bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cough physiology in elderly women with nontuberculous mycobacterial lung infections
Authors: Tsai Hsiu-Wen , Fennelly Kevin , Wheeler-Hegland Karen , Adams Sherry , Condrey Jillian , Hosford Jennifer L , Davenport Paul W. 
Published: March 2017

Elderly white, thin, nonsmoking women appear to be more susceptible to lung infections with Mycobacterium avium complex and other nontuberculous mycobacteria (NTM). It has been postulated that such disease in women is related to suppression of their cough. We hypothesized that patients with pulmonary NTM (pNTM) infections may have altered cough physiology compared with unaffected control subjects. We used capsaicin-induced cough to assess the cough reflex in pNTM subjects. Eight elderly white women with stable chronic pNTM infections and six unaffected age-matched control subjects were recruited. There was no significant difference between groups in capsaicin-elicited cough motor response, airflow pattern, or cough frequency. The urge-to-cough (UTC) score at the lowest capsaicin concentration was significantly lower in pNTM than control subjects ( P < 0.05). There were no significant differences in the UTC score between pNTM and control subjects at >50 μM capsaicin. These results suggest lower UTC sensitivity to the lowest concentration of capsaicin in pNTM than control subjects. In other words, the pNTM subjects do not sense a UTC when the stimulus is relatively small. NEW & NOTEWORTHY This study investigates the cough motor response and cough sensitivity in patients with nontuberculous mycobacteria (NTM) infection. In elderly white female pulmonary NTM subjects, we demonstrated a capacity to produce coughs similar to that of age-matched control subjects but decreased cough sensitivity in response to a low dose of capsaicin compared with control subjects. These findings are important to understand the pathophysiological mechanisms resulting in NTM disease in elderly white women and/or the syndrome developing in elderly white female NTM patients.
Hypercholesterolemia Increases Colorectal Cancer Incidence by Reducing Production of NKT and γδ T Cells from Hematopoietic Stem Cells
Authors: Tie Guodong , Yan Jinglian , Khair Lyne , Messina Julia A. , Deng April , Kang Joonsoo , Fazzio Thomas , Messina Louis M. 
Published: March 2017

Abstract
Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity of obesity, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia or any metabolic disorder increases cancer risk remains unknown. In this study, we show that hypercholesterolemia increases the incidence and pathologic severity of colorectal neoplasia in two independent mouse models. Hypocholesterolemia induced an oxidant stress–dependent increase in miR101c, which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and γδ T-cell differentiation. These effects reduced the number and function of terminally differentiated NKT and γδ T cells in the thymus, the colon submucosa, and during early tumorigenesis. These results suggest a novel mechanism by which a metabolic disorder induces epigenetic changes to reduce lineage priming of HSC toward immune cells, thereby compromising immunosurveillance against cancer. Cancer Res; 77(9); 2351–62. ©2017 AACR.
Individualized Breast Cancer Characterization through Single-Cell Analysis of Tumor and Adjacent Normal Cells
Authors: Anjanappa Manjushree , Cardoso Angelo , Cheng Lijun , Mohamad Safa , Gunawan Andrea , Rice Susan , Dong Yan , Li Lang , Sandusky George E. , Srour Edward F. , Nakshatri Harikrishna 
Published: March 2017

