tbuckley/cabot-search huggingface dataset:
Healthy Contact Lens Behaviors Communicated by Eye Care Providers and Recalled by Patients — United States, 2018
Authors: Nuadum M. Konne, Sarah A. Collier, Jennifer Spangler, Jennifer R. Cope
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

An estimated 45 million U.S. residents enjoy the benefits of contact lens wear, but many of them might be at increased risk for complications stemming from improper wear and care behaviors (1). One of the most serious complications of contact lens wear is a corneal infection known as microbial keratitis, which can sometimes result in reduced vision or blindness (2). In 2014, 50% of contact lens wearers reported ever sleeping in contact lenses, and 55% reported topping off* their contact lens solutions (3), which put them at greater risk for a contact lens-related eye infection (2,4). Data on communication between eye care providers and contact lens wearers on contact lens wear and care recommendations are limited. Two surveys were conducted to better understand and assess contact lens education about nine recommendations: the first assessed contact lens wearer experiences regarding recommendations received from eye care providers during their most recent appointment; the second evaluated provider-reported practices for communicating contact lens wear and care recommendations to their patients. One third (32.9%) of contact lens wearers aged ≥18 years recalled never hearing any lens wear and care recommendations. Fewer than half (47.9%) recalled hearing their provider recommend not sleeping in lenses at their last visit, and 19.8% recalled being told to avoid topping off their contact lens solution. A majority of providers reported sharing recommendations always or most of the time at initial visits, regular checkups, and complication-related visits. Providers reported sharing nearly all recommendations more frequently at initial and complication-related visits than at regular checkups. Of the nine recommendations for safe contact lens wear and care, eye care providers at regular checkups most often recommend complying with the recommended lens replacement schedules (85% of regular visits), not sleeping in lenses (79.0% of regular visits), and not topping off solutions (64.4% of regular visits). Eye care providers play an important role in the health of their contact lens-wearing patients and can share health communication messages with their patients to help educate them about healthy wear and care habits. These findings can assist in the creation of health communication messages to help encourage eye care providers to communicate more effectively with their patients.
Epidermal growth factor induced upregulation of WISP-2 mRNA expression in breast tumor cells is mediated through EGFR-ER-α dependent pathways
Authors: Snigdha Banerjee, Neela Saxena, Sushanta K. Banerjee
Journal: Cancer Research (2004)

4253  Purpose: WISP-2 (CCN5) is a Wnt-1-induced signaling protein identified as a member of CCN growth factor family. We have shown previously that WISP-2 is a serum, estrogen and progesterone-induced early responsive gene. Estrogen and progesterone-induced upregulations of this gene are mediated through ER-α and PR, respectively. Moreover, WISP-2 expression has been found to be associated with serum and estrogen-induced ER positive MCF-7 breast tumor cell proliferation, but not with the proliferation of ER negative normal mammary epithelial cells. As epidermal growth factor (EGF) is a mitogen for breast tumor cells and it has been proven that EGF occasionally cross-talks with ER-α to exert its activity, present study was undertaken to determine whether EGF induces WISP-2 mRNA expression in ER positive and ER negative breast tumor cell lines as well as in human mammary epithelial cells with or without ER transfected, and whether this effect is mediated through EGFR alone or EGFR-ER networking is essential. Materials and Methods: Experiments were performed using ER+-EGFR+ MCF-7, ER- and EGFR+ MDA-MB-231 breast tumor cells, and ER-α-transfected or vehicle transfected EGFR+ normal mammary epithelial cells. Effect of EGF on WISP-2 mRNA expression was determined using non-radioactive northern blot analyses. EGFR mediated regulation of WISP-2 expression was determined by silencing the EGFR expression using EGFR specific siRNA. Results: In the presence of 10 nM to 1 μM EGF for 24h WISP-2 mRNA expression was significantly increased in ER+ and EGFR+ MCF-7 breast tumor cells, while the effect of EGF was undetected in ER- but EGFR+ breast tumor cells as well as ER-α transfected EGFR+ normal mammary epithelial cells. Moreover, the up-regulatory effect of EGF on WISP-2 expression in MCF-7 cells was abolished by the blocking of EGFR expression using EGFR specific siRNAs. Conclusions: In summary this study indicates that EGF enhances WISP-2 mRNA expression in breast tumor cells but not in normal mammary epithelial cells and this upregulation is mediated through a complex EGFR-ER-α-signaling pathway.
Implant‐abutment connection as contributing factor to peri‐implant diseases
Authors: Theofilos Koutouzis
Journal: Periodontology 2000 (2019)

