bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Breast Pain Among Women With Histories of Breast-conserving Surgery for Breast Cancer Compared With Women Without Histories of Breast Surgery or Cancer
Authors: Edmond Sara N. , Shelby Rebecca A. , Keefe Francis J. , Fisher Hannah M. , Schmidt John E. , Soo Mary S. , Skinner Celette S. , Ahrendt Gretchen M. , Manculich Jessica , Sumkin Jules H. , Zuley Margarita L. , Bovbjerg Dana H. 
Published: March 2016

Objectives:
This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer.

Methods:
Breast cancer survivors (n=200) were recruited at their first postsurgical surveillance mammogram (6 to 15 mo postsurgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected.

Results:
Persistent breast pain (duration ≥6 mo) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (P<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared with survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared with women without a breast cancer history.

Discussion:
Results indicate that persistent breast pain negatively impacts women with a history of breast-conserving cancer surgery compared with women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors.
Differences in Clinical Pain and Experimental Pain Sensitivity Between Asian Americans and Whites With Knee Osteoarthritis
Authors: Ahn Hyochol , Weaver Michael , Lyon Debra E. , Kim Junglyun , Choi Eunyoung , Staud Roland , Fillingim Roger B. 
Published: March 2016

Objective:
Ethnicity has been associated with clinical and experimental pain responses. Whereas ethnic disparities in pain in other minority groups compared with whites are well described, pain in Asian Americans remains poorly understood. The purpose of this study was to characterize differences in clinical pain intensity and experimental pain sensitivity among older Asian American and non-Hispanic white (NHW) participants with knee osteoarthritis (OA).

Methods:
Data were collected from 50 Asian Americans ages 45 to 85 (28 Korean, 9 Chinese, 7 Japanese, 5 Filipino, and 1 Indian) and compared with 50 age-matched and sex-matched NHW individuals with symptomatic knee OA pain. The Western Ontario and McMaster Universities Osteoarthritis Index and Graded Chronic Pain Scale were used to assess the intensity of clinical knee pain. In addition, quantitative sensory testing was used to measure experimental sensitivity to heat-induced and mechanically induced pain.

Results:
Asian American participants had significantly higher levels of clinical pain intensity than NHW participants with knee OA. In addition, Asian American participants had significantly higher experimental pain sensitivity than NHW participants with knee OA.

Discussion:
These findings add to the growing literature regarding ethnic and racial differences in clinical pain intensity and experimental pain sensitivity. Asian Americans in particular may be at risk for clinical pain and heightened experimental pain sensitivity. Further investigation is needed to identify the mechanisms underlying ethnic group differences in pain between Asian Americans and NHWs, and to ensure that ethnic group disparities in pain are ameliorated.
Mindfulness is Associated With Increased Hedonic Capacity Among Chronic Pain Patients Receiving Extended Opioid Pharmacotherapy
Authors: Thomas Elizabeth A. , Garland Eric L. 
Published: March 2016

Objectives:
Chronic pain and long-term opioid use may lead to a persistent deficit in hedonic capacity, characterized by increased sensitivity to aversive states and insensitivity to natural rewards. Dispositional mindfulness has been linked with improved emotion regulation and pain coping. The aim of the current study was to examine associations between dispositional mindfulness, hedonic capacity, and pain-related interference in an opioid-using chronic pain sample.

Methods:
Data were obtained from a sample of 115 chronic pain patients on long-term opioid therapy (68% females, M age=48.3, SD=13.6) who completed the Five Facet Mindfulness Questionnaire (FFMQ), the Snaith-Hamilton Anhedonia and Pleasure Scale (SHAPS), the Brief Pain Inventory, and a psychiatric assessment of major depression. Bivariate correlations, hierarchical multiple regression, and path analysis were used to determine whether dispositional mindfulness scores (FFMQ) predicted variance in hedonic capacity (SHAPS), and whether hedonic capacity mediated the association between mindfulness and pain interference.

Results:
We observed a significant positive correlation between dispositional mindfulness and hedonic capacity scores (r=0.33, P<0.001). Hierarchical regression indicated that after controlling for pain interference and major depressive disorder diagnosis, dispositional mindfulness explained a significant portion of variance in hedonic capacity (β=0.30, P<0.01). The association between dispositional mindfulness and pain interference was mediated by hedonic capacity (b=−0.011, SE=0.005; 95% CI, −0.004 to −0.024, full model R
2=0.39).

