bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a Phase I Multiple-Dose Clinical Study of Ursodeoxycholic Acid
Authors: Hess Lisa M. , Krutzsch Mary F. , Guillen Jose , Chow H-H. Sherry , Einspahr Janine , Batta A.K. , Salen Gerald , Reid Mary E. , Earnest David L. , Alberts David S. 
Published: June 2022

Abstract
Background: The hydrophilic bile acid, ursodeoxycholic acid (UDCA), may indirectly protect against colon carcinogenesis by decreasing the overall proportion of the more hydrophobic bile acids, such as deoxycholic acid (DCA), in aqueous phase stool. In the AOM rat model, treatment with UDCA resulted in a significant decrease in adenoma formation and colorectal cancer. It was hypothesized that there is a dose-response relationship between treatment with the more hydrophilic bile acid, UDCA, and a reduction in the proportion of the more hydrophobic bile acid, DCA, in the aqueous stool phase, suggesting the potential of UDCA as a chemopreventive agent. Methods: Eighteen participants were randomized to 300, 600, or 900 mg/day UDCA for 21 days in this multiple-dose, double-blinded study. Seventy-two-hour stool samples were collected pretreatment and on days 18–20 of UDCA treatment for bile acid measurements. Pharmacokinetics were performed and blood bile acids were measured at days 1 and 21 of UDCA treatment. Results: There were no serious adverse events associated with UDCA treatment. There was a dose-response increase in the posttreatment to baseline ratio of UDCA to DCA from the 300 mg/day to the 600 mg/day group, but not between the 600 and the 900 mg/day groups, in both aqueous and solid phase stool. This posttreatment increase was statistically significant in aqueous phase stool for the 300 and 600 mg/day treatment groups (P = 0.038 and P = 0.014, respectively), but was only marginally significant in the 900 mg/day treatment group (P = 0.057). Following the first dose administration, a dose-dependent increase in plasma ursodeoxycholic concentrations was observed in fasting subjects; however, when these levels were measured postprandially following 3 weeks of treatment, the areas under the plasma concentration-time profile (AUC) were not statistically different and remained relatively unchanged over time. Conclusions: UDCA treatment did not decrease the quantity of DCA in fecal water or solids; however, it did decrease the proportion of DCA in fecal water and solids in relation to UDCA. Thus, 3 weeks of UDCA treatment resulted in an overall increase in hydrophilicity of bile acids in the aqueous phase stool, with a peak effect observed with a daily dose of 600 mg/day. Much larger studies are needed to determine the effect of ursodeoxycholic administration on deoxycholic concentration, overall hydrophilicity of stool bile acids, and the long-term effects on intermediate biomarkers of cellular damage.
Association of Cyclin D1 Genotype with Breast Cancer Risk and Survival
Authors: Shu Xiao Ou , Moore Derek B. , Cai Qiuyin , Cheng Jiarong , Wen Wanqing , Pierce Larry , Cai Hui , Gao Yu-Tang , Zheng Wei 
Published: June 2022

Abstract
Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G1 to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction &lt; 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis.
Helicobacter pylori and Malignant Lymphoma in Spain
Authors: de Sanjose Silvia , Dickie Andrew , Alvaro Tomas , Romagosa Vicens , Garcia Villanueva Mercedes , Domingo-Domenech Eva , Fernandez de Sevilla Alberto , El-Omar Emad 
Published: June 2022