Abstract Dental implant–supported prostheses are an established treatment modality for the functional and esthetic rehabilitation of partial and/or complete edentulous patients. One of the most essential factors for successful treatment outcomes stems from preservation of the peri‐implant bone. Early peri‐implant crestal bone loss has been a common observation, coincides with the time period where most treatment manipulations occur and has been considered as a complex multifactorial event. Microbial leakage at the implant‐abutment interface has been associated with inflammatory reactions that may jeopardize peri‐implant crestal bone stability. Prevention of microbial leakage at the implant‐abutment interface is a major challenge in the construction of two‐piece implant systems. Changes in the implant‐abutment complex design achieved reduction in the magnitude of microbial leakage and/or separation of the implant‐abutment interface from the osseous surface. However, it is still unclear if microbial leakage at the implant‐abutment interface plays a role beyond the initial crestal bone remodeling, namely on the development of peri‐implantitis. Therefore, the aim of this review is to analyze the knowledge available on the integrity of different types of implant‐abutment connections and their potential role on the development of peri‐implant crestal bone loss and peri‐implant diseases.
Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087
Authors: Robert Chen, Pier Luigi Zinzani, Hun Ju Lee, Philippe Armand, Nathalie A. Johnson, Pauline Brice, John Radford, Vincent Ribrag, Daniel Molin, Theodoros P. Vassilakopoulos, Akihiro Tomita, Bastian von Tresckow, Margaret A. Shipp, Jianxin Lin, Eunhee Kim, Akash Nahar, Arun Balakumaran, Craig H. Moskowitz
Journal: Blood (2019)
Association of increased levels of stem cell marker ALDH1 with overall survival in metastatic colon cancer.
Authors: Timothy Louis Fitzgerald, William J Partis, Shane Starr, George Sigounas
Journal: Journal of Clinical Oncology (2013)

e14635 Background: The clinical relevance of cancer stem cells (CSC’s) in solid organ malignancies is unclear. ALDH1 is thought to be a universal marker of stemness and is expressed in normal and neoplastic stem cells. We sought to determine the effects of stemness, expressed as levels of ALDH1, on survival for similarly staged metastatic colon cancer patients. Methods: Patients with lymph node positive colon cancer and unresectable liver metastasis diagnosed from 2004-2009 were identified. Sections were prepared from paraffin blocks and stained with an ALDH1 antibody. To determine quantitative expression of ALDH1, morphometric analysis with a Nikon microscope, SPOT video camera, and ImagePro software was performed with expression defined as stained area/total area. Ten to twenty randomly selected fields from were assessed. Patients were determined to have high expression of ALDH1 if respective levels were above the mean. Data analysis was performed with JMP. Results: A total of 16 patients were identified, with a median age of 64 years. The majority of patients were female (63%) and black (69%). Few primary tumors were poorly differentiated (25%). Median survival was 21.5 months (range: 1-47). Mean expression of ALDH1 was 0.041+0.01 for normal crypts, 0.031+0.01 for lymph node metastases, and 0.062+0.02 for primary tumors. ALDH1 expression was high in 31.3%, 20%, and 31.3% of patients for normal colon crypts, lymph node metastases, and primary cancers, respectively. Increased expression ALDH1 in tumors was strongly correlated with mortality (p=0.0013) and male sex (p=0.0166), but not with age (p=0.71) or race (p=0.50). Increased expression of ALDH1 in primary tumors was associated with a decreased overall survival, 27 vs. 6 months (p=0.0015). Increased expression of ALDH1 in normal colon crypts and lymph node metastases was not associated with survival, 27 vs. 19 (p=0.18) and 21 vs. 22 months (p=0.35), respectively. Conclusions: Increased stemness in primary colon cancers, expressed as ALDH1 levels, is associated with poor survival for similarly staged metastatic patients. These data suggest that an increase in stem cell fraction predicts a more aggressive clinical course.
Imaging the effect of doxorubicin on GFP-expressing hair-follicle-associated blood vessels
Authors: Mohamed A. El-Mahdy, Qianzheng Zhu, Wang Qi-En, Gulzar Wani, Mette Prætorius-Ibba, Altaf Wani
Journal: Cancer Research (2006)