Abstract
There is a need to individualize assays for tumor molecular phenotyping, given variations in the differentiation status of tumor and normal tissues in different patients. To address this, we performed single-cell genomics of breast tumors and adjacent normal cells propagated for a short duration under growth conditions that enable epithelial reprogramming. Cells analyzed were either unselected for a specific subpopulation or phenotypically defined as undifferentiated and highly clonogenic ALDH+/CD49f+/EpCAM+ luminal progenitors, which express both basal cell and luminal cell–enriched genes. We analyzed 420 tumor cells and 284 adjacent normal cells for expression of 93 genes that included a PAM50-intrinsic subtype classifier and stemness-related genes. ALDH+/CD49f+/EpCAM+ tumor and normal cells clustered differently compared with unselected tumor and normal cells. PAM50 gene-set analyses of ALDH+/CD49f+/EpCAM+ populations efficiently identified major and minor clones of tumor cells, with the major clone resembling clinical parameters of the tumor. Similarly, a stemness-associated gene set identified clones with divergent stemness pathway activation within the same tumor. This refined expression profiling technique distinguished genes truly deregulated in cancer from genes that identify cellular precursors of tumors. Collectively, the assays presented here enable more precise identification of cancer-deregulated genes, allow for early identification of therapeutically targetable tumor cell subpopulations, and ultimately provide a refinement of precision therapeutics for cancer treatment. Cancer Res; 77(10); 2759–69. ©2017 AACR.
Long-term Adherence to Colorectal Cancer Screening; 5-Year Results from the Systems of Support to Increase Colorectal Cancer Screening Trial
Authors: Green BB , Anderson ML , Chubak J , Fuller S , Meenan RT , Vernon SW 
Published: March 2017

Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer deaths. Mortality could be rapidly reduced through higher uptake and adherence to CRC screening. Information on long-term screening adherence comes from organized programs that lack a comparison group. Objective: Systems of Support to Increase Colorectal Cancer Screening is an ongoing trial testing a centralized mailed and phone-based program to increase long-term CRC screening adherence. We hypothesized that compared to usual care (UC) intervention-arm patients would have more time in compliance with CRC screening guidelines over 5 years. Methods: The setting was an integrated healthcare organization in Washington State. UC included patient-centered medical home with clinic-based strategies to increase screening. Participants included 4675 individuals initially aged 50–74, not current for CRC screening. Intervention arms combined were compared to UC. The primary outcome was the percent of time covered for CRC screening over 5 years of follow-up. Screening tests contributed covered time based on national guidelines for screening intervals. All participants contributed data, but were censored at disenrollment, death, age 76, or CRC diagnosis. Interventions: Patients were randomly assigned to receive UC, or one of three stepped care interventions: 1. Mailings including mailed fecal tests, a call-in number if colonoscopy or sigmoidoscopy was preferred; 2. Mailings plus brief telephone assistance; 3. Mailings and telephone assistance plus nurse navigation. In year 3, intervention group participants still CRC screening-eligible were randomized to stopped or continued mailed interventions only. Results: Compared to UC, intervention participants had 31% more time not in need of CRC testing (adjusted rate ratio, weighted for exposure time 1.31 [1.25–1.37], 47.2% vs. 62.0% covered time) over 5 years. Fecal testing was responsible for almost all additional covered time. Compared to intervention participants, UC individuals were more likely never to have completed any CRC testing over 5 years (17.4% vs. 10.3%, net difference 7.2%, P &lt; 0.001) Conclusions: An organized mail and phone program led to increased CRC screening adherence over 5 years, mainly because of regular fecal testing uptake.
Perceptions of Cervical Cancer Risk among Ohio Appalachian Women
Authors: Bernardo BM , Reiter PL , Pennell ML , Padamsee TJ , Ruffin MT , Paskett ED 
Published: March 2017