Abstract
Helicobacter pylori has been associated with gastric adenocarcinoma and gastric lymphoma. We report on the systematic evaluation of serologic detection of H. pylori in a lymphoma case-control study. Methods: Cases (N = 536) were consecutive patients newly diagnosed with a lymphoid malignancy between 1998 and 2002 in four centers in Spain. Lymphomas were diagnosed and classified using the WHO Classification. Controls (N = 603) were hospitalized patients frequency-matched to the cases by 5-year age group, sex, and study center. Severe immunocompromised patients were excluded as controls. Patients underwent a personal interview and blood sampling. H. pylori infection was evaluated by the presence of IgG antibodies using the Premier enzyme immunoassay kit (Meridian Diagnostics Inc., Cincinnati, OH). Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for lymphoma categories. Results: Anti-H. pylori antibodies were detected in 68.5% of the cases and 71.3% of the controls (P = 0.29) H. pylori was associated with a 3-fold excess risk of splenic marginal B-cell lymphoma (OR = 3.97, 95% CI = 0.92-17.16). H. pylori was not associated with an overall increased risk of extranodal lymphomas (OR = 0.73, 95% CI = 0.44-1.22) but when specific sites were explored, the four mucosa-associated lymphoid tissue and the six diffuse large B-cell lymphomas primary localized in the stomach were all H. pylori seropositive. Conclusion: Persistent infection with H. pylori may be implicated in the development of lymphomas of the gastric mucosa and of the spleen. These results could have clinical implications in the management of splenic marginal zone lymphomas.
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-Methylguanine-DNA Methyltransferase Gene: Epigenetic Silencing and Prognostic Value in Head and Neck Squamous Cell Carcinoma
Authors: Zuo Chunlai , Ai Lingbao , Ratliff Pam , Suen James Y. , Hanna Ehab , Brent Thomas P. , Fan Chun-Yang 
Published: June 2022

Abstract
Background: Alkylating N-nitroso compounds can interact directly with DNA, forming O6-alkylguanine, a DNA adduct proved to be mutagenic and carcinogenic if not sufficiently repaired. A specific DNA repair enzyme, O6-methylguanine-DNA methyltransferase (MGMT), can remove the alkyl group from the O6-position of the guanine, thereby preventing its mutagenic and carcinogenic effects. Inactivation of the MGMT gene in association with promoter hypermethylation results in persistence of O6-alkylguanine in DNA, leading to G:C to A:T transition mutation and these G:C to A:T transition mutations can inactivate p53 tumor suppressor gene or activate ras proto-oncogene. Methods: We analyzed MGMT promoter hypermethylation and protein expression patterns in 94 cases of primary head and neck squamous cell carcinoma (HNSCC) by methylation-specific PCR (MSP) and immunohistochemical staining. The results were then correlated with clinical follow-up data. Results: MGMT promoter hypermethylation was present in 17 of 94 patients (18.1%) and apparent loss of protein expression was seen in 19 of 93 HNSCC patients (20.4%). The presence of MGMT promoter hypermethylation was significantly correlated with loss of MGMT protein expression in HNSCC. Both MGMT promoter hypermethylation and loss of protein expression were significantly correlated to increased tumor recurrences and decreased patient survival, independent of other risk factors, such as tumor site, tumor size, nodal status, age, and chemoradiation therapy. Conclusions: MGMT promoter hypermethylation and apparent loss of protein expression are reliable and independent prognostic factors in HNSCC. The above study may also provide guideline or basis for applying alkylating antitumor agents to patients with HNSCC that display MGMT promoter hypermethylation and/or loss of MGMT protein expression.
Effects of Cruciferous Vegetable Consumption on Urinary Metabolites of the Tobacco-Specific Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Singapore Chinese
Authors: Hecht Stephen S. , Carmella Steven G. , Kenney Patrick M.J. , Low Siew-Hong , Arakawa Kazuko , Yu Mimi C. 
Published: June 2022

