tbuckley/cabot-search huggingface dataset:
TH2 Type Immune Responses in Patients with Chronic Progressive Pulmonary Aspergillosis
Authors: Kohta Itahashi, Yoshio Sakamoto, Sayaka Arakawa, Yuki Shinno, Saki Nagoshi, Yugo Okabe, Yuko Nakase, Masaki Kawakami, Masaru Suzuki
Journal: Journal of Allergy and Clinical Immunology (2015)
Incidence of Remission in Adults With Type 2 Diabetes: The Diabetes &amp; Aging Study
Authors: Andrew J. Karter, Shantanu Nundy, Melissa M. Parker, Howard H. Moffet, Elbert S. Huang
Journal: Diabetes Care (2014)

To estimate the incidence of remission in adults with type 2 diabetes not treated with bariatric surgery and to identify variables associated with remission.We quantified the incidence of diabetes remission and examined its correlates among 122,781 adults with type 2 diabetes in an integrated healthcare delivery system. Remission required the absence of ongoing drug therapy and was defined as follows: 1) partial: at least 1 year of subdiabetic hyperglycemia (hemoglobin A1c [HbA₁c] level 5.7-6.4% [39-46 mmol/mol]); 2) complete: at least 1 year of normoglycemia (HbA₁c level <5.7% [<39 mmol/mol]); and 3) prolonged: complete remission for at least 5 years.The incidence density (remissions per 1,000 person-years; 95% CI) of partial, complete, or prolonged remission was 2.8 (2.6-2.9), 0.24 (0.20-0.28), and 0.04 (0.01-0.06), respectively. The 7-year cumulative incidence of partial, complete, or prolonged remission was 1.47% (1.40-1.54%), 0.14% (0.12-0.16%), and 0.007% (0.003-0.020%), respectively. The 7-year cumulative incidence of achieving any remission was 1.60% in the whole cohort (1.53-1.68%) and 4.6% in the subgroup with new-onset diabetes (<2 years since diagnosis) (4.3-4.9%). After adjusting for demographic and clinical characteristics, correlates of remission included age >65 years, African American race, <2 years since diagnosis, baseline HbA₁c level <5.7% (<39 mmol/mol), and no diabetes medication at baseline.In community settings, remission of type 2 diabetes does occur without bariatric surgery, but it is very rare.
Screening for Alcohol Use Disorders Among Medical Outpatients: The Influence of Individual and Facility Characteristics
Authors: Mayur M Desai, Robert A Rosenheck, Thomas J Craig
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Screening of adults in primary care has been recommended to reduce alcohol misuse. This study determined the rates and predictors of alcohol screening, screening positive, follow-up evaluation, and subsequently diagnosed alcohol use disorder in a national sample of Department of Veterans Affairs (VA) medical outpatients. METHOD: Chart-abstracted quality improvement data from the VA's 2002 External Peer Review Program were merged with records for 15,580 medical outpatients drawn from 139 VA facilities nationwide. RESULTS: Nearly three-quarters of eligible patients (N=11,553) had chart-documented alcohol screening in the past year. Of these, 4.2% (N=484) screened positive. Of those who screened positive, three-fourths (N=370) received follow-up evaluation, and of these, 53.5% (N=198) were subsequently diagnosed with an alcohol use disorder—1.7% of the originally screened sample. Multivariate logistic regression revealed that several factors generally associated with increased risk of alcohol use disorders—including being younger, unmarried, and disabled, as well as having greater medical and psychiatric comorbidities—were actually associated with a decreased likelihood of alcohol screening. At the facility level, screening was less likely at more academically affiliated centers, and follow-up evaluation of a positive screening was less likely at the largest facilities. CONCLUSIONS: Routine alcohol screening yielded relatively few positive cases, raising questions about its cost-effectiveness. Targeted strategies may increase the value of case-finding activities among patients at greatest risk for alcohol use disorders and at more academically affiliated facilities. Targeted efforts are also needed to ensure proper follow-up evaluation at larger medical centers where patients may experience greater system-level barriers.
Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor–Positive and –Negative Cancers
Authors: Giampaolo Bianchini, Yuan Qi, Ricardo H. Alvarez, Takayuki Iwamoto, Charles Coutant, Nuhad K. Ibrahim, Vicente Valero, Massimo Cristofanilli, Marjorie C. Green, Laszlo Radvanyi, Christos Hatzis, Gabriel N. Hortobagyi, Fabrice Andre, Luca Gianni, W. Fraser Symmans, Lajos Pusztai
Journal: Journal of Clinical Oncology (2010)