Discussion:
Findings indicate that dispositional mindfulness was associated with hedonic capacity among this chronic pain sample. In light of this association, it is plausible that interventions that increase mindfulness may reduce pain-related impairment among opioid-using patients by enhancing hedonic capacity.
Prediction of Acute Postoperative Pain Following Breast Cancer Surgery Using the Pain Sensitivity Questionnaire
Authors: Rehberg Benno , Mathivon Stanislas , Combescure Christophe , Mercier Yannick , Savoldelli Georges L. 
Published: March 2016

Objectives:
Previous studies have indicated that preoperative pain sensitivity correlates with postoperative pain intensity, and thus may be used to predict severe postoperative pain. Self-rating of pain sensitivity using the “Pain Sensitivity Questionnaire (PSQ)” may be an adjunct to these measures.

Methods:
We tested the predictive ability of the PSQ as well as experimental parameters of pain sensitivity and other known risk factors for acute pain in 198 patients scheduled for breast cancer surgery. A multivariable logistic regression model was created for the binary outcome “maximum pain >3 during the first 24 hours postoperatively.”

Results:
The PSQ score proved to be an independent risk factor for at least moderate pain during the first 24 hours after surgery. Univariate analysis yielded in addition younger age, type of surgery (mastectomy vs. breast-conserving surgery), axillary dissection, expected pain, and the anxiety scores of the State-Trait Anxiety Inventory, as well as the score of the Beck Depression Inventory as risk factors. Of the experimental parameters of pain sensitivity, only the pain intensity elicited by a hot water bath was a predictor of at least moderate postoperative pain. Multivariable analysis led to a parsimonious model including only PSQ, the State-Trait Anxiety Inventory state score with a cutoff of ≥30, age with a cutoff of <55, mastectomy (vs. breast-conserving surgery), and axillary dissection.

Discussion:
Results need to be validated in a larger cohort and for other types of surgery, but use of the simple PSQ may help to identify patients at risk of intense acute postoperative pain.
High-density EMG Reveals Novel Evidence of Altered Masseter Muscle Activity During Symmetrical and Asymmetrical Bilateral Jaw Clenching Tasks in People With Chronic Nonspecific Neck Pain
Authors: Testa Marco , Geri Tommaso , Gizzi Leonardo , Falla Deborah 
Published: March 2016

Objectives:To characterize the distribution of masseter muscle activity and force control during bilateral jaw clenching tasks in people with chronic nonspecific neck pain, without an associated temporomandibular disorder.Methods:Twelve volunteers with nonspecific neck pain and 12 age-matched and sex-matched healthy individuals participated. Submaximal symmetrical and asymmetrical bilateral jaw clenching was performed with and without visual feedback of force. Force performance was assessed with indices of accuracy (mean distance, offset error) and precision (standard deviation, coefficient of variation of force). High-density, 2-dimensional, surface electromyography (EMG) was recorded to characterize bilateral masseter muscle activity. The EMG root mean square was computed for each location of the electrode grid to form a map of the EMG amplitude distribution, and the location of the center of activity was measured.Results:The patient group showed a different distribution of masseter muscle activity compared with pain-free individuals during both symmetrical and asymmetrical bilateral jaw clenching. The position of the center of activity was positioned more cranial (P<0.001; right masseter only) and more anteriorly in the patient group (P<0.0001). In addition, the patients with chronic neck pain displayed higher levels of masseter muscle activation compared with the control participants regardless of the specific task performed (P<0.0001).Discussion:People with chronic neck pain display increased activation and altered distribution of masseter muscle activity during a jaw-clenching coordination task. These results provide a greater appreciation of how secondary orofacial pain or temporomandibular disorders may develop in people with neck pain.
Prediction of Fat-Free Mass in Kidney Transplant Recipients
Authors: Størset Elisabet , von Düring Marit Elizabeth , Godang Kristin , Bergan Stein , Midtvedt Karsten , Åsberg Anders 
Published: March 2016

Background:
Individualization of drug doses is essential in kidney transplant recipients. For many drugs, the individual dose is better predicted when using fat-free mass (FFM) as a scaling factor. Multiple equations have been developed to predict FFM based on healthy subjects. These equations have not been evaluated in kidney transplant recipients. The objectives of this study were to develop a kidney transplant specific equation for FFM prediction and to evaluate its predictive performance compared with previously published equations.