Abstract
Vegetable consumption, including cruciferous vegetables, is protective against lung cancer, but the mechanisms are poorly understood. The purpose of this study was to investigate the effects of cruciferous vegetable consumption on the metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers. The study was carried out in Singapore Chinese, whose mean daily intake of cruciferous vegetables is three times greater than that of people in the United States. Eighty-four smokers provided urine samples and were interviewed about dietary habits using a structured questionnaire, which included questions on consumption of nine commonly consumed cruciferous vegetables. Samples of these vegetables obtained in Singapore markets at three different times of year were analyzed for glucosinolates. Urine was analyzed for metabolites of NNK: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Glucs). Glucobrassicins, which release indole-3-carbinols on chewing, were the major glucosinolates in seven of the nine cruciferous vegetables, accounting for 70.0% to 93.2% of all glucosinolates in these vegetables. There was a significant correlation (P = 0.01) between increased consumption of glucobrassicins and decreased levels of NNAL in urine after adjustment for number of cigarettes smoked per day; similar trends were observed for NNAL-Glucs (P = 0.08) and NNAL plus NNAL-Glucs (P = 0.03). These results are consistent with those of previous studies, which demonstrate that indole-3-carbinol decreases levels of urinary NNAL probably by inducing hepatic metabolism of NNK. The results are discussed with respect to the known chemopreventive activity of indole-3-carbinol against lung tumorigenesis by NNK in mice and the effects of isothiocyanates, which are also formed on consumption of cruciferous vegetables, on NNK metabolism. The results of this study demonstrate the complexities in assessing effects of cruciferous vegetables on carcinogen metabolism.
Multi-Cancer Early Detection Tests: Current Progress and Future Perspectives
Authors: Loomans-Kropp Holli A. , Umar Asad , Minasian Lori M. , Pinsky Paul F. 
Published: June 2022

AbstractAdvances in cancer screening and early detection methodologies may lead to the detection of precancerous lesions or early-stage cancer. The development of blood-based multi-cancer early detection (MCED) tests may aid in this challenge. Furthermore, MCED tests have the potential to address early detection gaps for cancers with and without screening modalities and lessen cancer disparities, but many unknowns remain. In this issue, Clarke and colleagues describe stage- and cancer-specific incidence and survival, derived from Surveillance, Epidemiology and End Results Program Data, stratified by race/ethnicity and sex. The investigators discuss the potential to identify earlier-stage cancers (stage shift) that could improve overall patient outcomes. In a simulation model, the authors found fewer cancer-related deaths when cancers were down-staged at the time of diagnosis. In this commentary, we discuss some unanswered questions in using MCED tests for screening, as well as what stage shifting may actually mean for patient outcomes.See related article by Clarke et al., p. 521
“I Wouldn’t Want to Be a Gender Expert:” Gender Experts in Peace Mediation
Authors: Sapiano Jenna , Heathcote Gina , True Jacqui , Aggestam Karin 
Published: June 2022

Abstract
Peace mediation is a professional practice that is increasingly reliant on thematic technical experts, including gender experts. The strategy of including gender expertise in peace mediation reflects the Women, Peace and Security agenda and the call to include dedicated gender expertise in all peacemaking efforts. Based on interviews with peace mediation practitioners, the article analyzes the role of gender experts in peace mediation. We argue that there is a tension between the art of mediation and the art of gender expertise that reflects the gendered power dynamics of peace mediation. We conclude that the strategy of appointing gender experts to peace mediation teams will not “dismantle the master’s house.” However, we acknowledge that without a gender expert very little will be accomplished on this issue. For peace mediation to address the gendered foundations of conflict we argue for the development of an alternate feminist peace mediation practice.
KIR3DL2 contributes to the typing of acute adult T-cell leukemia and is a potential therapeutic target
Authors: Cheminant Morgane , Lhermitte Ludovic , Bruneau Julie , Sicard Hélène , Bonnafous Cécile , Touzart Aurore , Bourbon Estelle , Ortonne Nicolas , Genestier Laurent , Gaulard Philippe , Palmic Patricia , Suarez Felipe , Frenzel Laurent , Naveau Louise , Bazarbachi Ali , Dussiot Mickaël , Waast Laetitia , Avettand-Fenoel Véronique , Brouzes Chantal , Pique Claudine , Lepelletier Yves , Asnafi Vahid , Marçais Ambroise , Hermine Olivier 
Published: June 2022

