bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of Guideline-Discordant Breast Cancer Care
Authors: McDougall Jean A. , Cook Linda S. , Tang Mei-Tzu C. , Linden Hannah M. , Thompson Beti , Li Christopher I. 
Published: October 2020

Abstract

Background:
Evidence-based breast cancer treatment guidelines recommend the most appropriate course of therapy based on tumor characteristics and extent of disease. Evaluating the multilevel factors associated with guideline discordance is critical to identifying strategies to eliminate breast cancer survival disparities.

Methods:
We identified females diagnosed with a first primary, stage I–III breast cancer between the ages of 20–69 years of age from the population-based Seattle-Puget Sound Surveillance, Epidemiology, and End Results registry. Participants completed a survey about social support, utilization of patient support services, hypothesized barriers to care, and initiation of breast cancer treatment. We used logistic regression to estimate odds ratios and 95% confidence intervals (CI).

Results:
Among 1,390 participants, 10% reported guideline-discordant care. In analyses adjusted for patient-level sociodemographic factors, individuals who did not have someone to go with them to appointments or drive them home (OR 1.96; 95% CI, 1.09–3.59) and those who had problems talking to their doctors or their staff (OR 2.03; 95% CI, 1.13–3.64) were more likely to be guideline discordant than those with social support or without such problems, respectively. Use of patient support services was associated with a 43% lower odds of guideline discordance (OR 0.57; 95% CI, 0.36–0.88).

Conclusions:
Although guideline discordance in this cohort of early-stage breast cancer survivors diagnosed &lt;70 years of age was low, instrumental social support, patient support services, and communication with doctors and their staff emerged as potential multilevel intervention targets for improving breast cancer care delivery.

Impact:
This study supports extending the reach of interventions designed to improve guideline concordance.
Activin A Promotes Regulatory T-cell–Mediated Immunosuppression in Irradiated Breast Cancer
Authors: De Martino Mara , Daviaud Camille , Diamond Julie M. , Kraynak Jeffrey , Alard Amandine , Formenti Silvia C. , Miller Lance D. , Demaria Sandra , Vanpouille-Box Claire 
Published: October 2020

Abstract
Increased regulatory T cells (Treg) after radiotherapy have been reported, but the mechanisms of their induction remain incompletely understood. TGFβ is known to foster Treg differentiation within tumors and is activated following radiotherapy. Thus, we hypothesized that TGFβ blockade would result in decreased Tregs within the irradiated tumor microenvironment. We found increased Tregs in the tumors of mice treated with focal radiotherapy and TGFβ blockade. This increase was mediated by upregulation of another TGFβ family member, activin A. In vitro, activin A secretion was increased following irradiation of mouse and human breast cancer cells, and its expression was further enhanced upon TGFβ blockade. In vivo, dual blockade of activin A and TGFβ was required to decrease intratumoral Tregs in the context of radiotherapy. This resulted in an increase in CD8+ T-cell priming and was associated with a reduced tumor recurrence rate. Combination of immune checkpoint inhibitors with the dual blockade of activin A and TGFβ led to the development of tumor-specific memory responses in irradiated breast cancer. Supporting the translational value of activin A targeting to reduce Treg-mediated immunosuppression, retrospective analysis of a public dataset of patients with breast cancer revealed a positive correlation between activin A gene expression and Treg abundance. Overall, these results shed light on an immune escape mechanism driven by activin A and suggest that dual targeting of activin A and TGFβ may be required to optimally unleash radiation-induced antitumor immunity against breast cancer.
The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma
Authors: Wang Xiuli , Huynh Christian , Urak Ryan , Weng Lihong , Walter Miriam , Lim Laura , Vyas Vibhuti , Chang Wen-Chung , Aguilar Brenda , Brito Alfonso , Sarkissian Aniee , Bandara N. Achini , Yang Lu , Wang Jinhui , Wu Xiwei , Zhang Jianying , Priceman Saul J. , Qin Hong , Kwak Larry W. , Budde Lihua E. , Thomas Sandra H. , Clark Mary C. , Popplewell Leslie , Siddiqi Tanya , Brown Christine E. , Forman Stephen J. 
Published: October 2020

