tbuckley/cabot-search huggingface dataset:
Cholesterol Screening in Children and Family History of Coronary Heart Disease.
Authors: Viktorina N Muratova, Syed S Islam, Emily C Spangler, Ellen W Demerath, William A Neal
Journal: Circulation (2001)

P94 Background: Selective blood cholesterol screening of children based upon National Cholesterol Education Program (NCEP) guidelines of family history of premature cardiovascular disease (CVD) or parental hypercholesterolemia is inadequate in a population with high prevalence of coronary heart disease (CHD), low levels of cholesterol screening, low socio-economic status (SES) and diminished access to preventive health care. We hypothesize that universal cholesterol screening of pre-pubertal school children may be effective in identifying children and their parents with abnormal lipid levels in this high risk rural population. Fifth grade school children from seven rural Appalachian counties participated in a school based cholesterol screening program. Data on family history of premature CHD, anthropometric and blood pressure measurements, tobacco smoke exposure, dietary history and physical activity levels were collected at the time of screening. Seven hundred and nine 5 th grade students ( mean age 10.8 years) participated in the program. One hundred seventy four (24.5%) were considered presumptively dyslipidemic after non-fasting finger- stick (FS) cholesterol screening. Thirty six percent of these dyslipidemic children had a fasting lipid profile done. Dyslipidemia was confirmed in 37(59%) of these children. FS cholesterol levels were significantly correlated with fasting TC (r=0.80 p &lt; 0.0001). Among confirmed dyslipidemic children, family history was not a good predictor of dyslipidemia (sensitivity 21.6%). Seventy nine parents of dyslipidemic children participated in fasting lipid profile assessment. Fifty two parents (67%) were dyslipidemic, most of them (79%) did not have a family history of premature CHD or hypercholesterolemia. FS cholesterol levels were also correlated with fasting TC of fathers (r=0.46 p=0.01), and mothers (r=0.32 p=0.02). Conclusion: Significant correlation exists between non-fasting FS cholesterol levels of children and subsequent fasting lipid profile of children and their parents. Family history has low sensitivity in predicting children with elevated serum cholesterol concentrations.
Antibody Drug Conjugates Targeted to CD45 or CD117 Enable Allogeneic Hematopoietic Stem Cell Transplantation in Animal Models
Authors: Rahul Palchaudhuri, Sharon L. Hyzy, Jennifer L Proctor, Hillary L Adams, Bradley R Pearse, Ganapathy Sarma, Sharon Aslanian, Geoff Gillard, Tahirih L Lamothe, Olga Burenkova, Melissa L. Brooks, Andrew D Gabros, Charlotte F McDonagh, Anthony E. Boitano, Michael P. Cooke
Journal: Blood (2018)
Multiplexing of Theta and Alpha Rhythms in the Amygdala-Hippocampal Circuit Supports Pattern Separation of Emotional Information
Authors: Jie Zheng, Rebecca F. Stevenson, Bryce A. Mander, Lilit Mnatsakanyan, Frank P.K. Hsu, Sumeet Vadera, Robert T. Knight, Michael A. Yassa, Jack J. Lin
Journal: Neuron (2019)
Abstract 19545: Prdm16 Deficiency Leads to Arterial Vascular Defects by Modulating the Activity of the Notch Signaling Cascade
Authors: Manu Beerens, Sander Craps, Calum MacRae, Aernout Luttun
Journal: Circulation (2016)

Aims: We recently identified the transcriptional co-regulator PRDM16 as a key component of a unique transcription factor code driving human arterial endothelial specification in vitro. We tested wh...
Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-Risk Leukemias: A Report from the LEAP Consortium
Authors: Yana Pikman, Sarah K. Tasian, Maria Luisa Sulis, Todd M Cooper, Melinda Pauly, Kelly W. Maloney, Michael J. Burke, Patrick Brown, Nathan Gossai, Peter Cole, Jennifer McNeer, Neerav Shukla, Beth Apsel Winger, Asmani A Adhav, Traci M. Blonquist, Amy Conway, Andrew E. Place, Lia Gore, Stephen P. Hunger, Katherine Janeway, Lewis B. Silverman, Jeffrey W. Tyner, Marian H. Harris, Mignon L. Loh, Kimberly Stegmaier
Journal: Blood (2018)
Feasibility of neurocognitove and psychological assessments in allogeneic stem cell transplantation: A pilot study.
Authors: Tara K. Gregory, Andrea Maikovich-Fong, Elizabeth Panter
Journal: Journal of Clinical Oncology (2014)

