tbuckley/cabot-search huggingface dataset:
Screening for Alcohol Use and Brief Counseling of Adults — 13 States and the District of Columbia, 2017
Authors: Lela R. McKnight-Eily, Catherine A. Okoro, Khadija Turay, Cristian Acero, Dan Hungerford
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Binge drinking* is a leading preventable public health problem. From 2006 to 2010, binge drinking contributed to approximately 49,000 annual deaths resulting from acute conditions (e.g., injuries and violence) (1). Binge drinking also increases the risk for adverse health conditions, including some chronic diseases (e.g., breast cancer) and fetal alcohol spectrum disorders (2). In 2004, 2013, and again in 2018, for all U.S. adults aged ≥18 years in primary care, the U.S. Preventive Services Task Force (USPSTF) recommended alcohol screening and brief intervention (alcohol SBI) or counseling for persons whose screening indicated drinking in excess of recommended limits or in ways that increase risk for poor health outcomes (3-5). However, previous CDC surveillance data indicate that patients report rarely talking to their provider about alcohol use,† and alcohol SBI is traditionally delivered through conversation. CDC recently analyzed 2017 data from the Behavioral Risk Factor Surveillance System (BRFSS) survey's five-question module, which asked adults in 13 states§ and the District of Columbia (DC) about the delivery of alcohol SBI during their most recent checkup in the past 2 years. Overall, 81.4% of adults (age-standardized estimate) reported being asked about alcohol use by a health professional in person or on a form during a checkup in the past 2 years, but only 37.8% reported being asked a question about binge-level alcohol consumption, which is included on USPSTF recommended instruments (3). Among module respondents who were asked about alcohol use at a checkup in the past 2 years and reported current binge drinking (past 30 days) at time of survey, only 41.7% were advised about the harms of drinking too much at a checkup in the past 2 years, and only 20.1% were advised to reduce or quit drinking at a checkup in the past 2 years. These findings suggest that missed opportunities remain for health care providers to intervene with patients who report binge drinking. Working to implement alcohol SBI at a systems level, including the provision of the new Healthcare Effectiveness Data Information Set (HEDIS) measure, Unhealthy Alcohol Use Screening and Follow-Up, can improve alcohol SBI's use and benefit in primary care.
Treating Parental Burnout: Impact of Two Treatment Modalities on Burnout Symptoms, Emotions, Hair Cortisol, and Parental Neglect and Violence
Authors: Maria Elena Brianda, Isabelle Roskam, James J. Gross, Aline Franssen, Florence  Kapala , France Gérard , Moïra Mikolajczak
Journal: Psychotherapy and Psychosomatics (2020)
CHRONIC PERINATAL HYPOXIA DELAYS CARDIAC MATURATION IN A MOUSE MODEL FOR CYANOTIC CONGENITAL HEART DISEASE
Authors: Jennifer Romanowicz, Zaenab Dhari, Manelle Ramadan, Devon Guerrelli, Marissa Reilly, Nina Ciccarelli, Luther Swift, Nobuyuki Ishibashi, Nikki G. Posnack
Journal: Journal of the American College of Cardiology (2020)
Hepatotoxicity with chemotherapy in patients infected with hepatitis B virus.