AbstractLymphomas with central nervous system (CNS) involvement confer a worse prognosis than those without CNS involvement, and patients currently have limited treatment options. T cells genetically engineered with CD19-targeted chimeric antigen receptors (CAR) are effective against B-cell malignancies and show tremendous potential in the treatment of systemic lymphoma. We aimed to leverage this strategy toward a more effective therapy for patients with lymphoma with CNS disease. NOD-scid IL2Rgammanull (NSG) mice with CNS and/or systemic lymphoma were treated with CD19-CAR T cells via intracerebroventricular (ICV) or intravenous (IV) injection. CAR T cells isolated after treatment were rigorously examined for phenotype, gene expression, and function. We observed that CAR T cells infused ICV, but not IV, completely and durably eradicated both CNS and systemic lymphoma. CAR T cells delivered ICV migrated efficiently to the periphery, homed to systemic tumors, and expanded in vivo, leading to complete elimination of disease and resistance to tumor rechallenge. Mechanistic studies indicated that ICV-delivered CAR T cells are conditioned by exposure to cerebrospinal fluid in the ICV environment for superior antilymphoma activity and memory function compared with IV-delivered CAR T cells. Further analysis suggested that manipulating cellular metabolism or preactivating therapeutic CAR T cells with antigen ex vivo may improve the efficacy of CAR T cells in vivo. Our demonstration that ICV-delivered CD19-CAR T cells had activity against CNS and systemic lymphoma could offer a valuable new strategy for treatment of B-cell malignancies with CNS involvement.
Relative Importance of Internal Climate Variability versus Anthropogenic Climate Change in Global Climate Change
Authors: Chen Jie , Li Xiangquan , Martel Jean-Luc , Brissette François P. , Zhang Xunchang J. , Frei Allan 
Published: October 2020

AbstractTo better understand the role of internal climate variability (ICV) in climate change impact studies, this study quantifies the importance of ICV [defined as the intermember variability of a single model initial-condition large ensemble (SMILE)] in relation to the anthropogenic climate change (ACC; defined as multimodel ensemble mean) in global and regional climate change using a criterion of time of emergence (ToE). The uncertainty of the estimated ToE is specifically investigated by using three SMILEs to estimate the ICV. The results show that using 1921–40 as a baseline period, the annual mean precipitation ACC is expected to emerge within this century over extratropical regions as well as along the equatorial band. However, ToEs are unlikely to occur, even by the end of this century, over intratropical regions outside of the equatorial band. In contrast, annual mean temperature ACC has already emerged from the temperature ICV for most of the globe. Similar spatial patterns are observed at the seasonal scale, while a weaker ACC for boreal summer (June–August) precipitation and additional ICV for boreal winter (December–February) temperature translate to later ToEs for some regions. In addition, the uncertainty of ToE related to the choice of a SMILE is mostly less than 20 years for annual mean precipitation and temperature. However, it can be as large as 90 years for annual mean precipitation over some regions. Overall, results indicate that the choice of a SMILE is a significant source of uncertainty in the estimation of ToE and results based on only one SMILE should be interpreted with caution.
Muscle Tension Dysphagia: Contributing Factors and Treatment Efficacy
Authors: Kang Christina H. , Zhang Nan , Lott David G. 
Published: October 2020

