Miracle-dz/UniFAR-FTUs huggingface dataset:
BRCA 1 and MicroRNAs : Emerging Networks and Potential Therapeutic Targets

BRCA1 is a well-known tumor suppressor implicated in familial breast and ovarian cancer. Since its cloning in 1994, numerous studies have established BRCA1’s role in diverse cellular and biochemical processes, such as DNA damage repair, cell cycle control, and transcriptional regulation as well as ubiquitination. In addition, a number of recent studies have functionally linked this tumor suppressor to another important cellular regulator, microRNAs, which are short (19-22 nt) RNAs that were discovered in the nematode in 1993. Soon their presence and function were validated in mammals, and since then, the role of microRNAs has been actively investigated in almost all biological processes, including cancer. In this review, we will describe recent progress in the understanding of the BRCA1 function through microRNAs and the role of microRNAs in regulating BRCA1, with emphasis on the implication of these processes on the development and progression of cancer. We will also discuss the therapeutic potential of microRNA mimics or inhibitors of microRNAs to affect BRCA1 function.
Causes of the 2011–14 California Drought

AbstractThe causes of the California drought during November–April winters of 2011/12–2013/14 are analyzed using observations and ensemble simulations with seven atmosphere models forced by observed SSTs. Historically, dry California winters are most commonly associated with a ridge off the west coast but no obvious SST forcing. Wet winters are most commonly associated with a trough off the west coast and an El Nino event. These attributes of dry and wet winters are captured by many of the seven models. According to the models, SST forcing can explain up to a third of California winter precipitation variance. SST forcing was key to sustaining a high pressure ridge over the west coast and suppressing precipitation during the three winters. In 2011/12 this was a response to a La Nina event, whereas in 2012/13 and 2013/14 it appears related to a warm west–cool east tropical Pacific SST pattern. All models contain a mode of variability linking such tropical Pacific SST anomalies to a wave train with a ridge o.
Prevalence, awareness, treatment, and control of hypertension among Black Surinamese, South Asian Surinamese and White Dutch in Amsterdam, The Netherlands: the SUNSET study

Objective To assess ethnic differences in prevalence, levels of awareness, treatment and control of hypertension among Dutch ethnic groups and to determine whether these differences are consistent with the UK findings. Design Cross-sectional survey. Setting South-east Amsterdam, The Netherlands. Participants A random sample of 1383 non-institutional adults aged 35–60 years. Of these, 36.7% were White, 42% were Black and 21.3% were South Asian people. Main outcome measures Prevalence of hypertension, rates of awareness, treatment, and control of hypertension. Results The Black and South Asian subjects had a higher prevalence of hypertension compared with White people. After adjustments for age, the odds ratios (95% confidence interval) for being hypertensive were 2.2 (1.4–3.4; P < 0.0001) and 3.8 (2.6–5.7; P < 0.0001) for Black men and women, respectively, and 1.7 (1.0–2.6; P = 0.039) and 2.8 (1.8–4.5; P < 0.0001) for South Asian men and women, compared with White people. There were no differences in awareness and pharmacological treatment of hypertension between the groups. However, Black hypertensive men 0.3 (0.1–0.7; P < 0.01) and women 0.5 (0.3–0.9; P < 0.05) were less likely to have their blood pressure adequately controlled compared with White people. Conclusion The higher prevalence of hypertension found among Black and South Asian people in The Netherlands is consistent with the UK studies. However, the lower control rates and the similar levels of awareness and treatment of hypertension in Black Surinamese contrast with the higher rates reported in African Caribbeans in the UK. The rates for the South Asians in The Netherlands were relatively favourable compared to similar South Asian groups in the UK. These findings underscore the urgent need to develop strategies aimed at improving the prevention and control of hypertension, especially among Black people, in The Netherlands.
Longer term outcomes from a randomised trial of prescribing strategies in otitis media.