Authors: Jean-Luc Szpakowski, Lue-Yen Tucker, Mary Pat Pauly, John Nanfro, David Hwang, David M. Baer
Journal: Journal of Clinical Oncology (2013)

9645 Background: Patients with chronic hepatitis B virus infection (HBV) are at risk for hepatotoxicity (HT) from viral reactivation during chemotherapy courses (TC). This can be minimized with antiviral prophylaxis (AV). Screening for HBV before TC remains controversial. Methods: A retrospective observational data only study was conducted at a Northern California integrated health care delivery system examining patients undergoing TC between 2000 and 2010. Patients were categorized as HBV positive (HBV+) if they had a positive HBsAg, HBeAg, or HBV DNA any time before and 1 year post TC. Grade 3 and 4 HT was determined using the National Cancer Institute Common Toxicity Criteria, with adaptation for those who had baseline abnormal liver function tests. We excluded patients with HIV, co-infection with both HBV and hepatitis C, and HBsAb of unclear provenance. Two control groups (CTRL1 and CTRL2) were established that had tested negative for HBV and HCV 1996 through 1 year after the last TC: CTRL1 tested negative for both before TC initiation (index TC); CTRL2 tested negative for one pre and the other post index TC or both at any time after index TC. AV prophylaxis (AVP+) was defined as anti-HBV medication given before HT; the remainder were AVP-, including those given AV after HT. Electronic medical record review was conducted on all HBV+ patients. Results: We identified 9,279 patients who received 15,960 TC; 57.8% were female with a mean age of 57.8 (±14.4) at TC initiation. 464 TC were given to 289 HBV+ patients; 22.8% had HT, with 7 deaths from HT, all AVP-. The rate of HT in the controls was 9.9% in CTRL1 (34/343), 12.6% in CTRL 2 (1907/15,153). Conclusions: These findings support the recommendation that all patients planning to receive TC should be screened for HBV. Those found positive should receive AV prophylaxis during therapy. [Table: see text]
<i>Notes from the Field:</i> Carbapenemase-Producing <i>Klebsiella pneumoniae</i> in a Ventilator-Capable Skilled Nursing Facility — Maricopa County, Arizona, July–November 2018
Authors: Sarah E. Scott, James Matthews, Katherine C. Hobbs, Keila Maldonado, Rachana Bhattarai, Rebecca Sunenshine, Siru Prasai
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Maricopa County Department of Public Health in Arizona investigated a cluster of two genetically similar antibiotic-resistant bacterial infections in residents of the ventilator-capable unit of a skilled nursing facility to look for health care–associated bacterial spread.
CARDIOLOGIST INVOLVEMENT IN BREAST CANCER PATIENTS TREATED WITH TRASTUZUMAB-BASED CANCER THERAPY REGIMEN
Authors: Biniyam G. Demissei, Srinath Adusumalli, Srinivas Denduluri, Rebecca A. Hubbard, Kelly Getz, Vivek Narayan, Amy S. Clark, Payal Shah, Hayley Knollman, Joseph R. Carver, Bonnie Ky
Journal: Journal of the American College of Cardiology (2020)
Prospective analysis of the epidermal growth factor receptor gene mutations in non-small cell lung cancer in Japan
Authors: N. Morikawa, A. Inoue, T. Suzuki, T. Fukuhara, S. Suzuki, T. Kondo, T. Moriya, Y. Saijo, T. Nukiwa
Journal: Journal of Clinical Oncology (2006)

7077 Background: Previous clinical trials have revealed that gefitinib is more likely to be effective in non-small cell lung cancer (NSCLC) with activating somatic mutations of epidermal growth factor receptor (EGFR). Most of those reports evaluated NSCLC patients who had post-operative recurrence and then received gefitinib retrospectively using their surgical specimens. However, many NSCLC patients are inoperable at diagnosis. Thus we conducted this study to examine EGFR mutation status by diagnostic tumor samples before gefitinib treatment and investigate the correlation between EGFR mutation and the efficacy of gefitinib. Methods: We prospectively evaluated various tumor samples obtained from NSCLC patients who had never received gefitinib for EGFR mutations in exon 18–23. For patients treated with gefitinib after the examination of EGFR mutations, the response to gefitinib was also evaluated. Results: From June 2004 to November 2005, 91 patients with advanced or post-operative recurrent NSCLC enrolled onto this study and 104 tumor samples were obtained from transbronchial biopsies, effusions, as well as surgical specimens. Thirty-two mutations including deletions in exon 19 in 23 patients and L858R in 9 patients were detected among those 91 patients; 30 in 81 adenocaricinoma, 1 in 2 adenosquamous cell carcinoma, and 1 in 5 large cell carcinoma. The mutations were found more frequently in female (51.9%) than male (12.8%), in never smoker (52.0%) than smoker (14.6%). Response rate of gefitinib in patients with EGFR mutations was 65.0% (13 of 20) compared to 37.5% (3 of 8) in patients without mutations. Among 7 patients with EGFR mutations who were examined multiple tumor samples, 3 had the discrepancy of EGFR gene status between different samples obtained at different time points, suggesting genetic heterogeneity of their tumors. The EGFR status of the most recent samples is likely to be correlated to the response to gefitinib. Conclusions: The EGFR mutation analysis was possible not only from surgical specimens but also from daily available diagnostic samples. For patients with EGFR mutations, gefitinib could achieve a promising high response rate. We propose to examine the most recent tumor samples to predict the sensitivity to gefitinib reliably. No significant financial relationships to disclose.
