Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNAs in clinical oncology: at the crossroads between promises and problems

MicroRNAs (miRNAs) are small RNAs that do not code for proteins, but function by controlling protein expression of other genes. miRNAs have been shown to control cell growth, differentiation and apoptosis. Shortly after their discovery, miRNAs have been found to be associated with cancer. Earlier reports have shown that human cancers frequently show a distorted expression profile of miRNAs. In this review, the biogenesis of miRNAs and potential mechanisms of their dysregulation and involvement in cancer pathogenesis are discussed. The current literature on potential applications of miRNAs in the field of clinical oncology from diagnostic to prognostic and predictive applications at the tissue, and more recently, serum levels, is reviewed. The potential therapeutic applications of miRNAs and RNAi in the field of cancer are summarised. Finally, some of the potential challenges that face the transition of miRNAs from a research setting into a clinical application are highlighted, with a future prospective of the incorporation of miRNAs in cancer patient management.
Use of an elastic stain to show venous invasion in colorectal carcinoma: a simple technique for detection of an important prognostic factor

Background: Venous invasion (VI) is an important prognostic factor in colorectal cancer; it is positively associated with visceral metastases and may affect the decision to treat with adjuvant therapy. Aims: To evaluate whether an elastic tissue (Movat) stain facilitates identification of VI, the number of Movat-stained blocks needed to detect VI, and whether VI identified with a Movat stain is prognostically equivalent to VI identified on H&E-stained slides. Methods: H&E-stained sections from colorectal carcinomas from the year 2000 (n = 92) were examined for VI and compared to Movat-stained slides. Clinical charts were reviewed to compare rates of metastases in VI-positive versus VI-negative patients. Results: With the Movat stain, VI was identified in 44% of cases previously categorised as negative (p<0.001) on review of H&E slides alone. One Movat-stained section was often sufficient to identify VI, with a statistically significant benefit to performing multiple stains if necessary. In H&E sections, two clues helped identify VI: the “unaccompanied artery” sign, where large arteries were seen without an accompanying vein; and the “protruding tongue” sign, where smooth tongues of tumour extended into pericolic/rectal fat. Metastases were present in 61% of cases positive for VI compared to 35% in VI-negative cases (p = 0.03). 45% of cases positive for intramural VI only developed metastases (p = 0.39), while 65% of cases positive for extramural VI only developed metastases (p = 0.03). Conclusions: Pathologists should look for morphological clues of VI in H&E stained sections; when VI is not apparent, an elastic tissue stain on all tumour blocks significantly improves identification of VI. Morphological clues include the “unaccompanied artery” and “protruding tongue” signs.
Filling the gaps in undergraduate teaching of clinical biochemistry

Despite considerable effort by the General Medical Council (GMC) in formulating, and UK medical schools in delivering, a curriculum fit for producing doctors in the 21st century,1 2 there is still some doubt as to whether the resulting changes in the undergraduate courses have produced doctors with appropriate skills.3 Following the first publication of Tomorrow's Doctors in 1993 by the GMC,4 medical schools in the UK embarked on comprehensive revision of their curricula and instituted significant changes in their teaching methods. Prior to this, many medical courses consisted of 2 or 3 years of academic study focussing on basic and applied medical sciences, followed by a course that was more of an apprenticeship where medical students were taught by clinical teams on the wards and learned many clinical skills opportunistically. One of the principal aims of Tomorrow's Doctors was to enable doctors to be better prepared for clinical practice, especially in their first year after qualification.1 4 To this end, greater emphasis was placed on learning practical and communication skills, with less emphasis on learning the basic sciences, indeed the second edition of Tomorrow's Doctors ,4 emphasised that ‘factual knowledge must be kept to the essential minimum’. This edict has led many medical schools to severely curtail the basic science tuition in their revised courses, and this has reduced the time available for teaching even basic pathology. The latest edition of Tomorrow's Doctors (2009) 2 has expanded the educational aims by including outcomes for training, the first category of which is ‘the Doctor as a scholar and a scientist’ with which most pathologists would identify. The first outcomes specified under this heading are that …
Serum CA19.9 levels are commonly elevated in primary ovarian mucinous tumours but cannot be used to predict the histological subtype

