tbuckley/cabot-search huggingface dataset:
Unmasking Latent Inhibitory Connections in Human Cortex to Reveal Dormant Cortical Memories
Authors: H.C. Barron, T.P. Vogels, U.E. Emir, T.R. Makin, J. O’Shea, S. Clare, S. Jbabdi, R.J. Dolan, T.E.J. Behrens
Journal: Neuron (2016)

Balance of cortical excitation and inhibition (EI) is thought to be disrupted in several neuropsychiatric conditions, yet it is not clear how it is maintained in the healthy human brain. When EI balance is disturbed during learning and memory in animal models, it can be restabilized via formation of inhibitory replicas of newly formed excitatory connections. Here we assess evidence for such selective inhibitory rebalancing in humans. Using fMRI repetition suppression we measure newly formed cortical associations in the human brain. We show that expression of these associations reduces over time despite persistence in behavior, consistent with inhibitory rebalancing. To test this, we modulated excitation/inhibition balance with transcranial direct current stimulation (tDCS). Using ultra-high-field (7T) MRI and spectroscopy, we show that reducing GABA allows cortical associations to be re-expressed. This suggests that in humans associative memories are stored in balanced excitatory-inhibitory ensembles that lie dormant unless latent inhibitory connections are unmasked.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJkZjU3MjgyNWI0N2Y4MjIwMjljYjBhOWVhNjEwYjhiNiIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3ODk2NzQ1fQ.BK91OSYcYAGwkiHQ8f8vgwz4Z90OzuIsiCDIt-LoHYmBe9Yegp1II61d24qGJ8Z6kpBAkOVSR0JourRBqnaUS9yCUWtI6ezN7ReexZmfXujbbPe-721tMIDetL_ew0_iKX4EcgNbtXSSF5YGfuDXCwwbw4mhZ5q7I4XvyyLSzyWvPEULYGgIf0cs3eL_1kCt8cOJR88uVRtaCuyyAJ3McigysZjFDTeGCCRR-fmk6LpNzSBm8rjVLnMKuzjmOE3YKByxU-RP9g4-RP6q-tm2el46Zm1jGRun-ii-Yj6uGDFY-FkP1-w7evGvw8vhLisPYceVrJHPMunyKfGOkDqGHg(mp4, (14.84 MB) Download video
Aging and Cancerigenesis. I. Immunity to Tumor and Skin Grafts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M. N. Teller, G. Stohr, W. Curlett, M. L. Kubisek, D. Curtis
Journal: JNCI Journal of the National Cancer Institute (1964)

An investigation involving the relationship of aging to cancerigenesis disclosed an impaired immune response in untreated, aging, randombred Swiss mice. The incidence of this abnormal immune reactivity increased with age, as did cumulative spontaneous tumor incidence. A xenogeneic graft (human tumor H.Ep.#3) grew in old but not in young adult female mice, and skin grafts survived significantly longer in similar old females, some to death of the host. A possible interrelationship between aging, immunity, and cancerigenesis is discussed.
Treating head injuries
Authors: V. Bonicalzi
Journal: BMJ (2002)

# Outcomes in specialist units using protocols may not be better {#article-title-2} EDITOR—Mortality and morbidity from head injury seem to have fallen, presumably with use of organised trauma care systems and adequate critical care.1 In his editorial on treating head injuries Wasserberg said that evidence now shows an overall improvement in the outcome of head injury from treatment in a specialist unit that uses protocol driven treatment.2 ![][1]</img> This statement is not based on a randomised controlled trial but a retrospective survey showing that in the whole referral population the tendency to increased favourable outcome after institution of protocol driven treatment did not reach significance and the overall mortality did not change significantly.3 Only patients with severe head injury showed an increase in favourable outcome, without a difference in mortality. Wasserberg's statement therefore seems unsubstantiated. All protocol driven treatments are based on successive introduction of hyperventilation, drainage of cerebrospinal fluid, infusion of mannitol, hypothermia, barbiturates, and (rarely) decompressive craniotomy—all treatments lowering intracranial pressure. Two studies cited by Raj and Narayan (by Roberts et al, reference 11, and Dickinson et al, reference 5) concluded on the basis of randomised controlled trials that it was impossible to refute either a moderate increase or a moderate decrease in the risk of death or disability from the use of hyperventilation, drainage of cerebrospinal fluid, mannitol, barbiturates, or corticosteroids.1 Wasserberg quotes a Cochrane review, concluding that no evidence exists that hypothermia is beneficial in head injury, forgetting that a … [1]: /embed/graphic-1.gif
Proliferative Lesions Found in Rat Kidneys After a Single Dose of Cisplatin&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R E Bulger, D C Dobyan
Journal: JNCI Journal of the National Cancer Institute (1984)