9572 Background: Neurocognitive and psychological measures may provide insightful and even prognostic information, yet are not routinely incorporated into pre-allogeneic hematopoietic stem cell transplant (HSCT) assessments. We conducted a longitudinal pilot study to assess the feasibility of using neurocognitive and psychological tools in the HSCT setting. Methods: Patients age 27-72 with diagnoses of hematologic malignancies underwent neurocognitive/psychological assessments within 4 weeks prior to HSCT, at day +100 and day +180. The Montreal Cognitive Assessment (MOCA) Version 7 assessed neurocognitive impairment. Center for Epidemiological Studies Depression Scale (CES-D), State-Trait Anxiety Inventory (STAI), and Neuropsychiatric Inventory(NPI), evaluated depression, anxiety, and caregiver interpretation of patient distress, respectively. Evaluations were performed by a clinical psychologist. Results: 21 successive patients scheduled for HSCT were evaluated for feasibility of conducting the above evaluations. One patient declined to participate in the full initial evaluation. The evaluation was scheduled during a pre-existing psychosocial intake and required an additional 30 minutes of clinician and patient time. The MOCA required 10 minutes. The CES-D, STAI, and EORTC QLQ–C30 required 5 minutes each. Scoring required 10 minutes. Neurocognitive impairment was frequent at baseline and worsened post-HCST. Pre-HSCT anxiety/depression was very severe (expected incidence <10%), and persisted in 6-month survivers. Most patients had sub-clinical levels of anxiety/depression which may impact function. Conclusions: Longitudinal neurocognitive/psychological inventories in the HSCT setting are feasible and informative. An expanded, prospective study will be performed to correlate the measures with post transplant outcomes and QoL. Measure Pre-HSCT n=20 Day 100 n=12 6 month n=8 MOCA Normal Low normal Below normal 30% 50% 20% 16% 25% 59% 0 38% 62% Depression severe 25% 8% 33% Anxiety severe 20% 8% 50% Global QoL 80+ 60-79 <60 30% 40% 30% 17% 50% 33% 25% 38% 38% Overall survival 100% 75% 50%
Phase 1b study of abiraterone acetate (AA) and docetaxel (D) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Scott T. Tagawa, Edwin M. Posadas, Justine Yang Bruce, Emerson A. Lim, Daniel Peter Petrylak, Weimin Peng, Raymond Scott Maul, Hans W. Smit, Namphuong Tran, David M. Nanus
Journal: Journal of Clinical Oncology (2014)