Aims CA19.9 is a monosialoganglioside secreted by mucinous tumours of the gastrointestinal tract, including the pancreas and biliary tree. Limited studies have shown that this tumour marker may also be elevated in primary ovarian mucinous neoplasms, but no study has assessed whether serum CA19.9 levels can be used to predict if a primary ovarian mucinous tumour is benign, borderline or malignant. The aim of this study was to correlate the serum CA19.9 level with the histological features in a large series of primary ovarian mucinous neoplasms. Methods 144 cases of primary ovarian mucinous neoplasm (79 benign, 45 borderline and 20 malignant) were identified in which a preoperative serum CA19.9 level had been performed. The association between the serum levels and the histological subtype and a variety of other parameters was investigated. In a subset of cases, immunohistochemical staining for CA19.9 was performed on tumour blocks. Results Serum CA19.9 levels were elevated in 27%, 38% and 40% of mucinous cystadenomas, borderline mucinous tumours and mucinous carcinomas, respectively. Markedly elevated levels of serum CA19.9 were observed in each group, with the highest serum CA19.9 measurements being noted in borderline mucinous tumours. There was no relationship between the serum CA19.9 level and whether the tumours were benign, borderline or malignant (Kruskal–Wallis test p value=0.32). A weak but statistically significant correlation was found between tumour maximum dimension and CA19.9 level (Spearman's rank correlation coefficient=0.17, p=0.04). In those cases in which CA19.9 immunohistochemistry was performed, all tumours showed positive staining for CA19.9, with 60% of these cases being associated with an elevated serum CA19.9 level. Conclusion Preoperative CA19.9 levels cannot be used to predict whether a suspected ovarian mucinous tumour is benign, borderline or malignant. Markedly elevated serum levels (>1000 U/ml) may be found in benign mucinous neoplasms as well as in borderline and malignant tumours.
Propositional skew Boolean logic

A non-commutative propositional logic is described. A Hilbert-style axiomatisation is given for the logic, and a multiple-valued interpretation is constructed. The logic is shown to be sound and complete with respect to this interpretation. We also show that the logic has no finite complete models. An application includes the specification and design of multiple-valued switching circuits.
Psychosis From Anticholinergic Medications Administered at a Smoking Cessation Clinic

Anticholinergic medications are used for a variety of reasons, from their effects on the central nervous system to their effects on the gastrointestinal tract. They are used in the treatment of Parkinson’s disease, vertigo, gastroesophageal reflux disease, and peptic ulcer disease. They have also been used in the treatment of motion sickness. These medications must be used with caution due to their effects on other systems, including the central nervous system. Common central nervous system side effects due to anticholinergic medications include sedation, delirium, amnesia, and in the case of the patient presented in this report, psychosis. A 61-year-old man presented to the emergency department with visual and auditory hallucinations secondary to anticholinergic medications (scopolamine and atropine) he received in a smoking cessation clinic. Previous cases of anticholinergic medication–induced psychosis are also summarized.
The cyber threat landscape: Challenges and future research directions

Cyber threats are becoming more sophisticated with the blending of once distinct types of attack into more damaging forms. Increased variety and volume of attacks is inevitable given the desire of financially and criminally-motivated actors to obtain personal and confidential information, as highlighted in this paper. We describe how the Routine Activity Theory can be applied to mitigate these risks by reducing the opportunities for cyber crime to occur, making cyber crime more difficult to commit and by increasing the risks of detection and punishment associated with committing cyber crime. Potential research questions are also identified.
Hand Hygiene Compliance and Nurse-Patient Ratio Using Videotaping and Self Report