Proliferative lesions in inbred F344 rat kidneys were studied at 6 and 15 months after a single injection of 6 mg cisplatin [CAS: 15663-27-1; cis-diamminedichloroplatinum (ll)]/kg body weight. Solid or cystic lesions developed from altered proximal tubular epithelial cells. The lesions affecting the renal proximal tubules had both granular (organelle-rich) and clear (organelle-poor) variants. These altered cells retained microvilli and contained numerous lysosomes, mitochondria, and abundant rough-surfaced endoplasmic reticulum and free ribosomes. In addition, papillary hyperplasia was seen at 15 months and involved the epithelium lining the renal papilla. The hyperplastic changes of the papillary epithelium were morphologically similar to those produced by other drugs.
Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon‐Free Nanoscale Ultrasound Contrast Agents
Authors: Adem Yildirim, Rajarshi Chattaraj, Nicholas T. Blum, Galen M. Goldscheitter, Andrew P. Goodwin
Journal: Advanced Healthcare Materials (2016)

While gas‐filled micrometer‐sized ultrasound contrast agents vastly improve signal‐to‐noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon‐based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 10 10 particles mL −1 , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate‐buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation.
Involvement of Ca2+-Dependent Hyperpolarization in Sleep Duration in Mammals
Authors: Fumiya Tatsuki, Genshiro A. Sunagawa, Shoi Shi, Etsuo A. Susaki, Hiroko Yukinaga, Dimitri Perrin, Kenta Sumiyama, Maki Ukai-Tadenuma, Hiroshi Fujishima, Rei-ichiro Ohno, Daisuke Tone, Koji L. Ode, Katsuhiko Matsumoto, Hiroki R. Ueda
Journal: Neuron (2016)
Second Allogeneic Stem Cell Transplantation (AlloSCT) In Patients With Relapsed Lymphoma After First Allosct. A Retrospective Study Of The EBMT Lymphoma Working Party
Authors: Kristin Horstmann, Ariane Boumendil, Herve Finel, Jane F. Apperley, Fabio Ciceri, Juergen Finke, Achiel Van Hoof, Norbert Ifrah, Slawomira Kyrcz-Krzemien, Gustavo Milone, Ghulam J Mufti, Elizabeth Naparstek, Reuven Or, Nigel H Russell, Peter Dreger
Journal: Blood (2013)
Ireland: state pays maximum of pound124 a week to the cost of a nursing home bed
Authors: M. Houston
Journal: BMJ (2002)

In the Republic of Ireland, the proportion of people aged 65 or over is set to increase from the current level of 11% to 24% by 2050. This growth will be particularly rapid after 2025, a direct result of the high birth rate in the 1960s and '70s.

Long term care for elderly people who are incapacitated is provided in several different ways.