5025 Background: Coadministration of D and AA may be beneficial due to complementary mechanisms of action. A phase 1b safety and pharmacokinetic (PK) study assessed the safety and efficacy of D + AA. Methods: 3 cohorts (C) of chemo-naive mCRPC pts received escalating doses of D + AA. Primary end point: proportion of pts with dose-limiting toxicity (DLT) between Wks 2 and 7, defined as grade (Gr) ≥ 3 non-heme toxicity, Gr 4 neutropenia > 7 days (or febrile neutropenia), Gr 4 thrombocytopenia, or other intolerable toxicity. Pts could continue AA after discontinuing D. D + AA was deemed safe if ≤ 2 pts/C experienced DLT; the maximum tolerated dose (MTD) was the highest safe combination of D + AA. PSA changes and PK parameters were evaluated. Results: 22 pts were treated; 18 pts were evaluable for DLT assessment. The combination dose received by C3 (1 pt had DLT) was deemed the MTD. With treatment ongoing, 90% and 70% of pts had ≥ 50% and ≥ 90% PSA decline from baseline, respectively (Table). With median follow-up of 11.8 months, there were 5 PSA progression events. PK parameters were comparable for both abiraterone and D alone and in combination. Conclusions: D + AA was well tolerated at full doses of each drug. PK was comparable when D and AA were given alone and in combination. The efficacy signal may justify further study. Clinical trial information: NCT01400555. Baseline characteristics C1 D 60 mg/m2 + AA 500 mga n = 7 C2 D 75 mg/m2 + AA 500 mga n = 8 C3 D 75 mg/m2 + AA 1000 mga n = 7 ECOG PS, n (%) 0 4 (57) 2 (25) 2 (29) 1 2 (29) 6 (75) 5 (71) 2 1 (14) 0 0 PSA, µg/L, median (range) 85.2 (5.9-234.3) 33 (4.8-62.6) 10 (2-504.8) LDH, U/L, median (range) 187 (139-463) 207.5 (134-344) 237 (136-768) ALP, U/L, median (range) 97 (76-513) 91 (64-392) 124 (42-242) Hemoglobin, g/dL, median (range) 121 (113-144) 120 (110-153) 129 (101-136) Lesions, n (%) Bone Measurable target Nontarget 7 (100) 2 (29) 4 (57) 7 (88) 4 (50) 4 (50) 5 (71) 4 (57) 2 (29) Efficacy outcomes n = 20 PSA declineb, n (%) ≥ 90% 14 (70) ≥ 50% 18 (90) Safety outcomes n = 6 n = 6 n = 6 DLT, n (%) Syncope Hypertension Neutropenia Hematuriac 1 (17) 1 (17) 0 0 0 0 1 (17) 0 0 0 0 1 (17) aAA and prednisone taken daily. D administered once q3wk; bC3 data is limited; cPt had elective cystolitholapaxy for preexisting hematuria.
Survival analysis of various treatment options in mucinous adenocarcinoma of the ano-rectal region: A SEER database analysis.
Authors: Babu P. Mohan, Praveena Iruku, Ritika Ohri, Douglas Y. Rowland, Keyvan Ravakhah
Journal: Journal of Clinical Oncology (2014)

e15178 Background: Mucinous Adenocarcinoma of the Ano-Rectal region is a rare entity with few reported cases across the world, and is known to carry a worse prognosis. Therapeutic options involve a combination of local radiotherapy and surgical excision, with few cases receiving chemotherapy. No study has looked into the survival advantage of the currently practiced therapeutic options in this rare tumor. Methods: Using data extracted from the SEER9 registry database, rates were calculated for the incidence of Adenocarcinoma of the Ano-Rectal region of the mucinous type. SEER-Stat ver 8.0.4 was used to extract the data and the same was used to run relative survival analysis and CanSurv ver.1.1 software to get the graphs. Results: 60 month survival results showed no statistical difference in the groups ‘no RT or surgical therapy’, ‘RT prior to surgery’ group, and ‘RT prior and after surgery’ group; and being significant only for 'RT after surgery' group with 20% increased relative survival at the end of 5 years (p< 0.05). Conclusions: Mucinous Adenocarcinoma of the ano-rectal region treated with surgery first, and then followed by radiotherapy gives the best survival results. Results from this SEER based epidemiological analysis needs to be assessed with caution. Our study limits in the lack of adjustments for chemotherapy, other socioeconomic and other lifestyle factors, which are not captured by SEER. But the rarity of the tumor makes SEER dataset a good source for study and the large national population based tumor registry lends generalizability of the results.
Laparoscopic partial nephrectomy: Double layer technique (DLT).
Authors: Sergey N Dimitriadi, Oleg Ivanovich Kit, Vladimir L. Medvedev
Journal: Journal of Clinical Oncology (2014)