Phase I dose-escalation study to evaluate the safety, pharmacokinetics, and pharmacodynamics of CEP-9722 (a PARP1-2 inhibitor) as single‑agent and in combination with temozolomide in patients with advanced solid tumors (NCT00920595).
Authors: Mario Campone, Ruth Plummer, Peter Stephens, Zahir Brakchi, Louiza Aissat-Daudigny, Fabrice Kasiborski, Anne Cambois, Gilbert Moachon, Peter D. Brown, Louis Kayitalire
Journal: Journal of Clinical Oncology (2012)

3052 Background: Poly-ADP-ribose (PAR) polymerases (PARPs) are essential in cellular processing of DNA damage via the base excision repair pathway. CEP-9722, an orally available PARP1-2 inhibitor, demonstrated single-agent antitumor activity and synergy with temozolomide (TMZ) in xenograft models. This phase I study evaluated the pharmacokinetics, pharmacodynamics, and the maximum tolerated dose (MTD) of CEP-9722 in monotherapy and combination with TMZ. Methods: Adult patients with advanced solid tumors were enrolled in cohorts of 3-6 patients to receive a 14-day cycle of CEP-9722 (days 1-5), followed by 28-day cycles of CEP-9722 (days 1-5) plus TMZ (150 mg/m 2 days 1-5). The dose of CEP-9722 was 150 mg/day in the first cohort and was escalated depending on the occurrence of dose-limiting toxicities (DLTs) during cycles 1 and 2. The safety, pharmacokinetics, and pharmacodynamics (PAR levels in peripheral blood mononuclear cells) of CEP-9722 were analyzed. Results: Overall, 26 patients (18F,8 M) 18 to 71 years of age were enrolled in 5 cohorts of 3-9 patients and treated with CEP-9722 at 150-1000 mg/day. The MTD of CEP-9722 in combination with TMZ (150 mg/m 2 ) was reached at 1000 mg/day. The recommended dose was 750 mg/day. A total of 9 patients were treated at the recommended dose. DLTs were observed in 2 patients during cycle 1 (1 grade 3 myositis at 750 mg/day and 1 grade 3 asthenia at 1000 mg/day) and 2 patients during cycle 2 (1 grade 3 asthenia at 300 mg/day and 1 persistent grade 2 weight loss at 1000 mg/day). Overall during this study, 4 grade 3 treatment-related adverse events were observed. The pharmacokinetics showed high intra- and inter-patient variability at all doses. The pharmacodynamic analysis demonstrated PARP inhibition at all doses, but the high inter- and intra-patient variability prevented any conclusion regarding a dose / PARP inhibition relationship. Conclusions: TheMTD of CEP-9722 when administered with TMZ was 1000 mg days 1-5 and the combination CEP-9722/TMZ was well tolerated. In addition, a clear signal of PARP inhibition was demonstrated.
Enhanced osteogenesis and therapy of osteoporosis using simvastatin loaded hybrid system
Authors: Tao Wu, Jing Sun, Lei Tan, Qi Yan, Lei Li, Liangwen Chen, Xiangmei Liu, Shi Bin
Journal: Bioactive Materials (2020)

Postmenopausal osteoporosis is a common chronic dynamic bone disorder, caused by estrogen deficiency. To address this issue, we constructed a controlled drug-release system composed of poly (N-isopropylacrylamide) brush modified mesoporous hydroxyapatite (MHA-SIM-P) loaded with simvastatin (SIM) using an ovariectomised (OVX) rat model. Quantitative alkaline phosphatase activity assay, alizarin red staining and RT-PCR were tested to evaluate the osteogenic ability
14-YEAR EXPERIENCE IN DOOR-TO-BALLOON TIMES WITH A 24/7 STEMI PROGRAM: SIXTY IS THE NEW NINETY
Authors: Xiaoxiao Qian, M. Fuad Jan, Suhail Allaqaband, Babak Haddadian, Khawaja Afzal Ammar, Tanvir Bajwa
Journal: Journal of the American College of Cardiology (2020)
A survey of thousands of tumor exomes and transcriptomes to expand clinical opportunities for crizotinib.
