tbuckley/cabot-search huggingface dataset:
Adjuvant Chemotherapy Following Neoadjuvant Chemotherapy Plus Surgery for Patients With Gastroesophageal Cancer—Is There Room for Improvement?
Authors: Elizabeth C. Smyth, David Cunningham
Journal: JAMA Oncology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Workforce pressures prompt more Scottish GPs to resign their contracts
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The number of patients in Scotland registered with GP practices run directly by health boards has nearly doubled in a decade because of the growing number of practices resigning their contracts, the Royal College of General Practitioners (RCGP) Scotland has said.

Figures released by the college show that more than 160 000 patients (2.8% of the total number) were registered with a “2c” practice in 2016. This is almost double the 83 290 (1.5% …
BONE‐MARROW EOSINOPHILIA IN THE MOUSE
Authors: P. A. J. J. M. de COCK, J. D. F. HABBEMA
Journal: Allergy (1977)

In this article a study on the influence on bone-marrow eosinophilia in the mouse of a single injection of various concentrations of egg-white and incomplete Freund's adjuvant, together and separately, is reported. The combination of egg-white (1 per cent) and adjuvant gave a peak value of 158.3% eosinophil leukocytes on the 14th day after the injection; separately, neither one led to divergence from the results in untreated mice. The combination gave the greatest effect at 1.0 per cent and 0.1 per cent egg-white, a moderate effect with 10 per cent and 0.01 per cent, and negligible effects with 0.001 per cent. The interpretation of the results is discussed, with special attention to the relationship with the atopy syndrome in man.
Incubation of Citrulline and Ammonia With Normal and Neoplastic Hepatic Tissues
Authors: Jesse P. Greenstein
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Incubation of Citrulline and Ammonia With Normal and Neoplastic Hepatic Tissues Get access Jesse P. Greenstein Jesse P. Greenstein senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 3, December 1942, Pages 293–296, https://doi.org/10.1093/jnci/3.3.293 Published: 01 December 1942
Neville Martin Bailey
Authors: Sheila Bailey
Journal: BMJ (2017)

Neville Martin Bailey served as house surgeon at Withington Hospital and then as house obstetrician at Saint Mary’s Hospital Manchester. National service was still obligatory, so he joined the Royal Air Force and served in fighter command as senior medical officer at RAF Odiham from 1 January 1956 to 31 December 1958. During this time the station was testing new aircraft, often flying round the clock, and Neville had to be available on call for very long periods. He decided to use the time to study for an external degree in zoology at London University and travelled to the University of Reading on an occasional free Saturday, where the professor of zoology allowed him to use the laboratory and kept back specimens for his practical work. In 1958 he was awarded a BSc (Hons) from the University of London. At this time, he was invited to join the Royal Air Force on a permanent commission, but progression would inevitably have meant working in London, and he was a countryman who disliked city life.

By this time, we had three children, and with a fourth due imminently, he decided to become a general practitioner—ideally in a country practice. But when a singlehanded retirement practice vacancy came up in Peterborough, he applied and was offered the appointment in mid-December 1958, but only on the condition that he could provide premises and a commitment to offer a service to the existing patients of the practice—24 hours a day, seven days a week, 365 days a year—from 1 January 1959. The RAF had provided a gratuity of £600, and Neville’s father lent us a deposit to enable us to buy a house. The house we bought in such a hurry soon proved to be in the wrong place and had no access to a …
Abstract P314: Moderate to Severe Thinness was Strongly Associated with High Risks of Cardiovascular and Infectious Disease-related Death and Incident Stroke Among Japanese Hemodialysis Patients
Authors: Kyoko Owada, Masaki Ohsawa, Kozo Tanno, Kazuyoshi Itai, Akira Okayama, Karen Kato, Yosuke Fujishima, Toshiyuki Onoda, Kiyomi Sakata, Takako Kidoguchi, Ritsuko Nekohira, Taeko Masuda, Tomoaki Fujioka
Journal: Circulation (2013)

