tbuckley/cabot-search huggingface dataset:
Lineage-specific events underlie aortic root aneurysm pathogenesis in Loeys-Dietz syndrome
Authors: Elena Gallo MacFarlane, Sarah J. Parker, Joseph Y. Shin, Shira G. Ziegler, Tyler J. Creamer, Rustam Bagirzadeh, Djahida Bedja, Yichun Chen, Juan F. Calderon, Katherine Weissler, Pamela A. Frischmeyer-Guerrerio, Mark E. Lindsay, Jennifer P. Habashi, Harry C. Dietz
Journal: Journal of Clinical Investigation (2019)

The aortic root is the predominant site for development of aneurysm caused by heterozygous loss-of-function mutations in positive effectors of the transforming growth factor-β (TGF-β) pathway. Using a mouse model of Loeys-Dietz syndrome (LDS) that carries a heterozygous kinase-inactivating mutation in TGF-β receptor I, we found that the effects of this mutation depend on the lineage of origin of vascular smooth muscle cells (VSMCs). Secondary heart field–derived (SHF-derived), but not neighboring cardiac neural crest–derived (CNC-derived), VSMCs showed impaired Smad2/3 activation in response to TGF-β, increased expression of angiotensin II (AngII) type 1 receptor (Agtr1a), enhanced responsiveness to AngII, and higher expression of TGF-β ligands. The preserved TGF-β signaling potential in CNC-derived VSMCs associated, in vivo, with increased Smad2/3 phosphorylation. CNC-, but not SHF-specific, deletion of Smad2 preserved aortic wall architecture and reduced aortic dilation in this mouse model of LDS. Taken together, these data suggest that aortic root aneurysm predisposition in this LDS mouse model depends both on defective Smad signaling in SHF-derived VSMCs and excessive Smad signaling in CNC-derived VSMCs. This work highlights the importance of considering the regional microenvironment and specifically lineage-dependent variation in the vulnerability to mutations in the development and testing of pathogenic models for aortic aneurysm.
Internal lymphedema correlation with subjective and objective measures of dysphagia in head and neck cancer.
Authors: Leanne Kolnick Jackson, Sheila H. Ridner, Jie Deng, Carmin Bartow, Kyle Mannion, Kenneth J. Niermann, Jill Gilbert, Mary S. Dietrich, Anthony Cmelak, Barbara A. Murphy
Journal: Journal of Clinical Oncology (2014)

6051 Background: Tumor/treatment-related external (EL) and/or internal lymphedema (IL) are associated with functional deficits and increased symptom burden in head and neck cancer (HNC) patients. We noted an association between EL/IL and patient-reported dysphagia using the Vanderbilt Head and Neck Symptom Survey (VHNSS) version 1.0. Consequently, we studied the relationship between EL/IL with subjective and objective measures of swallow function. Methods: 81 HNC patients completed: (1) the VHNSS version 2.0 which included 13 swallowing or nutrition related questions grouped into three clusters: swallow solids (ss), swallow liquids (sl), nutrition(nt); (2) physical assessment of EL using Foldi scale; (3) endoscopic assessment of IL using the Patterson scale (n=56); and (4) modified-barium videofluoroscopy (MBSS) rated by the Dysphagia Outcome and Severity Scale (DOSS) and in conjunction with a swallow evaluation, by the National Outcomes Measurement System (NOMS). Examinations were performed at varied time points to assess a spectrum of lymphedema, from baseline (n=15, 18.1%) to 18 months post therapy (n=20, 24.1%). Results: VHNSS swallow/nutrition items scores correlated with NOMS and DOSS ratings. The highest correlation was with the NOMS: ss (-.73; p<.001); sl (-.61; p<.001); nt (-.56; p<.001). VHNSS swallow/nutrition scores correlated with maximum grade of swelling for any single structure on the Patterson scale: ss (.43; p=.001); sl (.38; p=.004); nt (.41; p=.002). IL of the aryepiglottic and pharyngoepiglottic folds, epiglottis and pyriform sinus were most strongly correlated with VHNSS swallow/nutrition items and NOMS ratings. There was no correlation with VHNSS swallow/nutrition items or NOMS/DOSS ratings and EL. Conclusions: IL correlated with subjective and objective measures of swallow dysfunction. Longitudinal analysis of the trajectory and impact of IL/EL on dysphagia is ongoing. Clinical trial information: NCT01187173.
Can Ultrasound Be Used to Reassure Pregnant Women Infected by Zika Virus?
Authors: Deborah Levine
Journal: JAMA Network Open (2018)

