bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agomelatine: a new opportunity to reduce neuropathic pain—preclinical evidence
Authors: Chenaf Chouki , Chapuy Eric , Libert Frédéric , Marchand Fabien , Courteix Christine , Bertrand Marianne , Gabriel Cecilia , Mocaër Elisabeth , Eschalier Alain , Authier Nicolas 
Published: October 2016

Abstract
Antidepressants are first-line treatments of neuropathic pain but not all these drugs are really effective. Agomelatine is an antidepressant with a novel mode of action, acting as an MT1/MT2 melatonergic receptor agonist and a 5-HT2C receptor antagonist that involves indirect norepinephrine release. Melatonin, serotonin, and norepinephrine have been involved in the pathophysiology of neuropathic pain. Yet, no study has been conducted to determine agomelatine effects on neuropathic pain in animal models. Using 3 rat models of neuropathic pain of toxic (oxaliplatin/OXA), metabolic (streptozocin/STZ), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, we investigated the antihypersensitivity effect of acute and repeated agomelatine administration. We then determined the influence of melatonergic, 5-HT2C, α-2 and β-1/2 adrenergic receptor antagonists in the antihypersensitivity effect of agomelatine. The effect of the combination of agomelatine + gabapentin was evaluated using an isobolographic approach. In STZ and CCI models, single doses of agomelatine significantly and dose dependently reduced mechanical hypersensitivity. After daily administrations for 2 weeks, this effect was confirmed in the CCI model and agomelatine also displayed a marked antihypersensitivity effect in the OXA model. The antihypersensitivity effect of agomelatine involved melatonergic, 5-HT2C, and α-2 adrenergic receptors but not beta adrenoceptors. The isobolographic analysis demonstrated that the combination of agomelatine + gabapentin had additive effects. Agomelatine exerts a clear-cut antihypersensitivity effect in 3 different neuropathic pain models. Its effect is mediated by melatonergic and 5-HT2C receptors and, although agomelatine has no affinity, also by α-2 adrenergic receptors. Finally, agomelatine combined with gabapentin produces an additive antihypersensitivity effect.
Templated Interdisciplinary Rehabilitation Care Plan Documentation for Veterans With Traumatic Brain Injury
Authors: Scholten Joel , Danford Ellen , Leland Azadeh , Malecki Heather , Bidelspach Douglas , Taylor Brent , Sayer Nina 
Published: October 2016

Purpose of Study:
Individualized interdisciplinary care is the hallmark for rehabilitation following traumatic brain injury (TBI). Veterans Health Administration (VHA) utilizes an electronic note template to document Interdisciplinary Rehabilitation and Community Reintegration (IRCR) care plans for Veterans with TBI requiring rehabilitation. All Veterans with a TBI diagnosis, receiving skilled therapy for TBI-related issues, and followed by a case manager must receive a care plan. The purpose of this study was to determine the level of compliance with the IRCR care plan requirements used to identify Veterans with TBI in need of the care plan and to evaluate the reasons for inconsistent compliance. In addition, the study sought to provide a more objective assessment of Veterans with TBI requiring an IRCR to assist in establishing a target metric.

Primary Practice Setting:
TBI outpatient clinics.

Methodology and Sample:
Investigators conducted a retrospective medical record review of 546 Veterans with a TBI diagnosis seen at the Washington, DC VA Medical Center's outpatient polytrauma clinics in 2013. Cases were initially reviewed for referral or engagement with skilled therapy. Charts where Veterans were referred or engaged with skilled therapy were forwarded to 2 polytrauma clinicians to determine whether therapy was requested to treat a TBI-related condition. Finally, charts were reviewed for case management and analyzed for algorithm compliance. Analysis focused first on compliance with IRCR algorithm requirements and secondarily with identifying potential reasons for noncompliance.