Authors: Emma Bowden, Sean Eddy, Paul Williams, Nikolay Khazanov, Armand Bankhead, Dinesh Cyanam, Peter Wyngaard, Dan Rhodes
Journal: Journal of Clinical Oncology (2013)

11017 Background: Cancer driver events occur as a result of chromosomal rearrangements. There are several examples where targeted inhibition of the resulting fusion produces dramatic clinical response. For example, the EML4-ALK fusion in non-small cell lung cancer (NSCLC). Other ALK fusions have been described in NSCLC and other diseases including the NPM-ALK fusion in anaplastic large cell lymphoma (ALCL). The efficacy of crizotinib and other ALK inhibitors are being investigated in these diseases. ALK is also subject to activation via mutation and sensitivity to crizotinib is reported in ALK mutation positive neuroblastoma. Finally, crizotinib has activity not only against ALK, but also against ROS1, MST1R and MET. ROS1 fusions have been found in NSCLC and glioblastoma, and MET amplification events in gastric adenocarcinoma identify additional settings that may benefit from crizotinib treatment. Methods: To further understand the full therapeutic potential of Crizotinib, we undertook a genomic survey of ALK, ROS1, MET and MST1R across 1,000’s of patients from the The Cancer Genome Atlas (TCGA) and Oncomine. Results: We confirmed the presence of EML4-ALK fusions in both lung and colorectal cancer (CRC), and also identified a novel ALK fusion in CRC. ALK hotspot mutations and focal amplifications were confined to neuroblastoma, as previously described. Our survey of ROS1 identified rare novel fusions in NSCLC and glioblastoma, and high-level amplifications in liposarcoma (2%) and rarely in breast cancer (0.2%). No fusions were identified for MET, however high-level amplifications were observed in 1-5% of papillary renal cell carcinoma, the intestinal subtype of gastric adenocarcinoma, oliogodendroglioma, glioblastoma and lung adenocarcinoma. Hotspot mutations were frequently observed in squamous head and neck (11%), and more rarely in hepatocellular carcinoma, small cell lung and ovarian cancers. Conclusions: These results leverage all available genomic profiling data to provide a broadened scope of therapeutic opportunity for inhibitors like crizotinib. With the growing availability of next-generation sequencing, such surveys can support hypothesis-driven development of targeted therapies.
Antibody-independent ApoStream technology isolates folate receptor alpha (FRA)–positive circulating tumor cells from blood of non-small cell lung adenocarcinoma patients.
Authors: Darren W. Davis, Christopher Neal, Vishal Gupta, Vladislava O. Melnikova, Jacky Woo, Elizabeth Brooke Somers, Daniel O'Shannessy
Journal: Journal of Clinical Oncology (2012)

e21028 Background: The ability to enrich and interrogate circulating tumor cells (CTCs) from blood may allow for the analysis of metastatic dissemination and potential use of CTCs as surrogates for monitoring drug efficacy. We developed ApoStream, a dieletrophoresis field-flow fractionation based platform, for antibody-independent CTC isolation. We demonstrated that ApoStream successfully isolates non-small cell lung adenocarcinoma (NSCLC) CTCs that express Folate Receptor alpha (FRA), a GPI-anchored receptor, which has emerged as a cancer biomarker and potential therapeutic target in multiple cancer types. Methods: ApoStream technology was used to enrich CTCs from NSCLC patients’ blood. CTC enrichment by ApoStream was compared to that of the FDA cleared CellSearch CTC kit. A multiplexed immunofluorescent assay was developed to enable CTC enumeration (Cytokeratin+/CD45-/DAPI+ cells) and analysis of FRA expression (detection by murine antibody clone 26B3) using single cell quantitative laser scanning cytometry (LSC). Results: In a side-by-side comparison with the CellSearch CTC kit, ApoStream isolated significantly higher numbers of CTCs in 9 metastatic adenocarcinoma NSCLC patients (Apostream: mean =139, range 3-487 per 7.5 mL of blood, versus CellSearch kit: mean =2, range 0-8 per 7.5 mL of blood, n= 9, p=0.041). All patients were found to be CTC-positive by ApoStream, while only 3 of 9 (33%) patients were CTC-positive based on the CellSearch kit. LSC analysis demonstrated that 8-33% of all CTCs isolated expressed FRA and that FRA expression was confined to CTCs only. No false positive CTCs and no FRA-expressing cells were isolated by ApoStream from normal donor blood (n=15). Conclusions: All NSCLC adenocarcinoma patients analyzed had FRA-positive CTCs, suggesting that FRA may play a key role in metastasis and that screening of patients with the ApoStream CTC isolation system may identify patients who could benefit from FRA-targeted therapy.
