tbuckley/cabot-search huggingface dataset:
Bilateral pulmonary alveolar infiltrate and prostate tumour in a 54-year-old man
Authors: A. A Figueiredo, G. Brandao, L. C Dentz, C. M. Alves, A. E S Stroppa
Journal: Thorax (2007)

Figure 1 (A) CT scan of the pelvis showing a prostate tumour with bladder invasion.(B) Chest radiograph showing a bilateral perihilar alveolar infiltrate.(C) Chest CT scan showing ground-glass opacity.
One Size Does Not Fit All: Personalized Immune Therapies Poised to Take Center Stage
Authors: A. Azvolinsky
Journal: JNCI Journal of the National Cancer Institute (2013)

Researchers are taking a patient’s own T cells, arming the cells against that patient’s cancer, and injecting them back into the patient. The approach is working on metastatic cancer patients who have otherwise run out of treatment options. To date, only a few leukemia patients have been treated with the chimeric antigen receptor (CAR) technique, but researchers believe the CAR technique can benefit many patients—although many more studies are still needed. “We believe the early responses are every reason to be optimistic,” said David Porter, M.D., of the Abramson Cancer Center at the University of Pennsylvania, who along with Carl June, M.D., director of translational research, leads the CAR trials at Penn. So far, nine of 11 leukemia patients, including two children, have responded to CAR immunotherapy. Two patients have been in remission for more than 2 years.
Pathogenesis, Diagnosis, and Management of Reflux Esophagitis
Authors: D Kestenbaum, J Behar
Journal: Annual Review of Medicine (1981)

The most common symptoms associated with reflux esophagitis are heart­ burn and regurgitation. Heartburn is usually described as a substernal or retrosternal burning pain or discomfort with a moving quality from the xyphoid area up toward the suprasternal notch. The pain may radiate up toward the neck and jaw as well as down into the epigastric area. Rarely, the pain may radiate into the arms and simulate the pain of cardiac origin (1). Heartburn is frequently associated with regurgitation of sour or bitter fluid. These symptoms are exacerbated by meals or postural changes, usu­ ally made worse when the patient is recumbent or tenses his abdominal muscles as in lifting. Most patients (84%) experience symptoms of reflux for more than one year before seeking medical attention (2). Intermittent dysphagia occurs frequently with the first swallows of every meal. The symptom is often reported by patients with severe reflux eso­ phagitis. They do not often have mechanical obstruction to the passage of food. Usually the dysphagia will be mild and nonprogressive with no asso­ ciated weight loss. This is the result of a motility disturbance within the body of the esophagus induced by reflux of gastroduodenal contents (3) and occurs most frequently with the first bolus swallowed. Persistent dysphagia of solids in a patient with reflux esophagitis should indicate to the clinician that a peptic stricture has formed or that a carcinoma may have developed within the esophagus. Anemia has been described as the presenting symp­ tom in some patients with reflux esophagitis; it is a result of low-grade
ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors
Authors: Jianfeng Shen, Yang Peng, Leizhen Wei, Wei Zhang, Lin Yang, Li Lan, Prabodh Kapoor, Zhenlin Ju, Qianxing Mo, Ie-Ming Shih, Ivan P. Uray, Xiangwei Wu, Powel H. Brown, Xuetong Shen, Gordon B. Mills, Guang Peng
Journal: Cancer Discovery (2015)

ARID1A, SWI/SNF chromatin remodeling complex subunit, is a recently identified tumor suppressor that is mutated in a broad spectrum of human cancers. Thus, it is of fundamental clinical importance to understand its molecular functions and determine whether ARID1A deficiency can be exploited therapeutically. In this article, we report a key function of ARID1A in regulating the DNA damage checkpoint. ARID1A is recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA damage checkpoint kinase ATR. At the molecular level, ARID1A facilitates efficient processing of DSB to single-strand ends and sustains DNA damage signaling. Importantly, ARID1A deficiency sensitizes cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors.ARID1A has been identified as one of the most frequently mutated genes across human cancers. Our data suggest that clinical utility of PARP inhibitors might be extended beyond patients with BRCA mutations to a larger group of patients with ARID1A-mutant tumors, which may exhibit therapeutic vulnerability to PARP inhibitors.
Shoulder to shoulder: stabilising instability, re-establishing rhythm, and rescuing the rotators!
Authors: B M Pluim, R E H van Cingel, W B Kibler
Journal: British Journal of Sports Medicine (2010)

There have been tremendous advances in the diagnosis and management of shoulder injuries. For this issue of the BJSM , we target the world’s leading shoulder clinicians to share their insights. We outline the concept of scapular dyskinesis, simplify the classification and management of shoulder instability, and clarify the essentials of office shoulder examination. Are you at all confused as to how to diagnose whether shoulder pain is due to a superior labrum anterior posterior (SLAP) lesion? Do young pitchers with shoulder pain scare you? Then this issue is for you!