e15557 Background: The reconstruction stage of laparoscopic partial nephrectomy (LPN) requires the longest part of warm ischemia time (WIT) defining renal function after LPN. Methods: 62 LPN have been performed for 2 years. In 22 cases (35.5%) pelvicaliceal system (PCS) of the kidney was opened. These patients underwent DLT during LPN and formed the first group. Second group consisted of 40 (64.5%) patients whose PCS were not opened during LPN. Mean age in the first and second groups was 62.3+11.8 years (range 38-77) and 55.7 +13.5 years (range 33-74), mean tumor size – 35.3+6.8 mm (range 25-58) and 33.5 + 7.2 mm (range 23-58), mean RENAL nephrometry sum - 7.1+1.5 (range 5-10) and 6.7+1.2 (range 4-8) respectively. The DLT is used when an opening of the PCS is necessary during the resection stage of LPN. It involves the following steps: transperitoneal approach, atraumatic hilar clamping (en bloc or artery only) and tumor excision by cold endoshears. The reconstructive stage excludes separate PCS suture repair. The renal wound is sutured using “sliding clip” technique in two steps. Firstly, the deep parenchymal running suture through fibrous capsule of the kidney is applied. Wherein every stitch of the running suture is performed by two needle punctures of the every edge of the renal wound without gripping opened PCS edges. On completing the deep parenchymal suture through the whole wound of the kidney the hilar clamp is removed, the blood supply of the kidney is restored and WIT is measured. Secondly, the superficial parenchymal running suture through fibrous capsule of the kidney is applied. Results: Mean operative time in the first and second groups was 236.4+168.5 (range 80-1000) and 128.8+50.4 (range 80-300), mean WIT – 13.6+2.3 min.(range 9-18) and 12.3+3.1 (range 6-16) (p=0.09), mean blood loss – 257.5+237.9 ml (range 50-1100) and 124+132.7 ml (range 50-500) respectively. Intraoperative hemorrhage occurred in 2 patients of the first group. Delayed hemorrhage, urine leak, renal failure did not occur. All patients confirmed RCC with negative surgical margins. Mean follow up was 14.3+5.4 month (range 3-24). No local recurrence and no progression were diagnosed in the both groups. Conclusions: The implementing of DLT during LPN might allow to extend indications to LPN.
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Authors: Mikolaj Ogrodnik, Yi Zhu, Larissa G.P. Langhi, Tamar Tchkonia, Patrick Krüger, Edward Fielder, Stella Victorelli, Rifqha A. Ruswhandi, Nino Giorgadze, Tamar Pirtskhalava, Oleg Podgorni, Grigori Enikolopov, Kurt O. Johnson, Ming Xu, Christine Inman, Allyson K. Palmer, Marissa Schafer, Moritz Weigl, Yuji Ikeno, Terry C. Burns, João F. Passos, Thomas von Zglinicki, James L. Kirkland, Diana Jurk
Journal: Cell Metabolism (2019)

Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16
Primary and secondary malignant meningiomas: A clinical and histological comparison.
Authors: Tareq A. Juratli, Kathrin Geiger, Tim Lautenschlaeger, Matthias Kirsch, Gabriele Schackert
Journal: Journal of Clinical Oncology (2014)

2099 Background: Malignant meningiomas WHO Grade III (MM °III) represent the most rare but aggressive subtype of all meningioma. They may progress from low- grade meningiomas °I or °II (secondary MM) or develop as de novo primary MM. In this study, we compared clinical and histological factors influencing outcome and survival of primary and secondary MM. Methods: The dataset of over 1200 patients with intracranial meningiomas was used toidentify patients with histological proven MM. Of those patients clinical, histological, radiological, tumor- and treatment-related data were evaluated and analyzed. Results: We identified 22 MM patients (median follow-up of 8 years); 12 patients with a secondary MM and 10 patients with a primary MM. Histologically, primary and secondary MM were largely indistinguishable. Even the immunohistochemistry including proliferation index (MIB-1), vascular density as well as PDGFR-/ EGFR- and VEGFR-expression failed to show significant differences between either groups or a significant influence on the overall survival. A typical feature of secondary MM were that they are preferentially located at the skull base, whereas primary MM aroused at the convexity (p=0.049). Patients with secondary MM underwent in average 4 surgeries, in opposite to patients with primary MM who had in average a single operation (p=0.002). 8 patients with secondary MM and all patients with primary MM received radiotherapy; whereas only 3 patients in each group underwent adjuvant chemotherapy. Repeated operations demonstrated a marked survival benefit in both groups in respect to the extent of resection (p=0.025). The median overall survival rate for secondary MM following the confirmation of malignant histology was 2.2 years; whereas this wasn’t reached yet in the patients group with primary MM at follow-up after 10 years (p<0.05). Conclusions: Secondary MM seem to be of more aggressive nature than primary ones with a higher risk toward recurrence and with a significantly reduced survival time. Surgery is an effective treatment for secondary and primary MM WHO °III at initial presentation and recurrence. In addition, repeated surgery was the only identified significant prognostic factor for improved PFS and OS in both groups.
Happiness and Health
Authors: Andrew Steptoe
Journal: Annual Review of Public Health (2019)