Abstract
Adult T-cell leukemia (ATL) is a lymphoid neoplasm caused by human T-cell leukemia virus type 1 (HTLV-1), which encodes the transcriptional activator Tax, which participates in the immortalization of infected T cells. ATL is classified into 4 subtypes: smoldering, chronic, acute, and lymphoma. We determined whether natural killer receptors (NKRs) were expressed in ATL. NKR expression (KIR2DL1/2DS1, KIR2DL2/2DL3/2DS2, KIR3DL2, NKG2A, NKG2C, and NKp46) was assessed in a discovery cohort of 21 ATL, and KIR3DL2 was then assessed in 71 patients with ATL. KIR3DL2 was the only NKR among those studied frequently expressed by acute-type vs lymphoma- and chronic/smoldering-type ATL (36 of 40, 4 of 16, and 1 of 15, respectively; P = .001), although acute- and lymphoma-type ATL had similar mutation profiles by targeted exome sequencing. The correlation of KIR3DL2 expression with promoter demethylation was determined by microarray-based DNA methylation profiling. To explore the role of HTLV-1, KIR3DL2 and TAX messenger RNA (mRNA) expression levels were assessed by PrimeFlow RNA in primary ATL and in CD4+ T cells infected with HTLV-1 in vitro. TAX mRNA and KIR3DL2 protein expressions were correlated on ATL cells. HTLV-1 infection triggered KIR3DL2 by CD4+ cells but Tax alone did not induce KIR3DL2 expression. Ex vivo, autologous, antibody-dependent cell cytotoxicity using lacutamab, a first-in-class anti-KIR3DL2 humanized antibody, selectively killed KIR3DL2+ primary ATL cells ex vivo. To conclude, KIR3DL2 expression is associated with acute-type ATL. Transcription of KIR3DL2 may be triggered by HTLV-1 infection and correlates with hypomethylation of the promoter. The benefit of targeting KIR3DL2 with lacutamab is being further explored in a randomized phase 2 study in peripheral T-cell lymphoma, including ATL (registered on https://clinicaltrials.gov as #NCT04984837).
The association between oral health and nutritional status in older adults: a cross-sectional study
Authors: Khoury Claudine , Samot Johan , Helmer Catherine , Rosa Rafael Weber , Georget Aurore , Dartigues Jean-François , Arrivé Elise 
Published: June 2022

Abstract
Objectives
This work aimed to describe the nutritional status of French older adults (age ≥ 90 years) and studied the association between oral health and nutritional status.

Methods
A cross-sectional study was carried out in 2014 among the participants of a cohort on cerebral and functional aging in France at their 25-year follow up (the PAQUID cohort). Nutritional status (Mini Nutritional Assessment [MNA]) and oral health status (number of decayed, missing, and filled teeth [DMFT], number of posterior occluding pairs, xerostomia [Xerostomia Inventory], and prosthetic rehabilitation) were recorded at the participants’ living places by two dentists. Univariate and multivariate logistic regressions were used to explore the association between oral health and nutritional status, with adjustments for potential confounders. Odds ratios (OR) were estimated with their 95% confidence interval (CI).

Results
87 participants were included in the analyses: 74.7% were females and the mean age was 94.1 years (± 3.0). Malnutrition or risk of malnutrition (MNA < 24) was present in 23 participants (26.4%), with only one having malnutrition. The mean DMFT score was 26.5 (± 5.3). The mean number of posterior occluding pairs was 1.5 (± 2.3). Twenty-one participants had xerostomia (24.1%). Only 8.1% of the participants had all their teeth or adequate dentures; 47.1% had inadequate dentures, while 44.8% had no dentures despite tooth loss. After adjustment, xerostomia (OR = 8.79; 95% CI = 2.38–39.10; p = 0.002) was found to be associated with malnutrition or risk of malnutrition.