Jose Paulo Pereira Jr, MD; Karin Nielsen-Saines, MD; Jeffrey Sperling, MD; Melanie M. Maykin, MD; Luana Damasceno, PharmD; Renan Fonseca Cardozo, MD; Helena Abreu Valle, MD; Beatriz Ribeiro Torres Dutra, MD; Helder Dotta Gama, MD; Kristina Adachi, MD; Andrea A. Zin, MD, PhD; Irena Tsui, MD; Zilton Vasconcelos, PhD; Patricia Brasil, MD, PhD; Maria E. Moreira, MD, PhD; Stephanie L. Gaw, MD, PhD
Assessment of Pharmaceutical Company and Device Manufacturer Payments to Gastroenterologists and Their Participation in Clinical Practice Guideline Panels
Authors: Salman Nusrat, Taseen Syed, Sanober Nusrat, Sixia Chen, Wei-Jen Chen, Klaus Bielefeldt
Journal: JAMA Network Open (2018)

Payments from pharmaceutical and device manufacturers to physicians may influence the advice physicians give patients and peers.To investigate the nature and amounts of monetary and other benefits that gastroenterologists received and to determine the participation of those receiving benefits in the formulation of clinical practice guidelines.This cohort study analyzed information from the Centers for Medicare & Medicaid Services Open Payments database, including all reports about payments that pharmaceutical and device manufacturers gave to adult or pediatric gastroenterologists in 2016. PubMed was used to examine the professional affiliations and publication records of top payment recipients. Panelists of clinical guidelines who also received personal financial rewards listed in the Open Payments database were identified.Payments made to gastroenterologists by pharmaceutical company and device manufacturers.Of 15 497 gastroenterologists, 13 467 (86.9%) received a total of 432 463 payments accounting for a total expenditure of $67 144 862. Direct financial payments for consultations, talks, or other services were made to 2055 physicians and were responsible for 4.2% of payments (18 179 of 432 463), but for 62.7% of total expenditures ($42 086 207 of $67 144 862). Although a significant number of submissions were for food and beverages, they constituted only a small amount of total expenditure. For gastroenterologists treating adult patients, 10 products were linked to 63.8% of payments (11 221 of 17 588) related to direct financial rewards and 37.1% of the total expenditures ($24 892 643 of $67 144 862). Twenty-nine of 36 clinical practice guidelines included panelists who had received honoraria or consultation fees from industry sources, with amounts exceeding $10 000 in 8 of them (22%).Most gastroenterologists accept meals or gifts from industry, with 2055 of 15 497 gastroenterologists receiving direct payments and 8 of 36 clinical practice guidelines panelists having received more than $10 000. Considering the known impact of such benefits on prescribing patterns and other professional behaviors, policy makers should consider revising regulations governing interactions with industry and disclosure formats alerting others to their potential biasing impact.
Comparison of US County-Level Public Health Performance Rankings With County Cluster and National Rankings
Authors: Megan Wallace, Joshua M. Sharfstein, Joshua Kaminsky, Justin Lessler
Journal: JAMA Network Open (2019)