Research into the relationship between happiness and health is developing rapidly, exploring the possibility that impaired happiness is not only a consequence of ill-health but also a potential contributor to disease risk. Happiness encompasses several constructs, including affective well-being (feelings of joy and pleasure), eudaimonic well-being (sense of meaning and purpose in life), and evaluative well-being (life satisfaction). Happiness is generally associated with reduced mortality in prospective observational studies, albeit with several discrepant results. Confounding and reverse causation are major concerns. Associations with morbidity and disease prognosis have also been identified for a limited range of health conditions. The mechanisms potentially linking happiness with health include lifestyle factors, such as physical activity and dietary choice, and biological processes, involving neuroendocrine, inflammatory, and metabolic pathways. Interventions have yet to demonstrate substantial, sustained improvements in subjective well-being or direct impact on physical health outcomes. Nevertheless, this field shows great potential, with the promise of establishing a favorable effect on population health.
Rehabilitation Facilities in Ontario
Authors: C M GODFREY, A T JOUSSE
Journal: JAMA (1963)

Rehabilitation centres in Ontario were surveyed and categorized as in-patient and outpatient services, specialized centres for particular diseases, and vocational retraining centres. It is evident that many gaps exist in the pattern of rehabilitation facilities and services in the province. In some areas the facilities are grouped too closely together, necessitating transport of patients from great distances. The serious shortage of trained personnel is noted. There is little provision for mentally ill patients in existing rehabilitation centres. The use of mobile clinics is discussed. There is no evidence of duplication of services among those at present available.
Molecular profiling of HPV-positive and -negative HNSCC.
Authors: Rebecca Feldman, Anatole Ghazalpour, Joseph Knezetic, Zoran Gatalica, Panayiotis Savvides, Theodoros Nicholas Teknos
Journal: Journal of Clinical Oncology (2014)

6080 Background: Head and neck squamous cell carcinoma (HNSCC) is comprised of two subtypes: human papilloma virus (HPV)- and carcinogenic-associated (HPV-negative), both linked to inactivation of the TP53 pathway. We examined alterations in HPV positive (pos) and negative (neg) HNSCC to identify treatment options and elucidate differences in pathogenesis. Methods: Eighty HNSCC cases (24 HPV-pos and 33 HPV-neg) were profiled using a multiplatform (IHC, NGS, ISH) approach (Caris Life Sciences, Phoenix, AZ) aimed at identification of biomarkers of therapeutic drug responses. Results: HNSCC arising in the following anatomic sites were assessed: larynx, nasopharynx, oropharynx, oral cavity, tongue, and head and neck, NOS. HPV positivity was detected in: nasopharynx, oropharynx, tongue, and head and neck, NOS. Statistically significant differences between HPV-pos and HPV-neg HNSCC were observed for ER(20% (4/20) vs. 0% (0/31); p=0.02) and MGMT(75% (18/24) vs. 40% (13/32); p=0.02) expression (IHC). NGS detected variants in 69% (20/29) of HPV-neg, of which 90% (18/20) had TP53 mutations. 39% (7/18) had 2nd and 3rd hits in the following genes: APC, PTEN, PDGFRA, GNAQ, CDH1 and IDH1. Rare TP53 WT/HPV-neg (10% or 2/20) patients exhibited mutations in APC and PIK3CA. In HPV-pos cases NGS detected variants in 39% (9/23) including: APC, HNF1A , FBXW7, NRAS, PDGFRA, PIK3CA and PTEN. Co-occurrence of mutations included: PDGFRA, NRAS and FBXW7, and PIK3CA and PTEN. In patients with PTEN/PIK3CA mutations (both subgroups), 83%( 5/6) exhibit loss of PTEN expression indicating benefit of mTOR inhibitors. Novel therapies based on NGS data include Wnt pathway inhibitors, multi-kinase inhibitors (imatinib), MEK inhibitors and alkylating agents based on mutations in APC, PDGFRA, GNAQ/NRAS and IDH1, respectively. Conclusions: Common and HPV-specific biomarkers characterize HNSCC. ER over-expression indicates anti-hormonal therapies as a potential novel therapy option in HPV-pos, whereas alkylating agents may be of benefit in HPV-neg HNSCC. Novel therapies also include mTOR inhibitors based on alterations in PTEN/PIK3CA. Lower incidence of mutations in HPV-pos HNSCC indicates a need for a multi-platform approach in identifying theranostic biomarkers.
Oral dysesthesia in cancer patients (Pts) treated with multitargeted tyrosine kinase inhibitors (MT-TKI).
Authors: Anna D Yuan, Sharyn L. Kurtz, Constance Barysauskas, Amy P Pilotte, Andrew J. Wagner, Nathaniel S. Treister
Journal: Journal of Clinical Oncology (2014)

