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Interactive effects of hypoxia, hypercapnia and lung volume on sympathetic nerve activity in humans.

Recent Research Articles from UNTHSC - Thu, 07/02/2015 - 11:29pm

Interactive effects of hypoxia, hypercapnia and lung volume on sympathetic nerve activity in humans.

Exp Physiol. 2015 Jul 1;

Authors: Jouett NP, Watenpaugh DE, Dunlap ME, Smith ML

Abstract
We hypothesized that simultaneous stimulation of O2 - and CO2 -sensitive chemoreflexes produces synergistic activation of the sympathetic nervous system, and that this effect would be most apparent at low lung volume (expiratory) phases of respiration. Each subject (n = 11) breathed 16 gas mixtures in random order: a 4 × 4 matrix of normoxic to hypoxic (8, 12, 16, 21% O2 ) combined with normocapnic to hypercapnic gases (0, 2, 4 and 6% CO2 ). Tidal volume, arterial pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were measured continuously before and while breathing each gas mixture for 2 min. Changes in MSNA were determined for each gas mixture. MSNA was subdivided into low and high lung volume and respiratory phases to investigate further modulation by components of normal respiratory phase. Both hypoxia and hypercapnia increased mean MSNA independently. Mean and low lung volume MSNA increased exponentially with increasing levels of combined hypoxia and hypercapnia and resulted in a significant interaction (p<0.01). In contrast, MSNA during the high lung volume phase of respiration never increased significantly (P > 0.4). Similar, but less pronounced effects were found for expiratory and inspiratory phases of respiration. These effects created marked respiratory periodicity in MSNA at higher levels of combined hypoxia and hypercapnia. Finally, the response to hypoxia was not affected by hypocapnia, suggesting that the interaction occurs only during excitatory chemosensitive stimuli. These data indicate that hypoxia and hypercapnia interact to elicit synergistic sympathoexcitation, and that withdrawal of sympathoinhibitory effects of lung inflation exaggerates this chemoreflex interaction. This article is protected by copyright. All rights reserved.

PMID: 26132990 [PubMed - as supplied by publisher]

Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

Recent Research Articles from UNTHSC - Thu, 07/02/2015 - 11:29pm

Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

PLoS One. 2015;10(7):e0130331

Authors: Neuvonen AM, Putkonen M, Översti S, Sundell T, Onkamo P, Sajantila A, Palo JU

Abstract
It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.

PMID: 26132657 [PubMed - as supplied by publisher]

Estimating sleep from multisensory armband measurements: validity and reliability in teens.

Recent Research Articles from UNTHSC - Thu, 07/02/2015 - 11:29pm
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Estimating sleep from multisensory armband measurements: validity and reliability in teens.

J Sleep Res. 2015 Jul 1;

Authors: Roane BM, Van Reen E, Hart CN, Wing R, Carskadon MA

Abstract
Given the recognition that sleep may influence obesity risk, there is increasing interest in measuring sleep parameters within obesity studies. The goal of the current analyses was to determine whether the SenseWear(®) Pro3 Armband (armband), typically used to assess physical activity, is reliable at assessing sleep parameters. The armband was compared with the AMI Motionlogger(®) (actigraph), a validated activity monitor for sleep assessment, and with polysomnography, the gold standard for assessing sleep. Participants were 20 adolescents (mean age = 15.5 years) with a mean body mass index percentile of 63.7. All participants wore the armband and actigraph on their non-dominant arm while in-lab during a nocturnal polysomnographic recording (600 min). Epoch-by-epoch sleep/wake data and concordance of sleep parameters were examined. No significant sleep parameter differences were found between the armband and polysomnography; the actigraph tended to overestimate sleep and underestimate wake compared with polysomnography. Both devices showed high sleep sensitivity, but lower wake detection rates. Bland-Altman plots showed large individual differences in armband sleep parameter concordance rates. The armband did well estimating sleep overall, with group results more similar to polysomnography than the actigraph; however, the armband was less accurate at an individual level than the actigraph.

PMID: 26126746 [PubMed - as supplied by publisher]

Assessment of the role of DNA repair in damaged forensic samples.

Recent Research Articles from UNTHSC - Thu, 07/02/2015 - 11:29pm
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Assessment of the role of DNA repair in damaged forensic samples.