Good scapular stability and a normal scapulo-humeral rhythm are essential for good shoulder function. Being able to recognise an abnormal rhythm is the key to managing shoulder injuries. Kibler and Sciascia1 identify the causes of an altered scapular resting position and explain the concept of scapular dyskinesis ( see page 300 ). Note the step-by-step guide to the examination of a shoulder with scapular dyskinesis and the …
Validation of the U.K. Working Party diagnostic criteria for atopic eczema in a Xhosa-speaking African population
Authors: D.A. Chalmers, G. Todd, N. Saxe, J.T. Milne, S. Tolosana, P.N. Ngcelwane, B.N. Hlaba, L.N. Mngomeni, T.G. Nonxuba, H.C. Williams
Journal: British Journal of Dermatology (2006)

Reliable diagnostic criteria for eczema are important for epidemiological comparisons. Although the U.K. diagnostic criteria for atopic eczema have performed well in an English language setting, limited data are available from other countries where cultural and linguistic factors may affect their validity.We sought to determine the validity of the U.K. criteria for eczema in relation to clinical assessment by a dermatologist in a Xhosa-speaking South African population.A cross-sectional survey of 3067 children aged 3-11 years was conducted in rural, peri-urban and urban settings in South Africa. The prevalence of atopic eczema was determined using the U.K. diagnostic criteria and a clinical assessment by a dermatologist. Questions were translated into the local language (Xhosa). Trained researchers administered the questions to the children's parents or carers. The validity of the U.K. criteria was then determined by calculating the sensitivity, specificity, positive and negative predictive values, and Youden's Index in relation to the dermatologist's examination.The point prevalence of atopic eczema according to a dermatologist was 1.0% [95% confidence interval (CI) 0.6-1.4], while the prevalence of visible flexural eczema according to the U.K. protocol was 1.8% (95% CI 1.3-2.2). The sensitivity and specificity of the U.K. criteria in this setting was 43.7% (95% CI 26.3-62.3) and 97.9% (97.3-98.4), respectively. The positive and negative predictive values of the U.K. criteria were 18.4% (95% CI 10.4-28.9) and 99.4% (95% CI 99.0-99.6), respectively. The presence of visible flexural eczema according to the U.K. photographic protocol was the best predictor of atopic eczema, with a sensitivity and specificity of 81.2% (95% CI 63.5-92.7) and 99.0% (95% CI 98.6-99.3), respectively, and a positive and negative predictive value of 48.1% (95% CI 34.3-62.1) and 99.8% (95% CI 99.5-99.9), respectively.The validity of the full question-based version of the U.K. diagnostic criteria for atopic eczema in this South African setting is low, which may be due to a combination of translational and cultural issues. However, the one physical sign of visible flexural eczema performed well, suggesting that it alone might be a useful tool for future international comparative prevalence studies.
Respiratory Syncytial Virus Nonstructural Protein NS1 Colocalizes with Mitochondrial Antiviral Signaling (MAVS)Protein Following Infection
Authors: S. Boyapalle
Journal: Journal of Allergy and Clinical Immunology (2011)