e20626 Background: MT-TKIs are anti-neoplastic drugs associated with a variety of clinically relevant toxicities, many due to VEGFR2 inhibition. This retrospective study characterized the incidence and clinical features of oral toxicities among pts on MT-TKI therapies targeting VEGFR2. Methods: Electronic medical records of all cancer pts treated with sunitinib (SU), sorafenib (SO), pazopanib (PZ), imatinib (IM), and bevacizumab (BV) from 2009 to 2012 were included. BV, an anti-VEGF antibody, and IM, a TKI without VEGFR activity, were used as reference controls. Data collected included pt characteristics, oral toxicities including mucosal sensitivity/pain, dysgeusia/hypogeusia, ulcers/lesions, xerostomia, and numbness/tingling, and time to onset of oral toxicity. Results: 572 pts with were treated with SU (n = 130), SO (n = 136), PZ (n=94), IM (n = 78), or BV (n = 161) during the study period. Oral toxicity of any grade was reported in 24.1% of pts at a median of 0.9 mos after starting therapy. The most commonly reported oral toxicity was oral mucosal sensitivity, occurring in 12% of pts, and was typically without clinical findings. Oral toxicity was most frequent with SU (40%), SO (25.7%) and PZ (20.2%). Compared to IM, SU patients had the greatest risk of developing oral toxicity (HR: 8.12, 95% CI: 3.60 – 18.3, p=0.00), followed by SO (HR: 4.79, 95% CI: 2.07 – 11.11, p=0.00) and PZ (HR: 3.87, 95% CI: 1.58– 9.50, p=0.003). Compared to BV, SU patients had the greatest risk of developing a toxicity (HR: 2.73, 95% CI: 1.69 – 4.38, p=0.00), followed by SO (HR: 1.61, 95% CI: 0.96 – 2.69, p=0.07), and PZ (HR: 1.30, 95% CI: 0.72 – 2.36, p=0.39). IM patients had a 66% decreased risk of developing a toxicity compared to BV (HR: 0.34, 95% CI: 0.14 – 0.81, p=0.02). Conclusions: Oral toxicity reported in association with MT-TKI therapy is characterized by dysesthesia with lack of clinical signs. Oral dysesthesia was more commonly associated with MT-TKIs that directly block VEGFR2 activity than with BV or IM. Further investigation should focus on management of oral toxicities to minimize symptoms and potentially enhance drug exposure.
A Critical Role for Intratumoral and Circulating LAG3 in Classical Hodgkin Lymphoma: Analysis from the Rathl Prospective Phase III International Clinical Trial
Authors: Emad Uddin Abro, Soi C Law, Colm Keane, Simone Birch, Muhammed Bilal Sabdia, Joshua W.D. Tobin, Peter Johnson, Judith Trotman, Leanne Berkahn, Michael Fulham, Richard A Anderson, Anne L Saunderson, Jay Gunawardana, Donna Cross, Annette Hernandez, Sarah-Jane Halliday, Robert Bird, W P Law, Devinder Gill, Maher K Gandhi
Journal: Blood (2018)