tbuckley/cabot-search huggingface dataset:
Bevacizumab-induced hand-foot syndrome: circumscribed type
Authors: A. Munehiro, K. Yoneda, K. Nakai, T. Demitsu, T. Moriue, J. Moriue, I. Yokoi, N. Fujita, N. Matsuura, S. Ishikawa, H. Yokomise, Y. Kubota
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, The humanized monoclonal antibody bevacizumab is directed against vascular endothelial growth factor and the first antiangiogenic agent to be approved for advanced non‐small‐cell lung cancer, breast cancer and colorectal cancer. The addition of bevacizumab to paclitaxel plus carboplatin achieves a survival benefit in patients with non‐small‐cell lung cancer.1 Recently, Fife et al.2 reported a 67‐year‐old Vietnamese man receiving sunitinib, an oral tyrosine kinase inhibitor, who exhibited a new distinct form of hand‐foot syndrome. In this, the plantar lesions of sunitinib‐associated hand‐foot syndrome showed a clinically unique tendency to be localized and well demarcated over pressure areas and to form bullae rather than being diffuse. We report similar clinical features of hand‐foot syndrome in three patients treated with bevacizumab. To our knowledge, this is the first report of a possible correlation between bevacizumab and circumscribed hand‐foot syndrome. The first patient was a 68‐year‐old Japanese woman diagonosed in September 2006 as having stage III lung adenocarcinoma. After surgical excision, she was treated with docetaxel and carboplatin (one cycle), with incomplete response; thus, a second line of chemotherapy consisting of gemcitabine and vinorelbine was administered in October 2007. This chemotherapy was stopped due to liver damage. In April 2009, progression of lung metastases was observed; thus an erlotinib regimen was begun. Erlotinib was also stopped because of liver damage. In December 2009, progression of lung metastases continued; thus palliative docetaxel and carboplatin therapy was initiated, with the addition of bevacizumab (5 mg kg−1 every 2 weeks).3
Toxoplasma hosts ROP'd into STAT3 activation
Authors: Nicole LeBrasseur
Journal: The Journal of Experimental Medicine (2009)

A lone amino acid change determines success or failure for strains of Toxoplasma gondii , say [Yamamoto et al.][1] The group identifies a kinase mutation that thwarts one strain's ability to activate Stat3 and halt the host immune response.

![Figure][2] 

A polymorphism in the Toxoplasma
Does it look like melanoma? A pilot study of the effect of sunless tanning on dermoscopy of pigmented skin lesions
Authors: J. Dahlén Gyllencreutz, K. Bengsson Boström, K. Terstappen
Journal: British Journal of Dermatology (2013)

Background Dermoscopy has led to an improvement in diagnosing malignant melanoma (MM). Sunless tanning agents containing dihydroxyacetone (DHA) could lead to a decrease in ultraviolet exposure, decreasing the risk of MM. Importantly, DHA has been reported to change dermoscopic features and could thus endanger diagnostic improvement in dermoscopy. Objectives To investigate whether the use of DHA can lead to changes that simulate a real, clinically relevant dermoscopic change, suggesting malignant transformation either in facial solar lentigo/initial seborrhoeic keratosis (SL/ISK) or in naevi on the body. Methods Seven patients with 25 pigmented skin lesions (PSLs) were photographed, resulting in 38 dermoscopic images. Photographs were taken before, 1 week after and 1–2 months after the use of DHA. Two dermatologists separately evaluated the PSLs and their dermoscopic features. For lesions on the body Menzies' method was used, and for facial lesions the criteria defined by Stolz et al. were used. Results In facial PSLs equivocal lesions were registered by both evaluators significantly more often after DHA use than before (42% vs. 12%, P =0·021 and 69% vs. 19%, P =0·001). Furthermore, follicular pigmentation that partly mimics that of lentigo maligna was also seen significantly more often after DHA use than before (81% vs. 12%, P <0·001 and 69% vs. 15%, P <0·001) and in these instances the evaluators recommended a biopsy. Equivocal lesions in naevi on the body were not significantly increased after DHA use. Conclusions Dermoscopists that come across unclear dermoscopic findings, especially in facial PSL, should ask patients about the use of DHA.
Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey
Authors: Marco Ruggeri, Francesco Rodeghiero, Alberto Tosetto, Giancarlo Castaman, Francesca Scognamiglio, Guido Finazzi, Federica Delaini, Caterina Micò, Alessandro M. Vannucchi, Elisabetta Antonioli, Valerio De Stefano, Tommaso Za, Luigi Gugliotta, Alessia Tieghi, Maria Gabriella Mazzucconi, Cristina Santoro, Tiziano Barbui
Journal: Blood (2007)
Dissecting the Akt/Mammalian Target of Rapamycin Signaling Network: Emerging Results from the Head and Neck Cancer Tissue Array Initiative
Authors: Alfredo A. Molinolo, Stephen M. Hewitt, Panomwat Amornphimoltham, Somboon Keelawat, Samraeung Rangdaeng, Abelardo Meneses García, Ana R. Raimondi, Rafael Jufe, María Itoiz, Yan Gao, Dhananjaya Saranath, George S. Kaleebi, George H. Yoo, Lee Leak, Ernest M. Myers, Satoru Shintani, David Wong, H. Davis Massey, W. Andrew Yeudall, Fulvio Lonardo, John Ensley, J. Silvio Gutkind
Journal: Clinical Cancer Research (2007)