Abstract
OBJECTIVE: To describe how Ohio Appalachian women are over- or under-estimating risk for cervical cancer by comparing an objective measure of cervical cancer risk to subjective interpretations of risk. METHODS: A cervical cancer risk index was computed for 530 female participants recruited from clinics in Ohio Appalachia (2006–2008). Risk factors for cervical cancer, including human papillomavirus infection, number of sexual partners, parity, age at first intercourse, age at first pregnancy, oral contraceptive use and cigarette smoking were used to create a cervical cancer risk index. This index was used to categorize participants into low, average or high risk for cervical cancer. Subjective risk was assessed by asking women to indicate whether they believe their risk of cervical cancer to be below, about average, or higher than other women. Objective risk categories were compared to subjective risk to determine if women were accurately perceiving risk, or over- or under-estimating risk. A multinomial logistic regression model was used to determine correlates of risk perception accuracy. The outcome was a categorical variable consisting of over-estimating risk, underestimating risk and accurate risk perception, with accurate risk perception serving as the reference level in the model. RESULTS: Out of 530 women, 33.6% (n = 178) over-estimated risk and 24.9% (n = 132) under-estimated risk. Women with household incomes of &lt;$25 k were more likely to under-estimate cervical cancer risk, as opposed to being accurate in their risk perception, than women in households earning over $50 k [OR = 2.06, 95% CI (1.04–4.07)] as were women with less than a high-school education [OR = 2.52, 95% CI (1.06–5.96)] compared to women with a college education. Also, women who reported recent alcohol use were more likely to under-estimate risk [OR = 1.94, 95% CI (1.18–3.19)] compared to women with no self-reported recent alcohol use. No variables were found to be associated with risk over-estimation. CONCLUSIONS: Many women in Ohio Appalachia do not accurately perceive their cervical cancer risk. Low income and education are associated with under-estimating risk. Future studies should determine if risk misperceptions are associated with cervical cancer screening and other preventive behaviors.
Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma
Authors: Feng Xiaoyan , Zhang Li , Acharya Chirag , An Gang , Wen Kenneth , Qiu Lugui , Munshi Nikhil C. , Tai Yu-Tzu , Anderson Kenneth C. 
Published: March 2017

Abstract
Purpose: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ regulatory T cells (Treg) and further define immunomodulating effects of a therapeutic CD38 mAb isatuximab/SAR650984 in multiple myeloma.
Experimental Design: We evaluated percentages of CD38-expressing subsets in Tregs from normal donors and multiple myeloma patients. Peripheral blood mononuclear cells (PBMC) were then treated with isatuximab with or without lenalidomide or pomalidomide to identify their impact on the percentage and immunosuppressive activity of Tregs on CD4+CD25− T cells (Tcons). We investigated the mechanism of increased Tregs in multiple myeloma patients in ex vivo cocultures of multiple myeloma cells with PBMCs or Tcons.
Results: CD38 expression is higher on Tregs than Tcons from multiple myeloma patients versus normal donors. CD38 levels and the percentages of CD38high Tregs are increased by lenalidomide and pomalidomide. Isatuximab preferentially decreases Treg and increases Tcon frequencies, which is enhanced by pomalidomide/lenalidomide. Isatuximab reduces Foxp3 and IL10 in Tregs and restores proliferation and function of Tcons. It augments multiple myeloma cell lysis by CD8+ T and natural killer cells. Coculture of multiple myeloma cells with Tcons significantly induces Tregs (iTregs), which express even higher CD38, CD25, and FoxP3 than natural Tregs. This is associated with elevated circulating CD38+ Tregs in multiple myeloma patients versus normal donors. Conversely, isatuximab decreases multiple myeloma cell- and bone marrow stromal cell–induced iTreg by inhibiting both cell–cell contact and TGFβ/IL10. Finally, CD38 levels correlate with differential inhibition by isatuximab of Tregs from multiple myeloma versus normal donors.
Conclusions: Targeting CD38 by isatuximab can preferentially block immunosuppressive Tregs and thereby restore immune effector function against multiple myeloma. Clin Cancer Res; 23(15); 4290–300. ©2017 AACR.
Cardiovascular Disease and Patterns of Change in Functional Status Over 15 Years: Findings From the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kucharska‐Newton Anna , Griswold Michael , Yao Zhihao Howard , Foraker Randi , Rose Kathryn , Rosamond Wayne , Wagenknecht Lynne , Koton Silvia , Pompeii Lisa , Windham B. Gwen 
Published: March 2017

Background

Cardiovascular disease (
CVD
) is the leading cause of premature disability, yet few prospective studies have examined functional status (
FS
) among persons with
CVD
. Our aim was to examine patterns of change in
FS
prior to and after hospitalization for nonfatal myocardial infarction, stroke, and heart failure among members of the Atherosclerosis Risk in Communities (ARIC) study cohort.