Respiratory Syncytial Virus Nonstructural Protein NS1 Colocalizes with Mitochondrial Antiviral Signaling (MAVS) Protein Following Infection. Sandhya Boyapalle1, Terianne Wong1, Byeong Cha1, Subhra Mohapatra1 and Shyam Mohapatra1,2. University of South Florida College of Medicine1 and James A. Haley VA Medical Center2, Tampa, FL. RATIONALE: RSV NS1 protein plays a direct role in inhibiting the innate immune response by attenuating type-I IFN production during RSV infection. We investigated the role of NS1 in early infection and found that RSV replication and transcription occur near mitochondria. In this study, we examined colocalization of NS1 with antiviral mitochondrial protein, MAVS. METHODS: Human alveolar epithelial A549 cells or normal human bronchial epithelial cells were infected with wt RSV or RSV with an NS1 deletion. Colocalization and interaction of NS1 with MAVS on mitochondria was assessed by confocal microscopy and immuno-electron microscopy. Immunoprecipitation and western blotting were used to show NS1 interaction with MAVS, 12 and 24 h after RSV infection. RESULTS: Confocal microscopy showed NS1 localized to mitochondria and bound to the mitochondrial antiviral protein MAVS by 12 h postinfection. NS1 associated with MAVS at the mitochondria and was also found in the nucleus 24 h after infection. NS1 binding to MAVS was independent of NS2. Immunoelectron microscopy showed direct association of NS1 with MAVS. CONCLUSIONS: These results demonstrate that NS1 associates with MAVS early in infection. Since MAVS has been implicated in suppressing antiviral immune responses by interacting with RIG-I, the finding that NS1is associated with MAVS, could be exploited to develop novel therapeutics for RSV-induced lung diseases.
Liver disease in Egypt: Hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors
Authors: G. Thomas Strickland
Journal: Hepatology (2006)

In Egypt, schistosomiasis was traditionally the most important public health problem and infection with Schistosoma mansoni the major cause of liver disease. From the 1950s until the 1980s, the Egyptian Ministry of Health (MOH) undertook large control campaigns using intravenous tartar emetic, the standard treatment for schistosomiasis, as community-wide therapy. This commendable effort to control a major health problem unfortunately established a very large reservoir of hepatitis C virus (HCV) in the country. By the mid-1980s, the effective oral drug, praziquantel, replaced tartar emetic as treatment for schistosomiasis in the entire country. This both reduced schistosomal transmission and disease and interrupted the "occult" HCV epidemic. It was evident when diagnostic serology became available in the 1990s that HCV had replaced schistosomiasis as the predominant cause of chronic liver disease. Epidemiological studies reported a high prevalence and incidence of HCV, particularly within families in rural areas endemic for schistosomiasis. Clinical studies showed 70% to 90% of patients with chronic hepatitis, cirrhosis, or hepatocellular carcinoma had HCV infections. Co-infections with schistosomiasis caused more severe liver disease than infection with HCV alone. Schistosomiasis was reported to cause an imbalance in HCV-specific T-cell responses leading to increased viral load, a higher probability of HCV chronicity, and more rapid progression of complications in co-infected persons. As complications of HCV usually occur after 20 years of infection, the peak impact of the Egyptian outbreak has not yet occurred. Efforts have been initiated by the Egyptian MOH to prevent new infections and complications of HCV in the estimated 6 million infected persons. (HEPATOLOGY 2006;43:915–922.)
Specific immunotherapy with <i>Dermatophagoides pteronyssinus</i> and <i>D. farinae</i> results in decreased bronchial hyperreactivity
Authors: C. E. Pichler, A. Marquardsen, S. Sparholt, H. Løwenstein, A. Bircher, M. Bischof, W. J. Pichler
Journal: Allergy (1997)

To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts, we performed a double‐blind, placebo‐controlled immunotherapy study in 30 patients with proven allergy to mite allergens. The specific immunotherapy with standardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated. After 1 year of treatment, the actively treated group showed a significant improvement compared to their starting value as well as to the placebo‐treated patients with regard to skin prick test, conjunctival provocation test, and subjective rhinitis score. The subjective asthma score and bronchial hyperreactivity, measured by the methacholine provocation test, was improved in comparison to the starting value, but not to the placebo group, after 12 months. However, a further, open comparison of the placebo‐ and verum‐treated groups at 18 months revealed a significant reduction. The drug intake was not increased in the verum‐treated group. Exposure to mite levels was constant throughout this time period, as revealed by antigen measurement. We conclude that specific immunotherapy in perennial, mite‐allergen‐induced asthma may reduce not only immediate, IgE‐mediated symptoms but, after a rather long time period of 12–18 months, also the inflammatory component of bronchial asthma, thus leading to a reduction of unspecific hyperreactivity.
Mechanism of Recurrent/Persistent Ischemic/Functional Mitral Regurgitation in the Chronic Phase After Surgical Annuloplasty
Authors: Eiji Kuwahara, Yutaka Otsuji, Yoshifumi Iguro, Tetsuya Ueno, Fang Zhu, Naoko Mizukami, Kayoko Kubota, Kenichi Nakashiki, Toshinori Yuasa, Bo Yu, Takeshi Uemura, Kunitsugu Takasaki, Masaaki Miyata, Shuichi Hamasaki, Akira Kisanuki, Robert A. Levine, Ryuzo Sakata, Chuwa Tei
Journal: Circulation (2006)