Abstract Purpose: As an approach to evaluate the expression pattern and status of activation of signaling pathways in clinical specimens from head and neck squamous cell carcinoma (HNSCC) patients, we established the Head and Neck Cancer Tissue Array Initiative, an international consortium aimed at developing a high-density HNSCC tissue microarray, with a high representation of oral squamous cell carcinoma. Experimental Design: These tissue arrays were constructed by acquiring cylindrical biopsies from multiple individual tumor tissues and transferring them into tissue microarray blocks. From a total of 1,300 cases, 547 cores, including controls, were selected and used to build the array. Results: Emerging information by the use of phosphospecific antibodies detecting the activated state of signaling molecules indicates that the Akt-mammalian target of rapamycin (mTOR) pathway is frequently activated in HNSCC, but independently from the activation of epidermal growth factor receptor or the detection of mutant p53. Indeed, we identified a large group of tissue samples displaying active Akt and mTOR in the absence of epidermal growth factor receptor activation. Furthermore, we have also identified a small subgroup of patients in which the mTOR pathway is activated but not Akt, suggesting the existence of an Akt-independent signaling route stimulating mTOR. Conclusions: These findings provide important information about the nature of the dysregulated signaling networks in HNSCC and may also provide the rationale for the future development of novel mechanism-based therapies for HNSCC patients.
Hepatitis B reactivation in patients with hepatocellular carcinoma undergoing systemic chemotherapy
Authors: W. Yeo, K.C. Lam, B. Zee, P.S.K. Chan, F.K.F. Mo, W.M. Ho, W.L. Wong, T.W.T. Leung, A.T.C. Chan, B. Ma, T.S.K. Mok, P.J. Johnson
Journal: Annals of Oncology (2004)
Mammalian Target of Rapamycin and S6 Kinase 1 Positively Regulate 6-thioguanine-Induced Autophagy
Authors: Xuehuo Zeng, Timothy J. Kinsella
Journal: Cancer Research (2008)

