bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily Time of Radiation Treatment Is Associated with Subsequent Oral Mucositis Severity during Radiotherapy in Head and Neck Cancer Patients
Authors: Gu Fangyi , Farrugia Mark K. , Duncan William D. , Feng Yingdong , Hutson Alan D. , Schlecht Nicolas F. , Repasky Elizabeth A. , Antoch Marina P. , Miller Austin , Platek Alexis , Platek Mary E. , Iovoli Austin J. , Singh Anurag K. 
Published: February 2020

Abstract

Background:
Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer.

Methods:
We used electronic medical records of 190 patients with head and neck squamous cell carcinoma who completed radiotherapy, with or without concurrent chemotherapy, at Roswell Park Comprehensive Cancer Center (Buffalo, NY) between 2015 and 2017. Throughout a 7-week treatment course, patient mouth and throat soreness (MTS) was self-reported weekly using a validated oral mucositis questionnaire, with responses 0 (no) to 4 (extreme). Average treatment times from day 1 until the day before each mucositis survey were categorized into seven groups. Multivariable-adjusted marginal average scores (LSmeans) were estimated for the repeated- and maximum-MTS, using a linear-mixed model and generalized-linear model, respectively.

Results:
Radiation treatment time was significantly associated with oral mucositis severity using both repeated-MTS (n = 1,156; P = 0.02) and maximum-MTS (n = 190; P = 0.04), with consistent patterns. The severity was lowest for patients treated during 8:30 to &lt;9:30 am (LSmeans for maximum-MTS = 2.24; SE = 0.15), increased at later treatment times and peaked at early afternoon (11:30 am to &lt;3:00 pm, LSmeans = 2.66–2.71; SEs = 0.16/0.17), and then decreased substantially after 3 pm.

Conclusions:
We report a significant association between radiation treatment time and oral mucositis severity in patients with head and neck cancer.

Impact:
Although additional studies are needed, these data suggest a potential simple treatment time solution to limit severity of oral mucositis during radiotherapy without increasing cost.
Race May Not Impact Endocrine Therapy–Related Changes in Breast Density
Authors: Johnson Helen M. , Shivalingappa Hitesh , Irish William , Wong Jan H. , Muzaffar Mahvish , Verbanac Kathryn , Vohra Nasreen A. 
Published: February 2020

Abstract

Background:
Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD).

Methods:
This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor–positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model.

Results:
Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P &lt; 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = −0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P &lt; 0.0001), and VBD decreased (premenopausal slope = −0.063%, SE = 0.011; postmenopausal slope = −0.016%, SE = 0.004; P &lt; 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P &lt; 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time × BMI, P = 0.0098).

Conclusions:
Race does not appear to impact ET-related longitudinal changes in VBD.

Impact:
Racial disparities in estrogen receptor–positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.
Embedding Mobile Health Technology into the Nurses' Health Study 3 to Study Behavioral Risk Factors for Cancer
Authors: Fore Ruby , Hart Jaime E. , Choirat Christine , Thompson Jennifer W. , Lynch Kathleen , Laden Francine , Chavarro Jorge E. , James Peter 
Published: February 2020

Abstract

Background:
Physical activity and sleep are behavioral risk factors for cancer that may be influenced by environmental exposures, including built and natural environments. However, many studies in this area are limited by residence-based exposure assessment and/or self-reported, time-aggregated measures of behavior.

Methods:
The Nurses' Health Study 3 (NHS3) Mobile Health Substudy is a pilot study of 500 participants in the prospective NHS3 cohort who use a smartphone application and a Fitbit for seven-day periods, four times over a year, to measure minute-level location, physical activity, heart rate, and sleep.

Results:
We have collected data on 435 participants, comprising over 6 million participant-minutes of heart rate, step, sleep, and location. Over 90% of participants had five days of ≥600 minutes of Fitbit wear-time in their first sampling week, and this percentage dropped to 70% for weeks 2 to 4. Over 819 sampling weeks, we observed an average of 7,581 minutes of heart rate and step data [interquartile range (IQR): 6,651–9,645] per participant-week, and &gt;2 million minutes of sleep in over 5,700 sleep bouts. We have recorded location data for 5,237 unique participant-days, averaging 104 location observations per participant-day (IQR: 103–107).