BACKGROUND There are limited data about the longer-term outcomes in acute otitis media (AOM) when comparing the realistic alternatives of immediate prescription of antibiotics and a 'wait and see' or delayed prescribing policy. AIM The aim was to assess the medium and longer term outcomes of two prescribing strategies for otitis media. DESIGN OF STUDY Follow-up of a randomised controlled trial cohort. SETTING Primary care. METHOD Three-hundred and fifteen children aged 6 months to 10 years presenting with AOM were randomised to immediate antibiotics, or antibiotics delayed at the parents discretion 72 hours if the child still had significant otalgia or fever, or was not improving. Episodes of earache since study entry were documented, and a poor score (of 9 or more--the top 20%) on a reliable six-item functional rating scale (Cronbach's alpha = 0.75). RESULTS The delayed prescribing strategy did not significantly increase reported episodes of earache in the 3 months since randomisation (odds ratio [OR] = 0.89; 95% confidence interval [CI] = 0.48 to 1.65) or over 1 year (OR = 1.03; 95% CI = 0.60 to 1.78) nor of poor scores on the function scale at 3 months (OR = 1.16; 95% CI = 0.61 to 2.22) or 1 year (OR = 1.12; 95% CI = 0.57 to 2.19), and controlling for subsequent antibiotic use after the randomised episode did not alter these estimates. The number of prior episodes of AOM documented in the doctor's notes predicted episodes of earache reported (0, 1, > or = 2 episodes, respectively; OR = 1, 2.42, 2.61; chi2 for trend 8.04; P<0.01). There was weaker evidence that prior episodes also predicted poor function at 1 year (OR = 1, 1.86, 2.28; chi2 for trend 5.49; P = 0.019). For children with recurrent AOM (two or more previous episodes documented in the doctor's notes, n = 43) there was possible evidence of fewer episodes of earache in the 3 months since study entry in the immediate antibiotic group (10% compared to 39% in the delayed group, chi2 4.8, P = 0.029), but no effect from randomisation to 1 year. CONCLUSIONS For most children, delayed prescribing is not likely to have adverse longer-term consequences. Children with recurrent AOM are more likely to have poorer outcomes. Secondary analysis should be treated with caution and requires confirmation, but suggests that treating such children with antibiotics immediately may not alter longer-term outcomes.
Bicarbonate transport by rabbit cortical collecting tubules. Effect of acid and alkali loads in vivo on transport in vitro.

Rabbit cortical collecting tubules were perfused in vitro to investigate the control of bicarbonate transport. Bicarbonate was measured by microcalorimetry as total CO2. The perfusate and bath were identical solutions containing 25 mM bicarbonate at pH 7.4. The mean pH of the urine in the bladders of untreated rabbits at the time they were killed was 7.4. Their individual tubules, studied in vitro, either absorbed or secreted bicarbonate, and, combining the results, there was on the average no significant net transport. When the rabbits were treated with NH4Cl the day before the experiment, their urine was acidic and their tubules studied in vitro absorbed bicarbonate (i.e., there was net lumen-to-bath transport). In contrast, when the rabbits were treated with NaHCO3, their urine was significantly more alkaline, and their tubules studied in vitro generally secreted bicarbonate (i.e., net bath-to-lumen transport). Thus, the direction of bicarbonate transport by cortical collecting tubules studied under standard conditions in vitro correlated with the urine pH and was determined by the preceding treatment of the animals in vivo with acidifying or alkalinizing salts. These results demonstrate a previously unrecognized mechanism which contributes to the control of urinary bicarbonate excretion.
Hepatitis C virus and GBV‐C virus prevalence among patients with B‐cell lymphoma in different European regions: a case‐control study of the International Extranodal Lymphoma Study Group