Int J Legal Med. 2014 Nov;128(6):913-21

Authors: Ambers A, Turnbough M, Benjamin R, King J, Budowle B

Abstract
Previous studies on DNA damage and repair have involved in vitro laboratory procedures that induce a single type of lesion in naked templates. Although repair of singular, sequestered types of DNA damage has shown some success, forensic and ancient specimens likely contain a number of different types of lesions. This study sought to (1) develop protocols to damage DNA in its native state, (2) generate a pool of candidate samples for repair that more likely emulate authentic forensic samples, and (3) assess the ability of the PreCR(TM) Repair Mix to repair the resultant lesions. Complexed, native DNA is more difficult to damage than naked DNA. Modified procedures included the use of higher concentrations and longer exposure times. Three types of samples, those that demonstrated damage based on short tandem repeat (STR) profile signals, were selected for repair experiments: environmentally damaged bloodstains, bleach-damaged whole blood, and human skeletal remains. Results showed trends of improved performance of STR profiling of bleach-damaged DNA. However, the repair assay did not improve DNA profiles from environmentally damaged bloodstains or bone, and in some cases resulted in lower RFU values for STR alleles. The extensive spectrum of DNA damage and myriad combinations of lesions that can be present in forensic samples appears to pose a challenge for the in vitro PreCR(TM) assay. The data suggest that the use of PreCR in casework should be considered with caution due to the assay's varied results.

PMID: 24792635 [PubMed - indexed for MEDLINE]

Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

Recent Research Articles from UNTHSC - Thu, 07/02/2015 - 3:29am
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Clinical utility of sequential minimal residual disease measurements in the context of risk-based therapy in childhood acute lymphoblastic leukaemia: a prospective study.

Lancet Oncol. 2015 Apr;16(4):465-74

Authors: Pui CH, Pei D, Coustan-Smith E, Jeha S, Cheng C, Bowman WP, Sandlund JT, Ribeiro RC, Rubnitz JE, Inaba H, Bhojwani D, Gruber TA, Leung WH, Downing JR, Evans WE, Relling MV, Campana D

Abstract
BACKGROUND: The level of minimal residual disease during remission induction is the most important prognostic indicator in patients with acute lymphoblastic leukaemia (ALL). We aimed to establish the clinical significance of minimal residual disease in a prospective trial that used sequential minimal residual disease measurements to guide treatment decisions.
METHODS: Between June 7, 2000, and Oct 24, 2007, 498 assessable patients with newly diagnosed ALL were enrolled in a clinical trial at St Jude Children's Research Hospital. We provisionally classified the risk of relapse as low, standard, or high according to patients' baseline clinical and laboratory features. Final risk assignment to establish treatment intensity was based mainly on minimal residual disease levels measured on days 19 and 46 of remission induction, and on week 7 of maintenance treatment. Additional measurements of minimal residual disease were made on weeks 17, 48, and 120 (end of treatment). The primary aim was to establish the association between event-free survival and patients' minimal residual disease levels during remission induction and sequentially post-remission. This trial was registered at ClinicalTrials.gov, number NCT00137111.
FINDINGS: Irrespective of the provisional risk classification, 10-year event-free survival was significantly worse for patients with 1% or greater minimal residual disease levels on day 19 compared with patients with lower minimal residual disease levels (69·2%, 95% CI 49·6-82·4, n=36 vs 95·5%, 91·7-97·5, n=244; p<0·001 for the provisional low-risk group and 65·1%, 50·7-76·2, n=56 vs 82·9%, 75·6-88·2, n=142; p=0·01 for the provisional standard-risk group). 12 patients with provisional low-risk ALL and 1% or higher minimal residual disease levels on day 19 but negative minimal residual disease (<0·01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88·9% (43·3-98·4). For the 280 provisional low-risk patients, a minimal residual disease level of less than 1% on day 19 predicted a better outcome, irrespective of the minimal residual disease level on day 46. Of provisional standard-risk patients with minimal residual disease of less than 1% on day 19, the 15 with persistent minimal residual disease on day 46 seemed to have an inferior 10-year event-free survival compared with the 126 with negative minimal residual disease (72·7%, 42·5-88·8 vs 84·0%, 76·3-89·4; p=0·06) after receiving the same post-remission treatment for standard-risk ALL. Of patients attaining negative minimal residual disease status after remission induction, minimal residual disease re-emerged in four of 382 studied on week 7, one of 448 at week 17, and one of 437 at week 48; all but one of these six patients died despite additional treatment. By contrast, relapse occurred in only two of the 11 patients who had decreasing minimal residual disease levels between the end of induction and week 7 of maintenance therapy and were treated with chemotherapy alone.
INTERPRETATION: Minimal residual disease levels during remission induction treatment have important prognostic and therapeutic implications even in the context of minimal residual disease-guided treatment. Sequential minimal residual disease monitoring after remission induction is warranted for patients with detectable minimal residual disease.
FUNDING: National Institutes of Health and American Lebanese Syrian Associated Charities.

PMID: 25800893 [PubMed - indexed for MEDLINE]

Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Recent Research Articles from UNTHSC - Tue, 06/30/2015 - 3:28am
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Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Bioorg Med Chem Lett. 2015 Jun 6;

Authors: Visalli RJ, Ziobrowski H, Badri KR, He JJ, Zhang X, Arumugam SR, Zhao H

Abstract
Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼0.1-10μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9μM for compounds 1-5, respectively.