1063  Xeroderma pigmentosum (XP) complementation group E gene product, damaged DNA binding protein 2 (DDB2), is a subunit of DDB heterodimeric protein complex with high specificity for binding to a variety of DNA lesions. DDB is believed to play a role in the initial step of damage recognition in mammalian nucleotide excision repair (NER) of ultraviolet light (UV)-induced photolesions. It has been shown that DDB2 is rapidly degraded after cellular UV irradiation. However, the relevance of DDB2 degradation to its functionality in NER is still unknown. Here, we provide evidence that Cullin 4A (CUL-4A), a key component of CUL-4A-based ubiquitin ligase, mediates DDB2 degradation at the damage sites and regulates the recruitment of XPC and the repair of cyclobutane pyrimidine dimers (CPD). We show that CUL-4A can be identified in an UV-responsive protein complex containing both DDB subunits. CUL-4A was visualized in localized UV-irradiated sites together with DDB2 and XPC. Degradation of DDB2 could be blocked by silencing CUL-4A using siRNA or by treating cells with proteasome inhibitor MG132. This blockage resulted in prolonged retention of DDB2 at the subnuclear DNA damage foci within micropore irradiated cells. Knockdown of CUL-4A also decreased recruitment of the damage recognition factor, XPC, to the damaged foci and concomitantly reduced the removal of CPD from the entire genome. These results suggest that CUL-4A mediates the proteolytic degradation of DDB2 and that this degradation event, initiated at the lesion sites, regulates damage recognition by XPC during the early steps of NER. (Supported by NIH grants, ES2388, ES12991 and CA93413)
Yellow vests protests: facial injuries from rubber bullets
Authors: Rodolphe Lartizien, Thomas Schouman, Mathieu Raux, Alexandre Debelmas, Sophie Lanciaux-Lemoine, Aurore Chauvin, Adélaide Toutee, Valérie Touitou, Jean-Louis Bourges, Patrick Goudot, Chloé Bertolus, Jean-Philippe Foy
Journal: The Lancet (2019)
Antimicrobial use in acute care hospitals: national point prevalence survey on healthcare-associated infections and antimicrobial use, Switzerland, 2017
Authors: Walter Zingg, Aliki Metsini, Céline Gardiol, Carlo Balmelli, Michael Behnke, Nicolas Troillet, Andreas Widmer, Didier Pittet
Journal: Eurosurveillance (2019)

Background A point prevalence survey (PPS) on healthcare-associated infections (HAI) and antimicrobial use was conducted in Swiss acute care hospitals in 2017. Aim Our objective was to assess antimicrobial use in Swiss acute care hospitals. Methods All patients hospitalised in any acute care hospital in Switzerland were eligible. We used the most recent version of the PPS protocol of the European Centre for Disease Prevention and Control. Results Data from 12,931 patients of 96 hospitals were collected. Of these, 4,265 (33%; 95% confidence interval (CI): 32.2–33.8) were on 5,354 antimicrobials for 4,487 indications. Most of the 2,808 therapeutic indications addressed 1,886 community-acquired infections (67.2%; 95% CI: 65.4–68.9). Of the 1,176 surgical prophylaxes, 350 (29.8%; 95% CI: 27.1–32.4) exceeded the duration of 1 day. Of the 1,090 antimicrobial regimens that were changed, 309 (28.3%; 95% CI: 25.7–31.0) were escalated and 337 (30.9%; 95% CI: 28.2–33.7) were de-escalated. Amoxicillin/clavulanic acid was the most frequent antimicrobial (18.8%; 95% CI: 17.7–19.8), prescribed mainly for therapeutic indications (76.0%; 95% CI: 73.3–78.7). A total of 1,931 (37.4%; 95% CI: 36.1–38.8) of the 5,158 antimicrobials for systemic use were broad-spectrum antibiotics, most frequently third- and fourth-generation cephalosporins (35.9%; 95% CI: 33.8–38.1). Conclusions Antimicrobial consumption was at European average, the use of broad-spectrum antibiotics in the lower third. Swiss acute care hospitals should invest in antimicrobial stewardship, particularly in reducing the use of broad-spectrum antibiotics.
Genome scale validation of oncologic disease drug targets by in vivo functional analysis.
Authors: Brian Zambrowicz, Arthur Sands, Nan Zhang, Zhi-Qing Ma, Rick Finch, Wenhu Huang, Francis G. Kern
Journal: Cancer Research (2005)