Conclusions:
This study describes a protocol to incorporate mobile health technology into a nationwide prospective cohort to measure high-resolution objective data on environment and behavior.

Impact:
This project could provide translational insights into interventions for urban planning to optimize opportunities for physical activity and healthy sleep patterns to reduce cancer risk.
See all articles in this CEBP Focus section, “Modernizing Population Science.”
Anastrozole has an Association between Degree of Estrogen Suppression and Outcomes in Early Breast Cancer and is a Ligand for Estrogen Receptor α
Authors: Ingle James N. , Cairns Junmei , Suman Vera J. , Shepherd Lois E. , Fasching Peter A. , Hoskin Tanya L. , Singh Ravinder J. , Desta Zeruesenay , Kalari Krishna R. , Ellis Matthew J. , Goss Paul E. , Chen Bingshu E. , Volz Bernhard , Barman Poulami , Carlson Erin E. , Haddad Tufia , Goetz Matthew P. , Goodnature Barbara , Cuellar Matthew E. , Walters Michael A. , Correia Cristina , Kaufmann Scott H. , Weinshilboum Richard M. , Wang Liewei 
Published: February 2020

AbstractPurpose:To determine if the degree of estrogen suppression with aromatase inhibitors (AI: anastrozole, exemestane, letrozole) is associated with efficacy in early-stage breast cancer, and to examine for differences in the mechanism of action between the three AIs.Experimental Design:Matched case–control studies [247 matched sets from MA.27 (anastrozole vs. exemestane) and PreFace (letrozole) trials] were undertaken to assess whether estrone (E1) or estradiol (E2) concentrations after 6 months of adjuvant therapy were associated with risk of an early breast cancer event (EBCE). Preclinical laboratory studies included luciferase activity, cell proliferation, radio-labeled ligand estrogen receptor binding, surface plasmon resonance ligand receptor binding, and nuclear magnetic resonance assays.Results:Women with E1 ≥1.3 pg/mL and E2 ≥0.5 pg/mL after 6 months of AI treatment had a 2.2-fold increase in risk (P = 0.0005) of an EBCE, and in the anastrozole subgroup, the increase in risk of an EBCE was 3.0-fold (P = 0.001). Preclinical laboratory studies examined mechanisms of action in addition to aromatase inhibition and showed that only anastrozole could directly bind to estrogen receptor α (ERα), activate estrogen response element-dependent transcription, and stimulate growth of an aromatase-deficient CYP19A1−/− T47D breast cancer cell line.Conclusions:This matched case–control clinical study revealed that levels of estrone and estradiol above identified thresholds after 6 months of adjuvant anastrozole treatment were associated with increased risk of an EBCE. Preclinical laboratory studies revealed that anastrozole, but not exemestane or letrozole, is a ligand for ERα. These findings represent potential steps towards individualized anastrozole therapy.
Man’s Best Friend and Sometimes Target: Negative Interpersonal Relations Are Related to Animal Abuse Proclivity
Authors: Ford Jade , Bytheway Amber , Alleyne Emma 
Published: February 2020

Abstract
Emerging research regarding the psychological correlates of nonhuman animal abuse is warranted by the high prevalence of abuse. The few studies to examine factors related to animal abuse have found that those who commit such offenses commonly experience dysfunctional childhoods and high anxiety levels. Yet, no study has examined how attachment styles (by-products of maladaptive childhoods), social-anxiety, and animal abuse proclivity are inter-related. Therefore, this study assessed the association between attachment styles and social anxiety as indicators of animal abuse proclivity within an adult sample. It was found that an anxious attachment significantly correlated with direct proclivity (i.e., animal as the perceived provocateur) while the relationship between social anxiety and indirect animal abuse proclivity (i.e., animal as the outlet for aggression) was mediated by avoidant attachment. These findings emphasize the importance of exploring how interpersonal relationships influence our relationship with animals, to advance treatment and assessment of animal abusers.
Clinical Efficacy of Stent in Patients with Cervical Esophageal and/or Hypopharyngeal Stenosis after Total Laryngectomy
Authors: Zhao GuoRui , Ren JianZhuang , Duan XuHua , Zhang WenGuang , Li FangZheng , Han XinWei 
Published: February 2020

