bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Unique
cis
-Encoded Small Noncoding RNA Is Regulating
Legionella pneumophila
Hfq Expression in a Life Cycle-Dependent Manner
Authors: Oliva Giulia , Sahr Tobias , Rolando Monica , Knoth Maike , Buchrieser Carmen 
Published: January 2017

ABSTRACT

Legionella pneumophila
is an environmental bacterium that parasitizes protozoa, but it may also infect humans, thereby causing a severe pneumonia called Legionnaires’ disease. To cycle between the environment and a eukaryotic host,
L. pneumophila
is regulating the expression of virulence factors in a life cycle-dependent manner: replicating bacteria do not express virulence factors, whereas transmissive bacteria are highly motile and infective. Here we show that Hfq is an important regulator in this network. Hfq is highly expressed in transmissive bacteria but is expressed at very low levels in replicating bacteria. A
L. pneumophila hfq
deletion mutant exhibits reduced abilities to infect and multiply in
Acanthamoeba castellanii
at environmental temperatures. The life cycle-dependent regulation of Hfq expression depends on a unique
cis
-encoded small RNA named Anti-hfq that is transcribed antisense of the
hfq
transcript and overlaps its 5′ untranslated region. The Anti-hfq sRNA is highly expressed only in replicating
L. pneumophila
where it regulates
hfq
expression through binding to the complementary regions of the
hfq
transcripts. This results in reduced Hfq protein levels in exponentially growing cells. Both the small noncoding RNA (sRNA) and
hfq
mRNA are bound and stabilized by the Hfq protein, likely leading to the cleavage of the RNA duplex by the endoribonuclease RNase III. In contrast, after the switch to transmissive bacteria, the sRNA is not expressed, allowing now an efficient expression of the
hfq
gene and consequently Hfq. Our results place Hfq and its newly identified sRNA anti-
hfq
in the center of the regulatory network governing
L. pneumophila
differentiation from nonvirulent to virulent bacteria.

IMPORTANCE
The abilities of
L. pneumophila
to replicate intracellularly and to cause disease depend on its capacity to adapt to different extra- and intracellular environmental conditions. Therefore, a timely and fine-tuned expression of virulence factors and adaptation traits is crucial. Yet, the regulatory circuits governing the life cycle of
L. pneumophila
from replicating to virulent bacteria are only partly uncovered. Here we show that the life cycle-dependent regulation of the RNA chaperone Hfq relies on a small regulatory RNA encoded antisense to the
hfq
-encoding gene through a base pairing mechanism. Furthermore, Hfq regulates its own expression in an autoregulatory loop. The discovery of this RNA regulatory mechanism in
L. pneumophila
is an important step forward in the understanding of how the switch from inoffensive, replicating to highly virulent, transmissive
L. pneumophila
is regulated.
Effectiveness of a lumbopelvic monitor and feedback device to change postural behaviour: a protocol for the ELF cluster randomised controlled trial
Authors: Ribeiro Daniel Cury , Milosavljevic Stephan , Abbott J Haxby 
Published: January 2017