Methods and Results

FS
was assessed using a modified Rosow‐Breslau questionnaire administered during routine annual telephone interviews conducted from 1993 through 2007 among 15 277
ARIC
study participants. An
FS
score was constructed as a summary measure of responses to questions about participants' ability to perform selected tasks of daily living (eg, walking half a mile, climbing stairs). Incidence of
CVD
was assessed through
ARIC
surveillance of hospitalized events. Rate of change in
FS
over time prior to and following a
CVD
event was examined using generalized estimating equations. A decline in
FS
was observed on average 2 years prior to a myocardial infarction hospitalization and on average 3 years prior to a stroke or heart failure hospitalization.
FS
post–myocardial infarction declined relative to pre‐event levels but improved to close to pre–myocardial infarction levels within 3 years. Decline in
FS
following incident heart failure and stroke remained over time. Observed patterns of change in
FS
did not differ appreciably by race or sex.

Conclusions

This study documents that a decline in
FS
precedes incidence of
CVD
‐related hospitalization by at least 2 years, providing a strong argument for routine preventative assessment of
FS
among older adults.
Efficacy of Prophylactic Dexmedetomidine in Preventing Postoperative Junctional Ectopic Tachycardia After Pediatric Cardiac Surgery
Authors: El Amrousy Doaa Mohamed , Elshmaa Nagat S. , El‐Kashlan Mohamed , Hassan Samir , Elsanosy Mohamed , Hablas Nahed , Elrifaey Shimaa , El‐Feky Wael 
Published: March 2017

Background
Postoperative junctional ectopic tachycardia is one of the most serious arrhythmias that occur after pediatric cardiac surgery, difficult to treat and better to be prevented. Our aim was to assess the efficacy of prophylactic dexmedetomidine in preventing junctional ectopic tachycardia after pediatric cardiac surgery.

Methods and Results

A prospective controlled study was carried out on 90 children who underwent elective cardiac surgery for congenital heart diseases. Patients were randomized into 2 groups. Group I (dexmedetomidine group): 60 patients received dexmedetomidine; Group
II
(Placebo group): 30 patients received the same amount of normal saline intravenously. The primary outcome was the incidence of postoperative junctional ectopic tachycardia. Secondary outcomes included bradycardia, hypotension, vasoactive inotropic score, ventilation time, pediatric cardiac care unit stay, length of hospital stay, and perioperative mortality. The incidence of junctional ectopic tachycardia was significantly reduced in the dexmedetomidine group (3.3%) compared with the placebo group (16.7%) with
P
<0.005. Heart rate while coming off cardiopulmonary bypass was significantly lower in the dexmedetomidine group (130.6±9) than the placebo group (144±7.1) with
P
<0.001. Mean ventilation time, and mean duration of intensive care unit and hospital stay (days) were significantly shorter in the dexmedetomidine group than the placebo group (
P
<0.001). However, there was no significant difference between the 2 groups as regards mortality, bradycardia, or hypotension (
P
>0.005).

Conclusion
Prophylactic use of dexmedetomidine is associated with significantly decreased incidence of postoperative junctional ectopic tachycardia in children after congenital heart surgery without significant side effects.
Natural History of Ruptured but Untreated Intracranial Aneurysms
Authors: Korja Miikka , Kivisaari Riku , Rezai Jahromi Behnam , Lehto Hanna 
Published: March 2017

Background and Purpose—
Knowledge on a natural history of untreated ruptured intracranial aneurysms is based on a small historical cohort from 1960s. We calculated mortality rates for patients with untreated ruptured intracranial aneurysms using a more recent and relatively large hospital cohort.

Methods—
Patients admitted to the study hospital between 1968 and 2007 with saccular but untreated ruptured intracranial aneurysms were identified from the hospital aneurysm registry of 6850 patients. The study cohort included only patients who were followed up until death and for whom the date of symptom onset and the date of hospital admission were available.

