tbuckley/cabot-search huggingface dataset:
Integrating Clinical, Community, and Policy Perspectives on Human Papillomavirus Vaccination
Authors: María E. Fernández, Jennifer D. Allen, Ritesh Mistry, Jessica A. Kahn
Journal: Annual Review of Public Health (2009)

Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This review summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated framework can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.
Mucin gene expression in intestinal epithelial cells in Crohn's disease
Authors: M-P Buisine
Journal: Gut (2001)

<h3>BACKGROUND</h3> Crohn9s disease (CD) is a chronic relapsing inflammatory bowel disease of unknown origin. It is characterised by chronic mucosal ulcerations which affect any part of the intestine but most commonly are found in the ileum and proximal colon. <h3>AIMS</h3> Studies were undertaken to provide information regarding cell specific expression of mucin genes in the ileum of patients with CD. <h3>PATIENTS AND METHODS</h3> Expression of mucin genes was analysed in the ileal mucosa of patients with CD and controls by in situ hybridisation and immunohistochemistry. <h3>RESULTS</h3> In healthy ileal mucosa, patients with CD showed a pattern identical to normal controls with main expression of <i>MUC2</i> and<i>MUC3</i>, lesser expression of<i>MUC1</i> and <i>MUC4</i>, and no expression of <i>MUC5AC</i>,<i>MUC5B</i>, <i>MUC6</i>, or<i>MUC7</i>. In the involved mucosa, the pattern was somewhat comparable although heterogeneous to that observed in healthy ileal mucosa. Importantly, a particular mucin gene expression pattern was observed in ileal mucosa close to the ulcer margins in ulcer associated cell lineage, with the appearance of<i>MUC5AC</i> and <i>MUC6</i>mRNAs and peptides, which are normally restricted to the stomach (<i>MUC5AC</i> and <i>MUC6</i>) and duodenum (<i>MUC6</i>), and disappearance of<i>MUC2</i>. <h3>CONCLUSIONS</h3> Our results suggest that gel forming mucins (more particularly MUC5AC and MUC6) may have a role in epithelial wound healing after mucosal injury in inflammatory bowel diseases in addition to mucosal protection.
Familial Coaggregation of Cryptorchidism, Hypospadias, and Testicular Germ Cell Cancer: A Nationwide Cohort Study
Authors: Tine H. Schnack, Gry Poulsen, Charlotte Myrup, Jan Wohlfahrt, Mads Melbye
Journal: JNCI Journal of the National Cancer Institute (2009)

Cryptorchidism, hypospadias, and testicular germ cell cancer (TGCC) may be symptoms of a testicular dysgenesis syndrome that manifests during fetal life. To address the inheritability of this syndrome, we examined whether family history of cryptorchidism or hypospadias is associated with an increased risk of TGCC. A total of 2 159 883 men born since 1953, identified through Danish health registers, were followed from April 2, 1968, through May 31, 2008. First-, second-, and third-degree relatives were identified in the Danish Family Relations Database; cryptorchidism and hypospadias patients were identified in the Danish Hospital Discharge Register; and TGCC patients were identified in the Danish Cancer Register. Poisson regression was used to calculate the risk ratio for TGCC by family history of cryptorchidism or hypospadias. A total of 5441 patients developed TGCC. A personal history of cryptorchidism or hypospadias was associated with an increased relative risk (RR) of developing TGCC (RR = 3.71, 95% confidence interval [CI] = 3.29 to 4.19; and RR = 2.13, 95% CI = 1.26 to 3.61, respectively). For example, in men in their thirties, the overall rate per 100 000 is 25.1 in the cohort, but 88.6 and 55.4 in men born with cryptorchidism or hypospadias, respectively. In contrast, relatives of a hypospadias patient did not have a statistically significantly increased risk of TGCC nor did the first- and second-degree relatives of cryptorchidism patients. However, we found a small increased risk of TGCC for third-degree relatives of patients with cryptorchidism. Having hypospadias or cryptorchidism was associated with an increased risk of developing TGCC. However, our finding that family history of hypospadias or cryptorchidism generally was not associated with increased risk of developing TGCC does not support the hypothesis of shared inheritability of cryptorchidism, hypospadias, and TGCC.
CCK2R identifies and regulates gastric antral stem cell states and carcinogenesis
Authors: Yoku Hayakawa, Guangchun Jin, Hongshan Wang, Xiaowei Chen, Christoph B Westphalen, Samuel Asfaha, Bernhard W Renz, Hiroshi Ariyama, Zinaida A Dubeykovskaya, Yoshihiro Takemoto, Yoomi Lee, Ashlesha Muley, Yagnesh Tailor, Duan Chen, Sureshkumar Muthupalani, James G Fox, Arthur Shulkes, Daniel L Worthley, Shigeo Takaishi, Timothy C Wang
Journal: Gut (2014)