IntroductionLow back pain (LBP) is the most common, costly and disabling musculoskeletal disorder worldwide, and is prevalent in healthcare workers. Posture is a modifiable risk factor for LBP shown to reduce the prevalence of LBP. Our feasibility research suggests that postural feedback might help healthcare workers avoid hazardous postures. The Effectiveness of Lumbopelvic Feedback (ELF) trial will investigate the extent to which postural monitor and feedback (PMF) can reduce exposure to hazardous posture associated with LBP.MethodsThis is a participant-blinded, randomised controlled trial with blocked cluster random allocation. Participants will include volunteer healthcare workers recruited from aged care institutions and hospitals. A postural monitoring and feedback device will monitor and record lumbopelvic forward bending posture, and provide audio feedback whenever the user sustains a lumbopelvic forward bending posture that exceeds predefined thresholds. The primary outcome measure will be postural behaviour (exceeding thresholds). Secondary outcome measures will be incidence of LBP, participant-reported disability and adherence. Following baseline assessment, we will randomly assign participants to 1 of 2 intervention arms: a feedback group and a no-feedback control group. We will compare between-group differences of changes in postural behaviour by using a repeated measures mixed-effect model analysis of covariance (ANCOVA) at 6 weeks. Postural behaviour baseline scores, work-related psychosocial factors and disability scores will be input as covariates into the statistical models. We will use logistic mixed model analysis and Cox's proportional hazards for assessing the effect of a PMF on LBP incidence between groups.DiscussionPosture is a modifiable risk factor for low back disorders. Findings from the ELF trial will inform the design of future clinical trials assessing the effectiveness of wearable technology on minimising hazardous posture during daily living activities in patients with low back disorders.Trial registration numberACTRN12616000449437.
Accuracy of transbronchial biopsy as a rebiopsy method for patients with relapse of advanced non-small-cell lung cancer after systemic chemotherapy
Authors: Ishii Hidenobu , Azuma Koichi , Yamada Kazuhiko , Matsuo Norikazu , Nakamura Masayuki , Tokito Takaaki , Kinoshita Takashi , Hoshino Tomoaki 
Published: January 2017

IntroductionRebiopsy in patients with advanced non-small-cell lung cancer (NSCLC) resistant to systemic chemotherapy may yield information on the mechanisms of resistance and planning of subsequent treatment. Transbronchial biopsy (TBB) using a flexible bronchoscope has been commonly used for establishing the initial diagnosis of lung cancer. The aim of this study was to assess the accuracy and safety of TBB in patients with NSCLC relapse, and the factors affecting its diagnostic yield.MethodsWe retrospectively screened patients with advanced NSCLC who underwent TBB for rebiopsy after developing resistance to systemic chemotherapy at Kurume University Hospital between January 2012 and June 2016. A positive diagnostic result obtained by TBB was defined as malignancy determined on the basis of histological features that were adequate for mutational analysis or immunohistochemistry. Severe postprocedural complications were defined as those requiring invasive medical procedures or prolonged hospitalisation.Results109 patients were enrolled in this retrospective study. Adequate tumour samples were collected from 88 of these patients, giving a high diagnostic yield of 80.7%. The diagnostic yield of TBB was not associated with tumour mutational status, the previous treatment regimen, or efficacy of the previous treatment. There were no severe postprocedural complications such as pneumothorax or serious haemorrhage.ConclusionsTBB is considered one of the safest and most useful procedures for rebiopsy of NSCLC that has relapsed after chemotherapy, regardless of patient background and treatment history.
Estimate of false-positive breast cancer diagnoses from accuracy studies: a systematic review
Authors: Segnan Nereo , Minozzi Silvia , Ponti Antonio , Bellisario Cristina , Balduzzi Sara , González-Lorenzo Marien , Gianola Silvia , Armaroli Paola 
Published: January 2017

BackgroundFalse-positive histological diagnoses have the same consequences of overdiagnosis in terms of unnecessary treatment. The aim of this systematic review is to assess their frequency at needle core biopsy (CB) and/or surgical excision of the breast.MethodsPubMed, Embase, Cochrane Library were systematically searched up to 30 October 2015. Eligibility criteria: cross-sectional studies assessing diagnostic accuracy of CB compared with surgical excision; studies assessing reproducibility of pathologists reading the same slides. Outcomes: false-positive rates; Misclassification of Benign as Malignant (MBM) histological diagnosis; K statistic. Independent reviewers extracted data and assessed quality using an adapted QUADAS-2 tool.ResultsSixteen studies assessed CB false-positive rates. In 10 studies (41 989 screen-detected lesions), the range of false-positive rates was 0%–7.1%. Twenty-seven studies assessed pathologists' reproducibility. Studies with consecutive, random or stratified samples of all the specimens: at CB the MBM range was 0.25%–2.4% (K values 0.83–0.98); at surgical excision, it was 0.67%–1.2% (K values 0.86–0.94). Studies with enriched samples: the MBM range was 1.4%–6.2% (K values 0.57–0.86). Studies of cases selected for second opinion: the MBM range was 0.29%–12.2% (K values 0.48 and 0.50).ConclusionsHigh heterogeneity of the included studies precluded formal pooling estimates. When considering studies of higher sample size or methodological quality, false-positive rates and MBM are around 1%. The impact of false-positive histological diagnoses of breast cancer on unnecessary treatment, as well as that of overdiagnosis, is not negligible and is of importance in clinical practice.
Motor plan differs for young and older adults during similar movements
Authors: Casamento-Moran Agostina , Chen Yen-Ting , Lodha Neha , Yacoubi Basma , Christou Evangelos A. 
Published: January 2017