We retrospectively analyzed 17 patients with esophageal stent who underwent cervical esophageal and/or hypopharyngeal stenosis after total laryngectomy (TL) from January 2014 to January 2018. The success rate of stent implantation was 100%. Dysphagia in 16 patients improved to class 0 or 1 (16/17, 94.12%) after stent implantation and in 1 patient was improved to class 2 (1/17, 5.88%). Two patients died of tumor progression at 7 months and 11 months after stent implantation, respectively, but both could eat semi‐solid/solid food before death. Dysphagia was resolved in the remaining 15 patients, and there was no recurrence of dysphagia including feeding obstruction during follow‐up. Therefore, this case series concludes that the esophageal stent position after TL can be much higher than that of patients with normal pharyngeal structures. Esophageal stent implantation is a feasible and effective treatment for patients with laryngopharyngeal/esophageal stenosis following TL.
Systemic exosomal miR-193b-3p delivery attenuates neuroinflammation in early brain injury after subarachnoid hemorrhage in mice
Authors: Lai Niansheng , Wu Degang , Liang Tianyu , Pan Pengjie , Yuan Guiqiang , Li Xiang , Li Haiying , Shen Haitao , Wang Zhong , Chen Gang 
Published: February 2020

Abstract
Background
Inflammation is a potential crucial factor in the pathogenesis of subarachnoid hemorrhage (SAH). Circulating microRNAs (miRNAs) are involved in the regulation of diverse aspects of neuronal dysfunction. The therapeutic potential of miRNAs has been demonstrated in several CNS disorders and is thought to involve modulation of neuroinflammation. Here, we found that peripherally injected modified exosomes (Exos) delivered miRNAs to the brains of mice with SAH and that the potential mechanism was regulated by regulation of neuroinflammation.

Methods
Next-generation sequencing (NGS) and qRT-PCR were used to define the global miRNA profile of plasma exosomes in aSAH patients and healthy controls. We peripherally injected RVG/Exos/miR-193b-3p to achieve delivery of miR-193b-3p to the brain of mice with SAH. The effects of miR-193b-3p on SAH were assayed using a neurological score, brain water content, blood-brain barrier (BBB) injury, and Fluoro-Jade C (FJC) staining. Western blotting analysis, enzyme-linked immunosorbent assay (ELISA), and qRT-PCR were used to measure various proteins and mRNA levels.

Results
NGS and qRT-PCR revealed that four circulating exosomal miRNAs were differentially expressed. RVG/Exos exhibited improved targeting to the brains of SAH mice. MiR-193b-3p suppressed the expression and activity of HDAC3, upregulating the acetylation of NF-κB p65. Finally, miR-193b-3p treatment mitigated the neurological behavioral impairment, brain edema, BBB injury, and neurodegeneration induced by SAH, and reduced inflammatory cytokine expression in the brains of mice after SAH.

Conclusions
Exos/miR-193b-3p treatment attenuated the inflammatory response by acetylation of the NF-κB p65 via suppressed expression and activity of HDAC3. These effects alleviated neurobehavioral impairments and neuroinflammation following SAH.
Astroglial TLR9 antagonism promotes chemotaxis and alternative activation of macrophages via modulation of astrocyte-derived signals: implications for spinal cord injury
Authors: Li Lun , Ni Li , Heary Robert F. , Elkabes Stella 
Published: February 2020

Abstract
Background
The recruitment of immune system cells into the central nervous system (CNS) has a profound effect on the outcomes of injury and disease. Glia-derived chemoattractants, including chemokines, play a pivotal role in this process. In addition, cytokines and chemokines influence the phenotype of infiltrating immune cells. Depending on the stimuli present in the local milieu, infiltrating macrophages acquire the classically activated M1 or alternatively activated M2 phenotypes. The polarization of macrophages into detrimental M1 versus beneficial M2 phenotypes significantly influences CNS pathophysiology. Earlier studies indicated that a toll-like receptor 9 (TLR9) antagonist modulates astrocyte-derived cytokine and chemokine release. However, it is not known whether these molecular changes affect astrocyte-induced chemotaxis and polarization of macrophages. The present studies were undertaken to address these issues.