Progastrin is the incompletely cleaved precursor of gastrin that is secreted by G-cells in the gastric antrum. Both gastrin and progastrin bind to the CCK2 receptor (Cckbr or CCK2R) expressed on a subset of gastric epithelial cells. Little is known about how gastrin peptides and CCK2R regulate gastric stem cells and carcinogenesis. Interconversion among progenitors in the intestine is documented, but the mechanisms by which this occurs are poorly defined.We generated CCK2R-CreERT mice and performed inducible lineage tracing experiments. CCK2R+ antral cells and Lgr5+ antral stem cells were cultured in a three-dimensional in vitro system. We crossed progastrin-overexpressing mice with Lgr5-GFP-CreERT mice and examined the role of progastrin and CCK2R in Lgr5+ stem cells during MNU-induced carcinogenesis.Through lineage tracing experiments, we found that CCK2R defines antral stem cells at position +4, which overlapped with an Lgr5(neg or low) cell population but was distinct from typical antral Lgr5(high) stem cells. Treatment with progastrin interconverts Lgr5(neg or low) CCK2R+ cells into Lgr5(high) cells, increases CCK2R+ cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansion and carcinogenesis.CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.
The normal IGHV1-69–derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL
Authors: Francesco Forconi, Kathleen N. Potter, Isla Wheatley, Nikos Darzentas, Elisa Sozzi, Kostas Stamatopoulos, C. Ian Mockridge, Graham Packham, Freda K. Stevenson
Journal: Blood (2009)
Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.
Authors: D W Cockcroft, B A Berscheid
Journal: Thorax (1983)

The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (log dose v response, mean r2 = 0.93), the difference being significant (p less than 0.001). There was a strong negative correlation between the PC20-Fev1 and the slope (r = -0.98, p much less than 0.001) and a weak negative correlation between the PC20-FEV1 and the log-dose-response slope (r = -0.38, p greater than 0.05). Sixteen normal subjects and 16 asthmatic patients were compared on the basis of histamine dose-response curves measuring fal in sGaw. In this study there was no difference between r2 for the linear determination and for the logarithmic determination (0.91 v 0.90, p less than 0.05). The PC35-sGaw showed a strong negative correlation with the dose-response slope (r = -0.95, p much less than 0.01) and no correlation with the log-dose-response slope (r = 0.09, p greater than 0.05). In the two studies there appeared to be little information gained from the determination of either the dose-response slope or the log-dose-response slope. The slope and the PC20-FEV1 were equally reproducible, duplicate determinations showing less than a two-fold difference in 14 of 15 paired PC20 measurements and in 13 of 15 paired slope measurements. In summary, the slope of the histamine dose-response curve appears to fit the linear model better than the logarithmic model. It is feasible to calculate it from the results of a standardised histamine inhalation test; determination of either the slope or the log-dose-response slope, however, appears to add little useful information. It is recommended that bronchial provocation test results should be expressed in terms of a threshold concentration such as the PC20-FEV1 or the PC35-sGaw.
Increased Severity of Local and Systemic Anaphylactic Reactions in Gp49b1-Deficient Mice
Authors: Massoud Daheshia, Daniel S. Friend, Michael J. Grusby, K. Frank Austen, Howard R. Katz
Journal: The Journal of Experimental Medicine (2001)