Older adults exhibit altered activation of the agonist and antagonist muscles during goal-directed movements compared with young adults. However, it remains unclear whether the differential activation of the antagonistic muscles in older adults results from an impaired motor plan or an altered ability of the muscle to contract. The purpose of this study, therefore, was to determine whether the motor plan differs for young and older adults. Ten young (26.1 ± 4.3 yr, 4 women) and 16 older adults (71.9 ± 6.9 yr, 9 women) participated in the study. Participants performed 100 trials of fast goal directed movements with ankle dorsiflexion while we recorded the electromyographic activity of the primary agonist (tibialis anterior; TA) and antagonist (soleus; SOL) muscles. From those 100 trials we selected 5 trials in each of 3 movement end-point categories (fast, accurate, and slow). We investigated age-associated differences in the motor plan by quantifying the individual activity and coordination of the agonist and antagonist muscles. During similar movement end points, older adults exhibited similar activation of the agonist (TA) and antagonist (SOL) muscles compared with young adults. In addition, the coordination of the agonist and antagonist muscles (TA and SOL) was different between the two age groups. Specifically, older adults exhibited lower TA-SOL overlap ( F1,23 = 41.2, P < 0.001) and greater TA-SOL peak EMG delay ( F1,25 = 35.5, P < 0.001). This finding suggests that although subjects in both age groups displayed similar movement end points, they exhibited a different motor plan, as demonstrated by altered coordination between the agonist and antagonist muscles. NEW & NOTEWORTHY We aimed to determine whether the altered activation of muscles in older adults compared with young adults during fast goal-directed movements is related to an altered motor plan. For matched movements, there were differences in the coordination of antagonistic muscles but no differences in the individual activation of muscles. We provide novel evidence that the differential activation of muscles in older adults is related to an altered motor plan.
Role of the cerebellum in high stages of motor planning hierarchy
Authors: Casartelli Luca , Federici Alessandra , Cesareo Ambra , Biffi Emilia , Valtorta Giulia , Molteni Massimo , Ronconi Luca , Borgatti Renato 
Published: January 2017

Motor planning is not a monolithic process, and distinct stages of motor planning are responsible for encoding different levels of abstractness. However, how these distinct components are mapped into different neural substrates remains an open question. We studied one of these high-level motor planning components, defined as second-order motor planning, in a patient (R.G.) with an extremely rare case of cerebellar agenesis but without any other cortical malformations. Second-order motor planning dictates that when two acts must be performed sequentially, planning of the second act can influence execution of the first. We used an optoelectronic system for kinematic analysis to compare R.G.’s performance with age-matched controls in a second-order motor planning task. The first act was to reach for an object, and the second was to place it into a small or large container. Our results showed that despite the expected difficulties in fine-motor skills, second-order motor planning (i.e., the ability to modulate the first act as a function of the nature of the second act) was preserved even in the patient with congenital absence of the cerebellum. These results open new intriguing speculations about the role of the cerebellum in motor planning abilities. Although prudence is imperative when suggesting conclusions made on the basis of single-case findings, this evidence suggests fascinating hypotheses about the neural circuits that support distinct stages of the motor planning hierarchy, and regarding the functional role of second-order motor planning in motor cognition and its potential dysfunction in autism. NEW & NOTEWORTHY Traditionally, the cerebellum was considered essential for motor planning. By studying an extremely rare patient with cerebellar agenesis and a group of neurotypical controls, we found that high stages of the motor planning hierarchy can be preserved even in this patient with congenital absence of the cerebellum. Our results provide interesting insights that shed light on the neural circuits supporting distinct levels of motor planning. Furthermore, the results are intriguing because of their potential clinical implications in autism.
Auditory adaptation improves tactile frequency perception
Authors: Crommett Lexi E. , Pérez-Bellido Alexis , Yau Jeffrey M. 
Published: January 2017