Objective: To determine factors contributing to disease etiology and treatment efficacy. Study Design: Original Report. Setting: Tertiary academic center. Methods: IRB approved prospective study of 20 patients with reported dysphagia who exhibited normal oropharyngeal and esophageal swallowing function as evidenced by videofluoroscopic swallow study, esophagogastroduodenoscopy, high-resolution esophageal manometry with stationary impedance, and Bravo pH probe off proton pump inhibitor. Patients underwent speech-language pathology intervention. Results: Atypical laryngeal muscle tension was present in 100% of patients. Forty percent of patients had diagnosed positive gastroesophageal reflux disease. Sixty-five percent of patients showed signs of non-specific laryngeal inflammation and laryngeal hyperresponsiveness during strobolaryngoscopy. All patients reported a mean of 90% recovery by the completion of voice therapy directed toward unloading muscle tension. Conclusion: The study results suggest an association between laryngeal muscle tension and these patients’ dysphagia symptoms regardless of associated conditions. Speech-language pathology intervention showed high treatment efficacy. Level of Evidence: 2c- Outcomes research.
Efficacy and Safety of Transarterial Chemoembolization Combined With Anlotinib for Unresectable Hepatocellular Carcinoma: A Retrospective Study
Authors: Guo Wenbo , Chen Song , Wu Zhiqiang , Zhuang Wenquan , Yang Jianyong 
Published: October 2020

Objective: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone. Methods: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan–Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant. Results: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment. Conclusion: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.
Delayed Gastric Emptying Post-Esophagectomy: A Single-Institution Experience
Authors: Frederick Allison B. , Lorenz William R. , Self Stella , Schammel Christine , Bolton William D. , Stephenson James E. , Ben-Or Sharon 
Published: October 2020

Objective Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy in patients with esophageal carcinoma. Management of DGE varies widely and it is unclear how comorbidities influence the postoperative course. This study sought to determine factors that influence postoperative DGE. Methods This retrospective study evaluates patients who underwent esophagectomy with gastric pull-up between 2007 and 2019. The cohort was stratified in various ways to determine if postoperative care and outcomes differed, including patient demographics, comorbidities, intraoperative and postoperative procedures. Results During the study period, 149 patients underwent esophagectomy and 37 had diabetes. Overall incidence of DGE, as defined in this study, was 76.5%. Surgery type was significantly different between DGE and normal emptying cohorts ( P = 0.005). Comparing diabetic and nondiabetic patients, there was no significant difference noted in DGE ( P = 0.25). Additionally, there was no difference in presence of DGE for patients who underwent any intraoperative pyloric procedure compared to those who did not ( P = 0.36). Of significance, all 16 patients with chronic obstructive pulmonary disease had a delay in gastric emptying ( P = 0.01). Conclusions A higher proportion of patients with DGE post-esophagectomy were identified compared to the literature. There is little consensus on a true definition of DGE, but we believe this definition identifies patients suffering in the immediate postoperative period and in follow-up. There is no evidence to support a different postoperative course for patients with diabetes, but the link between chronic obstructive pulmonary disease and DGE warrants further investigation.
Evaluating the Impact of Outpatient Multi-Dose Medication Packaging Service (MDMPS) on Medication Adherence and Clinical Outcomes
Authors: Nair Pratibha , Kee Kok Wai , Mah Choon Siong , Lee Eng Sing 
Published: October 2020

Background: There is limited understanding on the impact of the multidose medication packaging service (MDMPS). Objectives: The main objective of this study was to evaluate changes in medication adherence in patients using MDMPS compared to patients receiving standard medication packaging (control group). The other objectives were to determine the association between medication adherence and clinical outcomes, and to assess patients’/caregivers’ perceptions toward MDMPS. Methods: A retrospective cohort study was conducted among primary care patients in Singapore enrolled into MDMPS between 2012 and 2017. Eligible patients were taking at least five chronic medications, diagnosed with Hypertension, Hyperlipidemia and/or Type 2 Diabetes, with prescription records for at least six months before and after the index period. They were matched to control patients based on the type of comorbidities and medication adherence status. Medication Possession Ratio (MPR), glycated hemoglobin (HbA1c), blood pressure and low-density lipoprotein-cholesterol (LDL-C) of both groups were compared between baseline and at least six months post-index period. Interviewer-administered questionnaires were also conducted for MDMPS patients. Results: The MPR of MDMPS patients (n = 100) increased by 0.37% ( P < .001) compared to the control group (n = 100). MDMPS patients with diabetes had reduced HbA1c by 0.1% after six months ( P = .022) but was not significant after 12 months. No significant changes were seen in blood pressure and LDL-C between both groups. At least 50% of patients were highly satisfied with MDMPS. Conclusion: MDMPS can improve medication adherence. Further studies are needed to understand its clinical impact.
Oral Health-Related Quality of Life (OHRQoL) in Patients with Definitive Maxillary Obturator Prostheses: A Prospective Study
Authors: Kalaignan S. Parithimar , Ahmed Syed Ershad 
Published: October 2020