Background— Surgical annuloplasty can potentially hoist the posterior annulus anteriorly, exaggerate posterior leaflet (PML) tethering, and lead to recurrent ischemic/functional mitral regurgitation (MR). Characteristics of leaflet configurations in late postoperative MR were investigated. Methods and Results— In 30 patients with surgical annuloplasty for ischemic MR and 20 controls, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, posterior and apical displacement of the coaptation and the MR grade were measured by echocardiography before, early after, and late after surgery. Early after surgery, grade of MR and AML tethering generally decreased ( P &lt;0.01), whereas PML tethering significantly worsened ( P &lt;0.01). Nine of the 30 patients showed recurrent/persistent MR late after surgery. Compared with patients without late MR, those with the MR showed similar reduction in the annular area, significant re-increase in posterior displacement of the coaptation, and progressive worsening in PML tethering ( P &lt;0.05) late after surgery in comparison to the early phase. Both preoperative MR and late postoperative MR were significantly correlated with all tethering variables in univariate analysis. Although apical displacement of the coaptation was the primary determinant of preoperative MR ( r 2 =0.60, P &lt;0.0001), increased PML tethering was the primary determinant of late MR ( r 2 =0.75, P &lt;0.0001). Conclusions— Whereas both leaflets tethering is related to preoperative ischemic MR, both leaflets tethering but with predominant contribution from augmented and progressive PML tethering is related to recurrent/persistent ischemic/functional MR late after surgical annuloplasty.
Should We Screen for Risk of Type 1 Diabetes?
Authors: Mikael Knip
Journal: Diabetes Care (2008)

Thus far, the consensus within the diabetes community has been that we should screen for risk of type 1 diabetes only in the context of research studies. This view follows the World Health Organization recommendation on screening of clinical conditions, which states that you should screen only for diseases for which there is effective prevention or treatment (1). Data from the DAISY study suggest that the identification of subjects at increased risk for type 1 diabetes and prospective monitoring of risk individuals results in early diagnosis of clinical disease and the avoidance of severe metabolic decompensation at diagnosis among those who progress to overt diabetes (2). The Finnish DIPP Study has generated similar experiences by reducing the frequency of diabetic ketoacidosis at diagnosis from 20 to <2% (K. Nanto-Salonen, H. Hyoty, J. Ilonen, R. Veijola, T. Simell, M. Knip, and O. Simell, unpublished data). Given that diabetic ketoacidosis is a potentially life-threatening condition and that severe metabolic decompensation at diagnosis is associated with a reduced residual β-cell function and impaired metabolic control subsequently (3,4), one may ask whether it would be meaningful to screen for high-risk individuals and monitor them sequentially for progression to type 1 diabetes.

In this issue, Sosenko et al. (5) introduce a risk score for type 1 diabetes derived from the Diabetes Prevention Trial–Type 1 (DPT-1) (5). The authors divided the DPT-1 cohort into development and validation samples. From the former, a risk score was established based on a model including the logarithm of BMI, age, the logarithm of fasting C-peptide, and total glucose and C-peptide sums from a 2-h oral glucose tolerance test (OGTT). This risk score strongly predicted type 1 diabetes in the validation sample. The predictive value of the risk score did not increase by including …
The incidence of malaria after splenectomy in Papua New Guinea
Authors: K. E Boone, D. A K Watters
Journal: BMJ (1995)

In the tropics, as in the developed world, the spleen is the commonest intra-abdominal organ to be injured.1 2 Splenic enlargement due to chronic malaria predisposes to splenic injury, particularly in low velocity blunt trauma due to domestic violence or assault, both of which are common in Papua New Guinea. In developed countries the risk of sepsis after splenectomy has resulted in a more conservative approach to splenic trauma.3 4 In the tropics death from malaria after splenectomy has been reported, but no formal study has been undertaken.2 5 We studied the sequelae of splenic trauma and splenectomy in patients living in an area of Papua New Guinea where malaria is endemic.