Abstract DNA mismatch repair (MMR) ensures the fidelity of DNA replication and is required for activation of cell cycle arrest and apoptosis in response to certain classes of DNA damage. We recently reported that MMR is also implicated in initiation of an autophagic response after MMR processing of 6-thioguanine (6-TG). It is now generally believed that autophagy is negatively controlled by mammalian target of rapamycin (mTOR) activity. To determine whether mTOR is involved in 6-TG–induced autophagy, we used rapamycin, a potential anticancer agent, to inhibit mTOR activity. Surprisingly, we find that rapamycin cotreatment inhibits 6-TG–induced autophagy in MMR-proficient human colorectal cancer HCT116 (MLH1+) and HT29 cells as measured by LC3 immunoblotting, GFP-LC3 relocalization, and acridine orange staining. Consistently, short interfering RNA silencing of the 70-kDa ribosomal S6 kinase 1 (S6K1), the downstream effector of mTOR, markedly reduces 6-TG–induced autophagy. Furthermore, we show that inhibition of mTOR by rapamycin induces the activation of Akt as shown by increased Akt phosphorylation at Ser473 and the inhibition of 6-TG–induced apoptosis and cell death. Activated Akt is a well-known inhibitor of autophagy. In conclusion, our data indicate that mTOR-S6K1 positively regulates autophagy after MMR processing of 6-TG probably through its negative feedback inhibition of Akt. [Cancer Res 2008;68(7):2384–90]
Calibration of Seven ICU Ventilators for Mechanical Ventilation with Helium–Oxygen Mixtures
Authors: DIDIER TASSAUX, PHILIPPE JOLLIET, JEAN-MARC THOURET, JEAN ROESELER, RENÉ DORNE, JEAN-CLAUDE CHEVROLET
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The study evaluated seven intensive care unit (ICU) ventilators (Veolar FT, Galileo, Evita 2, Evita 4, Servo 900C, Servo 300, Nellcor Puritan Bennett 7200 Series) with helium–oxygen (HeO2), using a lung model, to develop correction factors for the safe use of HeO2. A 70:28 helium–O2 mixture (heliox) replaced air and combined with O2 (HeO2). Theoretical impact of HeO2 on inspiratory valves and gas mixing was computed. True fraction of inspired oxygen (Fi O2 del) was compared with fraction of inspired oxygen (Fi O2 ) set on the ventilator (Fi O2 set). True tidal volume (Vtdel) was compared with Vt set on the ventilator (Vtset) in volume control and with control Vtdel at Fi O2 1.0 in pressure control. Fi O2 del minimally exceeded Fi O2 set ( ⩽ 5%) except with the 7200 Series (Fi O2 del > Fi O2 set by 125%). In volume control, with the Veolar FT, Galileo, Evita 2, and Servo 900C, Vtdel > Vtset, with the 7200 Series Vtdel < Vtset (linear relationship, magnitude of discrepancy inversely related to Fi O2 set). With the Evita 4, Vtdel > Vtset (nonlinear relationship), whereas with the Servo 300 Vtdel = Vtset. In pressure control, Vtdel was identical to control measurements, except with the 7200 Series (ventilator malfunction). Correction factors were developed that can be applied to most ventilators.
Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise
Authors: E. Healy, S.J. Brown, S.M. Langan, S.G. Nicholls, K. Shams, N.J. Reynolds
Journal: British Journal of Dermatology (2015)

Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders.
Cellular immune selection with hepatitis C virus persistence in humans
Authors: Andrea L. Cox, Timothy Mosbruger, Qing Mao, Zhi Liu, Xiao-Hong Wang, Hung-Chih Yang, John Sidney, Alessandro Sette, Drew Pardoll, David L. Thomas, Stuart C. Ray
Journal: The Journal of Experimental Medicine (2005)

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P &amp;lt; 0.001, range 5–38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.
The neglected role of antibody in protection against bacteremia caused by nontyphoidal strains of Salmonella in African children
Authors: Calman A. MacLennan, Esther N. Gondwe, Chisomo L. Msefula, Robert A. Kingsley, Nicholas R. Thomson, Sarah A. White, Margaret Goodall, Derek J. Pickard, Stephen M. Graham, Gordon Dougan, C. Anthony Hart, Malcolm E. Molyneux, Mark T. Drayson
Journal: Journal of Clinical Investigation (2008)

Nontyphoidal strains of Salmonella (NTS) are a common cause of bacteremia among African children. Cell-mediated immune responses control intracellular infection, but they do not protect against extracellular growth of NTS in the blood. We investigated whether antibody protects against NTS bacteremia in Malawian children, because we found this condition mainly occurs before 2 years of age, with relative sparing of infants younger than 4 months old. Sera from all healthy Malawian children tested aged more than 16 months contained anti-Salmonella antibody and successfully killed NTS. Killing was mediated by complement membrane attack complex and not augmented in the presence of blood leukocytes. Sera from most healthy children less than 16 months old lacked NTS-specific antibody, and sera lacking antibody did not kill NTS despite normal complement function. Addition of Salmonella-specific antibody, but not mannose-binding lectin, enabled NTS killing. All NTS strains tested had long-chain lipopolysaccharide and the rck gene, features that resist direct complement-mediated killing. Disruption of lipopolysaccharide biosynthesis enabled killing of NTS by serum lacking Salmonella-specific antibody. We conclude that Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children. This finding and the age-incidence of NTS bacteremia suggest that antibody protects against NTS bacteremia and support the development of vaccines against NTS that induce protective antibody.
Neutralization of meningococcal endotoxin by antibody to core glycolipid.
Authors: C E Davis, E J Ziegler, K F Arnold
Journal: The Journal of Experimental Medicine (1978)