Background: Overweight and obese is shown to be associated with a high risk for cardiovascular morbidity and mortality in the general population. While, inverse relationship between body mass index (BMI) and a risk for all-cause death was observed in dialysis patients. Thinner dialysis patients are supposed to be a high risk population. However, whether cardiovascular death contributes to a high risk for all-cause mortality or whether non-cardiovascular death contributes to a high risk for all-cause mortality in thinner dialysis patients has not been fully elucidated. Methods: A population-based prospective study of adult hemodialysis patients was carried out. A total of 1209 male and female hemodialysis patients were enrolled and divided into four groups according to BMI (G1: BMI &lt; 17.0; G2: 17.0 ≤ BMI &lt; 18.5; G3: 18.5 ≤ BMI &lt; 25.0; G4: BMI ≥ 25.0 kg/ m 2 ). Main outcomes were all-cause death (ACD), cardiovascular death (CVD), infectious disease-related death (IFD), malignant disease-related death (MAD), incident acute myocardial infarction (AMI) and stroke. Sex- and age-adjusted mortality and incidence rates were estimated in the groups using Poisson’s regression analysis. Results: A total of 453 patients died during the 5 year observation period (4,790 person-years). Overweight (BMI ≥ 25.0 kg/ m 2 ) was not associated with a high risk for ACD, CVD, IFD, MAD, AMI and stroke, while moderate to severe thinness was strongly associated with excessive risks of ACD, CVD, IFD and stroke. Associations between BMI and risks for MAD and AMI were not observed (see table). Conclusion: Skinny hemodialysis patients are supposed to be a high risk population for infectious disease-related and stroke-related death and the findings should be known to hemodialysis patients and their caretakers.
Prenatal Fluoride Exposure and Cognitive Outcomes in Children at 4 and 6–12 Years of Age in Mexico
Authors: Morteza Bashash, Deena Thomas, Howard Hu, E. Angeles Martinez-Mier, Brisa N. Sanchez, Niladri Basu, Karen E. Peterson, Adrienne S. Ettinger, Robert Wright, Zhenzhen Zhang, Yun Liu, Lourdes Schnaas, Adriana Mercado-García, Martha María Téllez-Rojo, Mauricio Hernández-Avila
Journal: Environmental Health Perspectives (2017)

Some evidence suggests that fluoride may be neurotoxic to children. Few of the epidemiologic studies have been longitudinal, had individual measures of fluoride exposure, addressed the impact of prenatal exposures or involved more than 100 participants.Our aim was to estimate the association of prenatal exposure to fluoride with offspring neurocognitive development.We studied participants from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project. An ion-selective electrode technique was used to measure fluoride in archived urine samples taken from mothers during pregnancy and from their children when 6-12 y old, adjusted for urinary creatinine and specific gravity, respectively. Child intelligence was measured by the General Cognitive Index (GCI) of the McCarthy Scales of Children's Abilities at age 4 and full scale intelligence quotient (IQ) from the Wechsler Abbreviated Scale of Intelligence (WASI) at age 6-12.We had complete data on 299 mother-child pairs, of whom 287 and 211 had data for the GCI and IQ analyses, respectively. Mean (SD) values for urinary fluoride in all of the mothers (n=299) and children with available urine samples (n=211) were 0.90 (0.35) mg/L and 0.82 (0.38) mg/L, respectively. In multivariate models we found that an increase in maternal urine fluoride of 0.5mg/L (approximately the IQR) predicted 3.15 (95% CI: -5.42, -0.87) and 2.50 (95% CI -4.12, -0.59) lower offspring GCI and IQ scores, respectively.In this study, higher prenatal fluoride exposure, in the general range of exposures reported for other general population samples of pregnant women and nonpregnant adults, was associated with lower scores on tests of cognitive function in the offspring at age 4 and 6-12 y. https://doi.org/10.1289/EHP655.
Time management
Authors: C. Gray
Journal: BMJ (1998)

“But at my back I alwaies hear Times winged Charriot hurrying near” wrote the 17th century poet Andrew Marvell.(1) His words are still relevant today, and time is central to medicine. From our Apgar scores at birth to the widening intervals of Cheyne-Stokes respiration, medical episodes are measured chronologically. Patients must wait in the waiting room: “Dr Godot will see you now.” Taking a patient's history turns on time: “When did it start?” “How often are the contractions coming?” “Why didn't you report this sinister sign sooner?”

The human body works chronobiologically, and cardiac arrests, histopathology reports, and triennial reviews have their own response times. But the practice of medicine is frustrated by time wasting. Medical employment is contracted by notional time. Seniors have half days, and trainees have duty hours, but never enough to do all the work. Acute punctualist or chronic time-waster, the use of time in a medical career determines its success. Finding a moment to peruse Career Focus is a healthy sign, but are you wasting most of the billion seconds available in your 30 year career - Oops! There goes another one, two, three…

Many doctors are failing in their use of time: white rabbits in white coats looking at pocket watches and scurrying along corridors muttering, “Oh my ears and whiskers, how late it's getting.” Almost every problem in medical practice relates to the efficient use of time. Clinics, theatre lists, and surgeries often overrun, diagnostic tests are reported late or not at all, and administration is in chronic frame shift to the right. Late doctors waste the time and money of all those next on their list: patients, other professionals and students, but mostly themselves.