Results—
For 510 patients identified, the median survival time from symptom onset to death was 20 days. The 1-year mortality rate was 65%, but varied substantially by admission delays and clinical status on admission, being lowest (13%) for patients admitted later than a month after symptom onset and highest (89%) for poor-grade patients. The 1-year mortality rate was 75% for good-grade patients admitted within a week.

Conclusions—
Mortality rates for patients with untreated ruptured intracranial aneurysms are even worse than presented in the historical study. When discussing with subarachnoid hemorrhage patients and their relatives about treatment options, the presented natural history figures are of use.
Effectiveness of an Intervention to Improve Risk Factor Knowledge in Patients With Stroke
Authors: Olaiya Muideen T. , Cadilhac Dominique A. , Kim Joosup , Ung David , Nelson Mark R. , Srikanth Velandai K. , Bladin Christopher F. , Gerraty Richard P. , Fitzgerald Sharyn M. , Phan Thanh , Frayne Judith , Thrift Amanda G. 
Published: March 2017

Background and Purpose—
Despite the benefit of risk awareness in secondary prevention, survivors of stroke are often unaware of their risk factors. We determined whether a nurse-led intervention improved knowledge of risk factors in people with stroke or transient ischemic attack.

Methods—
Prospective study nested within a randomized controlled trial of risk factor management in survivors of stroke or transient ischemic attack. Intervention: 3 nurse education visits and specialist review of care plans. Outcome: unprompted knowledge of risk factors of stroke or transient ischemic attack at 24 months. Effect of intervention on knowledge and factors associated with knowledge were determined using multivariable regression models.

Results—
Knowledge was assessed in 268 consecutive participants from the main trial, 128 in usual care and 140 in the intervention. Overall, 34% of participants were unable to name any risk factor. In adjusted analyses, the intervention group had better overall knowledge than controls (incidence risk ratio, 1.26; 95% confidence interval, 1.00–1.58). Greater functional ability and polypharmacy were associated with better knowledge and older age and having more comorbidities associated with poorer knowledge.

Conclusions—
Overall knowledge of risk factors of stroke or transient ischemic attack was better in the intervention group than controls. However, knowledge was generally poor. New and more effective strategies are required, especially in subgroups identified as having poor knowledge.

Clinical Trial Registration—

URL:
http://www.anzctr.org.au
. Unique identifier: ACTRN12608000166370.
Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions
Authors: Seyed-Allaei Shima , Avanaki Zahra Nasiri , Bahrami Bahador , Shallice Tim 
Published: March 2017

Abstract
An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35–39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.
A Double Dissociation between Anterior and Posterior Superior Temporal Gyrus for Processing Audiovisual Speech Demonstrated by Electrocorticography
Authors: Ozker Muge , Schepers Inga M. , Magnotti John F. , Yoshor Daniel , Beauchamp Michael S. 
Published: March 2017

Abstract
Human speech can be comprehended using only auditory information from the talker's voice. However, comprehension is improved if the talker's face is visible, especially if the auditory information is degraded as occurs in noisy environments or with hearing loss. We explored the neural substrates of audiovisual speech perception using electrocorticography, direct recording of neural activity using electrodes implanted on the cortical surface. We observed a double dissociation in the responses to audiovisual speech with clear and noisy auditory component within the superior temporal gyrus (STG), a region long known to be important for speech perception. Anterior STG showed greater neural activity to audiovisual speech with clear auditory component, whereas posterior STG showed similar or greater neural activity to audiovisual speech in which the speech was replaced with speech-like noise. A distinct border between the two response patterns was observed, demarcated by a landmark corresponding to the posterior margin of Heschl's gyrus. To further investigate the computational roles of both regions, we considered Bayesian models of multisensory integration, which predict that combining the independent sources of information available from different modalities should reduce variability in the neural responses. We tested this prediction by measuring the variability of the neural responses to single audiovisual words. Posterior STG showed smaller variability than anterior STG during presentation of audiovisual speech with noisy auditory component. Taken together, these results suggest that posterior STG but not anterior STG is important for multisensory integration of noisy auditory and visual speech.