Antibodies to Escherichia coli J5, a uridine 5'-diphosphate-galactose epimerase-less mutant of E. coli 0111, neutralized meningococcal endotoxemia from all three major capsular serogroups. We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because meningococcal lipopolysaccharide (LPS) is a uniquely potent cause of dermal purpura and necrosis. Meningococcal antisera raised against LPS from MGC A, B, and C also provided good protection against endotoxemia from the homologous capsular groups, but it was inconsistent against the heterologous serogroups. The superiority of J5 antibodies (purified IgG as well as antiserum) is probably due to the fact that J5 LPS contains only the endotoxin core. Consequently, immunization with this mutant stimulates production of antibodies to core LPS without interference by the "0" antigenic determinants of the side chains. These observations indicate that the endotoxin core is the toxic moiety of meningococcal LPS, that the core LPS of meningococcus (MGC) is immunologically similar to enteric LPS, and that the antigenically variable "0" side chains of MGC LPS interfere with antibody production against the common core. They also suggest that antibodies prepared against this E. coli mutant could interrupt the devastating course of meningococcal endotoxemia in man, regardless of the capsular serogroup of the infecting strain.
Heterogeneity of pulmonary rehabilitation: like apples and oranges - both healthy fruit
Authors: Carolyn L. Rochester, Antonio Spanevello
Journal: European Respiratory Journal (2014)

Pulmonary rehabilitation is an essential component of comprehensive integrated care, and indeed is one of the most effective interventions, for persons with chronic obstructive pulmonary disease (COPD) and other forms of chronic respiratory disease [1–4]. It has been convincingly demonstrated to improve patients’ exercise tolerance [4, 5], symptoms of dyspnoea [6] and quality of life [1], and to reduce anxiety, depression [7], hospitalisations for COPD exacerbations [1, 8, 9] and urgent healthcare utilisation [10]. It is effective even for persons with complex medical comorbidities such as concurrent cardiovascular and metabolic disease [11] and for chronically critically ill persons admitted to intensive care units [12]. Several published guidelines and statements on the science and optimal implementation of pulmonary rehabilitation exist [1, 13–17]. However, despite the extensive knowledge and published evidence base regarding its benefits pulmonary rehabilitation remains severely underutilised worldwide.

In this issue of the European Respiratory Journal, Spruit et al. [18] report the findings of a 12-question survey, adapted from an existing survey of pulmonary rehabilitation [19, 20], regarding the content and organisational aspects of pulmonary rehabilitation programmes from 430 centres from 40 countries. The majority of respondents were from Europe and North America. The authors found a wide degree of heterogeneity in the content, components, structure and organisation of pulmonary rehabilitation programmes worldwide. Heterogeneity was found in terms of pulmonary rehabilitation programme setting, duration, source of funding and payer reimbursement, number and type of team members, referral sources, patient types, interventions provided, and outcomes measured. The authors conclude that it is important for pulmonary rehabilitation providers to consider development of uniform performance and process metrics …
Complement Activation in Angiotensin II–Induced Organ Damage
Authors: Erdenechimeg Shagdarsuren, Maren Wellner, Jan-Hinrich Braesen, Joon-Keun Park, Anette Fiebeler, Norbert Henke, Ralf Dechend, Petra Gratze, Friedrich C. Luft, Dominik N. Muller
Journal: Circulation Research (2005)