If a 74 year old woman had a stroke, for example, and required nursing home care, several options are available. She could be placed in the long stay …
Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials
Authors: Jason A. Roberts, Mohd-Hafiz Abdul-Aziz, Joshua S. Davis, Joel M. Dulhunty, Menino O. Cotta, John Myburgh, Rinaldo Bellomo, Jeffrey Lipman
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
Abstract 16156: More Frequent Chocolate Consumption is Linked to Better Word Memory
Authors: Beatrice A Golomb, Zoe Vomberg, Katherine Huynh, Athena Hathaway Meskimen
Journal: Circulation (2012)

Chocolate has antioxidant and cell energy benefits in animal studies. The brain is the most energy demanding organ. We conjectured that chocolate consumption could relate to better memory performan...
Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected] [published erratum appears in Blood 1992 Jun 15;79(12):3397]
Authors: HG Klingemann, AP Grigg, K Wilkie-Boyd, MJ Barnett, AC Eaves, DE Reece, JD Shepherd, GL Phillips
Journal: Blood (1991)
Abstract P274: Predictive Value of the International Physical Activity Questionnaire of the Aerobic Capacity in Sedentary Hypertensive Women.
Authors: Miguel Bravo, Tomás Romero, Camila X Romero, Elard Koch, Daniela Sandoval, Sebastián Gatica, Ivonne Ahlers, Oscar HenrÍquez, Javiera Garrido
Journal: Circulation (2012)

Background: There is consensus in the value of assessing and counseling hypertensive patients in reference to their physical activities (PA). The International Physical Activity Questionnaire (IPAQ) is a commonly used instrument to asses the energy expenditure (EE) through different domains of daily activity. Objectives: The main purpose of this study was to assess the relation of self-reported PA through the IPAQ and the aerobic capacity using oxygen consumption (VO 2 ) measured directly in hypertensive sedentary women. Methods: Cross-sectional study in a simple random sub-sample of 64 hypertensive women between 35 and 55 years old, without physical limitation or coronary event. PA was evaluated using the Spanish version of the IPAQ to assess the energy expenditure (EE) and PA intensity (moderate or vigorous) in different domains (work, transport, domestic, leisure). VO 2 peak was measured directly, breath to breath (Fitmate Pro®), at a submaximal (85% [85 of 100] maximal heart rate) exercise test with 25 watt/3 min load increments in a bicycle ergometer. Results: Mean age was 48.4±5.2 years. Measured peak VO 2 was 16.5±2.6 mL/Kg/min with a predicted VO 2 max of 23±3.7 mL/Kg/min, both corresponding to a sedentary level. The greater proportion of EE was observed in work and domestic domains in contrast to leisure activities that had the lowest. Over 50% (1 of 2) of the PA was done at moderate intensity. Peak VO 2 showed a direct correlation with total EE, work and domestic, and finally, with the cost in PA done at moderate intensity. Table. Relationship between self-reported PA (IPAQ) and direct measurements of VO 2 Domain or PA type IPAQ EE (MET-min/week) * EE(%) † Pearson's Correlation coefficient VO 2 peak (ml/Kg/min) p-value IPAQ total 3,613 (1,976 - 5,589) − 0.539 0.001 Work 358 (0 - 2,230) 25.4 0.577 0.001 Transport 396 (89 - 795) 15.5 −0.103 0.542 Domestic 1,465 (893 - 2,520) 47.1 0.385 0.018 Leisure 153 (0 - 664) 13.1 −0.011 0.950 Moderate 1,672 (978 - 3,275) 57.4 0.560 0.001 Vigorous 0 (0 - 1,216) 12.8 0.249 0.136 * Data expressed as median (percentiles 25 and 75) † Percentage of mean EE of the domain or PA type according to total EE. Conclusion: In sedentary hypertensive women self reported PA using IPAQ is predominantly related to domestic and work activities at moderate intensity. Work, and domestic EE or moderate intensity global PA correlated well with the peak VO 2 directly measured during a sub maximal exercise test. Thus, IPAQ appears as an adequate instrument to assess the EE of hypertensive patients and its impact on their aerobic capacity.
Blocking Indolamine-2,3-Dioxygenase Rebound Immune Suppression Boosts Antitumor Effects of Radio-Immunotherapy in Murine Models and Spontaneous Canine Malignancies
Authors: Arta M. Monjazeb, Michael S. Kent, Steven K. Grossenbacher, Christine Mall, Anthony E. Zamora, Annie Mirsoian, Mingyi Chen, Amir Kol, Stephen L. Shiao, Abhinav Reddy, Julian R. Perks, William T.N. Culp, Ellen E. Sparger, Robert J. Canter, Gail D. Sckisel, William J. Murphy
Journal: Clinical Cancer Research (2016)