Results:
In 2013, 42% of the TBI cohort met the criteria for an IRCR. The vast majority of cases with a TBI diagnosis complied with IRCR algorithm criteria; however, 14% of all reviewed cases required an IRCR but did not receive one. Provision of case management outside of the TBI/polytrauma clinic characterized a majority of noncompliant cases.

Implications for Case Management:
Interdisciplinary care can be challenging, particularly in the outpatient setting, due to patient availability and access to care. Improved documentation in the electronic health record may assist case managers and other clinicians in coordinating rehabilitation care for Veterans with TBI. Case managers in the VA and other settings may find templates and trackable health factors helpful to identify patients in need of care plans.
Adolescent Intentional Abuse Ingestions
Authors: Sheridan David C. , Hendrickson Robert G. , Beauchamp Gillian , Laurie Amber , Fu Rongwei , Horowitz B. Zane 
Published: October 2016

Objective
Adolescent intentional ingestions remain a significant public health problem in the United States with little research to date on the over-the-counter or prescription medicines that adolescents abuse. These data are important for anticipatory guidance by primary care providers, preventive health, and poison center outreach.

Methods
This was an observational study using the American Association of Poison Control Centers National Poison Data System. The study population consisted of all cases of patients aged 13 to 19 years from 2004 to 2013 with a coding of “intentional abuse.”

Results
There were 95,695 patient calls that were coded for intentional abuse between 2004 and 2013 for adolescents aged 13 to 19 years. The most common agent reportedly ingested in intentional-abuse cases was antihistamine and/or decongestant with dextromethorphan, and this agent remained the most common throughout the 10-year study period. The next 4 most common agents remained similar across the study period as well and included ethanol, benzodiazepines, dextromethorphan alone, and marijuana. These 5 agents remained the most commonly reported across the study period for all US regions (West, Midwest, South Northeast, and US territories).

Conclusions
Over a recent 10-year period, common cough preparations remain the most commonly reported intentional abuse ingestion among all years and regions for adolescents.
Big data need big theory too
Authors: Coveney Peter V. , Dougherty Edward R. , Highfield Roger R. 
Published: October 2016

The current interest in big data, machine learning and data analytics has generated the widespread impression that such methods are capable of solving most problems without the need for conventional scientific methods of inquiry. Interest in these methods is intensifying, accelerated by the ease with which digitized data can be acquired in virtually all fields of endeavour, from science, healthcare and cybersecurity to economics, social sciences and the humanities. In multiscale modelling, machine learning appears to provide a shortcut to reveal correlations of arbitrary complexity between processes at the atomic, molecular, meso- and macroscales. Here, we point out the weaknesses of pure big data approaches with particular focus on biology and medicine, which fail to provide conceptual accounts for the processes to which they are applied. No matter their ‘depth’ and the sophistication of data-driven methods, such as artificial neural nets, in the end they merely fit curves to existing data. Not only do these methods invariably require far larger quantities of data than anticipated by big data aficionados in order to produce statistically reliable results, but they can also fail in circumstances beyond the range of the data used to train them because they are not designed to model the structural characteristics of the underlying system. We argue that it is vital to use theory as a guide to experimental design for maximal efficiency of data collection and to produce reliable predictive models and conceptual knowledge. Rather than continuing to fund, pursue and promote ‘blind’ big data projects with massive budgets, we call for more funding to be allocated to the elucidation of the multiscale and stochastic processes controlling the behaviour of complex systems, including those of life, medicine and healthcare.
This article is part of the themed issue ‘Multiscale modelling at the physics–chemistry–biology interface’.
Unsupervised extraction of stable expression signatures from public compendia with eADAGE
Authors: Tan Jie , Doing Georgia , Lewis Kimberley A. , Price Courtney E. , Chen Kathleen M. , Cady Kyle C. , Perchuk Barret , Laub Michael T. , Hogan Deborah A. , Greene Casey S. 
Published: October 2016