We tested whether or not complement activation participates in angiotensin (Ang) II–induced vasculopathy. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan or the human renin inhibitor aliskiren. Sprague–Dawley (SD) rats were controls. DTGR had increased blood pressure at week 5 that increased further by week 7. Albuminuria was absent at week 5 but increased markedly in weeks 6 and 7. C-reactive protein (CRP) elevation, macrophages, T cells, tumor necrosis factor (TNF)-α, C1q, C3, C3c, and C5b-9 expression preceded albuminuria. C1q, C3, C3c, and C5b-9 were observed in the dTGR vessel media. C5b-9 colocalized with interleukin (IL)-6. Losartan and aliskiren reduced albuminuria and complement expression. We also studied vascular smooth muscle cells (VSMC) from dTGR compared VSMC from SD. C3 and IL-6 mRNA were analyzed after Ang II, TNF-α, and CRP stimulation. VSMC from dTGR showed increased proliferation and C3 expression compared with SD. Ang II did not induce C3 mRNA in either VSMC type. However, TNF-α and CRP induced C3 mRNA slightly in SD VSMC but markedly in dTGR VSMC, whereas IL-6 induction was similar in both. Thus, complement activation and cell infiltration occurred before the onset of albuminuria in Ang II–mediated renal damage. TNF-α and CRP played a major role in C3 activation. VSMC from dTGR are more sensitive for C3 activation. Our data show that, in this Ang II–induced model, complement activation is a major participant and suggest that TNF-α and CRP may play a role in its induction.
Spikes in acute workload are associated with increased injury risk in elite cricket fast bowlers
Authors: Billy T Hulin, Tim J Gabbett, Peter Blanch, Paul Chapman, David Bailey, John W Orchard
Journal: British Journal of Sports Medicine (2013)

To determine if the comparison of acute and chronic workload is associated with increased injury risk in elite cricket fast bowlers.Data were collected from 28 fast bowlers who completed a total of 43 individual seasons over a 6-year period. Workloads were estimated by summarising the total number of balls bowled per week (external workload), and by multiplying the session rating of perceived exertion by the session duration (internal workload). One-week data (acute workload), together with 4-week rolling average data (chronic workload), were calculated for external and internal workloads. The size of the acute workload in relation to the chronic workload provided either a negative or positive training-stress balance.A negative training-stress balance was associated with an increased risk of injury in the week after exposure, for internal workload (relative risk (RR)=2.2 (CI 1.91 to 2.53), p=0.009), and external workload (RR=2.1 (CI 1.81 to 2.44), p=0.01). Fast bowlers with an internal workload training-stress balance of greater than 200% had a RR of injury of 4.5 (CI 3.43 to 5.90, p=0.009) compared with those with a training-stress balance between 50% and 99%. Fast bowlers with an external workload training-stress balance of more than 200% had a RR of injury of 3.3 (CI 1.50 to 7.25, p=0.033) in comparison to fast bowlers with an external workload training-stress balance between 50% and 99%.These findings demonstrate that large increases in acute workload are associated with increased injury risk in elite cricket fast bowlers.
Pindolol Potentiation of Paroxetine for Generalized Social Phobia: A Double-Blind, Placebo-Controlled, Crossover Study
Authors: Murray B. Stein, Jitender Sareen, Shadha Hami, Jeffrey Chao
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The effectiveness of pindolol as an adjunctive treatment to boost response to selective serotonin reuptake inhibitors (SSRIs) in patients with generalized social phobia was tested. METHOD: A double-blind, placebo-controlled, crossover design was used to compare addition of 5 mg of pindolol t.i.d. or placebo for 4 weeks to a steady paroxetine dose. Subjects were 14 patients with generalized social phobia who were less than "very much improved" on the Clinical Global Impression scale after at least 10 weeks of treatment with a maximally tolerated dose of paroxetine. Changes on the Liebowitz Social Anxiety Scale and the Social Phobia Inventory scores were compared across the two crossover periods. RESULTS: Pindolol was not significantly superior to placebo for augmenting the effects of paroxetine on social anxiety symptoms. None of the 14 subjects was deemed a responder to the pindolol arm of the crossover. CONCLUSIONS: Pindolol was no more effective than placebo in augmenting the effects of SSRI treatment for generalized social phobia.