PMID: 26112446 [PubMed - as supplied by publisher]

CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Recent Research Articles from UNTHSC - Tue, 06/30/2015 - 3:28am
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CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Curr Drug Targets. 2015 Jun 26;

Authors: Mamika MK, Ghorpadeb A

Abstract
Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected individuals with neurocognitive impairment, indicating its role in neuroinflammation associated with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via G-protein coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection. We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein, negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases, including HIV-associated neurocognitive disorders.

PMID: 26112047 [PubMed - as supplied by publisher]

Efficacy of a Telehealth Intervention on Colonoscopy Uptake when Cost is a Barrier: The Family CARE Cluster Randomized Controlled Trial.

Recent Research Articles from UNTHSC - Sat, 06/27/2015 - 3:31am
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Efficacy of a Telehealth Intervention on Colonoscopy Uptake when Cost is a Barrier: The Family CARE Cluster Randomized Controlled Trial.

Cancer Epidemiol Biomarkers Prev. 2015 Jun 22;

Authors: Steffen LE, Boucher KM, Damron BH, Pappas LM, Walters ST, Flores KG, Boonyasiriwat W, Vernon SW, Stroup AM, Schwartz MD, Edwards SL, Kohlmann WK, Lowery JT, Wiggins CL, Hill DA, Higginbotham JC, Burt R, Simmons RG, Kinney AY

Abstract
BACKGROUND: We tested the efficacy of a remote tailored intervention (TeleCARE) compared to a mailed educational brochure for improving colonoscopy uptake among at-risk relatives of colorectal cancer patients and examined subgroup differences based on participant reported cost barriers.
METHODS: Family members of colorectal cancer patients who were not up-to-date with colonoscopy were randomly assigned as family units to TeleCARE (N=232) or an educational brochure (N=249). At the 9-month follow-up, a cost resource letter listing resources for free or reduced-cost colonoscopy was mailed to participants who had reported cost barriers and remained non-adherent. Rates of medically-verified colonoscopy at the 15-month follow-up were compared based on group assignment and within group stratification by cost barriers.
RESULTS: In intent-to-treat analysis, 42.7% of participants in TeleCARE and 24.1% of participants in the educational brochure group had a medically-verified colonoscopy [OR = 2.37; 95% confidence interval (CI) 1.59 to 3.52]. Cost was identified as a barrier in both groups (TeleCARE = 62.5%; educational brochure = 57.0%). When cost was not a barrier, the TeleCARE group was almost four times as likely as the comparison to have a colonoscopy (OR = 3.66; 95% CI= 1.85 to 7.24). The intervention was efficacious among those who reported cost barriers; the TeleCARE group was nearly twice as likely to have a colonoscopy (OR = 1.99; 95% CI = 1.12 to 3.52).
CONCLUSIONS: TeleCARE increased colonoscopy regardless of cost barriers.
IMPACT: Remote interventions may bolster screening colonoscopy regardless of cost barriers and be more efficacious when cost barriers are absent.

PMID: 26101306 [PubMed - as supplied by publisher]

Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Recent Research Articles from UNTHSC - Sat, 06/27/2015 - 3:31am
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Δ9-Tetrahydrocannabinol-like discriminative stimulus effects of compounds commonly found in K2/Spice.

Behav Pharmacol. 2014 Dec;25(8):750-7

Authors: Gatch MB, Forster MJ

Abstract
A number of cannabinoid compounds are being sold in the form of incense as 'legal' alternatives to marijuana. The purpose of these experiments was to determine whether the most common of these compounds have discriminative stimulus effects similar to Δ-tetrahydrocannabinol (Δ-THC), the main active component in marijuana. Locomotor depressant effects of JWH-018, JWH-073, JWH-200, JWH-203, JWH-250, AM-2201, and CP 47,497-C8-homolog were tested in mice. The compounds were then tested for substitution in rats trained to discriminate Δ-THC (3 mg/kg, intraperitoneally). The time course of the peak dose of each compound was also tested. Each of the synthetic cannabinoids dose-dependently decreased locomotor activity for 1-2 h. Each of the compounds fully substituted for the discriminative stimulus effects of Δ-THC, mostly at doses that produced only marginal amounts of rate suppression. JWH-250 and CP 47,497-C8-homolog suppressed response rates at doses that fully substituted for Δ-THC. The time courses varied markedly between compounds. Most of the compounds had a shorter onset than Δ-THC, and the effects of three of the compounds lasted substantially longer (JWH-073, JWH-250, and CP 47,497-C8-homolog). Several of the most commonly used synthetic cannabinoids produce behavioral effects comparable with those of Δ-THC, which suggests that these compounds may share the psychoactive effects of marijuana responsible for abuse liability. The extremely long time course of the discriminative stimulus effects and adverse effects of CP 47,497-C8-homolog suggest that CP 47,497-C8-homolog may be associated with increased hazards among humans.