Methods:
Ten weeks after transplantation, FFM was measured by dual-energy X-ray absorptiometry. Data from a consecutive cohort of 369 kidney transplant recipients were randomly assigned to an equation development data set (n = 245) or an evaluation data set (n = 124). Prediction equations were developed using linear and nonlinear regression analysis. The predictive performance of the developed equation and previously published equations in the evaluation data set was assessed.

Results:
The following equation was developed: FFM (kg) = {FFMmax × body weight (kg)/[81.3 + body weight (kg)]} × [1 + height (cm) × 0.052] × [1−age (years) × 0.0007], where FFMmax was estimated to be 11.4 in males and 10.2 in females. This equation provided an unbiased, precise prediction of FFM in the evaluation data set: mean error (ME) (95% CI), −0.71 kg (−1.60 to 0.19 kg) in males and −0.36 kg (−1.52 to 0.80 kg) in females, root mean squared error 4.21 kg (1.65–6.77 kg) in males and 3.49 kg (1.15–5.84 kg) in females. Using previously published equations, FFM was systematically overpredicted in kidney-transplanted males [ME +1.33 kg (0.40–2.25 kg) to +5.01 kg (4.06–5.95 kg)], but not in females [ME −2.99 kg (−4.07 to −1.90 kg) to +3.45 kg (2.29–4.61) kg].

Conclusions:
A new equation for FFM prediction in kidney transplant recipients has been developed. The equation may be used for population pharmacokinetic modeling and clinical dose selection in kidney transplant recipients.
Relieving pain using dose-extending placebos: a scoping review
Authors: Colloca Luana , Enck Paul , DeGrazia David 
Published: March 2016

AbstractPlacebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22 studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Provided that nondisclosure is preauthorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated.
The musculoskeletal diagnosis cohort: examining pain and pain care among veterans
Authors: Goulet Joseph L. , Kerns Robert D. , Bair Matthew , Becker William C. , Brennan Penny , Burgess Diana J. , Carroll Constance M. , Dobscha Steven , Driscoll Mary A. , Fenton Brenda T. , Fraenkel Liana , Haskell Sally G. , Heapy Alicia A. , Higgins Diana M. , Hoff Rani A. , Hwang Ula , Justice Amy C. , Piette John D. , Sinnott Patsi , Wandner Laura , Womack Julie A. , Brandt Cynthia A. 
Published: March 2016

Abstract
Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly disorders. The MSD Cohort was created to characterize variation in pain, comorbidities, treatment, and outcomes among patients with MSD receiving Veterans Health Administration care across demographic groups, geographic regions, and facilities. We searched electronic health records to identify patients treated in Veterans Health Administration who had ICD-9-CM codes for diagnoses including, but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort inclusion criteria were 2 or more outpatient visits occurring within 18 months of one another or one inpatient visit with an MSD diagnosis between 2000 and 2011. The first diagnosis is the index date. Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively. The cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15% identified as black, and 18% reported severe pain (NRS ≥ 7) on the index date. Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%) were the most common MSD diagnoses. Patients entering the cohort in recent years had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich resource for collaborative pain-relevant health service research.
Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine
Authors: Oliveira Margarida-Martins , Akerman Simon , Tavares Isaura , Goadsby Peter J. 
Published: March 2016