The purpose of this study was to identify genes enriched in breast cancer stroma, assess the stromal gene expression differences between estrogen receptor (ER) -positive and -negative cancers, and separately determine their prognostic value in these two subtypes of breast cancers.We compared gene expression profiles of pairs of fine-needle (stroma-poor) and core-needle (stroma-rich) biopsies from 37 cancers to identify stroma-associated genes. We defined stromal metagenes and tested their prognostic values in 684 node-negative patients who received no systemic adjuvant therapy and 259 tamoxifen-treated patients.We identified 293 probe sets overexpressed in core biopsies; these included five highly coexpressed gene clusters (metagenes) corresponding to immune functions and extracellular matrix components. These genes showed quantitative and qualitative differences between ER-positive and ER-negative cancers. A B-cell/plasma cell metagene showed strong prognostic value in ER-positive highly proliferative cancers, a lesser prognostic value in ER-negative cancers, and no prognostic value in ER-positive cancers with low proliferation. The hazard ratio for distant relapse in the lowest compared with the highest tertile of the pooled prognostic data set was 4.29 (95% CI, 2.04 to 9.01; P = .001) in ER-positive cancers and 3.34 (95% CI, 1.60 to 6.97; P = .001) in ER-negative cancers. This remained significant in multivariate analysis including routine variables and other genomic prognostic scores. As a result of quantitative differences in this metagene between ER-positive and ER-negative cancers, different thresholds apply in the two subgroups. Other stromal metagenes had inconsistent prognostic value.Among ER-negative and ER-positive highly proliferative cancers, a subset of tumors with high expression of a B-cell/plasma cell metagene carries a favorable prognosis.
Murine Double Minute-2 Prevents p53-Overactivation-Related Cell Death (Podoptosis) of Podocytes
Authors: Dana Thomasova, Hauke A. Bruns, Victoria Kretschmer, Martrez Ebrahim, Simone Romoli, Helen Liapis, Ahmed M. Kotb, Nicole Endlich, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2014)

Murine double minute-2 (MDM2), an E3 ligase that regulates the cell cycle and inflammation, is highly expressed in podocytes. In podocyte injury, MDM2 drives podocyte loss by mitotic catastrophe, but the function of MDM2 in resting podocytes has not been explored. Here, we investigated the effects of podocyte MDM2 deletion in vitro and invivo. In vitro, MDM2 knockdown by siRNA caused increased expression of p53 and podocyte death, which was completely rescued by coknockdown of p53. Apoptosis, pyroptosis, pyronecrosis, necroptosis, ferroptosis, and parthanatos were excluded as modes of occurrence for this p53-overactivation-related cell death (here referred to as podoptosis). Podoptosis was associated with cytoplasmic vacuolization, endoplasmic reticulum stress, and dysregulated autophagy (previously described as paraptosis). MDM2 knockdown caused podocyte loss and proteinuria in a zebrafish model, which was consistent with the phenotype of podocyte-specific MDM2-knockout mice that also showed the aforementioned ultrastructual podocyte abnormalities before and during progressive glomerulosclerosis. The phenotype of both animal models was entirely rescued by codeletion of p53. We conclude that MDM2 maintains homeostasis and long-term survival in podocytes by preventing podoptosis, a p53-regulated form of cell death with unspecific features previously classified as paraptosis.
Abstract A4: Androgen receptor (AR) degradation is controlled by the co-operation of PMEPA1 and the E3 ubiquitin ligase NEDD4-1
Authors: Hua Li, Albert Dobi, Shiv Srivastava
Journal: Cancer Research (2012)