MBD4 and SEI1 as new prognostic markers in colorectal cancer patients receiving adjuvant 5-fluorouracil
Authors: J. Ju, A. Formentini, G. Nakajima, M. Kornmann, Y. Xi
Journal: Journal of Clinical Oncology (2006)

20085 Background: Previous studies from our laboratory have identified a number of marker genes associated with chemosensitivity to 5-fluorouracil (5-FU). In this study, the in vivo significance of several marker genes in terms of prognostic potential were evaluated using colorectal cancer patient samples treated with 5-FU based therapy. Eight marker genes were selected based on their functional roles and significant fold changes in expression. They are SERTA domain containing 1(SEI1), Ribonucleotide reductase M2 polypeptide (RRM2), Origin recognition complex, subunit 6 homolog-like (ORC6L), Eukaryotic translation initiation factor 4E (EIF4E), Thymidylate Synthase (TS), SET and MYND domain containing 3 (SMYD3), Dickkopf homolog 4 (DKK4) and Methyl-CpG binding domain protein 4 (MBD4). Methods: Forty eight snap frozen clinical colorectal samples (24 normal and 24 paired colorectal cancer patient samples) were selected with detailed clinical follow-up information. cDNAs were synthesized and the expression levels of marker genes were quantified via qRT-PCR analysis. The statistical significance of these markers for disease prognosis was evaluated using two tailed paired T-test. Kaplan-Meier survival curve was generated and analyzed by Logrank test. Results: Based on the quantitative expression analysis, RRM2 (p = 0.0001, 95% CI, 2.0 to 4.5), ORC6L (p = 0.0001, 95% CI, 1.8 to 4.6), EIF4E (p = 0.0002, 95% CI, 0.3 to 0.9), TS (p = 0.0005, 95% CI, 0.7 to 2.2) and SMYD3 (p = 0.0001, 95% CI, 0.8 to 1.5) was over-expressed in tumor tissues. However, the expression of SEI1 was decreased in tumors (p = 0.02, 95% CI, 0.1 to 1.3), consistent with the function of SEI1 as a potential tumor suppressor. Kaplan-Meier survival analysis indicated that MBD4 is a significant prognostic factor for patient’s survival (p = 0.03). MBD4 was a key protein involved in DNA methylation. The expression of TS was associated with tumor stage as it had significant higher expression level in UICC stage I and II compared to stage IV patients (p = 0.03). Conclusion: MBD4 may be potential novel prognostic markers for predicting patient survival for colorectal cancer. No significant financial relationships to disclose.