PMID: 25325289 [PubMed - indexed for MEDLINE]

Orthopedic emergencies: a practical emergency department classification (US-VAGON) in pelvic fractures.

Recent Research Articles from UNTHSC - Sat, 06/27/2015 - 3:31am
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Orthopedic emergencies: a practical emergency department classification (US-VAGON) in pelvic fractures.

Emerg Med Clin North Am. 2015 May;33(2):451-73

Authors: Wang H, Coppola PT, Coppola M

Abstract
Trauma is one of the leading causes of death before the age of 40 years and approximately 5% of patients with trauma who require hospital admission have pelvic fractures. This article updates the emergency department classification of pelvic fractures first described in 2000. This information is of practical value to emergency physicians in identifying the potential vascular, genitourinary, gastrointestinal, orthopedic, and neurologic complications and further assists them in the initial evaluation and treatment of patients with pelvic fractures.

PMID: 25892731 [PubMed - indexed for MEDLINE]

Total testosterone and neuropsychiatric symptoms in elderly men with Alzheimer's disease

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Hall, J.R. | Wiechmann, A.R. | Cunningham, R.L. | Johnson, L.A. | Edwards, M. | Barber, R.C. | Singh, M. | Winter, S. | O'Bryant, S.E.
Publication year: 2015
Journal / Book title: Alzheimer's Research and Therapy

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Motivational tools to improve probationer treatment outcomes

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Taxman, F.S. | Walters, S.T. | Sloas, L.B. | Lerch, J. | Rodriguez, M.
Publication year: 2015
Journal / Book title: Contemporary Clinical Trials

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Mitochondrial dihydrolipoamide dehydrogenase is upregulated in response to intermittent hypoxic preconditioning

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Li, R. | Luo, X. | Wu, J. | Thangthaeng, N. | Jung, M.E. | Jing, S. | Li, L. | Ellis, D.Z. | Liu, L. | Ding, Z. | Forster, M.J. | Yan, L.-J.
Publication year: 2015
Journal / Book title: International Journal of Medical Sciences

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Large-scale recent expansion of European patrilineages shown by population resequencing

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Batini, C. | Hallast, P. | Zadik, D. | Delser, P.M. | Benazzo, A. | Ghirotto, S. | Arroyo-Pardo, E. | Cavalleri, G.L. | De Knijff, P. | Dupuy, B.M. | Eriksen, H.A. | King, T.E. | De Munain, A.L. | López-Parra, A.M. | Loutradis, A. | Milasin, J. | Novelletto, A. | Pamjav, H. | Sajantila, A. | Tolun, A. | Winney, B. | Jobling, M.A.
Publication year: 2015
Journal / Book title: Nature Communications

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Therapeutic potential of cancer stem cells

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Yang, C. | Jin, K. | Tong, Y. | Cho, W.C.
Publication year: 2015
Journal / Book title: Medical Oncology

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The effects of sigma (σ1) receptor-selective ligands on muscarinic receptor antagonist-induced cognitive deficits in mice

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Malik, M. | Rangel-Barajas, C. | Sumien, N. | Su, C. | Singh, M. | Chen, Z. | Huang, R.-Q. | Meunier, J. | Maurice, T. | Mach, R.H. | Luedtke, R.R.
Publication year: 2015
Journal / Book title: British Journal of Pharmacology

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Exosomes are unlikely involved in intercellular Nef transfer

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Luo, X. | Fan, Y. | Park, I.-W. | He, J.J.
Publication year: 2015
Journal / Book title: PLoS ONE

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Neonatal variables, altitude of residence and Aymara Ancestry in Northern Chile

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Rothhammer, F. | Fuentes-Guajardo, M. | Chakraborty, R. | Bermejo, J.L. | Dittmar, M.
Publication year: 2015
Journal / Book title: PLoS ONE

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C-Jun NH<inf>2</inf>-terminal kinase-induced proteasomal degradation of c-FLIP<inf>L/S</inf> and Bcl<inf>2</inf> sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Chaudhary, P. | Vishwanatha, J.K.
Publication year: 2015
Journal / Book title: Biochemical Pharmacology

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Activation of mTOR: A culprit of Alzheimer’s disease?

Latest UNTHSC Articles in Scopus - Fri, 06/26/2015 - 7:30pm
Author(s):Cai, Z. | Chen, G. | He, W. | Xiao, M. | Yan, L.-J.
Publication year: 2015
Journal / Book title: Neuropsychiatric Disease and Treatment

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