tbuckley/cabot-search huggingface dataset:
An Early CD4+ T Cell–dependent Immunoglobulin A Response to Influenza Infection in the Absence of Key Cognate T–B Interactions
Authors: Mark Y. Sangster, Janice M. Riberdy, Maricela Gonzalez, David J. Topham, Nicole Baumgarth, Peter C. Doherty
Journal: The Journal of Experimental Medicine (2003)

Contact-mediated interactions between CD4+ T cells and B cells are considered crucial for T cell–dependent B cell responses. To investigate the ability of activated CD4+ T cells to drive in vivo B cell responses in the absence of key cognate T–B interactions, we constructed radiation bone marrow chimeras in which CD4+ T cells would be activated by wild-type (WT) dendritic cells, but would interact with B cells that lacked expression of either major histocompatibility complex class II (MHC II) or CD40. B cell responses were assessed after influenza virus infection of the respiratory tract, which elicits a vigorous, CD4+ T cell–dependent antibody response in WT mice. The influenza-specific antibody response was strongly reduced in MHC II knockout and CD40 knockout mice. MHC II–deficient and CD40-deficient B cells in the chimera environment also produced little virus-specific immunoglobulin (Ig)M and IgG, but generated a strong virus-specific IgA response with virus-neutralizing activity. The IgA response was entirely influenza specific, in contrast to the IgG2a response, which had a substantial nonvirus-specific component. Our study demonstrates a CD4+ T cell–dependent, antiviral IgA response that is generated in the absence of B cell signaling via MHC II or CD40, and is restricted exclusively to virus-specific B cells.
The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (DaivobetR/ DovobetR) on the quality of life in patients with psoriasis vulgaris: a randomized controlled trial
Authors: P.C.M. Van De Kerkhof
Journal: British Journal of Dermatology (2004)

Background Psoriasis is a common disease and may have a significant impact on patients' quality of life (QoL). Objectives To assess the impact on QoL of a new two‐compound product (TCP) (Daivobet®/Dovobet®; LEO Pharma) which combines the topical vitamin D analogue calcipotriol (50 µg g−1) and the World Health Organization group III corticosteroid betamethasone dipropionate (0·5 mg g−1) in a single ointment vs. calcipotriol monotherapy using a placebo‐controlled study design. Methods The Psoriasis Disability Index and the EuroQoL 5D questionnaire and visual analogue scale (VAS) were used in this study, which enrolled 828 patients with psoriasis vulgaris for treatment lasting up to 4 weeks. These QoL instruments were completed by patients before and after treatment with the TCP of calcipotriol and betamethasone dipropionate used once or twice daily, calcipotriol alone twice daily and vehicle twice daily. Results The TCP used once or twice daily and calcipotriol used twice daily were found to have statistically significant beneficial effects on patients' QoL over the course of treatment, and each was demonstrated to have a statistically significant benefit on QoL over vehicle. The TCP, applied once daily, was superior to calcipotriol twice daily in terms of reductions on the EuroQoL 5D questionnaire and VAS. Conclusions The results suggest that calcipotriol twice daily and the new TCP applied twice daily have a substantial effect on QoL. Once‐daily application of the TCP is superior to calcipotriol twice daily terms of QoL, which reflects the superior efficacy of this combination and the advantage of once‐daily application when compared with twice‐daily application.
Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans
Authors: Y. Yoo, J. Yu, D. K. Kim, S. H. Choi, C. K. Kim, Y. Y. Koh
Journal: European Respiratory Journal (2005)

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5′-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second ( PC 20 ) of &lt;16 mg·mL −1 , but only six (21.4%) were hyperreactive to AMP with a PC 20 of &lt;200 mg·mL −1 . All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5′-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.
Effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy to treat patients with depression: randomised controlled trial
Authors: M. King
Journal: BMJ (2002)

To assess the effectiveness of teaching general practitioners skills in brief cognitive behaviour therapy.Parallel group, cluster randomised, controlled trial of an educational package on cognitive behaviour therapy.General practices in north London.84 general practitioner principals and 272 patients attending their practices who scored above the threshold for psychological distress on the hospital anxiety and depression scale.A training package of four half days on brief cognitive behaviour therapy.Scores on the depression attitude questionnaire (general practitioners) and the Beck depression inventory (patients).Doctors' knowledge of depression and attitudes towards its treatment showed no major difference between intervention and control groups after 6 months. The training had no discernible impact on patients' outcomes.General practitioners may require more training and support than a basic educational package on brief cognitive behaviour therapy to acquire skills to help patients with depression.
Effect of Granulocyte Colony-Stimulating Factor after Intensive Induction Therapy in Relapsed or Refractory Acute Leukemia
Authors: Ryuzo Ohno, Masao Tomonaga, Tohru Kobayashi, Akihisa Kanamaru, Shigeru Shirakawa, Tohru Masaoka, Mitsuhiro Omine, Hakumei Oh, Takeo Nomura, Yasunobu Sakai, Masami Hirano, Shozo Yokomaku, Shiro Nakayama, Yutaka Yoshida, Akira B. Miura, Yasuo Morishima, Hiroo Dohy, Yoshiyuki Niho, Nobuyuki Hamajima, Fumimaro Takaku
Journal: New England Journal of Medicine (1990)

Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies.
Activity and toxicity of GI147211 in breast, colorectal and non-small-cell lung cancer patients: An EORTC—ECSG phase II clinical study
Authors: T. Gamucci, R. Paridaens, B. Heinrich, J.H. Schellens, N. Pavlidis, J. Verweij, C. Sessa, S. Kaye, M. Roelvink, J. Wanders, A. Hanauske
Journal: Annals of Oncology (2000)
Pioglitazone Use and Heart Failure in Patients With Type 2 Diabetes and Preexisting Cardiovascular Disease
Authors: Erland Erdmann, Bernard Charbonnel, Robert G. Wilcox, Allan M. Skene, Massimo Massi-Benedetti, John Yates, Meng Tan, Robert Spanheimer, Eberhard Standl, John A. Dormandy
Journal: Diabetes Care (2007)

PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) enrolled patients with type 2 diabetes and preexisting cardiovascular disease. These patients were at high risk for heart failure, so any therapeutic benefit could potentially be offset by risk of associated heart failure mortality. We analyzed the heart failure cases to assess the effects of treatment on morbidity and mortality after reports of serious heart failure.PROactive was an outcome study in 5,238 patients randomized to pioglitazone or placebo. Patients with New York Heart Association Class II-IV heart failure at screening were excluded. A serious adverse event of heart failure was defined as heart failure that required hospitalization or prolonged a hospitalization stay, was fatal or life threatening, or resulted in persistent significant disability or incapacity. Heart failure risk was evaluated by multivariate regression.More pioglitazone (5.7%) than placebo patients (4.1%) had a serious heart failure event during the study (P = 0.007). However, mortality due to heart failure was similar (25 of 2,605 [0.96%] for pioglitazone vs. 22 of 2,633 [0.84%] for placebo; P = 0.639). Among patients with a serious heart failure event, subsequent all-cause mortality was proportionately lower with pioglitazone (40 of 149 [26.8%] vs. 37 of 108 [34.3%] with placebo; P = 0.1338). Proportionately fewer pioglitazone patients with serious heart failure went on to have an event in the primary (47.7% with pioglitazone vs. 57.4% with placebo; P = 0.0593) or main secondary end point (34.9% with pioglitazone vs. 47.2% with placebo; P = 0.025).Although the incidence of serious heart failure was increased with pioglitazone versus placebo in the total PROactive population of patients with type 2 diabetes and macrovascular disease, subsequent mortality or morbidity was not increased in patients with serious heart failure.
What about GPs in the fight against tuberculosis?
Authors: S. Singh
Journal: Journal of the Royal Society of Medicine (2003)

Dr Davies's article on tuberculosis (TB) is fascinating and I agree with many of his sentiments (June 2003 JRSM1). But why were general practitioners (GPs) not mentioned in this fight against TB? I, too, have come across a patient in the past few months who almost died of meningeal tuberculosis. She was middle-aged, living with a family I had known for many years (but not registered with a GP). She developed a cough, weight loss, and sweats and finally ended up in intensive care with meningeal TB. Happily she survived and is now well. What is particularly galling is that, as a practice, we take an active interest in infectious diseases.2 This brings me back to my main point.

Respiratory physicians cannot do all this alone; I don't know if some of Davies's comments are directed at GPs specifically (re-education of the medical and allied professionals), but general TB surveillance cannot be done without primary care. Let me say why.

I have heard it said many times that TB management should be totally within the remit of secondary care specialists. If the model of care is one that emulates HIV/AIDS care—hospital driven and directed—then please do not blame GPs for not identifying cases earlier.3 If you involve GPs in decisions regarding their tubercular patients, then primary care can be expected to work with specialists on early identification, management and most importantly, follow-up. Since January 2003 we have registered almost 400 patients from all five continents and including warravaged places such as Afghanistan, Iraq, Ivory Coast, Congo as well as those countries now recovering from the effects of war such as Albania and Kosovo. This is probably why up to 40% of new cases occur in London. With this in mind, it is incumbent on all health professionals to think about TB in cases where it might be a remote, or not so remote, possibility. Davies's article would have been more compelling if GPs had been mentioned at least once.
Association of Deep Brain Stimulation Washout Effects With Parkinson Disease Duration
Authors: Scott E. Cooper, Cameron C. McIntyre, Hubert H. Fernandez, Jerrold L. Vitek
Journal: JAMA Neurology (2012)