Methods
The chemotaxis and polarization of mouse peritoneal macrophages by spinal cord astrocytes were evaluated in a Transwell co-culture system. Arrays and ELISA were utilized to quantify chemokines in the conditioned medium (CM) of pure astrocyte cultures. Immunostaining for M1- and M2-specific markers characterized the macrophage phenotype. The percentage of M2 macrophages at the glial scar was determined by stereological approaches in mice sustaining a mid-thoracic spinal cord contusion injury (SCI) and intrathecally treated with oligodeoxynucleotide 2088 (ODN 2088), the TLR9 antagonist. Statistical analyses used two-tailed independent-sample t-test and one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. A p value < 0.05 was considered to be statistically significant.

Results
ODN 2088-treated astrocytes significantly increased the chemotaxis of peritoneal macrophages via release of chemokine (C-C motif) ligand 1 (CCL1). Vehicle-treated astrocytes polarized macrophages into the M2 phenotype and ODN 2088-treated astrocytes promoted further M2 polarization. Reduced CCL2 and CCL9 release by astrocytes in response to ODN 2088 facilitated the acquisition of the M2 phenotype, suggesting that CCL2 and CCL9 are negative regulators of M2 polarization. The percentage of M2 macrophages at the glial scar was higher in mice sustaining a SCI and receiving ODN 2088 treatment as compared to vehicle-treated injured controls.

Conclusions
TLR9 antagonism could create a favorable environment during SCI by supporting M2 macrophage polarization and chemotaxis via modulation of astrocyte-to-macrophage signals.
Perspectives on the prospective development of stroke-specific lower extremity wearable monitoring technology: a qualitative focus group study with physical therapists and individuals with stroke
Authors: Louie Dennis R. , Bird Marie-Louise , Menon Carlo , Eng Janice J. 
Published: February 2020

Abstract
Background
Wearable activity monitors that track step count can increase the wearer’s physical activity and motivation but are infrequently designed for the slower gait speed and compensatory patterns after stroke. New and available technology may allow for the design of stroke-specific wearable monitoring devices, capable of detecting more than just step counts, which may enhance how rehabilitation is delivered. The objective of this study was to identify important considerations in the development of stroke-specific lower extremity wearable monitoring technology for rehabilitation, from the perspective of physical therapists and individuals with stroke.

Methods
A qualitative research design with focus groups was used to collect data. Five focus groups were conducted, audio recorded, and transcribed verbatim. Data were analyzed using content analysis to generate overarching categories representing the stakeholder considerations for the development of stroke-specific wearable monitor technology for the lower extremity.

Results
A total of 17 physical therapists took part in four focus group discussions and three individuals with stroke participated in the fifth focus group. Our analysis identified four main categories for consideration: 1) ‘Variability’ described the heterogeneity of patient presentation, therapy approaches, and therapeutic goals that are taken into account for stroke rehabilitation; 2) ‘Context of use’ described the different settings and purposes for which stakeholders could foresee employing stroke-specific wearable technology; 3) ‘Crucial design features’ identified the measures, functions, and device characteristics that should be considered for incorporation into prospective technology to enhance uptake; and 4) ‘Barriers to adopting technology’ highlighted challenges, including personal attitudes and design flaws, that may limit the integration of current and future wearable monitoring technology into clinical practice.

Conclusions
The findings from this qualitative study suggest that the development of stroke-specific lower extremity wearable monitoring technology is viewed positively by physical therapists and individuals with stroke. While a single, specific device or function may not accommodate all the variable needs of therapists and their clients, it was agreed that wearable monitoring technology could enhance how physical therapists assess and treat their clients. Future wearable devices should be developed in consideration of the highlighted design features and potential barriers for uptake.
Effects of co-infection on the clinical outcomes of Clostridium difficile infection
Authors: Shafiq Muhammad , Alturkmani Hani , Zafar Yousaf , Mittal Vishal , Lodhi Hafsa , Ullah Waqas , Brewer Joseph 
Published: February 2020

Abstract
Background
Clostridium difficile (C. difficile) is a spore-forming, Gram-positive rod that is known to be associated with antibiotic use. It is one of the leading causes of nosocomial diarrhea in the industrialized world and therefore warrants further study of its nature. It isn’t clear if co-infection by other organisms can affect the outcome of C. difficile infection (CDI).