Previous studies demonstrate that intratumoral CpG immunotherapy in combination with radiotherapy acts as an in-situ vaccine inducing antitumor immune responses capable of eradicating systemic disease. Unfortunately, most patients fail to respond. We hypothesized that immunotherapy can paradoxically upregulate immunosuppressive pathways, a phenomenon we term "rebound immune suppression," limiting clinical responses. We further hypothesized that the immunosuppressive enzyme indolamine-2,3-dioxygenase (IDO) is a mechanism of rebound immune suppression and that IDO blockade would improve immunotherapy efficacy.We examined the efficacy and immunologic effects of a novel triple therapy consisting of local radiotherapy, intratumoral CpG, and systemic IDO blockade in murine models and a pilot canine clinical trial.In murine models, we observed marked increase in intratumoral IDO expression after treatment with radiotherapy, CpG, or other immunotherapies. The addition of IDO blockade to radiotherapy + CpG decreased IDO activity, reduced tumor growth, and reduced immunosuppressive factors, such as regulatory T cells in the tumor microenvironment. This triple combination induced systemic antitumor effects, decreasing metastases, and improving survival in a CD8(+) T-cell-dependent manner. We evaluated this novel triple therapy in a canine clinical trial, because spontaneous canine malignancies closely reflect human cancer. Mirroring our mouse studies, the therapy was well tolerated, reduced intratumoral immunosuppression, and induced robust systemic antitumor effects.These results suggest that IDO maintains immune suppression in the tumor after therapy, and IDO blockade promotes a local antitumor immune response with systemic consequences. The efficacy and limited toxicity of this strategy are attractive for clinical translation. Clin Cancer Res; 22(17); 4328-40. ©2016 AACR.
A mind-breaking cause of acute kidney injury
Authors: Arenda H. van Beek, Jacobien C. Verhave
Journal: Kidney International (2016)

A 27-year-old woman without a significant medical history presented with vomiting, diarrhea, and fatigue. Her blood pressure was 110/85 mm Hg and her pulse was 93 beats per minute. The serum creatinine level was 2.4 mg/dl, the serum sodium level was 146 mmol/l, the urine sediment was bland, and the urinary sodium was <10 mmol/l. Ultrasonography showed normal-sized kidneys. After volume repletion with saline 0.9%, renal function normalized (serum creatinine level, 0.9 mg/dl). However, her serum sodium level was 149 mmol/l with plasma osmolality of 310/kg and urine of 109 mOsm/kg. Twenty-four–hour urinary volume was high (9 l/24 h). Retrospectively, the patient noted that she always needed to drink large volumes of fluid. There were no signs of systemic disorders associated with inappropriate antidiuretic hormone functioning, and the patient used no medication that affected diuresis. There were no family members with reduced urinary concentrating abilities. Magnetic resonance imaging revealed a 4-cm cerebral tumor in the corpus callosum (Figure 1). Biopsy revealed an intracranial germ cell tumor. Computed tomography of the thorax and abdomen showed no other tumor localization, and tumor markers (alpha-fetoprotein and β-human chorionic gonadotropin) were in the normal range. Cerebrospinal fluid contained no malignant cells. Desmopressin (an antidiuretic hormone analogue) normalized urine volume and the patient began radiotherapy. In summary, this patient initially presented with acute kidney injury from volume depletion thought to be induced by gastroenteritis. However, after correction of the volume deficit and subsequent improvement of renal function, a classic manifestation of central diabetes insipidus from an intracranial tumor was revealed.
Predicting LVOT Obstruction in Transcatheter Mitral Valve Implantation
Authors: Philipp Blanke, Christopher Naoum, Danny Dvir, Vinayak Bapat, Kevin Ong, David Muller, Anson Cheung, Jian Ye, James K Min, Nicolo Piazza, Pascal Theriault-Lauzier, John Webb, Jonathon Leipsic
Journal: JACC. Cardiovascular imaging (2016)
Effect of Degradation Rate of 5-Fu and Genetic Polymorphisms of Dpd, Tser and Mthrf on Toxicity and Survival of 5-Fu-Based Chemotherapy in Gastric Cancer
Authors: F. Mazzuca, A. Botticelli, L. Lionetto, M. La Torre, R. Giusti, C. Maddalena, P. Pellegrini, G. Gentile, F.R. Ciabatta, M. Borro, V. Ziparo, M. Simmaco, P. Marchetti
Journal: Annals of Oncology (2014)
Risk of End‐Stage Renal Disease in Patients With Lupus Nephritis, 1971–2015: A Systematic Review and Bayesian Meta‐Analysis
Authors: Maria G. Tektonidou, Abhijit Dasgupta, Michael M. Ward
Journal: Arthritis & Rheumatology (2016)