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves symptoms of Parkinson disease (PD), including bradykinesia. When stimulation ceases abruptly, bradykinesia returns gradually. The duration of the gradual, slow washout varies across patients, and although the origin of this variability is unclear, it is hypothesized to be related to 1 or more clinical characteristics of patients.To determine if a correlation exists between clinical characteristics of patients with Parkinson disease (age, age at disease onset, disease severity, disease duration, medication dose, or time since surgery) and the washout rate for bradykinesia when STN DBS is discontinued.Serial quantitative assessments of bradykinesia were performed during a defined period following cessation of STN DBS.Academic research.Twenty-four patients with Parkinson disease who underwent STN DBS were enrolled in the study. Patients were assessed while off medication (medication had been discontinued 10½ to 16½ hours before testing), and stimulator settings were unchanged for a mean (median) of 20 (14) months.We measured bradykinesia in the dominant hand by assessing finger tapping (item 23 on the Unified Parkinson Disease Rating Scale), which was quantified using an angular velocity transducer strapped on the index finger. Finger tapping was assessed every 2 minutes for 20 seconds at a time. This was performed during a 20-minute period with DBS on (baseline period), during a 50-minute period following discontinuation of STN DBS for the dominant hand, and again during a 20-minute period after turning on the device.When STN DBS was turned off, an initial fast but partial loss of benefit was observed, which was followed by a further slow washout of the residual therapeutic effect. The half-life of the slow washout phase varied significantly across patients, and this variation was strongly related to disease duration: patients with shorter disease duration experienced slower washout, while patients with longer disease duration experienced faster washout.Washout of STN DBS effects varies with Parkinson disease duration. Estimates of proper washout time based on one patient population may not apply to populations with different disease durations. In DBS clinical trials, washout intervals should be chosen conservatively or adjusted for individual variation in the rate at which washout occurs.
Intracerebral Neural Implants: Neuronal Replacement and Reconstruction of Damaged Circuitries
Authors: Anders Björklund, Ulf Stenevi
Journal: Annual Review of Neuroscience (1984)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Change of Cardiac Rhythm in the Rabbit after an Atrial Premature Beat
Authors: F. I. BONKE, L. N. BOUMAN, H. E. VAN RIJN
Journal: Circulation Research (1969)

In the isolated right atrium of the rabbit, premature beats were elicited by electrical stimulation.When the activation front of a premature beat did not reach the sinoatrial (S-A) node soon enough to discharge the pacemaker prematurely, the pause following the premature beat was compensatory.However, when the activation front forced the pacemaker to discharge prematurely, the premature beat cycle outlasted the normal spontaneous pause, although it was not completely compensatory.Moreover, several cycles after the premature beat were prolonged.The postextrasystolic pause lasted longer if the premature beat was elicited earlier in the atrial cycle.Several changes in the activity of the S-A node caused the prolonged diastole after the atrial premature beat; the most prominent change was a pacemaker shift that persisted several cycles after the premature beat.We found a progressive decrease of the conduction velocity within the S-A node when the latency between the spontaneous discharge of the pacemaker and the arrival of the premature impulse from the atrium in the S-A node was shortened.This may explain the occurrence within the S-A node of a shift of the pacemaker in the direction of the ectopic focus.The rhythm of the new pacemaker was slower than that of the original one.
A survey of flexibility training protocols and hamstring strains in professional football clubs in England
Authors: B Dadebo, J White, K P George
Journal: British Journal of Sports Medicine (2004)

Objectives: To investigate the relation between current flexibility training protocols, including stretching, and hamstring strain rates (HSRs) in English professional football clubs. Method: Questionnaire based data on flexibility training methods and HSRs were collected from 30 English professional football clubs in the four divisions during the 1998/99 season. Data were coded and analysed using cross tabulation, correlation, and multiple regression. Results: Flexibility training protocols were characterised by wide variability, with static stretching the most popular stretching technique used. Hamstring strains represented 11% of all injuries and one third of all muscle strains. About 14% of hamstring strains were reinjuries. HSRs were highest in the Premiership (13.3 (9.4)/1000 hours) with the lowest rates in Division 2 (7.8 (2.9)/1000 hours); values are mean (SD). Most (97%) hamstring strains were grade I and II, two thirds of which occurred late during training/matches. Forwards were injured most often. Use of the standard stretching protocol (SSP) was the only factor significantly related to HSR ( r = −0.45, p = 0.031) in the correlation analysis, suggesting that the more SSP is used, the lower the HSR. About 80% of HSR variability was accounted for by stretching holding time (SHT), SSP, and stretching technique (STE) in the multiple regression equation: HSR = 37.79 − (0.33SHT − 10.05SSP + 2.24STE) ± 2.34. SHT (negatively correlated with HSR) was the single highest predictor, and accounted for 30% of HSR variability, and an additional 40% in combination with SSP. Conclusions: Flexibility training protocols in the professional clubs were variable and appeared to depend on staffing expertise. Hamstring stretching was the most important training factor associated with HSR. The use of SSP, STE, and SHT are probably involved in a complex synergism which may reduce hamstring strains. Modification of current training patterns, especially stretching protocols, may reduce HSRs in professional footballers.
A case report of subacute bronchial toxicity induced by an electronic cigarette: Table 1
Authors: José Hureaux, Martine Drouet, Thierry Urban
Journal: Thorax (2014)