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcstraightepsilonRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.
Prevalence of joint pain is higher among women in rural Japan than urban Japanese-American women in Hawaii
Authors: K. Aoyagi, P. D Ross, C. Huang, R. D Wasnich, T. Hayashi, T.-i. Takemoto
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> Environmental factors such as farming contribute to the frequency of joint symptoms. The purpose of this study is to explore the possible role of environment (lifestyle), by comparing the prevalence of joint pain between Japanese in a rural farming district in Japan and in urban Hawaii. <h3>SUBJECTS AND METHODS</h3> Current or previous pain at specific joints was surveyed among 222 women in rural Japan and 638 Japanese women in urban Hawaii aged 60–79. The age adjusted prevalence was compared using logistic regression. <h3>RESULTS</h3> The prevalence of pain at one or more joints was approximately 70% in Japan and 50% in Hawaii. The prevalence of knee pain in Japan ranged from 36% at ages 60–69 years to 53% at 70–79 years (mean 41%), whereas knee pain affected only 20% of women in Hawaii in both age groups. The odds ratio (and 95% CI) was 3.2 (2.1, 4.8) for knee pain, and 4.0 (2.2, 7.4) for mid-back pain in Japan, compared with Hawaii. Pain was also significantly more common in Japan at the shoulder, elbow, and ankle, but not at other joints. Women in Japan were shorter and weighed less than in Hawaii. Adjustment for body mass index increased the odds ratios to 4.4 (2.9, 6.8) for knee, and 4.5 (2.4, 8.5) for mid-back pain. <h3>CONCLUSION</h3> Although the potential influence of cultural factors or other sources of bias cannot be ruled out, the large differences in the prevalence of pain at specific joints suggest that environmental factors are probably responsible, because both populations are of similar genetic stock.
Socioeconomic Status and Health: The Potential Role of Environmental Risk Exposure
Authors: Gary W. Evans, Elyse Kantrowitz
Journal: Annual Review of Public Health (2002)

▪ Abstract Among several viable explanations for the ubiquitous SES-health gradient is differential exposure to environmental risk. We document evidence of inverse relations between income and other indices of SES with environmental risk factors including hazardous wastes and other toxins, ambient and indoor air pollutants, water quality, ambient noise, residential crowding, housing quality, educational facilities, work environments, and neighborhood conditions. We then briefly overview evidence that such exposures are inimical to health and well-being. We conclude with a discussion of the research and policy implications of environmental justice, arguing that a particularly salient feature of poverty for health consequences is exposure to multiple environmental risk factors.
Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study
Authors: Yoshiya Tanaka, Shintaro Hirata, Satoshi Kubo, Shunsuke Fukuyo, Kentaro Hanami, Norifumi Sawamukai, Kazuhisa Nakano, Shingo Nakayamada, Kunihiro Yamaoka, Fusae Sawamura, Kazuyoshi Saito
Journal: Annals of the Rheumatic Diseases (2013)

We present a case report of a 23-year-old Pakistani woman who had a second trimester spontaneous miscarriage while visiting her family in the Kingdom of Saudi Arabia. A dilatation and curettage (D&amp;C) was done after the miscarriage. She developed sepsis and acute respiratory distress syndrome, requiring intensive care unit admission a few days after the D&amp;C. An exploratory laparotomy was done and she was found to have a pelvic abscess. Despite adequate broad spectrum antimicrobial cover, she continued to drain a copious amount of serous fluid from the peritoneal cavity, with persistent fever and a stiff lung with difficult weaning off mechanical ventilation. Tuberculosis PCR of the peritoneal fluid came back positive. A histological finding of necrotising granuloma from the postoperative omental specimen and a positive culture from the ascitic fluid confirmed the diagnosis of <i>Mycobacterium tuberculosis</i>. Antituberculous treatment was started and she made a speedy recovery.
The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels
Authors: Natalia Rydz, Laura L. Swystun, Colleen Notley, Andrew D. Paterson, J. Jacob Riches, Kate Sponagle, Boonchai Boonyawat, Robert R. Montgomery, Paula D. James, David Lillicrap
Journal: Blood (2013)
799 TIMING OF HCV NEGATIVITY AND POSSIBLE SVR MAY BE PREDICTABLE BY HCVRNA LEVELS MEASURED WITH TAQMAN HCV IN EARLY TREATMENT PHASE
Authors: Y. Karino, J. Toyota, T. Arakawa, Y. Kuwata, J. Akaike, I. Ozeki, K. Yamazaki, T. Sato, T. Ohmura
Journal: Journal of Hepatology (2008)
Pharmacokinetic and Pharmacodynamic Properties of Calaspargase Pegol <i>Escherichia coli</i> L-Asparaginase in the Treatment of Patients With Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Study AALL07P4
Authors: Anne L. Angiolillo, Reuven J. Schore, Meenakshi Devidas, Michael J. Borowitz, Andrew J. Carroll, Julie M. Gastier-Foster, Nyla A. Heerema, Taha Keilani, Ashley R. Lane, Mignon L. Loh, Gregory H. Reaman, Peter C. Adamson, Brent Wood, Charlotte Wood, Hao W. Zheng, Elizabeth A. Raetz, Naomi J. Winick, William L. Carroll, Stephen P. Hunger
Journal: Journal of Clinical Oncology (2014)