Health departments can be grouped together based on sociodemographic characteristics of the population served. Comparisons within these groups can then help with monitoring and improving the health of their populations.To compare county-level percentile rankings on outcomes of smoking, motor vehicle crash deaths, and obesity within sociodemographic peer clusters vs nationwide rankings.This cross-sectional, population-based study of demographic and health data from the 2014 Behavioral Risk Factor Surveillance System and the 2016 Robert Wood Johnson Foundation County Health Rankings data set was conducted at 3139 of 3143 US counties and county-equivalents. Four locations were excluded due to incomplete data. Data analysis was conducted between January and August 2017.Random forest algorithms were used to identify sociodemographic characteristics most associated with the outcomes of interest. These characteristics were race and ethnicity, educational attainment, age, marital status, employment status, sex, and health insurance status. k-means clustering was used to cluster counties based on these sociodemographic characteristics and the percentage of the county classified as rural.County-level smoking prevalence, motor vehicle crash death rate, and obesity prevalence. County percentile rankings on the outcomes of interest were compared in the national context and the within-cluster context.A total of 318 856 967 individuals (mean [SD] individuals per county, 101 579.2 [326 315]; 161 911 910 women [50.8%]) were represented by the 3139 counties used in this analysis. Eight distinct sociodemographic clusters throughout the United States were found. Cluster-specific percentile rankings for both smoking prevalence and motor vehicle crash death rates improved more than 70 percentile points for several counties in the rural, American Indian cluster compared with the nationwide percentiles. Conversely, the young, urban, middle to high socioeconomic status cluster included counties with cluster-specific percentile rankings that declined by 60 percentile points or more compared with the nationwide rankings for all 3 outcomes of interest.Comparing county health outcomes on a nationwide or statewide basis fails to adequately account for sociodemographic context. Clustering counties by sociodemographic factors related to the outcome of interest allows a better understanding of other factors that may be shaping the prevalence of health outcomes. These groupings may also aid learning exchange.
Meeting the needs of at-home siblings of pediatric hematopoietic stem cell transplant patients.
Authors: Rebecca D. Pentz, Taylor E White, Kristopher A Hendershot, Melissa Alderfer, Margie Dixon, Wendy Pelletier, Kristin A. Stegenga, Pamela S. Hinds
Journal: Journal of Clinical Oncology (2014)

e21002 Background: At-home siblings of pediatric cancer HSCT patients report lack of information, lack of inclusion, family separation, and additional responsibilities during the family’s transplant experience (Pentz RD et al, Pediatrics in press). Although resources currently exist to help these siblings, e.g. support groups and activities sponsored by local hospital and community agencies, these children may benefit from personal attention and information during the family’s HSCT experience. This study identified strategies for helping at-home siblings. Methods: We conducted a secondary semantic analysis of qualitative interviews completed with family members of pediatric HSCT patients, coding the data for strategies the family used during the cancer experience. We also interviewed HSCT healthcare team members regarding current resources for at-home siblings and additional interventions to meet their needs. Results: 42 family interviews were coded and 15 healthcare workers were interviewed, including Certified Child Life Specialists (CCLS), inpatient nurses, midlevel providers, a psychologist, a social worker, and a physician. The most frequent strategies to help siblings were meetings with a member of the healthcare team, sharing all information with the child, using phone calls or Skype to communicate more often, having parents split time between hospital and home, attending sibling support groups or workshops, giving the sibling a special role, having the sibling visit the hospital, and having a special day or event for the sibling. Twelve (80%) healthcare workers expressed concern about at-home sibling distress not addressed by current support which requires travel, 11 about lack of sibling inclusion, and 5 about lack of information. All 15 nominated CCLS to intervene with these siblings via Skype to address the needs felt by at-home siblings. Conclusions: Existing resources are inadequate to meet the needs of at-home siblings of children undergoing HSCT. These children may benefit from personal information and support delivered through a variety of strategies by both family members and healthcare workers. A novel CCLS virtual intervention approach may help alleviate siblings’ needs.
The use and beliefs regarding complementary and alternative medicine (CAM) among veteran cancer patients.
Authors: Chen Wang, Nichelle Bowman, Rasna Neelam, Debra Arnoldi, Kemp Bailey Cease, Shruti Jolly
Journal: Journal of Clinical Oncology (2014)