Abstract Introduction and Objective: Androgen receptor (AR) plays critical roles in prostate growth and differentiation and prostate tumorigenesis. Our recent investigations have discovered a novel mechanism of AR degradation in CaP cells involving PMEPA1 and NEDD4-1 which is independent of MDM2. Previously we have shown that PMEPA1 is a highly androgen-inducible gene in CaP cells that recruits the NEDD4-1, an E3 ubiquitin ligase, to degrade AR. In an independent study NEDD4-1 has been identified as an E3 ligase controlling the levels of PTEN. We hypothesize that decreased or loss of PMPEA1 expression that is frequently observed in human prostate tumor cells may lead to enhanced AR functions. Elevated AR levels may increase NEDD4-1 and in turn destabilize PTEN in prostate cancer cells. Here, we further investigate the co-operation between PMEPA1 and NEDD4-1 to alter AR and PTEN protein levels. Methods: PMEPA1 and NEDD4-1 were ectopically expressed in androgen responsive LNCaP and VCaP cells by pCMV-XL4 and pcDNA3.1 vectors, respectively. AR, PMEPA1, NEDD4-1, MDM2 and PTEN were silenced by using specific siRNAs. Cell growth was monitored in response modulation of PMEPA1, NEDD4 and AR. Protein levels of AR, PMEPA1, NEDD4-1, PTEN and PSA were assessed by immunoblot assays. Results: Decreases in AR protein levels, inhibited AR signaling and cell growth in response to heterologous expression of NEDD4-1. Consistent with this observation, inhibition of NEDD4-1 by siRNA resulted in elevated AR protein levels, AR signaling and increased cell growth. Reduced cell growth by AR knock-down or by heterologous expression of NEDD4-, were rescued by the knockdown of PMEPA1. It was also shown that AR up-regulates the expression of NEDD4-1 in hormone responsive CaP cells. In VCaP cells, overexpression of NEDD4-1 resulted in decreased PTEN protein levels. Remarkably, PMEPA1 knockdown resulted in elevated AR and NEDD4-1 levels and the downregulation of PTEN protein. Conclusions: NEDD4-1 mediated AR degradation in hormone responsive CaP cells requires PMEPA1. The frequently observed decreased expression of PMEPA1 results in elevated AR protein levels and may facilitate NEDD4-1 mediated degradation of PTEN in CaP. Our findings revealed a complex interplay of the AR, PMEPA1, NEDD4 and PTEN underscoring the impact of the loss of PMEPA1 to increased AR and decreased PTEN, both proteins critical in prostate tumorigenesis. Citation Format: Hua Li, Albert Dobi, Shiv Srivastava. Androgen receptor (AR)degradation is controlled by the cooperation of PMEPA1 and the E3 ubiquitin ligase NEDD4-1 [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A4.
The Pelvic Floor: Its Function and Disorders: Edited by J H Pemberton, M Swash, M M Henry. Harcourt, 2002, pound79.95, pp 487. ISBN 0-7020-2307-8
Authors: P Denis
Journal: Gut (2003)

Osteoporosis and liver disease: additional reasons for coeliac disease screeningWe read with great interest the recently published guidelines on the management of osteoporosis associated with chronic liver disease (Gut 2002;50(suppl I):i1-9).However, we would like to add a few words of comment.Associations between coeliac disease (CD) and primary biliary cirrhosis in particular and other autoimmune liver diseases in general have been reported. [1]2][3] In addition, it has been suggested that these individuals should be considered as an at risk group for whom serological testing for CD is indicated. 1Patients with CD are at high risk of developing low bone mineral density and bone turnover impairment, 1 and it has been shown that adherence to a gluten free diet has a significant positive impact on these parameters. 4 Thus we suggest that physicians caring for patients with the above mentioned liver diseases should screen them for CD in the presence of signs and symptoms suggestive of malabsorption such as osteoporosis.This seems a reasonable strategy as detection of CD will allow for a more rational therapeutic approach to the risks determined by this association.Complications due to the presence of CD, such as malnutrition, anaemia, and osteoporosis, may have a considerable impact on liver disease management and the need/success of transplantation.
Psychotherapy: The Restoration of Morale
Authors: JEROME D. FRANK
Journal: American Journal of Psychiatry (1974)

The author suggests that the primary function of all psychotherapies is to combat demoralization—which aggravates and is aggravated psychiatric symptoms—through restoring the patient's sense of mastery. All psychotherapeutic rationales and rituals perform this function despite differences in content. The author reviews the evidence consistent with this hypothesis, pointing out the potential implications for classification of candidates for therapy and for research on sources of the therapist's healing powers.
Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial
Authors: Jaap Verweij, Paolo G Casali, John Zalcberg, Axel LeCesne, Peter Reichardt, Jean-Yves Blay, Rolf Issels, Allan van Oosterom, Pancras CW Hogendoorn, Martine Van Glabbeke, Rossella Bertulli, Ian Judson
Journal: The Lancet (2004)
New Careers and New Mental Health Services: Fantasy or Future?
Authors: JUNE JACKSON CHRISTMAS, HILDA WALLACE, JOSE EDWARDS
Journal: American Journal of Psychiatry (1970)