Aim: To assess the impact of definitive maxillary obturator prostheses on oral health-related quality of life (OHRQol). Materials and Methods: A presented prospective study comprising 50 patients with maxillectomy defects was selected for the study. Patients with any active or persistent lesion in relation to the defect site, restrictive mouth opening along with poor general health were excluded from the study. All the patients were rehabilitated with definitive maxillary obturator prostheses, respectively. These patients were subjected for assessment of OHRQol and obturator prostheses functioning. These assessments were done using three scales OHIP-Edent-19, obturator functioning scale (OFS-15) and a novel scale—maxillofacial prosthesis performance scale (MFPPS). The assessment was done on all the patients after 2 weeks and 3 months of prosthesis function. The data were tabulated and analysed using paired sample t-test and the Wilcoxon signed rank test for paired groups and unpaired sample t-test for independent groups. Results: The scores of OHIP-Edent, OFS and MFPPS for definitive maxillary obturator prostheses after 2 weeks were 37.56, 30.48 and 20.50. The scores of OHIP-Edent, OFS and MFPPS for definitive maxillary obturator prostheses after 3 months were 30.30, 24.26 and 16.10, respectively. Conclusion: Mean differences of OHIP-Edent (7.260), OFS (6.220) and MFPPS (4.400) were observed after 2 weeks and 3 months of obturator prosthesis function. These findings show significant improvements of prosthesis in terms of functional, physical, psychological and social parameters after long-term follow-up (3 months).
Esthetic Rehabilitation With Nanohybrid Composite: Case Report Series
Authors: Qaiser Shazeena , Devadiga Darshana , Hegde Mithra N 
Published: October 2020

Composite resins represent the current state of the art in the field of restorative materials, for they present a standard aesthetic potential with satisfactory durability and are less cost-effective than a comparable ceramic restoration. The most recent addition to this is a nanohybrid direct composite that demonstrates exceptional handling properties and superior aesthetics. These series of case reports illustrate the three different scenarios where nanohybrid composite was used as a direct restorative material owing to its high smoothness and favorable mechanical properties; the first case being the fracture of an upper lateral incisor, second of Class IV caries in upper central incisors, and lastly the discolored restoration and Class III caries in upper central incisors. The nanohybrids used provided an acceptable color match in all the three cases with a conservative technique and were relatively easy to maintain.
Return to Play Following Isolated and Combined Anterior Cruciate Ligament Reconstruction: 25+ Years of Experience Treating National Football League Athletes
Authors: Khair Michael , Riboh Jonathan , Solis Jaicus , Maurer Jim , Brown J. Britt , Vandermeer Robert D. , Cooper Daniel E. 
Published: October 2020