e20632 Background: Population studies indicate that 40% of cancer patients use CAM. Most are not well informed of their chosen CAM and do not discuss it with their healthcare providers. However, no information exists on the use of CAM among the growing number of Veteran cancer survivors. We evaluated the type/prevalence of CAM use among VA cancer patients, disclosure with providers, and the beliefs regarding CAM therapies. Methods: Patients from Radiation Oncology and Medical Oncology outpatient clinics of a VA medical center were surveyed over a 3-month period. An anonymous validated survey regarding attitudes and beliefs of CAM was used to evaluate patients’ responses. Relationship of CAM use and beliefs regarding CAM therapies were analyzed using the student t-test. Results: One hundred ninety-six completed surveys of222 distributed were collected from mostly male (97%) Veterans with an 88.3% response rate. Overall, 14.8% patients reported CAM use, with dietary (55.2%) and herbal (41.4%) supplement use being most common, and acupuncture/meditation (6.9%) being the least common. Of CAM users, 89.7% of patients discussed the use with their physicians. CAM users believed that CAM improves physical health (p<0.001), boosts immune system (p<0.001), reduces stress and cancer/treatment symptoms (p<0.05), prolongs life (p<0.05), helps cure cancer (p<0.05), prevents future health problems (p<0.001), and helps them cope (p<0.001). CAM users felt its use was encouraged by their family (p<0.001), their healthcare providers (p<0.05), and felt their providers were open to the use of CAM (p<0.05). CAM non-users believed that CAM was not based on scientific research (p<0.001), interferes with cancer therapy (p<0.001), costs too much money (p<0.05), and also that they lacked both time for CAM treatments (p<0.05), and overall knowledge about CAM (p<0.05). Conclusions: This study is the first to show that prevalence of CAM use among Veteran cancer patients is lower than the general population, but also that Veterans may be more likely to report CAM use to their healthcare providers. Veterans have divergent beliefs regarding CAM and may benefit from education regarding the risks and benefits of these supplemental modalities.
Potential role of annexin A1 (ANXA1) as a growth inhibitor in breast cancer cell lines
Authors: Kazumi Kawase, Ying X. Hu, Jinsong Liu, Constance T. Albarracin
Journal: Cancer Research (2005)

2876  Annexin I (ANXA I) is a calcium and phospholipid binding protein which serves as a substrate for the tyrosine kinase of the epidermal growth factor receptor (EGFR). ANXA1 has been implicated in apoptosis, cell differentiation and proliferation. Alterations in ANXA1 expression have been described in several tumor types, including breast cancer. However, the precise role and function of ANXA1 in breast cancer have yet to be established. Our goal was to study ANXA1 function in breast cancer cells using cellular in vitro models with defined levels of ANXA1 expression. To evaluate ANXA1 expression in breast cancer cells, Western blot analysis was performed. Low ANXA1 protein expression was detected in MDA-MB-453 whereas high levels of ANXA1 were found in MCF7 and MDA-MB-231. To study the effects of ANXA1 overexpression, retrovirus was used to infect MDA-MB-453 with an expression vector containing ANXA1 cDNA. Conversely, to evaluate the effects of silencing ANXA1 expression, MCF7 and MDA-MB-231, were stably infected with small inhibitory RNAs (siRNA) specific for ANXA1. The siRNAs resulted in varying levels of attenuation of endogenous ANXA1 protein expression in the three different cell lines as assessed by Western blot analysis. The generated cell lines were used to evaluate the effects of ANXA1 on anchorage independent growth in soft agar. Overexpression of ANXA1 resulted in a 50% reduction of colony growth of MDA-MB-453/cDNA cells. In contrast, suppression of ANXA1 in both MCF7 and MDA-MB-231 resulted in a two-fold increase in anchorage independent growth. We wanted to determine whether ANXA1 interacts with HER2/neu, an important? protein in breast cancer and a member of the EGFR family. ANXA1 protein levels were measured in BT-474 and MDA-MB-435 with silenced HER2/neu. In these cell lines, silenced HER2/neu have been previously shown to decrease proliferation and decrease tumor growth in nude mice (J Biol Chem. 6;279:4339,04). In both BT-474 and MDA-MB-435, silenced of HER2/neu was associated with higher ANXA1 protein expression. In conclusion, our studies indicate that ANXA1 has a potential role in the suppression of breast cancer cell growth. We have successfully developed in vitro models to further study the role and function of ANXA1 in breast cancer and to determine whether the interaction of ANXA1 and HER2/neu can be used as a therapeutic site.
Improving the management of fever and suspected chemotherapy-induced neutropenia: A tertiary care center experience.
Authors: Reem Al Sudairy, Mohsen Al Zahrani, Maha Fayadh, Mona Al Shami, Abdul Rahman Jazieh
Journal: Journal of Clinical Oncology (2014)