The new careers program of the Harlem Rehabilitation Center seeks to develop new professional, paraprofessional, and patient-client roles to meet the needs of chronically ill persons, to broaden the mental health field, and to alter conditions that may have been among the determinants of mental disorder. In these aims, the center's program extends beyond the mere provision of jobs or reform in existing systems; it is a potential dynamic force for constructive change in human services. The authors discuss some of the problems that remain to be solved if the program is to meet the critical need for relevant and effective services in the center community.
How Is Maternal Nutrition Related to Preterm Birth?
Authors: Frank H. Bloomfield
Journal: Annual Review of Nutrition (2011)

The incidence of preterm birth in developed countries is increasing, and in some countries, including the United States, it is almost as high as in developing countries. Demographic changes in women becoming pregnant can account for only a relatively small proportion of the increase. A significant proportion of spontaneous preterm birth continues to be of unknown cause. Experimental data from animal studies suggesting that maternal undernutrition may play a role in spontaneous, noninfectious, preterm birth are supported by observational data in human populations, which support a role for maternal prepregnancy nutritional status in determining gestation length. In addition, intakes or lack of specific nutrients during pregnancy may influence gestation length and thus the risk of preterm birth. As yet, the role of paternal nutrition in contributing to gestation length is unexplored.
Bronchoscopy with bronchoalveolar lavage: determinants of yield and impact on management in immunosuppressed patients
Authors: R. M. Kottmann, J. Kelly, E. Lyda, M. Gurell, J. Stalica, W. Ormsby, K. Moon, D. Trawick, P. J. Sime
Journal: Thorax (2010)

Fibreoptic bronchoscopy with bronchoalveolar lavage (FOB/BAL) is a common modality for the evaluation of pulmonary infiltrates.1 2 We recognised there are limitations of comparison between subgroups of immunosuppressed patients, non-uniform definitions of a positive yield, suboptimal description of the impact of concurrent antimicrobial use at the time of the bronchoscopy and sometimes insufficient assessment of management decisions surrounding FOB/BAL.3–5 To address these issues, we performed a retrospective analysis of 190 immunosuppressed patients who underwent FOB/BAL for a pulmonary abnormality (clinical or radiographic) at the University of Rochester Medical Center from 2005 to 2008. A positive yield was defined as one of the following: (1) positive culture—bacterial, viral or fungal (not including Candida albicans alone); (2) positive finding on cytopathology or fungal stain; or (3) diffuse alveolar haemorrhage. Antimicrobial and corticosteroid treatment changes …
Role of Checkpoint Kinase 1 in Preventing Premature Mitosis in Response to Gemcitabine
Authors: Meredith A. Morgan, Leslie A. Parsels, Joshua D. Parsels, Alefiyah K. Mesiwala, Jonathan Maybaum, Theodore S. Lawrence
Journal: Cancer Research (2005)

The deoxycytidine analogue 2',2'-difluoro-2'-deoxycytidine (gemcitabine) is a potent radiation sensitizer in a variety of solid tumors and tumor cell lines. Previous studies have shown that radiosensitization by gemcitabine is accompanied by simultaneous depletion of dATP pools (through ribonucleotide reductase inhibition) and accumulation in the S-phase of the cell cycle. Because of the importance of cell cycle redistribution in gemcitabine-mediated radiosensitization, we investigated the role of checkpoint kinase (Chk) 1 and Chk2 in gemcitabine-induced cell cycle arrest. We hypothesized that gemcitabine might induce Chk1 or Chk2 signal transduction pathways that mediate S-phase arrest. We found that radiosensitizing concentrations of gemcitabine induced accumulation of phosphorylated Chk1 and Chk2 and down-regulation of Cdc25A in BxPC-3 (10 nmol/L), Panc-1 (100 nmol/L), A549 (30 nmol/L), RKO (30 nmol/L), and SW620 (30 nmol/L) cells. Depletion of Chk1 from Panc-1 cells prevented the down-regulation of Cdc25A in response to gemcitabine. Furthermore, Chk1 depletion permitted Panc-1 and SW620 cells treated with gemcitabine to enter mitosis despite incomplete DNA synthesis. However, depletion of neither Chk1 nor Chk2 abrogated the inhibition of DNA synthesis in response to gemcitabine. These results provide evidence that Chk1 negatively regulates entry into mitosis in response to gemcitabine. Furthermore, these data imply that Chk1 acts to coordinate the cell cycle with DNA synthesis, thus preventing premature mitotic entry in gemcitabine-treated cells.
All hospital bookings to be done electronically by end of 2005
Authors: Rebecca Coombes
Journal: BMJ (2004)

The electronic booking service is designed to make it easier and faster for GPs and other primary care staff to book first outpatient and day case appointments for patients.