End-stage renal disease (ESRD) is a major consequence of lupus nephritis, but how this risk has changed over time is unknown. We conducted this systematic review to examine changes in ESRD among adults with lupus nephritis from 1971 to 2015 and to estimate risks of ESRD among contemporary patients.We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for cohort studies and clinical trials on ESRD in adults with lupus nephritis. We analyzed studies from developed and developing countries separately. The outcome was probability of ESRD at 5, 10, and 15 years of lupus nephritis.We included 187 articles that reported on 18,309 patients. In developed countries, the 5-year risk of ESRD decreased from 16% (95% confidence interval [95% CI] 14-17%) in 1970-1979 to 11% (95% CI 10-12%) in the mid-1990s and then plateaued. ESRD risks at 10 years and 15 years showed steeper declines in the 1970s and 1980s but also plateaued in 1993-1997, with a notable increase in the late 2000s. The decrease in risk after 1980 coincided with increased use of cyclophosphamide. The 15-year ESRD risk was higher in developing countries than in developed countries. Patients with class IV lupus nephritis had the greatest risk of ESRD, with a 15-year risk of 44% during the 2000s.Risks of ESRD in lupus nephritis improved between the 1970s and the mid-1990s and then plateaued, with an increase in the late 2000s. This pattern suggests limitations in the effectiveness of, or access to, current treatments.
Vaccine against Pneumococcal Pneumonia in Adults
Authors: James D Leo
Journal: New England Journal of Medicine (2015)

The authors reply: Our study was a pragmatic comparative-effectiveness trial evaluating functional testing versus coronary CTA in patients with stable chest pain and, as such, reflects actual care provided across its 193 North American sites.Each study site met current standards for imaging quality and was certified in all techniques.However, it is likely that testing at some sites reflects better available practices than at others.Whereas Bom et al. correctly point out that expert sites may use lower doses of radiation in performing CTA than were recorded for some patients in our study, this is also true for nuclear testing.Pragmatic design principles also governed the selection of the type of functional test, which was at the discretion of the local care team.Although we did not record the appropriateness of testing according to technique, all patients were symptomatic and middle-aged or older, and more than 97% had at least one cardiovascular risk factor.Stress testing with the use of any technique is generally considered to be appropriate in such patients.We agree with Martin that many features of exercise stress testing predict the risk of death, and in our study, we compared the effect of all the information derived from testing on outcomes.Stratification of randomization according to the intended diagnostic test allowed for a comparison of outcomes in the approximately 1100 patients (a reasonably large cohort) who were assigned to undergo either exercise ECG or CTA, and the two strategies were found to be equivalent.Blumenthal and Wasfy correctly point out that
A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity
Authors: Hui Jing, Jing Hu, Bin He, Yashira L. Negrón Abril, Jack Stupinski, Keren Weiser, Marisa Carbonaro, Ying-Ling Chiang, Teresa Southard, Paraskevi Giannakakou, Robert S. Weiss, Hening Lin
Journal: Cancer Cell (2016)