AbstractCross experiment comparisons in public data compendia are challenged by unmatched conditions and technical noise. The ADAGE method, which performs unsupervised integration with neural networks, can effectively identify biological patterns, but because ADAGE models, like many neural networks, are over-parameterized, different ADAGE models perform equally well. To enhance model robustness and better build signatures consistent with biological pathways, we developed an ensemble ADAGE (eADAGE) that integrated stable signatures across models. We applied eADAGE to aPseudomonas aeruginosacompendium containing experiments performed in 78 media. eADAGE revealed a phosphate starvation response controlled by PhoB. While we expected PhoB activity in limiting phosphate conditions, our analyses found PhoB activity in other media with moderate phosphate and predicted that a second stimulus provided by the sensor kinase, KinB, is required for PhoB activation in this setting. We validated this relationship using both targeted and unbiased genetic approaches. eADAGE, which captures stable biological patterns, enables cross-experiment comparisons that can highlight measured but undiscovered relationships.
A Hypothesis to Explain Cancers in Confined Colonies of Naked Mole Rats
Authors: Hochberg Michael E. , Noble Robert J. , Braude Stanton 
Published: October 2016

AbstractNaked mole rats (NMRs) are subterranean eusocial mammals, known for their virtual absence of aging in their first 20 to 30 years of life, and their apparent resistance to cancer development. As such, this species has become an important biological model for investigating the physiological and molecular mechanisms behind cancer resistance. Two recent studies have discovered middle and late-aged worker (that is, non-breeding) NMRs in captive populations exhibiting neoplasms, consistent with cancer development, challenging the claim that NMRs are cancer resistant. These cases are possibly artefacts of inbreeding or certain rearing conditions in captivity, but they are also consistent with evolutionary theory.We present field data showing that worker NMRs live on average for 1 to 2 years. This, together with considerable knowledge about the biology of this species, provides the basis for an evolutionary explanation for why debilitating cancers in NMRs should be rare in captive populations and absent in the wild. Whereas workers are important for maintaining tunnels, colony defence, brood care, and foraging, they are highly vulnerable to predation. However, surviving workers either replace dead breeders, or assume other less active functions whilst preparing for possible dispersal. These countervailing forces (selection resulting in aging due to early-life investments in worker function, and selection for breeder longevity) along with the fact that all breeders derive from the worker morph, can explain the low levels of cancer observed by these recent studies in captive colonies. Because workers in the field typically never reach ages where cancer becomes a risk to performance or mortality, those rare observations of neoplastic growth should be confined to the artificial environments where workers survive to ages rarely if ever occurring in the wild. Thus, we predict that the worker phenotype fortuitously benefits from anti-aging and cancer protection in captive populations.
Nutritional dynamics during the development of xylophagous beetles related to changes in the stoichiometry of 11 elements
Authors: Filipiak Michał , Weiner January 
Published: October 2016

AbstractThe present study examines the adaptive strategy used by wood‐boring beetles to compensate for the lack of nutrients in dead wood. The contents of nutritional elements in growing wood‐boring beetles (Stictoleptura rubraL. andChalcophora marianaDejean) are compared with the elemental composition of decaying dead wood (pine stumps), showing changes during the beetles' ontogenetic (i.e. larval) development. The stoichiometric ratios ofCand other nutritional elements (N,P,K,Na,Ca,Mg,Fe,Zn,Mn andCu) are investigated to identify the most important nutrients for larval development. The degree of nutritional mismatch that is encountered by the beetle larvae changes dramatically over 3–4 years of simultaneous larval growth and wood decay. ExcludingC, the relative contents of nutritional elements increase substantially in decaying wood, whereas the opposite tendency is found in larvae, most likely because of carbon deposition in fat. The elements limiting larval development because of their scarcity in dead wood areN,P,K,Na,Mg,Zn andCu. Fungal activity (i.e. the transport of nutrients from the surrounding environment to decaying stumps) can explain the observed mitigation of the original mismatch, although prolongation of the larval development time is still necessary to compensate for the scarcity of some of the required elements in food.
Intracellular
d
-Serine Accumulation Promotes Genetic Diversity via Modulated Induction of RecA in Enterohemorrhagic Escherichia coli
Authors: Connolly James P. R. , Roe Andrew J. 
Published: October 2016