Our ability to process temporal frequency information by touch underlies our capacity to perceive and discriminate surface textures. Auditory signals, which also provide extensive temporal frequency information, can systematically alter the perception of vibrations on the hand. How auditory signals shape tactile processing is unclear; perceptual interactions between contemporaneous sounds and vibrations are consistent with multiple neural mechanisms. Here we used a crossmodal adaptation paradigm, which separated auditory and tactile stimulation in time, to test the hypothesis that tactile frequency perception depends on neural circuits that also process auditory frequency. We reasoned that auditory adaptation effects would transfer to touch only if signals from both senses converge on common representations. We found that auditory adaptation can improve tactile frequency discrimination thresholds. This occurred only when adaptor and test frequencies overlapped. In contrast, auditory adaptation did not influence tactile intensity judgments. Thus auditory adaptation enhances touch in a frequency- and feature-specific manner. A simple network model in which tactile frequency information is decoded from sensory neurons that are susceptible to auditory adaptation recapitulates these behavioral results. Our results imply that the neural circuits supporting tactile frequency perception also process auditory signals. This finding is consistent with the notion of supramodal operators performing canonical operations, like temporal frequency processing, regardless of input modality. NEW & NOTEWORTHY Auditory signals can influence the tactile perception of temporal frequency. Multiple neural mechanisms could account for the perceptual interactions between contemporaneous auditory and tactile signals. Using a crossmodal adaptation paradigm, we found that auditory adaptation causes frequency- and feature-specific improvements in tactile perception. This crossmodal transfer of aftereffects between audition and touch implies that tactile frequency perception relies on neural circuits that also process auditory frequency.
Preparatory α-band oscillations reflect spatial gating independently of predictions regarding target identity
Authors: Wildegger T. , van Ede F. , Woolrich M. , Gillebert C. R. , Nobre A. C. 
Published: January 2017

Preparatory modulations of cortical α-band oscillations are a reliable index of the voluntary allocation of covert spatial attention. It is currently unclear whether attentional cues containing information about a target’s identity (such as its visual orientation), in addition to its location, might additionally shape preparatory α modulations. Here, we explore this question by directly comparing spatial and feature-based attention in the same visual detection task while recording brain activity using magnetoencephalography (MEG). At the behavioral level, preparatory feature-based and spatial attention cues both improved performance and did so independently of each other. Using MEG, we replicated robust α lateralization following spatial cues: in preparation for a visual target, α power decreased contralaterally and increased ipsilaterally to the attended location. Critically, however, preparatory α lateralization was not significantly modulated by predictions regarding target identity, as carried via the behaviorally effective feature-based attention cues. Furthermore, nonlateralized α power during the cue-target interval did not differentiate between uninformative cues and cues carrying feature-based predictions either. Based on these results we propose that preparatory α modulations play a role in the gating of information between spatially segregated cortical regions and are therefore particularly well suited for spatial gating of information. NEW & NOTEWORTHY The present work clarifies if and how human brain oscillations in the α-band support multiple types of anticipatory attention. Using magnetoencephalography, we show that posterior α-band oscillations are modulated by predictions regarding the spatial location of an upcoming visual target, but not by feature-based predictions regarding its identity, despite robust behavioral benefits. This provides novel insights into the functional role of preparatory α mechanisms and suggests a limited specificity with which they may operate.
DNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy
Authors: Nemec Antonia A. , Abriola Laura , Merkel Jane S. , de Stanchina Elisa , DeVeaux Michelle , Zelterman Daniel , Glazer Peter M. , Sweasy Joann B. 
Published: January 2017