AbstractMigraine is a painful neurologic disorder with premonitory symptomatology that can include disturbed appetite. Migraine pathophysiology involves abnormal activation of trigeminocervical complex (TCC) neurons. Neuropeptide Y (NPY) is synthesized in the brain and is involved in pain modulation. NPY receptors are present in trigeminal ganglia and trigeminal nucleus caudalis suggesting a role in migraine pathophysiology. The present study aimed to determine the effect of systemic administration of NPY on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We performed in vivo electrophysiology in anesthetized rats, administered NPY (10, 30, and 100 µg·kg−1), and investigated the receptors involved by studying NPY Y1(30 µg·kg−1), Y2(30 µg·kg−1), and Y5receptor agonists (100·µg·kg−1), and NPY Y1receptor antagonist (30 µg·kg−1). NPY (30 and 100 µg·kg−1) significantly reduced TCC neuronal firing in response to dural-evoked trigeminovascular activation, but only NPY (30 µg·kg−1) significantly reduced spontaneous trigeminal firing. NPY Y1receptor agonist also significantly reduced dural-evoked and spontaneous TCC neuronal firing. NPY (10 µg·kg−1), NPY Y2, and Y5receptor agonists, and the NPY Y1receptor antagonist had no significant effects on nociceptive dural-evoked neuronal firing in the TCC or spontaneous trigeminal firing. This study demonstrates that NPY dose dependently inhibits dural-evoked trigeminal activity, through NPY Y1receptor activation, indicating antinociceptive actions of NPY in a migraine animal model. Based on the role of NPY in appetite regulation, it is possible that disruption of the NPY system might explain changes of appetite in migraineurs.
Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis
Authors: Ditre Joseph W. , Heckman Bryan W. , Zale Emily L. , Kosiba Jesse D. , Maisto Stephen A. 
Published: March 2016

Abstract
Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.
Recognizing the Continuous Nature of Expression Heterogeneity and Clinical Outcomes in Clear Cell Renal Cell Carcinoma
Authors: Wei Xiaona , Choudhury Yukti , Lim Weng Khong , Anema John , Kahnoski Richard J. , Lane Brian , Ludlow John , Takahashi Masayuki , Kanayama Hiro-omi , Belldegrun Arie , Kim Hyung L. , Rogers Craig , Nicol David , Teh Bin Tean , Tan Min-Han 
Published: March 2016

AbstractPURPOSEEvaluation of 12 ccRCC publicly-available ccRCC gene expression datasets showed that previously proposed discrete molecular subtypes are unstable. To reflect the continuous nature of gene expression observed, we developed a quantitative score (Continuous Linear Enhanced Assessment of Renal cell carcinoma, or CLEAR) using expression analysis founded on pathologic parameters.MATERIALS AND METHODS265 ccRCC gene expression profiles were used to develop the CLEAR score, representing a genetic correlate of the continuum of morphological tumor grade. A signature derivation method based on correlation of CLEAR score with gene expression ranking was used to derive an 18-transcript signature. External validation was conducted in multiple public expression datasets.ResultsAs a measure of intertumoral gene expression heterogeneity, the CLEAR score demonstrated both superior prognostic estimates (94% vs 83% adequacy index in TCGA dataset) and inverse correlation with anti-angiogenic tyrosine-kinase inhibition (65% vs 55% adequacy index) in comparison to previously proposed discrete subtyping classifications. Inverse correlation with high-dose interleukin-2 outcomes was also observed for the CLEAR score (p=0.05). Multiple somatic mutations (VHL, PBRM1, SETD2, KDM5C, TP53, BAP1, PTEN, MTOR) were associated with the CLEAR score. Application of the CLEAR score to independent expression profiling of intratumoral ccRCC regions demonstrated its ability to reflect intratumoral expression heterogeneity and further analysis showed average intertumoral heterogeneity exceeded intratumoral heterogeneity.ConclusionsThe CLEAR score, a gene expression signature developed on histopathology, outperformed discrete subtype-classification in prognostic estimates and correlated better with treatment outcomes. Recognizing cancer as a continuum has important implications for laboratory and clinical research.
Genome-wide association study identifies 17 new loci influencing concentrations of circulating cytokines and growth factors
Authors: Ahola-Olli AV , Würtz P , Havulinna AS , Aalto K , Pitkänen N , Lehtimäki T , Kähönen M , Lyytikäinen LP , Raitoharju E , Seppälä I , Sarin AP , Ripatti S , Palotie A , Perola M , Viikari JS , Jalkanen S , Maksimow M , Salomaa V , Salmi M , Kettunen J , Raitakari OT 
Published: March 2016

AbstractCirculating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) up to n=8,293 Finns we identified 27 loci with genome-wide association (P-value<1.2×10-9) for one or more cytokines, including 17 unidentified in previous GWASes. Fifteen of the associated SNPs had expression quantitative trait loci in whole blood. We provide strong genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link known autoimmune disease variants including Crohn's disease, multiple sclerosis and ulcerative colitis with new inflammatory markers, which elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.