ABSTRACT

We recently discovered that exposure of enterohemorrhagic
Escherichia coli
(EHEC) to
d
-serine resulted in accumulation of this unusual amino acid, induction of the SOS regulon, and downregulation of the type III secretion system that is essential for efficient colonization of the host. Here, we have investigated the physiological relevance of this elevated SOS response, which is of particular interest given the presence of Stx toxin-carrying lysogenic prophages on the EHEC chromosome that are activated during the SOS response. We found that RecA elevation in response to
d
-serine, while being significant, was heterogeneous and not capable of activating
stx
expression or
stx
phage transduction to a nonlysogenic recipient. This “SOS-like response” was, however, capable of increasing the mutation frequency associated with low-level RecA activity, thus promoting genetic diversity. Furthermore, this response was entirely dependent on RecA and enhanced in the presence of a DNA-damaging agent, indicating a functional SOS response, but did not result in observable cleavage of the LexA repressor alone, indicating a controlled mechanism of induction. This work demonstrates that environmental factors not usually associated with DNA damage are capable of promoting an SOS-like response. We propose that this modulated induction of RecA allows EHEC to adapt to environmental insults such as
d
-serine while avoiding unwanted phage-induced lysis.

IMPORTANCE
The SOS response is a global stress network that is triggered by the presence of DNA damage due to breakage or stalled replication forks. Activation of the SOS response can trigger the replication of lytic bacteriophages and promote genetic diversification through error-prone polymerases. We have demonstrated that the host-associated metabolite
d
-serine contributes to
Escherichia coli
niche specification and accumulates inside cells that cannot catabolize it. This results in a modulated activation of the SOS antirepressor RecA that is insufficient to trigger lytic bacteriophage but capable of increasing the SOS-associated mutation frequency. These findings describe how relevant signals not normally associated with DNA damage can hijack the SOS response, promoting diversity as
E. coli
strains adapt while avoiding unwanted phage lysis.
The Small RNA GcvB Promotes Mutagenic Break Repair by Opposing the Membrane Stress Response
Authors: Barreto Brittany , Rogers Elizabeth , Xia Jun , Frisch Ryan L. , Richters Megan , Fitzgerald Devon M. , Rosenberg Susan M. 
Published: October 2016

ABSTRACT

Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In
Escherichia coli
, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σ
S
) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ
S
response, achieved via opposing the membrane stress (σ
E
) response. Cells that lack
gcvB
were MBR deficient and displayed reduced σ
S
-dependent transcription but not reduced σ
S
protein levels. The defects in MBR and σ
S
-dependent transcription in Δ
gcvB
cells were alleviated by artificially increasing σ
S
levels, implying that GcvB promotes mutagenesis by allowing a normal σ
S
response. Δ
gcvB
cells were highly induced for the σ
E
response, and blocking σ
E
response induction restored both mutagenesis and σ
S
-promoted transcription. We suggest that GcvB may promote the σ
S
response and mutagenesis indirectly, by promoting membrane integrity, which keeps σ
E
levels lower. At high levels, σ
E
might outcompete σ
S
for binding RNA polymerase and so reduce the σ
S
response and mutagenesis. The data show the delicate balance of stress response modulation of mutagenesis.

