar and disorganized spindles that are not competent for chromosome segregation. Instead, following a prolonged mitosis, these cells experience catastrophic divisions that result in grossly aneuploid, and non-proliferative daughter cells. Aurora A inhibition in a panel of Acute Myeloid Leukemia cancer cells has a similarly disparate impact on cells with supernumerary centrosomes, suggesting that centrosome number and spindle polarity may serve as predictive biomarkers for response to therapeutic approaches that target Aurora A kinase function.
Cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and antagonist for amylin fibrillation
Authors: Sahoo Bikash R. , Genjo Takuya , Stoddard Andrea K. , Yasuhara Kazuma , Fierke Carol A. , Ramamoorthy Ayyalusamy 
Published: August 2018

AbstractIn human, amyloid-beta (Aβ) and islet amyloid polypeptide (hIAPP) aggregations are linked to Alzheimer’s disease and Type-2 Diabetes, respectively. There is significant interest in better understanding the aggregation process by using chemical tools. Here, we show the ability of a cationic polymethacrylate-copolymer (PMAQA) to quickly induce β-hairpin structure and promote fibrillation in Aβ40, and to constrain the conformational plasticity of hIAPP for several days and inhibit its aggregation at sub-micromolar concentrations. NMR experiments and atomistic molecular dynamics simulations reveal that PMAQA electrostatically interacts with Aβ40’s Glu22 and Asp23 followed by β-sheet induction while it binds strongly to the closest proximity of amyloid core domain (NFGAIL) of hIAPP and restrain its structural rearrangement. This study provides a valuable approach to develop polymer-based anti-amyloid inhibitors that may diminish the population of intermediates of Aβ40 or hIAPP.
Parasite-mediated anorexia increases or decreases virulence evolution, depending on dietary context
Authors: Hite J. L. , Cressler C. E. 
Published: August 2018

AbstractParasite-mediated anorexia is a ubiquitous, but poorly understood component of host-parasite interactions. These temporary but substantial reductions in food intake (range: 4-100%) limit exposure to parasites and alter within-host physiological processes that regulate parasite development, production, and survival, such as energy allocation, immune function, host-microbiota interactions, and gastrointestinal conditions. By altering the duration, severity, and spread of infection, anorexia could substantially alter ecological, evolutionary, and epidemiological dynamics. However, these higher-order implications are typically overlooked and remain poorly understood — even though medical (e.g., non-steroidal anti-inflammatory drugs, vaccines, targeted signaling pathways, calorie restriction) and husbandry practices (e.g., antibiotic and diet use for rapid growth, nutrient supplementation) often directly or indirectly alter host appetite and nutrient intake. Here, we develop theory that helps elucidate why reduced food intake (anorexia) can enhance or diminish disease severity and illustrates that the population-level outcomes often contrast with the individual-level outcomes: treatments that increase the intake of high quality nutrients (suppressing anorexia), can drive rapid individual-level recovery, but inadvertently increase infection prevalence and select for more virulent parasites. Such a theory-guided approach offers a tool to improve targeting host nutrition to manage disease in both human and livestock populations by revealing a means to predict how nutrient-driven feedbacks will affect both the host and parasite.
SABER enables highly multiplexed and amplified detection of DNA and RNA in cells and tissues
Authors: Kishi Jocelyn Y. , Beliveau Brian J. , Lapan Sylvain W. , West Emma R. , Zhu Allen , Sasaki Hiroshi M. , Saka Sinem K. , Wang Yu , Cepko Constance L. , Yin Peng 
Published: August 2018