Methods
A single center retrospective study was done and it used inclusion criteria of 18 years of age and being tested positive for CDI on FilmArray® multiplex gastro-intestinal (GI) panel. Exclusion criteria were a GI panel performed on an outpatient basis, recurrent CDI, and the presence of end-stage renal disease, cirrhosis, or a non-GI infection. The stool sample for all patients were collected within 48 h of presentation to the hospital. There were 235 of 2576 GI panels selected for a retrospective chart review based on the above criteria. Among these 235 patients, 38 had a co-infection (CDI+ another GI infection = group A or cases) and the rest had only CDI (group B or controls). Group A was compared with group B for CDI severity, its response to treatment, recurrence, and length of the hospital stay, using 0.05 as the alpha criterion.

Results
Most patients with CDI were female and above the age of 60 years. Co infection did not increase the severity of CDI based both on the American College of Gastroenterology criteria (p 0.16) as well as Infectious Disease Society of America criteria (p 0.77). Co infection group also didn’t have significantly different CDI related treatment failure rate (p 0.23), or CDI recurrence rate (p 0.49). Co-infection was also not associated with lengthier hospital stay (p 0.41).

Conclusion
Our study suggests that co-infection doesn’t affect the severity of CDI or can cause treatment failures. Additionally, there was no significant increase in hospital stay, or increase in CDI recurrence associated with co-infection. Therefore, if CDI is the leading clinical diagnosis and a patient is tested positive for co-infection in addition to CDI on FilmArray® multiplex GI panel, this co-infection shouldn’t change the management for CDI. Limitations of this study (including retrospective nature of the study, small sample size, single site study, not including all microbiome and non-inclusion of race) should also be taken into account, while considering the applicability of the results of this study.
Reduced 90-day postoperative mortality through geriatric comanagement after cancer surgery.
Authors: Shahrokni Armin , Tin Amy , Sarraf Saman , Alexander Koshy , Kim Soo Jung , Yulico Heidi , McMillan Sincere , Downey Robert J. , Vickers Andrew , Korc-Grodzicki Beatriz 
Published: February 2020

11512 Background: We explored the association between geriatric comanagement and 90-day postoperative mortality of cancer patients aged 75 or older. Methods: A retrospective review of a prospectively maintained database was performed on patients over 75 years old who underwent elective surgery with hospital length of stay of ≥1 day at Memorial Sloan Kettering Cancer Center from 2015-2018. Geriatric comanagement group (GCG) patients had geriatric preoperative evaluation and inpatient geriatric comanagement. Patients in the surgical management group (SMG) did not have geriatric preoperative evaluation or postoperative geriatric comanagement. We utilized a multivariable logistic regression model with 90-day mortality as the outcome, geriatric co-management as the predictor, and adjusted for age, gender, American Society of Anesthesiology score, Memorial Sloan Kettering Frailty Index, preoperative albumin level, operation time, and estimated blood loss. The same logistic model was used to assess the association between adverse surgical events within 30-days (any major complication, readmission, or urgent care center visit) and geriatric comanagement. Results: Of 1,855 patients (median age 80), 1,009 patients (54%) were co-managed by geriatricians. GCG patients were slightly older, less likely to be male, had longer operation time, and stayed in the hospital longer. Adjusted rates of 90-day mortality was lower in GCG vs. SMG (4.3% and 9.2%, respectively; 95% CI around difference -7.3%, -2.5%; p-value < 0.0001). We did not find evidence of a difference in adverse surgical events between groups (OR 0.96, p-value = 0.8). A greater proportion of GCG patients received inpatient physical therapy (80% vs. 64%) and occupational therapy (37% vs. 25%) compared to SMG patients. Conclusions: Our study shows that geriatric comanagement is associated with reduced 90-day postoperative mortality in cancer patients aged ≥75. A randomized trial study is needed to confirm this finding.