IMPORTANCE
Mutagenesis mechanisms upregulated by stress responses promote
de novo
antibiotic resistance and cross-resistance in bacteria, antifungal drug resistance in yeasts, and genome instability in cancer cells under hypoxic stress. This paper describes the role of a small RNA (sRNA) in promoting a stress-inducible-mutagenesis mechanism, mutagenic DNA break repair in
Escherichia coli
. The roles of many sRNAs in
E. coli
remain unknown. This study shows that Δ
gcvB
cells, which lack the GcvB sRNA, display a hyperactivated membrane stress response and reduced general stress response, possibly because of sigma factor competition for RNA polymerase. This results in a mutagenic break repair defect. The data illuminate a function of GcvB sRNA in opposing the membrane stress response, and thus indirectly upregulating mutagenesis.
Acupuncture for a First Episode of Acute Ischaemic Stroke: An Observer-Blinded Randomised Controlled Pilot Study
Authors: Liu Ching-Hsiung , Hsieh Yu-Ting , Tseng Hung-Pin , Lin Hung-Chih , Lin Chun-Liang , Wu Tai-Yi , Lin Shu-Hua , Tsao Szu-Hung , Zhang Hong 
Published: October 2016

Objective To determine the required sample size for, and feasibility of, a RCT examining the effectiveness of early acupuncture for acute ischaemic stroke. Methods Thirty-eight patients aged 40–85 years with a first episode of acute ischaemic stroke presenting within 72 h of stroke onset were randomly assigned to receive manual acupuncture (MA group; n=20) plus standard care or standard care only (control group, n=18). The acupuncture treatment was provided daily for 2 weeks. The primary outcome was the change in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 4 weeks. Secondary outcomes included changes in the Fugl–Meyer assessment (FMA) and the functional independence measure scores between baseline and 4 weeks, and changes in NIHSS, Barthel Index and modified Rankin Scale scores at 12 weeks. Results Thirty-one patients completed the study (dropout rate=18%) and adverse effects were minimal. No significant differences were seen between groups in the improvements in NIHSS scores, although there tended to be a greater reduction in NIHSS score after 1 week in the MA group relative to the control group (p=0.066). The post-stroke motor activity at 4 weeks was associated with a significantly increased FMA score in the acupuncture group compared with the control group (p<0.05), but not supported by intergroup analysis. Conclusions This pilot study indicates that acupuncture appears to be safe for patients in the acute stage of ischaemic stroke. A subsequent trial with a larger sample size (estimated at n=122) is required to confirm whether early acupuncture intervention contributes to earlier functional improvement and to assess the longer-term clinical efficacy of acupuncture. Trial Registration Number NCT02210988; Results.
Prevalence and predictors of latent tuberculosis infection among Italian State Policemen engaged in assistance to migrants: a national cross-sectional study
Authors: Durando Paolo , Garbarino Sergio , Orsi Andrea , Alicino Cristiano , Dini Guglielmo , Toletone Alessandra , Ciprani Fabrizio , Conte Giuseppe , Santorsa Roberto , Icardi Giancarlo 
Published: October 2016

ObjectivesBetter knowledge about tuberculosis (TB) and latent TB infection (LTBI) epidemiology is a crucial step for the development of effective strategies towards the control and elimination of this deadliest and persistent health threat. No study has investigated LTBI epidemiology in policemen who act as an interface with cross-border migrants.MethodsA survey to measure the LTBI prevalence and assess the demographic, professional and clinical features potentially associated with tuberculin skin test (TST) positivity was performed in Italian State Police (ISP) employees engaged, even occasionally, in relief activities, hospitality, photographical identification, escorting and accompanying of migrants, regardless of contact with active TB cases. Variables potentially associated with TST positivity were evaluated with univariate and multivariate analysis.ResultsFrom September to December 2014, 4225 ISP workers underwent TST screening and completed the questionnaire for data collection, according to study procedures. The TST was positive in 9.9% of individuals: no active TB cases were registered among the entire study population. Age, previous BCG vaccination and work category resulted independently associated with TST positivity.ConclusionsThis is the first study providing updated data about LTBI epidemiology among ISP employees engaged in assistance to migrants and furnish preliminary evidence of possible associations between TST positivity and different conditions that need to be deeply investigated with prospective studies.