SUMMARYFluorescentin situhybridization (FISH) reveals the abun-dance and positioning of nucleic acid sequences in fixed sam-ples and can be combined with cell segmentation to produce a powerful single cell gene expression assay. However, it re-mains difficult to label more than a few targets and to visu-alize nucleic acids in environments such as thick tissue sam-ples using conventional FISH technologies. Recently, meth-ods have been developed for multiplexed amplification of FISH signals, yet it remains challenging to achieve high lev-els of simultaneous multiplexing combined with high sam-pling efficiency and simple workflows. Here, we introduce signal amplification by exchange reaction (SABER), which endows oligo-based FISH probes with long, single-stranded DNA concatemers that serve as targets for sensitive fluores-cent detection. We establish that SABER effectively ampli-fies the signal of probes targeting nucleic acids in fixed cells and tissues, can be deployed against at least 17 targets si-multaneously, and detects mRNAs with high efficiency. As a demonstration of the utility of SABER in assays involv-ing genetic manipulations, we apply multiplexed FISH of reporters and cell type markers to the identification of en-hancers with cell type-specific activity in the mouse retina. SABER represents a simple and versatile molecular toolkit to allow rapid and cost effective multiplexed imaging.
Enabling tools forToxoplasmaglycobiology
Authors: Gas-Pascual Elisabet , Ichikawa H. Travis , Sheikh M. Osman , Serji M. Isabella , Deng Bowen , Mandalasi Msano , Bandini Giulia , Samuelson John , Wells Lance , West Christopher M. 
Published: August 2018

ABSTRACTInfection by the protozoan parasiteToxoplasma gondiiis a major health risk owing to its chronic nature, ability to reactivate to cause blindness and encephalitis, and high prevalence in human populations. Like nearly all eukaryotes,Toxoplasmaglycosylates many of its proteins and lipids and assembles polysaccharides. Unlike most eukaryotes,Toxoplasmadivides and differentiates in vacuoles within host cells. While their glycans resemble canonical models, they exhibit species-specific variations that have inhibited deeper investigations into their roles in parasite biology and virulence. The genome ofToxoplasmaencodes a suite of likely glycogenes expected to assemble a range ofN-glycans,O-glycans, aC-glycan, GPI-anchors, and polysaccharides, along with their requisite precursors and membrane transporters. To facilitate genetic approaches to investigate the roles of specific glycans, we mapped probable connections between 59 glycogenes, their enzyme products, and the glycans to which they contribute. We adapted a double-CRISPR/Cas9 strategy and a mass spectrometry-based glycomics workflow to test these relationships, and conducted infection studies in fibroblast monolayers to probe cellular functions. Through the validated disruption of 17 glycogenes, we also discovered novel Glc0-2-Man6-GlcNAc2-type N-glycans, GalNAc2- and Glc-Fuc-type O-glycans, and a nuclear O-Fuc type glycan. We describe the guide sequences, disruption constructs, and mutant strains, which are freely available to practitioners for application in the context of the relational map to investigate the roles of glycans in their favorite biological processes.
CTP synthase regulation by miR-975 controls cell proliferation and differentiation inDrosophila melanogaster
Authors: Kan Woo Wai , Dzaki Najat , Azzam Ghows 
Published: August 2018

AbstractCTP synthase (CTPsyn) is an essential metabolic enzyme. As a key regulator of the nucleotide pool, the protein has been found to be elevated in cancer models. In many organisms, CTPsyn compartmentalizes into filaments termed cytoophidia. ForD. melanogaster, it is only its Isoform C i.e. CTPsynIsoC which forms the structure. The fruit fly’s testis is home to somatic and germline stem cells. Both micro and macro-cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located and development is at its most rapid. Here, we report thatCTPsynIsoCoverexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately one-third of like-genotyped males. Immunostaining shows that the cause of this tumour-like phenotype is most likely due to increased numbers of both germline cells and spermatocytes. We also report that under conditions wherebymiR-975is overexpressed, greater incidences of the same bulged-phenotype coincides with induced upregulation ofCTPsynIsoC.However, RT-qPCR assays reveal that either overexpression genotype provokes a differential response in expression of a number of genes concurrently associated with CTPsyn and cancer, showing that the pathwaysCTPsynIsoCaffect andmiR-975regulate may be completely independent of each other. This study presents the first instance of consequences of miRNA-asserted regulation uponCTPsyninD. melanogaster, and further reaffirms the enzyme’s close ties to cancer and carcinogenesis.