Jose Hureaux (JH): I would like to present the case of a 43-year-old patient who presented with bronchial syndrome associated with deterioration of pulmonary function tests (PFTs) after starting to use an electronic cigarette. He had a history of primary lung adenocarcinoma with a documented isolated brain metastasis (stage pT3N0M1b) treated by stereotactic brain radiotherapy, right upper lobectomy and chemotherapy. The patient had been under surveillance for 7 months. This patient, an active smoker (45 pack-years) undergoing smoking cessation with the assistance of his general practitioner based on a reduction strategy accompanied by nicotine replacement therapy (21 mg patch), continued to smoke about 20 cigarettes a day. In order to completely stop smoking, he decided to try an electronic cigarette on the advice of a friend.

Thierry Urban (TU): Smoking cessation is useful in all patients operated for lung cancer, and must be encouraged. The e-cigarette provides nicotine via the inhaled route from which it is rapidly absorbed by a modality corresponding to the usual actions of smoking, while reducing the exposure of individuals to carcinogenic substances present in tobacco smoke. However, the real place of e-cigarettes in the therapeutic aid to smoking cessation is unknown.

JH: He purchased an e-cigarette (‘La dynamique’ by CIGARTEX) and two …
Lipid accumulation and dendritic cell dysfunction in cancer
Authors: Donna L Herber, Wei Cao, Yulia Nefedova, Sergey V Novitskiy, Srinivas Nagaraj, Vladimir A Tyurin, Alex Corzo, Hyun-Il Cho, Esteban Celis, Brianna Lennox, Stella C Knight, Tapan Padhya, Thomas V McCaffrey, Judith C McCaffrey, Scott Antonia, Mayer Fishman, Robert L Ferris, Valerian E Kagan, Dmitry I Gabrilovich
Journal: Nature Medicine (2010)
Extensive tissue-regenerative capacity of neonatal human keratinocyte stem cells and their progeny
Authors: Amy Li, Normand Pouliot, Richard Redvers, Pritinder Kaur
Journal: Journal of Clinical Investigation (2004)

Given our recent discovery that it is possible to separate human epidermal stem cells of the skin from their more committed progeny (i.e., transit-amplifying cells and early differentiating cells) using FACS techniques, we sought to determine the comparative tissue regeneration ability of these keratinocyte progenitors. We demonstrate that the ability to regenerate a fully stratified epidermis with appropriate spatial and temporal expression of differentiation markers in a short-term in vitro organotypic culture system is an intrinsic characteristic of both epidermal stem and transit-amplifying cells, although the stem cell fraction is most capable of achieving homeostasis. Early differentiating keratinocytes exhibited limited short-term tissue regeneration under specific experimental conditions in this assay, although significant improvement was obtained by manipulating microenvironmental factors, that is, coculture with minimally passaged dermal cells or exogenous supply of the ECM protein laminin-10/11. Importantly, transplantation of all classes of keratinocyte progenitors into an in vivo setting demonstrated that tissue regeneration can be elicited from stem, transit-amplifying, and early differentiating keratinocytes for up to 10 weeks. These data illustrate that significant proliferative and tissue-regenerative capacity resides not only in keratinocyte stem cells as expected, but also in their more committed progeny, including early differentiating cells.
Conventional ultrasound integrated with elastosonography and B-flow imaging in the diagnosis of thyroid nodular lesions
Authors: Alfonso Reginelli, Fabrizio Urraro, Graziella di Grezia, Giuseppina Napolitano, Nicola Maggialetti, Salvatore Cappabianca, Luca Brunese, Ettore Squillaci
Journal: International Journal of Surgery (2014)
Vitiligo is an independent favourable prognostic factor in stage III and IV metastatic melanoma patients: results from a single-institution hospital-based observational cohort study
Authors: P. Quaglino, F. Marenco, S. Osella-Abate, N. Cappello, M. Ortoncelli, B. Salomone, M.T. Fierro, P. Savoia, M.G. Bernengo
Journal: Annals of Oncology (2009)