Background: The first case series to report on return to play (RTP) in National Football League (NFL) players after primary anterior cruciate ligament (ACL) reconstruction (ACLR) published an RTP rate of 63%. Other studies that have attempted to estimate RTP after ACLR in these elite athletes have been largely based on secondary sources. This study is the second to report the authors’ own results in treating ACL injuries in NFL players spanning a study period of 25+ years. Purpose: To report the senior authors’ experience treating ACL injuries in NFL players as well as revisit the concept of RTP as it is currently used to measure successful surgical outcomes in professional athletes. Study Design: Case series; Level of evidence, 4. Methods: A total of 47 NFL players were treated at our institution for knee injuries that included a complete tear of the ACL; of these, 41 were primary ACLR and 6 were revision ACLR. Of the primary ACLRs, 6 were classified as ACL plus additional ligament and 3 were classified as multiligament. Return to game play (RTGP) was defined as returning to play in a regular-season game. Successful return to previous participation (RTPP) was defined as return to a level of participation equal to the level the player had reached before injury. Multivariate analysis was used to assess predictors of successful RTPP. Results: Using the RTGP criteria proposed by prior authors, the RTGP after primary ACLR was 73%. Using our proposed RTPP criteria, 87.8% of players successfully returned to the same level of participation after primary ACLR. RTGP percentage for all NFL players after ACLR (including multiligament injuries) was 67.6%, and the overall RTPP for those patients was 87.8%. In multivariate analysis, age ≤25 years was predictive of successful RTPP. High draft picks and offensive players played more seasons after primary ACLR. ACL graft rupture occurred in 4.3% of this cohort. Contralateral ACL tear occurred in 8.5%. Conclusion: Regardless of which definition is used to measure a successful outcome after ACLR surgery, the findings of this study suggest that successful return after primary ACLR in NFL athletes is higher than previously reported. While concomitant reconstruction of a single collateral ligament did not affect RTPP, revision ACLR or bicruciate plus collateral ligament reconstruction was associated with a lower RTPP rate. Age ≤25 years predicted successful RTPP. The risk of a future ACL tear of either knee after index reconstruction was approximately 13%.
Neuromuscular Training Improves Self-Reported Function and Single-Leg Landing Hip Biomechanics in Athletes After Anterior Cruciate Ligament Reconstruction
Authors: Nagelli Christopher , Di Stasi Stephanie , Tatarski Rachel , Chen Albert , Wordeman Samuel , Hoffman Joshua , Hewett Timothy E. 
Published: October 2020

Background: Neuromuscular training (NMT) has been shown to attenuate high-risk biomechanics in uninjured athletes. At the time that athletes return to sport after anterior cruciate ligament (ACL) reconstruction (ACLR), they demonstrate hip biomechanical deficits associated with injury to the reconstructed knee versus the uninjured contralateral knee. Purpose: The primary purpose of the study was to examine whether an NMT program can improve single-leg drop (SLD) landing hip biomechanics for athletes after ACLR. Secondarily, we compared the posttraining SLD hip biomechanics of athletes after ACLR with a control group of athletes who also completed the NMT program. Study Design: Controlled laboratory study. Methods: A total of 18 ACLR and 10 uninjured athletes were recruited and completed a 12-session NMT program. A knee-specific questionnaire and biomechanics of an SLD task was evaluated for each athlete before and after NMT. Paired t tests were used to compare pre- and posttraining International Knee Documentation Committee (IKDC) scores. Repeated-measures analysis of variance (ANOVA) was performed to assess the main effects and interactions of testing session × limb for the ACLR athletes. A 2-way ANOVA was conducted to quantify the interactions and main effects of group × limb. Results: There was a significant increase ( P = .03) in IKDC scores from pre- to posttraining. For the ACLR athletes, there was a significant session × limb interaction for hip external rotation moment ( P = .02) and hip abduction angle ( P = .013). Despite increases in hip external rotation moment, no significant changes from pre- to posttraining were observed for the involved limbs. No significant changes were observed for hip abduction angle of the involved limbs between training sessions. Significant main effects of session ( P < .05) revealed that athletes landed with greater hip excursion, lower hip flexion moment, and lower ground-reaction force after training. The posttraining comparison between the ACLR and control groups found no significant group × limb interactions for any of the hip kinematic or kinetic variables. A significant main effect of group ( P < .05) revealed that the ACLR athletes landed with greater hip flexion angle and hip external rotation moment. Conclusion: ACLR athletes demonstrated an improvement in SLD hip biomechanics and neuromuscular control after participating in an NMT program. Clinical Relevance: This evidence indicates a potential role for NMT to improve hip biomechanics during an SLD task so as to reduce ACL injury risk.