Purpose Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL. Patients and Methods A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m 2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m 2 (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500. Results The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5× longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity ≥ 100 mIU/mL and ≥ 400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups. Conclusion SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL.
HDAC Inhibitors Augmented Cell Migration and Metastasis through Induction of PKCs Leading to Identification of Low Toxicity Modalities for Combination Cancer Therapy
Authors: Kuen-Tyng Lin, Yi-Wei Wang, Chiung-Tong Chen, Chun-Ming Ho, Wen-Hui Su, Yuh-Shan Jou
Journal: Clinical Cancer Research (2012)

Histone deacetylase inhibitors (HDACi) are actively explored as new-generation epigenetic drugs but have low efficacy in cancer monotherapy. To reveal new mechanism for combination therapy, we show that HDACi induce cell death but simultaneously activate tumor-progressive genes to ruin therapeutic efficacy. Combined treatments to target tumorigenesis and HDACi-activated metastasis with low toxic modalities could develop new strategies for long-term cancer therapy.Because metastasis is the major cause of cancer mortality, we measured cell migration activity and profiled metastasis-related gene expressions in HDACi-treated cancer cells. We developed low toxic combination modalities targeting tumorigenesis and HDACi-activated metastasis for preclinical therapies in mice.We showed that cell migration activity was dramatically and dose dependently enhanced by various classes of HDACi treatments in 13 of 30 examined human breast, gastric, liver, and lung cancer cell lines. Tumor metastasis was also enhanced in HDACi-treated mice. HDACi treatments activated multiple PKCs and downstream substrates along with upregulated proapoptotic p21. For targeting tumorigenesis and metastasis with immediate clinical impact, we showed that new modalities of HDACi combined drugs with PKC inhibitory agent, curcumin or tamoxifen, not only suppressed HDACi-activated tumor progressive proteins and cell migration in vitro but also inhibited tumor growth and metastasis in vivo.Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease.
A comparison of the use of Aldactone and Aldactone A in the treatment of hepatic ascites
Authors: S. Shaldon, J. A. Ryder, M. Garsenstein
Journal: Gut (1963)

In eight patients with cirrhosis and stable ascites controlled on chlorothiazide and spironolactone, a small particle preparation of spironolactone (Aldactone A) was as effective, at one quarter the dosage, as conventional spironolactone (Aldactone). Plasma spironolactone metabolite levels and urinary excretion of spironolactone metabolite were equivalent with both preparations. The variable dosage requirement of spironolactone in patients with cirrhosis and ascites is discussed in relation to these observations.
Is It Time to Take a Different Approach to Screening People at High Risk for Type 1 Diabetes?
Authors: Edward J. Boyko, Jerry P. Palmer
Journal: Diabetes Care (2009)

It is generally believed that the onset of type 2 diabetes can be insidious and evade detection for prolonged time periods (1,2). Type 1 diabetes, however, often displays a sudden clinical onset due to the development of insufficient insulin secretory capacity following a pre-diabetic period characterized by the presence of pancreatic islet autoantibodies. Type 1 diabetes usually presents with symptoms, the most frequent being polyuria and polydipsia (97%) and weight loss (46%) in one recent study of newly diagnosed patients (3).

The article by Triolo et al. (4), in this issue of Diabetes Care , addresses the period in the development of type 1 diabetes between the onset of hyperglycemia that meets diagnostic criteria for diabetes and its clinical presentation. Triolo et al. present evidence that the onset of type 1 diabetes can occur without clinical symptoms and be difficult to detect with the current approach to diagnosis, which is based on fasting plasma glucose (FPG) measurement (5). These conclusions are based on the results of semiannual oral glucose tolerance tests for diabetes diagnosis among the Diabetes Prevention Trial–Type 1 (DPT-1) participants. The occurrence of asymptomatic type 1 diabetes in the DPT-1 population has been previously reported (6). The important additional findings are the value of A1C in the detection of diabetes and the comparatively low occurrence of diabetic ketoacidosis (DKA) at diagnosis of diabetes. The authors conclude by advising that “high-risk relatives may benefit from close attention or screening in order to prevent DKA at diagnosis” (4).

The …
Seven in 10 junior doctors will leave NHS if new contract is imposed, survey finds
Authors: Zosia Kmietowicz
Journal: BMJ (2015)

Nearly three quarters of junior doctors (72%) plan to leave the NHS if the government imposes a new contract in August 2016, a survey has found. The respondents were recruited from a closed junior doctors’ forum on a social networking site.

Responses to the online survey from 4150 junior doctors—8% of the 53 000 doctors set to be affected by the new contract—also showed that 99% felt demoralised and devalued, did not support …