Hepatitis C virus (HCV) infection is associated with some B‐cell non‐Hodgkin lymphoma (B cell‐NHLs). Patients with HCV infection frequently show co‐infections with GB virus C (GBV‐C, formerly known as hepatitis G virus), and some studies have suggested a higher incidence of GBV‐C infection in patients with B cell‐NHLs. The aim of this study was to prospectively evaluate the association between HCV and/or GBV‐C infection and B cell‐NHLs in different geographic areas. One hundred thirty‐seven lymphoma cases and 125 non‐lymphoma matched controls were enrolled in an international case‐control study conducted in Switzerland (Bellinzona), Spain (Barcelona) and England (Southampton) on samples collected from 2001 to 2002. In Bellinzona (41 cases and 81 controls), the overall prevalence of HCV was 3.3% (4.9% in NHLs), and the overall prevalence of GBV‐C was 24% (22% in NHLs). In Barcelona (46 cases and 44 controls), the prevalence of HCV was 10% (8.7% in NHLs) and the prevalence of GBV‐C 20% (13% in NHLs). There was no statistically significant difference in the frequency of both infections between patients with NHL and controls. In Southampton, 50 NHL cases were analysed, none of them was found to be HCV‐positive; therefore, no control group was analysed and GBV‐C analysis was not performed, too. Both in Bellinzona and in Barcelona, the seropositivity rate was significantly lower for HCV than for GBV‐C, suggesting that their transmission can be independent. The incidence of HCV was significantly higher in Barcelona than that in Bellinzona. This study confirmed the existence of marked geographic differences in the prevalence of HCV in NHL but cannot provide any significant evidence for an association between HCV and/or GBV‐C and B‐cell NHLs. Copyright © 2011 John Wiley & Sons, Ltd.
Radiation defects in CaF2 and SrF2 crystals doped with cadmium or zinc

The formation of radiation defects in calcium and strontium fluoride single crystals doped with cadmium or zinc has been investigated by luminescence and absorption spectroscopy, as well as by electron spin resonance spectroscopy. It was found that x-irradiation could convert divalent impurity ions located at essentially cubic sites into the univalent state. Three types of Cd+ or Zn+ centers differing by local environment with point symmetries Oh, C3v and C2v are identified in the crystals. The formation of the last two results from the interaction between reduced impurities in the cubic environment and anion vacancies. The latter are intrinsic radiation defects and are not created by x-irradiation in undoped crystals. We also discuss the possible implications of the electric field of the charge impurity defects on separation of the intrinsic radiation defects in these crystals.
Interventions for smoking cessation in hospitalised patients.

BACKGROUND An admission to hospital provides an opportunity to help people stop smoking. Individuals may be more open to help at a time of perceived vulnerability, and may find it easier to quit in an environment where smoking is restricted or prohibited. Providing smoking cessation services during hospitalisation may help more people to attempt and sustain a quit attempt. OBJECTIVES To determine the effectiveness of interventions for smoking cessation in hospitalised patients. SEARCH STRATEGY We searched the Cochrane Tobacco Addiction Group register, CINAHL and the Smoking and Health database for studies of interventions for smoking cessation in hospitalised patients. SELECTION CRITERIA Randomised and quasi-randomised trials of behavioural, pharmacological or multicomponent interventions to help patients stop smoking conducted with hospitalised patients who were current smokers or recent quitters. We excluded studies of patients admitted for psychiatric disorders or substance abuse, those that did not report abstinence rates and those with follow-up of less than six months. DATA COLLECTION AND ANALYSIS Two authors extracted data independently for each paper, with disagreements resolved by consensus. MAIN RESULTS Intensive intervention (inpatient contact plus follow-up for at least one month) was associated with a significantly higher quit rate compared to control (Peto Odds Ratio 1.82, 95% CI 1.49-2.22). There was insufficient evidence to judge the effect of interventions delivered only during the hospital stay. Although the interventions increased quit rates irrespective of whether nicotine replacement therapy was used, the results for nicotine replacement therapy (NRT) were compatible with other data indicating that it increases quit rates. There was no strong evidence that clinical diagnosis affected the likelihood of quitting. REVIEWER'S CONCLUSIONS High intensity behavioural interventions that include at least one month of follow-up contact are effective in promoting smoking cessation in hospitalised patients. The findings of the review were compatible with research in other settings showing that NRT increases quit rates.
Health and growth status of immigrant and refugee children in Toronto, Ontario: A retrospective chart review.