Few deliberately delay: time failure is more fundamental than mere endemic lateness. The typical picture is doing …
Laser-Induced Neocollagenesis in Focal Dermal Hypoplasia Associated With Goltz Syndrome in a Girl
Authors: Andrew C. Krakowski, David M. Ozog, David Ginsberg, Carol Cheng, Marsha L. Chaffins
Journal: JAMA Dermatology (2017)

Current models of Goltz syndrome cannot estimate the overall neocollagenesis and marked shift in collagen types after ablative fractional laser resurfacing (AFR) within treated areas of focal dermal hypoplasia (FDH).To clinically improve FDH by using AFR to characterize the specific ratio of collagen types associated with observed clinical changes.This case report of a girl with Goltz syndrome used extensive laboratory evaluation and multiple observers blinded to the patient's clinical status. Serial samples of clinically unaffected skin constituted internal control specimens, with clinical and histologic evaluations performed as part of a multicenter investigation. The analysis tested the hypothesis that thermal microtrauma caused by AFR created a unique environment that activated latent genes, inducing neocollagenesis and allowing the patient to adaptively produce the collagen subtype that was specifically deficient at baseline.Two AFR treatments were administered within an area of FDH. Histologic comparison of the pretreatment and posttreatment skin was performed using serial internal controls.Histologic changes, including Herovici collagen staining to differentiate between types I and III collagen, within a treated area of mosaically affected FDH compared with clinically unaffected skin.This female patient presented in the second decade of life with self-described red, itchy skin within a large plaque of FDH on her left posterior thigh and calf. After AFR, skin tightening and symptomatic relief were reported. Histologic findings demonstrated objective thickening of the dermal collagen. A marked shift in collagen predominance from type III (fetal/early wound) to type I (adult/mature) was observed.Although further study is needed, this report shows promising results and raises important questions about gene expression and the epigenetics of Goltz syndrome-associated mutations and the local effects of AFR. Coupled with more rigorous investigation, this novel technique may help reveal molecular workarounds permitting innovative therapies that take advantage of the subtly different collagens that exist within the skin.
Abstract 268: Myofilament Tyrosine Phosphorylation by Src Kinase is upregulated in ErbB2 Transgenic Mice
Authors: Mingguo Xu, Genaro A Ramirez-Correa, Zongming Fu, Polina S Shah, Frances Belmonte, Kathleen Gabrielson, Anne M Murphy
Journal: Circulation Research (2015)

Objectives: Tyrosine (Tyr) phosphorylation of the myofilament is an emerging, and potentially important, post-translational modification in cardiomyopathy. ErbB2, a Tyr receptor kinase, was overexpressed in transgenic mice (ErbB2-Tg) resulting in significant cardiac hypertrophy. We hypothesize that the development of cardiac hypertrophy in ErbB2-Tg is associated with increased myofilament Tyr phosphorylation and may implicate myofilament Tyr phosphorylation in cardiac hypertrophy. Methods: Proteins were isolated from ErbB2-Tg and Ntg heart homogenates ( n =4 per group). Reduction/alkylation was followed by trypsinization. Resulting peptides were desalted in C 18 columns and lyophilized. Phosphorylated Tyr (p-Tyr) enrichment was performed on 20 mg of peptides using a p-Tyr Mouse mAb kit (Cell Signaling). Immuno-precipitated and desalted peptides were analyzed by LC-MS/MS (Orbitrap Elite, Thermo). Raw data were searched with Mascot 2.3. Label-free quantification with MS1 extracted ion chromatograms was performed using Skyline. Western blot analysis for total and phosphorylated Src kinase was performed per manufacturer’s protocol (Cell Signaling). Results: We found a total of 286 p-Tyr modified peptides in ErbB2-Tg compared to 226 in control NTg mice. Over 70 p-Tyr sites on myofilament protein were up-regulated in ErbB2-Tg, including troponin I, myosin heavy chain, titin, α-tropomyosin, myosin-binding protein-C3, myosin regulatory light chain-2 and myosin light chain-1. We used PhosphoMotif Finder to search the potential responsible kinase. Most of the p-Tyr sites were consistent with Src kinase motifs. Furthermore, Western blot analysis showed that total, and phospho-Src (Y416) expression was increased in ErbB2-Tg mice. Conclusion: We concluded that these novel p-Tyr sites on myofilament proteins are increased in ErbB2-Tg mice and correlate with up-regulated Src kinase activity. Thus increased tyrosine myofilament phosphorylation may be involved in the development of cardiac hypertrophy. Since ErbB2 is a therapeutic target of trastuzumab therapy this may also have translational implications to ameliorate off target effects of cancer treatment.
Associations Between Diabetes and Both Cardiovascular Disease and All-Cause Mortality Are Modified by Grip Strength: Evidence From UK Biobank, a Prospective Population-Based Cohort Study
Authors: Carlos A. Celis-Morales, Fanny Petermann, Li Hui, Donald M. Lyall, Stamatina Iliodromiti, James McLaren, Jana Anderson, Paul Welsh, Daniel F. Mackay, Jill P. Pell, Naveed Sattar, Jason M.R. Gill, Stuart R. Gray
Journal: Diabetes Care (2017)

OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS A total of 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P &amp;lt; 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk.
Overall survival prognosis of patients in immuno-oncology phase I trials: The Gustave Roussy score.
Authors: Frederic Bigot, Eduardo Castanon, Capucine Baldini, Sandrine Aspeslagh, Aurelien Marabelle, Christophe Massard, Antoine Hollebecque, Sophie Postel-Vinay, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2017)

3029 Background: The evaluation of patient’s life expectancy is crucial to select patients who may benefit from phase I studies. The Royal Marsden Hospital (RMH) prognostic score, based on 3 objective variables (number of metastatic sites, LDH and serum albumin) was validated in patients treated with cytotoxic and targeted therapies. We aimed to determine if those factors were applicable to immunotherapy (IT) phase I trials. Methods: A retrospective analysis for risk factors of survival was conducted in a discovery cohort of 155 patients enrolled into IT phase I trials at our institution. We computed univariate and multivariate analysis (MVA) of demographics, clinical and biological data to assess their prognostic value for overall survival (OS). MVA results were used to build a prognostic score for OS. A validation cohort of 113 patients enrolled in IT phase I trials was used to prospectively re-validate this score. Results: 155 patients receiving an experimental IT between March 2012 and January 2016 were included in the discovery cohort. A MVA assessing the RMH Score variables showed that albumin &lt; 35 g/dL (HR 1.73, 95% CI 1.05-2.86) and LDH &gt; upper normal limit (1.88, 95% CI 1.12-3.15) were independent negative prognostic factors for OS. As opposed to the RMH score, number of metastases was not associated with a poorer outcome for this IT cohort (0.83 95% CI 0.51-1.35). Interestingly, a neutrophil to lymphocyte ratio (N/L) &gt; 6 (1.75, 95% CI 1.04-2.95) was associated with a worse OS. A risk analysis based on the results of the MVA showed that patients presenting a high score (2-3) had a significantly shorter OS (20.4 weeks; 95% CI 5.7-35.2) compared to those with a low score (0-1) (68.9 weeks; 95% CI 50-83.7) (HR = 2.9 95% CI 1.87-4.64). In the validation cohort of 113 patients, the patients presenting a high score showed an inferior OS (HR = 6.3, 95% CI 2.7-14.8). Conclusions: In phase I trials of IT, traditional prognostic variables included in the RMH Score are suboptimal to determine patient’s prognosis. In this context, the N/L ratio, which reflects the immune contexture, is a significant prognostic variable. The new Gustave Roussy Score, based on albumin, LDH and N/L ratio allows to better select patients for IT phase I trials.
HGG-22. TARGETING NEURONAL ACTIVITY-REGULATED NEUROLIGIN-3 DEPENDENCY FOR HIGH-GRADE GLIOMA THERAPY
Authors: Humsa S Venkatesh, Lydia T Tam, Pamelyn J Woo, Michelle Monje
Journal: Neuro-Oncology (2017)

Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. Here, we demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG) fail to grow in Nlgn3 knockout mice. Using genetic mouse models, we illustrate that Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of an ADAM10 inhibitor robustly blocks pGBM and DIPG xenograft growth via modulation of the tumor microenvironment. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.
Palbociclib plus letrozole as first-line treatment for ER-positive and HER2-negative advanced breast cancer in Chinese women: a phase 1 study
Authors: Huiping Li, Qingyuan Zhang, Wei Li, Shusen Wang, Ning Liao, Peng Shen, Bin Shao, Wenhui Zhao, Wan Sun, Ping Yan, Diane Wang, Vince (Bai) Li, Carlos Linn, Haihong Shi, Melissa O'Gorman, Binghe Xu
Journal: The Lancet Oncology (2017)
Detection and treatment of Fiebig stage I HIV-1 infection in young at-risk women in South Africa: a prospective cohort study
Authors: Krista L Dong, Amber Moodley, Douglas S Kwon, Musie S Ghebremichael, Mary Dong, Nasreen Ismail, Zaza M Ndhlovu, Jenniffer M Mabuka, Daniel M Muema, Karyn Pretorius, Nina Lin, Bruce D Walker, Thumbi Ndung'u
Journal: The Lancet HIV (2017)