Abstract
Resistance to cancer chemotherapies leads to deadly consequences, yet current research focuses only on the roles of somatically acquired mutations in this resistance. The mutational status of the germline is also likely to play a role in the way cells respond to chemotherapy. The carrier status for the POLB rs3136797 germline mutation encoding P242R DNA polymerase beta (Pol β) is associated with poor prognosis for lung cancer, specifically in response to treatment with cisplatin. Here, it is revealed that the P242R mutation is sufficient to promote resistance to cisplatin in human cells and in mouse xenografts. Mechanistically, P242R Pol β acts as a translesion polymerase and prefers to insert the correct nucleotide opposite cisplatin intrastrand cross-links, leading to the activation of the nucleotide excision repair (NER) pathway, removal of crosslinks, and resistance to cisplatin. In contrast, wild-type (WT) Pol β preferentially inserts the incorrect nucleotide initiating mismatch repair and cell death. Importantly, in a mouse xenograft model, tumors derived from lung cancer cells expressing WT Pol β displayed a slower rate of growth when treated with cisplatin, whereas tumors expressing P242R Pol β had no response to cisplatin. Pol β is critical for mediating crosstalk in response to cisplatin. The current data strongly suggest that the status of Pol β influences cellular responses to crosslinking agents and that Pol β is a promising biomarker to predict responses to specific chemotherapies. Finally, these results highlight that the genetic status of the germline is a critical factor in the response to cancer treatment.
Implications: Pol β has prognostic biomarker potential in the treatment of cancer with cisplatin and perhaps other intrastrand crosslinking agents. Mol Cancer Res; 15(3); 269–80. ©2017 AACR.
Characterization of Mineralocorticoid Receptor Antagonist Therapy Initiation in High-Risk Patients With Heart Failure
Authors: Cooper Lauren B. , Hammill Bradley G. , Peterson Eric D. , Pitt Bertram , Maciejewski Matthew L. , Curtis Lesley H. , Hernandez Adrian F. 
Published: January 2017

Background—
Heart failure guidelines recommend routine monitoring of serum potassium, and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). How these recommendations are implemented in high-risk patients or according to setting of drug initiation is poorly characterized.

Methods and Results—
We conducted a retrospective cohort study of Medicare beneficiaries linked to laboratory data in 10 states with prevalent heart failure as of July 1, 2011, and incident MRA use between May 1 and September 30, 2011. Outcomes included laboratory testing before MRA initiation and in the early (days 1–10) and extended (days 11–90) post-initiation periods, based on setting of drug initiation and the presence of renal insufficiency. Additional outcomes included abnormal laboratory results and adverse events proximate to MRA initiation. Of 10 443 Medicare beneficiaries with heart failure started on an MRA, 19.7% were initiated during a hospitalization. Appropriate follow-up laboratory testing across all time periods occurred in 25.2% of patients with inpatient initiation compared with 2.8% of patients begun as an outpatient. Patients with chronic kidney disease had higher rates of both hyperkalemia and acute kidney failure in the early (1.3% and 2.7%, respectively) and extended (5.6% and 9.8%, respectively) post-initiation periods compared with those without chronic kidney disease.

Conclusions—
Patients initiated on MRA therapy as an outpatient had extremely poor rates of guideline indicated follow-up laboratory monitoring after drug initiation. In particular, patients with chronic kidney disease are at high risk for adverse events after MRA initiation. Quality improvement initiatives focused on systems to improve appropriate laboratory monitoring are needed.