e21029 Background: Chemotherapy induced febrile neutropenia is a major cause of morbidity and mortality in cancer patients especially if not treated promptly. As we were facing considerable delays in the management of patients with chemotherapy induced febrile neutropenia in the Emergency Department (ED), we initiated an improvement project aiming at “Door to antibiotic time” of 60 minutes for all patients with fever and suspected chemotherapy induced neutropenia. Methods: A multidisciplinary team was assembled to achieve the set goal. By mapping the existing process and implementing various improvement tools, the following changes have been implemented: improving the triaging process, creating an electronic “Chemotherapy alert caution,” developing evidence-based order sets for physicians, and utilizing the hot line by nurses to call the pharmacy to expedite the process of preparation. Outcome and process measures were collected weekly: analyzed and discussed thoroughly by the team. Run charts were used to monitor the progress. Results: After going through 10 plan-do-study-act (PDSA) cycles, all process measures improved and ultimately our main measure, the “Door to antibiotic time” improved from 450 minutes to 49 minutes. Improvement in nursing staff skills and education was noted as an important balancing measure. Conclusions: The project was successful and it achieved its goal in 6 months as a result of adherence to sound methodological approach, the commitment of the multidisciplinary team members and the support from the institute’s leadership. The team is focusing now on sustainability and spread of this improvement project to other facilities.
Variable Bruton Tyrosine Kinase (BTK) Resynthesis across Patients with Chronic Lymphocytic Leukemia (CLL) on Acalabrutinib Therapy Affect Target Occupancy and Reactivation of B-Cell Receptor (BCR) Signaling
Authors: Anfal A. Alsadhan, Jean Cheung, Michael Gulrajani, Erika M. Cook, Stefania Pittaluga, Theresa Davies-Hill, Raquel Izumi, Clare C. Sun, Todd Covey, Adrian Wiestner, Sarah E. M. Herman
Journal: Blood (2018)
Physicians’ experiences with the treatment of seriously ill and dying patients in acute care hospitals in Germany beyond palliative care.
Authors: Asita Behzadi, Anja Hermann, Gesine Leithaeuser, Peter C. Thuss-Patience
Journal: Journal of Clinical Oncology (2014)

e20725 Background: In Germany, as in other industrialized countries, most people die in acute care hospitals (47%). Hence the care for seriously ill and dying patients is, in addition to acute care, cure and prevention, a central challenge for physicians of all medical specialties in a hospital. Little is known about how physicians experience this balancing act in the requirements. Methods: Using a qualitative study design based on the Grounded Theory, we examined the experiences of physicians caring for this group of patients and the resources at their wards. Interviews with thirty physicians of thirteen medical specialties from two acute care hospitals were conducted and analyzed in view of structural and individuals needs. Results: Physicians in hospitals experience an enormous discrepancy between ambitions to treat the seriously ill and dying with dignity and everyday clinical reality. Structural inadequacies, lack of training and team discussions, personnel shortages, and minimally integrated offerings of psychosocial assistance are balanced by individual commitment. Decisions concerning reducing or ending therapy are ethical challenges for which assistant physicians feel ill-prepared. Such decisions are experienced as being dependent on the person and very hierarchical. In ward routine, the question of the when of dying is asked before the how of dying. Palliative care aspects such as quality of life, quality of dying and easing symptoms become the focus only late in the treatment. Here especially nursing is experienced as competent and responsible. Even when physicians have knowledge of palliative medicine to fall back on, the opportunities to practice it are described as limited against the backdrop of shortened hospital stays and a lack of recognition. Conclusions: The results show: (a) Ethical issues that have not been clarified by society must be answered every day in clinical practice. This fact has received little structural recognition or support. (b) This happens against the backdrop of increasing economizing in Germany’s health care System. (c) The hospital must be viewed as a place of learning where head physicians and specialists need act as mentors.