Both Prediabetes and Type 2 Diabetes Are Associated With Lower Heart Rate Variability: The Maastricht Study
Authors: Charlotte Coopmans, Tan Lai Zhou, Ronald M.A. Henry, Jordi Heijman, Nicolaas C. Schaper, Annemarie Koster, Miranda T. Schram, Carla J.H. van der Kallen, Anke Wesselius, Robert J.A. den Engelsman, Harry J.G.M. Crijns, Coen D.A. Stehouwer
Journal: Diabetes Care (2020)

OBJECTIVE Low heart rate variability (HRV), a marker for cardiac autonomic dysfunction, is a known feature of type 2 diabetes, but it remains incompletely understood whether this also applies to prediabetes or across the whole glycemic spectrum. Therefore, we investigated the association among prediabetes, type 2 diabetes, and measures of glycemia and HRV. RESEARCH DESIGN AND METHODS In the population-based Maastricht Study (n = 2,107; mean ± SD age 59 ± 8 years; 52% men; normal glucose metabolism [n = 1,226], prediabetes [n = 331], and type 2 diabetes [n = 550, oversampled]), we determined 24-h electrocardiogram-derived HRV in time and frequency domains (individual z-scores, based upon seven and six variables, respectively). We used linear regression with adjustments for age, sex, and major cardiovascular risk factors. RESULTS After adjustments, both time and frequency domain HRV were lower in prediabetes and type 2 diabetes as compared with normal glucose metabolism (standardized β [95% CI] for time domain: −0.15 [−0.27; −0.03] and −0.34 [−0.46; −0.22], respectively, P for trend &amp;lt;0.001; for frequency domain: −0.14 [−0.26; −0.02] and −0.31 [−0.43; −0.19], respectively, P for trend &amp;lt;0.001). In addition, 1-SD higher glycated hemoglobin, fasting plasma glucose, and 2-h postload glucose were associated with lower HRV in both domains (time domain: −0.16 [−0.21; −0.12], −0.16 [−0.21; −0.12], and −0.15 [−0.20; −0.10], respectively; frequency domain: −0.14 [−0.19; −0.10], −0.14 [−0.18; −0.09], and −0.13 [−0.18; −0.08], respectively). CONCLUSIONS Both prediabetes and type 2 diabetes were independently associated with lower HRV. This is further substantiated by independent continuous associations between measures of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is already present in prediabetes.
Association of the genetic variants in the nucleotide excision repair genes XPA and XPC with cisplatin-induced hearing loss in patients with osteosarcoma.
Authors: Melanie M. Hagleitner, Marieke J.H. Coenen, Hans Gelderblom, Peter Hoogerbrugge, Henk-jan Guchelaar, Dunja Maroeslea W.M. Te Loo
Journal: Journal of Clinical Oncology (2012)

10077 Background: Cisplatin is a widely used and effective chemotherapeutic agent in the treatment of osteosarcoma. However, cisplatin-induced ototoxicity is a serious problem, affecting more than 60% of patients and compromising language and cognitive development. Unfortunately, individuals at risk to develop ototoxicity cannot be identified upfront. Genetic variants in genes involved in the metabolism of cisplatin may predispose to cisplatin-induced hearing loss and help to identify patients at risk. Methods: In a candidate gene pathway approach, we selected 224 SNPs in 30 candidate genes related to Platinum-DNA repair pathways and genotyped for a discovery group of 105 patients with osteosarcoma for these variants. Cisplatin-induced ototoxicity (n = 47), defined as the development of grade 2–4 hearing impairment using Common Terminology Criteria for Adverse Events (CTCAE version 3), showing a hearing loss of &gt;25 dB at frequencies of 4–8 kHz, was associated with genetic variation. A replication study was performed in a independent cohort of 51 patients with osteosarcoma. Genotyping was performed using the Illumina GoldenGate assay. Association analysis and meta-analysis were performed using the whole genome association analysis toolset PLINK. Results: In the discovery cohort a total of 13 SNPs were significantly (p value &lt; 0.05) associated with ototoxicity. Upon meta-analysis, addition of the replication set resulted in lower p-values for 2 SNPs. The two SNPs showing a strong association with hearing loss in patients with osteosarcoma were rs2805835 in the gene XPA (p-value 0.01, OR=2.7 (95%CI: 1.20-6.15) and rs2227999 in XPC (p-value 0.02; OR=3.2 (95% CI:1.19-8.80). Conclusions: The Nucleotide Excision Repair (NER) genes XPA and XPC form an important molecular mechanism by which cisplatin DNA adducts can be repaired and it has recently been shown that these genes have a high expression in the cochlea. Our data suggest that genetic variants in these genes, may contribute to cisplatin ototoxicity. This study should be viewed as the first step in the development of genetic markers to predict cisplatin-induced ototoxicity in individual patients.