The study was performed in East New Britain in the …
Perverted priorities. The physician/scientist as spokesman and salesman for biomedical research. Presidential address to the American Society for Clinical Investigation, Washington, DC, 29 April 1989.
Authors: C R Kahn
Journal: Journal of Clinical Investigation (1989)

Fellow members of the ASCI, members the AFCR and AAP, and guests.On behalf of myself and the officers and council- lors of the ASCI, I want to thank you for having given us an opportunity to serve the Society.The ASCI represents the fin- est of young physician/scientists, and to have served the Soci- ety as president is indeed an honor.One of the foremost aspects of this honor is the opportunity to address you, the members of the Society, my colleagues and friends, about a topic that I feel is of prime importance to all of us; namely, what is the future ofbiomedical research, and what should our roles be in determining its future?Biomedical research is truly in a golden era.The advent of molecular biology, sophisticated biochemical techniques, cell biology, and advanced methods to study whole body physiology and pathophysiology have allowed us to increase our un- derstanding of disease at an unprecedented rate.One need only look at the six abstracts that were just presented, as well as the others presented throughout this meeting, to realize that over these few days there will be more diseases whose mecha- nisms will be elucidated at a molecular level than in any decade in the first half of this century.Novel approaches to diag- nosis, therapy, and the prevention of disease are being offered at an unprecedented rate.Despite this boom ofbiotechnology, the physician/scientist, and in fact all scientists, find them- selves under increasing pressure to justify their research, to document both the scientific and administrative aspects of the work, and to prioritize competing research projects and needs.If we are to move forward at the pace ofwhich we are capable, we must take greater control of our destiny.To achieve this goal, however, we must ask ourselves four important questions that will form the basis of our approach when seeking research support for the future.First, how much research is enough?Second, is biomedical research cost effective?Third, who should pay for biomedical research?And finally, what should we as physicians and scientists do to im- prove research funding?To answer these questions we must understand more about ourselves, our industry (and biomedi- cal research is indeed an industry), the society in which we live, and its priorities.Currently in the United States about 14 billion dollars are spent on biomedical research.Of this, about 7 billion dollars come from federal sources, about 6 billion from industry, and a little less than I billion from various types of nonprofit foundations and associations (1).
NHS must prepare for tough financial times despite surplus
Authors: A. O'Dowd
Journal: BMJ (2009)

The NHS should resist the temptation to feel complacent because it is in surplus and prepare for more challenging financial times in the next few years, MPs have been told.

The NHS’s surplus of £1.7bn (€1.9bn; $2.4bn) should help it to get ready for a slowing down of government investment in the next two years, witnesses told MPs on the parliamentary public accounts committee.

The committee, as part of its inquiry this week into the National Audit Office and Audit Commission’s report, Financial Management in the NHS: Report on the NHS Summarised Accounts 2007-8 , asked Department of Health witnesses about …
APO010, a synthetic hexameric CD95 ligand, induces human glioma cell death in vitro and in vivo
Authors: G. Eisele, P. Roth, K. Hasenbach, S. Aulwurm, F. Wolpert, G. Tabatabai, W. Wick, M. Weller
Journal: Neuro-Oncology (2010)

Death receptor targeting has emerged as one of the promising novel approaches of cancer therapy. The activation of one such prototypic death receptor, CD95 (Fas/APO-1), has remained controversial because CD95 agonistic molecules have exhibited either too strong toxicity or too little activity. The natural CD95 ligand (CD95L) is a cytokine, which needs to trimerize to mediate a cell death signal. Mega-Fas-Ligand, now referred to as APO010, is a synthetic hexameric CD95 agonist that exhibits strong antitumor activity in various tumor models. Here, we studied the effects of APO010 in human glioma models in vitro and in vivo. Compared with a cross-linked soluble CD95L or a CD95-agonistic antibody, APO010 exhibited superior activity in glioma cell lines expressing CD95 and triggered caspase-dependent cell death. APO010 reduced glioma cell viability in synergy when combined with temozolomide. The locoregional administration of APO010 induced glioma cell death in vivo and prolonged the survival of tumor-bearing mice. A further exploration of APO010 as a novel antiglioma agent is warranted.