OBJECTIVE To describe selected anthropometric and health status variables among immigrant and refugee children ≤6 years of age within an inner city clinic in Toronto, Ontario. METHODS A retrospective chart review of patients born between January 1, 1998 and December 31, 2008, was conducted at a Toronto community health centre serving a primarily immigrant and refugee population. Outcome measures included calculated age-specific percentiles for height and weight, and the prevalence of anemia, iron deficiency, enteric parasites, elevated lead levels, HIV and hepatitis B. Postal codes were collected and used to determine the patient's neighbourhood income quintile. RESULTS A total of 331 patients, born between January 1, 1998 and December 31, 2008, were identified. Of these, a total of 210 charts were manually reviewed. The prevalence of height-for-age and weight-for-age under the third percentile on the Centers for Disease Control and Prevention Growth Charts were 7.2% and 11.6%, respectively, and 8.4% and 5.0%, respectively, on the WHO Growth Standards Chart. Prevalence rates were also calculated for anemia (22.8%), iron deficiency (53.3%), hepatitis B (2.5%), parasitic infections (33.6%), elevated blood lead levels (4.9%) and HIV (0%). Neighbourhood income quintiles revealed that 46.7% of patients were residing in the lowest (ie, poorest) income quintile neighbourhoods. CONCLUSION These findings reveal a high burden of illness within the population presenting to an immigrant/refugee health clinic, and illustrate the need for further research in this area, as well as increased efforts to ensure appropriate screening within clinics serving a high volume of newcomer patients.
Association between Group 2 Innate Lymphoid Cells enrichment, nasal polyps and allergy in Chronic Rhinosinusitis

Group 2 innate lymphoid cells (ILC2s) were shown to be involved in the initiation and coordination of Th2‐type immune responses in allergic disease animal models. Recently, ILC2s enrichment was noted in chronic rhinosinusitis (CRS) patients; however, the role of ILC2s in coordinating the Th2 response in CRS remains to be elucidated. Here, we characterize the ILC2 compartment in CRS by investigating the correlations between ILC2s, Th2 cells and Th2 cytokines expression in CRS patients.
A retrospective cohort study of cause‐specific mortality and incidence of hematopoietic malignancies in Chinese benzene‐exposed workers

Benzene exposure has been causally linked with acute myeloid leukemia (AML), but inconsistently associated with other hematopoietic, lymphoproliferative and related disorders (HLD) or solid tumors in humans. Many neoplasms have been described in experimental animals exposed to benzene. We used Poisson regression to estimate adjusted relative risks (RR) and the likelihood ratio statistic to derive confidence intervals for cause‐specific mortality and HLD incidence in 73,789 benzene‐exposed compared with 34,504 unexposed workers in a retrospective cohort study in 12 cities in China. Follow‐up and outcome assessment was based on factory, medical and other records. Benzene‐exposed workers experienced increased risks for all‐cause mortality (RR = 1.1, 95% CI = 1.1, 1.2) due to excesses of all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95% CI = 1.2, 2.3) and diseases of blood forming organs (RR = ∞, 95% CI = 3.4, ∞). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI = 1.2, 1.9) with similar RRs for males and females, based on three‐fold more cases than in our previous follow‐up. Significantly elevated incidence of all myeloid disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI = 0.8, 11), and increases of all lymphoid disorders included excesses of non‐Hodgkin lymphoma (RR = 3.9, 95%CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4, 95%CI = 1.0, 99). The 28‐year follow‐up of Chinese benzene‐exposed workers demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases and suggested possible associations with other malignant and non‐malignant disorders.
Fibroblast growth factor blocks Sonic hedgehog signaling in neuronal precursors and tumor cells