125  The sequencing of the human genome has provided an unprecedented opportunity to identify novel drug targets that can enable the discovery of new therapeutics. In order to accelerate drug development, reduce costs, and improve success rates, it is critical to identify the key targets that, when modulated, can produce therapeutic effects. Gene knockout (KO) mice can be used to identify promising drug targets through in-depth phenotypic analysis designed to detect desirable physiological profiles with potential therapeutic implications for medicine. By virtue of the inactivation of specific genes, knockout mice may be used to genetically model the actions of perfectly selective and potent chemical or biological antagonists. In fact, careful analysis of the phenotypes of KO mice can allow one to make predictions with regard to mechanism of action and potential on-target side effects of future drugs without having to first develop a candidate small molecule or biotherapeutic agent with which to validate the target. The power of this approach has been demonstrated by studies examining the targets of the best-selling drugs and current pharmaceutical pipelines. These analyses revealed that the therapeutic effect of established drugs show a strong correlation with the KO mouse phenotype of the corresponding target. We have implemented this target validation approach by developing systems and infrastructure to generate and comprehensively phenotype mutant mice at a rate of more than fifteen targets per week. The battery of tests encompassed by our analysis has been specifically selected to reveal those genes that encode key control points in mammalian physiology and behavior. Tests to detect potential oncology targets include: adult skin fibroblast proliferation assay, radiation sensitivity, gene expression profiling, developmental defects in the mammary gland, tissue-specific defects in the development of other organs, angiography, embryonic lethality, and matrigel plug assay. For targets found to be of interest, additional assays are performed to more thoroughly examine gene function. Data will be presented illustrating the process from knockout through an oncologic phenotypic analysis.
Population pharmacokinetics of trabectedin (ET-743) in subjects with cancer
Authors: J. J. Perez Ruixo, P. Zannikos, S. Hirankarn, K. Stuyckens, K. Liolios, A. Soto-Matos, L. Lopez-Lazaro, C. Pico, A. Yver, J. Owen
Journal: Journal of Clinical Oncology (2006)

2030 Background: Trabectedin (T) is a DNA minor-groove intercalating agent. The objective of this study is to characterize the population pharmacokinetics of T in cancer subjects. Methods: A total of 603 subjects (945 cycles) receiving intravenous T as monotherapy at doses ranging from 0.024 to 1.8 mg/m 2 and given as 1, 3 or 24 hrs infusion every 21 days; 3 hrs infusion on day 1, 8, 15 every 28 days; or 1 hr infusion daily for 5 consecutive days every 21 days were included in the analysis. An open four-compartment pharmacokinetic model with linear elimination, linear and non-linear distribution to the deep and shallow peripheral compartments, respectively, and a catenary compartment off the shallow compartment was developed to best describe a total of 4251 concentrations from 274 subjects (Index Dataset) using NONMEM V. The effect of selected covariates on T pharmacokinetics was investigated. Model was evaluated using goodness of fit plots and relative error measurements for 2362 concentrations from 329 subjects (Test Dataset). Computer simulations were undertaken to evaluate the covariate effects on T pharmacokinetics. Results: Mean (SD) of T terminal half-life was ≈180 (61.4) h. Plasma accumulation was limited when T was given every three weeks. Systemic clearance, 31.5 L/h (CV = 51%), was 19.2% higher in subjects receiving concomitant dexamethasone. Typical values of volume of distribution at steady-state for males and females were 6070 L and 5240 L, respectively. Age, body size variables, AST, ALT, LDH, creatinine clearance, albumin, total protein and presence of liver metastases were not related to T pharmacokinetics. No difference in model parameters was observed for the infusion durations evaluated. T AUC and C max were dose proportional for each schedule evaluated and consistent across cancer types. Conclusions: The integration of phase I/II pharmacokinetic data demonstrated T linear elimination, dose-proportionality up to 1800 μg/m 2 , and time-independent pharmacokinetics. Given the moderate to large interindividual variability in T pharmacokinetics, the clinical relevance of dexamethasone and gender covariates is probably limited since a substantial overlap in simulated concentration-time profiles was observed. [Table: see text]
First-in-Human Study of Mivebresib (ABBV-075), an Oral Pan-Inhibitor of Bromodomain and Extra Terminal Proteins, in Patients with Relapsed/Refractory Solid Tumors
Authors: Sarina A. Piha-Paul, Jasgit C. Sachdev, Minal Barve, Patricia LoRusso, Russell Szmulewitz, Sapna Pradyuman Patel, Primo N. Lara, Xiaotian Chen, Beibei Hu, Kevin J. Freise, Dimple Modi, Anjla Sood, Jessica E. Hutti, Johannes Wolff, Bert H. O'Neil
Journal: Clinical Cancer Research (2019)