The system, which has been likened to that used by travel operators such as lastminute.com has been undergoing stringent testing since late 2003. The tests have involved building a database containing three billion records and simulating a transaction load of 2400 simultaneous users.

Despite recent press reports to the contrary, the National Programme for IT says that e-booking will be introduced throughout the NHS in England during summer 2004 with total coverage expected by the end of 2005. The London and North East regions will go live with e-booking first.

Doubts about …
A Modified <i>Sleeping Beauty</i> Transposon System That Can Be Used to Model a Wide Variety of Human Cancers in Mice
Authors: Adam J. Dupuy, Laura M. Rogers, Jinsil Kim, Kishore Nannapaneni, Timothy K. Starr, Pentao Liu, David A. Largaespada, Todd E. Scheetz, Nancy A. Jenkins, Neal G. Copeland
Journal: Cancer Research (2009)

Recent advances in cancer therapeutics stress the need for a better understanding of the molecular mechanisms driving tumor formation. This can be accomplished by obtaining a more complete description of the genes that contribute to cancer. We previously described an approach using the Sleeping Beauty (SB) transposon system to model hematopoietic malignancies in mice. Here, we describe modifications of the SB system that provide additional flexibility in generating mouse models of cancer. First, we describe a Cre-inducible SBase allele, RosaSBase(LsL), that allows the restriction of transposon mutagenesis to a specific tissue of interest. This allele was used to generate a model of germinal center B-cell lymphoma by activating SBase expression with an Aid-Cre allele. In a second approach, a novel transposon was generated, T2/Onc3, in which the CMV enhancer/chicken beta-actin promoter drives oncogene expression. When combined with ubiquitous SBase expression, the T2/Onc3 transposon produced nearly 200 independent tumors of more than 20 different types in a cohort of 62 mice. Analysis of transposon insertion sites identified novel candidate genes, including Zmiz1 and Rian, involved in squamous cell carcinoma and hepatocellular carcinoma, respectively. These novel alleles provide additional tools for the SB system and provide some insight into how this mutagenesis system can be manipulated to model cancer in mice.
Variation of chemical composition with age in human femoral head cartilage.
Authors: M F Venn
Journal: Annals of the Rheumatic Diseases (1978)

The chemical composition of intact femoral head cartilage was investigated with age. Full-depth cartilage showed a decrease in water content and an increase in keratan sulphate and noncollagenous material with age. When analyzed through the depth of the cartilage, keratan sulphate was shown to appear first in the deep zones and later in the surface, while water content was lost mainly in the deep zones. On a dry weight basis collagen content decreased with age. This was not a real loss but was due to a change in the proportions of other materials, mainly in the deep zones.
Multiple Sclerosis: Fas Signaling in Oligodendrocyte Cell Death
Authors: Sameer D. D'Souza, Bruno Bonetti, Vijayabalan Balasingam, Neil R. Cashman, Philip A. Barker, Anthony B. Troutt, Cedric S. Raine, Jack P. Antel
Journal: The Journal of Experimental Medicine (1996)

Fas is a cell surface receptor that transduces cell death signals when cross-linked by agonist antibodies or by fas ligand. In this study, we examined the potential of fas to contribute to oligodendrocyte (OL) injury and demyelination as they occur in the human demyelinating disease multiple sclerosis (MS). Immunohistochemical study of central nervous system (CNS) tissue from MS subjects demonstrated elevated fas expression on OLs in chronic active and chronic silent MS lesions compared with OLs in control tissue from subjects with or without other neurologic diseases. In such lesions, microglia and infiltrating lymphocytes displayed intense immunoreactivity to fas ligand. In dissociated glial cell cultures prepared from human adult CNS tissue, fas expression was restricted to OLs. Fas ligation with the anti-fas monoclonal antibody M3 or with the fas–ligand induced rapid OL cell membrane lysis, assessed by LDH release and trypan blue uptake and subsequent cell death. In contrast to the activity of fas in other cellular systems, dying OLs did not exhibit evidence of apoptosis, assessed morphologically and by terminal transferase–mediated d-uridine triphosphate-biotin nick-end-labeling staining for DNA fragmentation. Other stimuli such as C2-ceramide were capable of inducing rapid apoptosis in OLs. Antibodies directed at other surface molecules expressed on OLs or the M33 nonactivating anti-fas monoclonal antibody did not induce cytolysis of OLs. Our results suggest that fas-mediated signaling might contribute in a novel cytolytic manner to immune-mediated OL injury in MS.