The Sonic hedgehog (Shh) and FGF signaling pathways regulate growth and differentiation in many regions of the nervous system, but interactions between these pathways have not been studied extensively. Here, we examine the relationship between Shh and FGF signaling in granule cell precursors (GCPs), which are the most abundant neural progenitors in the cerebellum and the putative cell of origin for the childhood brain tumor medulloblastoma. In these cells, Shh induces a potent proliferative response that is abolished by coincubation with basic FGF. FGF also inhibits transcription of Shh target genes and prevents activation of a Gli-responsive promoter in fibroblasts, which suggests that it blocks Shh signaling upstream of Gli-mediated transcription. FGF-mediated inhibition of Shh responses requires activation of FGF receptors and of ERK and JNK kinases, because it can be blocked by inhibitors of these enzymes. Finally, FGF promotes differentiation of GCPs in vitro and in vivo and halts proliferation of tumor cells from patched (ptc) mutant mice, a model for medulloblastoma. These findings suggest that FGF is a potent inhibitor of Shh signaling and may be a useful therapy for tumors involving activation of the hedgehog pathway.
Pathophysiology of ischaemia–reperfusion injury

Reperfusion of ischaemic tissues is often associated with microvascular dysfunction that is manifested as impaired endothelium‐dependent dilation in arterioles, enhanced fluid filtration and leukocyte plugging in capillaries, and the trafficking of leukocytes and plasma protein extravasation in postcapillary venules. Activated endothelial cells in all segments of the microcirculation produce more oxygen radicals, but less nitric oxide, in the initial period following reperfusion. The resulting imbalance between superoxide and nitric oxide in endothelial cells leads to the production and release of inflammatory mediators (e.g. platelet‐activating factor, tumour necrosis factor) and enhances the biosynthesis of adhesion molecules that mediate leukocyte–endothelial cell adhesion. Some of the known risk factors for cardiovascular disease (hypercholesterolaemia, hypertension, and diabetes) appear to exaggerate many of the microvascular alterations elicited by ischaemia and reperfusion (I/R). The inflammatory mediators released as a consequence of reperfusion also appear to activate endothelial cells in remote organs that are not exposed to the initial ischaemic insult. This distant response to I/R can result in leukocyte‐dependent microvascular injury that is characteristic of the multiple organ dysfunction syndrome. Adaptational responses to I/R injury have been demonstrated that allow for protection of briefly ischaemic tissues against the harmful effects of subsequent, prolonged ischaemia, a phenomenon called ischaemic preconditioning. There are two temporally and mechanistically distinct types of protection afforded by this adaptational response, i.e. acute and delayed preconditioning. The factors (e.g. protein kinase C activation) that initiate the acute and delayed preconditioning responses appear to be similar; however the protective effects of acute preconditioning are protein synthesis‐independent, while the effects of delayed preconditioning require protein synthesis. The published literature in this field of investigation suggests that there are several potential targets for therapeutic intervention against I/R‐induced microvascular injury. Copyright © 2000 John Wiley & Sons, Ltd.
Effect of ankle taping and bracing on vertical ground reaction forces during drop landings before and after treadmill jogging.

STUDY DESIGN Single-group repeated-measures experimental design. OBJECTIVES The purpose of this study was to evaluate the effects of prophylactic ankle stabilization on vertical ground reaction forces before and after treadmill jogging. BACKGROUND Previous research has demonstrated acute effects of ankle taping and bracing on ankle joint kinematics and vertical ground reaction forces during drop landings. Based on the number of investigations demonstrating increased range of motion of the braced or taped ankle following exercise, it may be plausible that the aforementioned landing alterations may return to normal following an exercise bout. METHODS AND MEASURES Fourteen healthy recreational participants performed stiff and soft drop landings before and after a 20-minute treadmill exercise bout under 3 different ankle stabilizer conditions (no stabilizer, ankle brace, and ankle tape). A forceplate was used to collect ground reaction force data under the dominant foot. The first and second peak impact force, as well as the time to each of the 2 peak forces, were determined for each trial and used as dependent variables. RESULTS The time to reach peak forces were significantly less under the ankle brace and tape conditions in comparison to the control (no-stabilizer) condition. CONCLUSIONS It appears that ankle taping and bracing decrease the time to reach peak impact forces. These alterations indicate that during dynamic activity the musculoskeletal structures of the body may be subjected to loads within shorter time periods. Whether these effects are detrimental over time remains speculative at this point and requires further research.