Bromodomain and extraterminal (BET) proteins play important roles in transcriptional regulation relevant to cancer pathogenesis, and therapeutic targeting/inhibition of BET causes apoptosis of cancer cells in vitro. In this first-in-human study of the pan-BET inhibitor mivebresib (ABBV-075), the safety profile, MTD, and recommended phase II dose (RP2D) were determined in patients with advanced solid tumors.A 3 + 3 dose escalation for different mivebresib dosing schedules [daily, Monday/Wednesday/Friday (M-W-F), 4 days on/3 off (4/7)] was followed by dose expansion in patients with prostate cancer. Endpoints were safety, tolerability, pharmacokinetics, and preliminary antitumor activity.Seventy-two patients with solid tumors (14% uveal melanoma; 11% colorectal; 11% breast; 8% pancreatic; 7% head/neck; 49% others) were treated with mivebresib during dose escalation, and 12 additional patients with prostate cancer in expansion cohort. Most common treatment-emergent adverse events (TEAE) related to mivebresib were dysgeusia (49%), thrombocytopenia (48%), fatigue (26%), and nausea (25%). Most common grade 3/4 TEAEs related to mivebresib were thrombocytopenia (35%) and anemia (6%). Dose-limiting toxicities included thrombocytopenia (2 mg daily; 4.5 mg M-W-F), gastrointestinal bleed (2 mg daily), hypertension (2-3 mg 4/7), fatigue, decreased appetite, and aspartate aminotransferase elevation (4 mg M-W-F). Of 61 evaluable patients from dose escalation, 26 (43%) had stable disease and 35 (57%) had progressive disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.8-1.9).On the basis of safety and tolerability, mivebresib RP2D is 1.5 mg for the daily schedule, 2.5 mg for 4/7, and 3 mg for M-W-F. Mivebresib has a tolerable safety profile, and stable disease was observed in some patients with malignant solid tumors.
Association of Electronic Health Record Design and Use Factors With Clinician Stress and Burnout
Authors: Philip J. Kroth, Nancy Morioka-Douglas, Sharry Veres, Stewart Babbott, Sara Poplau, Fares Qeadan, Carolyn Parshall, Kathryne Corrigan, Mark Linzer
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Many believe a major cause of the epidemic of clinician burnout is poorly designed electronic health records (EHRs). <h3>Objectives</h3> To determine which EHR design and use factors are associated with clinician stress and burnout and to identify other sources that contribute to this problem. <h3>Design, Setting, and Participants</h3> This survey study of 282 ambulatory primary care and subspecialty clinicians from 3 institutions measured stress and burnout, opinions on EHR design and use factors, and helpful coping strategies. Linear and logistic regressions were used to estimate associations of work conditions with stress on a continuous scale and burnout as a binary outcome from an ordered categorical scale. The survey was conducted between August 2016 and July 2017, with data analyzed from January 2019 to May 2019. <h3>Main Outcomes and Measures</h3> Clinician stress and burnout as measured with validated questions, the EHR design and use factors identified by clinicians as most associated with stress and burnout, and measures of clinician working conditions. <h3>Results</h3> Of 640 clinicians, 282 (44.1%) responded. Of these, 241 (85.5%) were physicians, 160 (56.7%) were women, and 193 (68.4%) worked in primary care. The most prevalent concerns about EHR design and use were excessive data entry requirements (245 [86.9%]), long cut-and-pasted notes (212 [75.2%]), inaccessibility of information from multiple institutions (206 [73.1%]), notes geared toward billing (206 [73.1%]), interference with work-life balance (178 [63.1%]), and problems with posture (144 [51.1%]) and pain (134 [47.5%]) attributed to the use of EHRs. Overall, EHR design and use factors accounted for 12.5% of variance in measures of stress and 6.8% of variance in measures of burnout. Work conditions, including EHR use and design factors, accounted for 58.1% of variance in stress; key work conditions were office atmospheres (<i>β̂</i> = 1.26;<i>P</i> &lt; .001), control of workload (for optimal control:<i>β̂</i> = −7.86;<i>P</i> &lt; .001), and physical symptoms attributed to EHR use (<i>β̂</i> = 1.29;<i>P</i> &lt; .001). Work conditions accounted for 36.2% of variance in burnout, where challenges included chaos (adjusted odds ratio, 1.39; 95% CI, 1.10-1.75;<i>P</i> = .006) and physical symptoms perceived to be from EHR use (adjusted odds ratio, 2.01; 95% CI, 1.48-2.74;<i>P</i> &lt; .001). Coping strategies were associated with only 2.4% of the variability in stress and 1.7% of the variability in burnout. <h3>Conclusions and Relevance</h3> Although EHR design and use factors are associated with clinician stress and burnout, other challenges, such as chaotic clinic atmospheres and workload control, explain considerably more of the variance in these adverse clinician outcomes.