Conclusion
Being at risk of malnutrition was common among people ≥ 90 years old and was associated with xerostomia. NCT04065828.
Association of health literacy and nutritional literacy with sun exposure in adults using structural equation modelling
Authors: SaeidiFard Nasim , Haeri-Mehrizi Ali Asghar , Akbarzadeh Zahra , Janbozorgi Nasim , Montazeri Ali , Yaseri Mehdi , Shab-Bidar Sakineh 
Published: June 2022

Abstract
Background
Inadequate health and nutritional literacy is a common problem among adults, associated with poor health outcomes. Therefore, this study aimed to investigate the relationship between health literacy and nutritional literacy to sun exposure behaviour.

Methods
We conducted a cross-sectional study on 261 adults (18–65 years) in Iran. Data was collected on knowledge, motivation, health literacy, nutritional literacy, and sun exposure behaviour using an interview-assisted questionnaire. Using the information–motivation–behavioural skills model and structural equation modeling, we tested whether health and nutritional literacy were associated with the relationships between knowledge of vitamin D, attitudes toward sun exposure, and sun exposure behaviour. Different models using structural equation modeling were performed to analyze the data.

Results
The finding showed that health literacy (β = 0.29, p < 0.001) and nutritional literacy (β = 0.14, p = 0.02) was directly associated with sunlight exposure. Indirect relationships also existed between knowledge and sunlight exposure through health literacy (β = 0.33, p < 0.001) and nutritional literacy (β = 0.22, p = 0.01). The model had good fit (x2/df = 1.422; RMSEA = 0.040; CFI = 0.851; NFI = 0.657). There was no significant relationship between health literacy and motivation (β = 0.11, p = 0.16), nutritional literacy and motivation (β = 0.06, p = 0.42) and motivation and sun exposure (β = 0.01, p = 0.91).

Conclusions
The findings showed that individuals with sufficient health literacy and nutritional literacy were more likely to have exposure to sunlight. Health and nutritional literacy should be considered when educating adults about vitamin D supplements and sunlight exposure.
Prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy in Uganda: a cross sectional study
Authors: Arubaku Wilfred , Kwizera Godfrey , Tusubira Deusdedit , Kanyesigye Michael , Chamut Steffany , Seymour Brittany Anne , Siedner Mark J. , Niyonzima Vallence , Najjuma Josephine N. , Maling Samuel 
Published: June 2022

Abstract
Background
Oral diseases are estimated to affect half of people living with HIV in the western world, and are often marked by pain, discomfort, disfigurement and reduced quality of life. Both HIV-specific and antiretroviral therapy-associated oral diseases have been found in this population. However, the prevalence, correlates and treatment needs of dental caries among people on antiretroviral therapy has not been well studied in rural Africa where majority of people living with HIV reside. Moreover, health behaviors and access to dental care vary significantly from high-income countries in the global north.

Methods
A cross-sectional study was conducted among people living with HIV attending a high-volume HIV clinic with an enrollment of 10,000 patients in a regional referral hospital in Southwestern Uganda. The clinic is located in an urban setting with a large rural catchment area. Oral health data was collected using the modified World Health Organization oral health questionnaire for adults. Dental examinations were conducted to identify and classify dental caries using the decayed, missing, filled, teeth (DMFT) index and compute the treatment need. Logistic regression models were employed to identify correlate of dental caries.

Results
A total of 194 participants were included in the study. The majority were female (124/194, 63.9%) with a median age of 42 years (IQR 36–49). The prevalence of dental caries experience among study participants was 67%, (130/194, 95% CI 60–75%). The mean DMFT index score was 4 (IQR 2–6) and treatment need was 96% (192/200). A higher CD4 count was associated with the presence of dental caries (OR 0.403, 95% CI 0.175–0.932) although it was not significant in multivariate analysis.

Conclusion
There is a high prevalence of dental caries among people living with HIV on ART in Uganda. Our data demonstrate a high oral treatment need among this population. We recommend inclusion of preventive and therapeutic oral care into HIV care in this region.