Background:Appropriately implemented, hand hygiene can prevent nosocomial infections, but there is a lack of research on the effect of specific nurse-patient ratios on hand hygiene compliance rates. Furthermore, there have been few studies of infection control practices in Jordanian hospitals. Methods:One hundred registered nurses from a private health care setting in Jordan who worked in intensive care units and medical-surgical wards participated. Two methods, videotaping and self-report, were used to collect data on hand hygiene. Subjects also completed a questionnaire to assess hand hygiene behavior, attitudes, and beliefs. Results:The overall hand hygiene compliance rate was 32%. Nurse-patient ratios affected hand hygiene before beginning patient care only. The lowest hand hygiene compliance rates were in intensive care units when the nurse-patient ratio was less than 1:2. Females had higher compliance rates than males. ConclusionsThe observed low level of overall hand hygiene compliance, lower compliance rates in higher acuity settings, and gender-related differences in compliance are consistent with findings from previous studies of hand hygiene over the past 2 decades.
Performance of the Iris iQ®200 Elite analyser in the cell counting of serous effusion fluids and cerebrospinal drainage fluids

Aims Evaluation of the Iris iQ®200 Elite analyser, initially designed for urinary cell counting, for the analysis of biological fluids (serous effusion fluids and cerebrospinal drainage fluids) and comparison of its performance with that of the manual microscopic method. Methods Routine samples (ascite fluids, pleural fluids and cerebrospinal fluids) were evaluated in terms of red blood cells and nucleated elements using the iQ®200 analyser and the manual method. The authors compared the reliability, repeatability and speed of the two techniques. In addition, the authors assessed the contribution of two different sample dilution processes to the improvement of iQ®200 analyser cytological results. Results Very good agreements were found between the two methods and between the two sample dilution processes. Regarding the repeatability, the coefficients of variation obtained with the iQ200 were slightly higher than those obtained by the manual method. Besides, the difference in the speed of the two methods was not significantly different for series with <10 samples. Conclusions The Iris iQ®200 Elite analyser has allowed us to obtain reliable results, equivalent to that of the manual method, for cell enumeration in biological fluids. Although the speed of this instrument needs to be improved for larger series of samples, it enables standardised and objective cytological results to be obtained and represents an alternative to the usual manual microscopic method. Moreover, automation of such analyses permits saving of technician time.
Peripheral neuropathy as an adverse effect of imatinib therapy

Imatinib, a tyrosine kinase inhibitor, has transformed treatment options for patients with chronic myeloid leukaemia (CML). It is effective in the management of all phases of CML by selectively inhibiting the BCR-ABL protein, the molecular consequence of the Philadelphia chromosome (Ph). The overall survival and disease-free survival of CML have significantly improved with the use of imatinib. We report a novel and dose-limiting complication of imatinib therapy. We report a 58-year-old man with Ph-positive CML who was initially treated with hydroxyurea followed by alpha-interferon and imatinib. He achieved complete cytogenetic and molecular remission on combination therapy at 6 and 30 months, respectively. Due to extreme fatigue, interferon therapy (25 μg once weekly) was discontinued after 3 years with good response. Subsequent to 5.5 years of imatinib therapy, he complained of bilateral lower limb paraesthesia. His symptoms progressed over the next 6 months resulting in ankle weakness and tripping. On examination, he had a brisk ankle jerk with diminished vibration and position sense. His C-reactive protein, blood …
A pyrosequencing-based test for detection and relative quantification of the BCR-ABL1 T315I point mutation

Aims The BCR-ABL1 T315I mutation imparts resistance to tyrosine kinase inhibitors currently available for treatment of chronic myelogenous leukaemia. Thus, quantitative monitoring of the emergence and expansion of T315I-positive subclones may be clinically useful. The goals of this study were to retrospectively review the authors' experience with Sanger sequencing-based BCR-ABL1 kinase domain mutation testing, paying particular attention to the T315I mutation, and to develop an alternative test for relative quantification of T315I using pyrosequencing. Methods The performance of a new T315I pyrosequencing assay was evaluated. Total RNA was isolated from whole blood and reverse-transcribed. The resulting cDNA was subjected to an initial round of PCR across the BCR-ABL1 breakpoint followed by a second round to amplify the sequence flanking ABL1 codon 315. The final PCR product was pyrosequenced to detect and quantify the T315I point mutation. Additional experiments were carried out to determine the effects of background untranslocated ABL1 on assay sensitivity in samples with low tumour burden. Results The results show that T315I was the most commonly detected kinase domain mutation and was persistent in follow-up testing. All 26 specimens that tested positive by Sanger sequencing for the T315I mutation were also positive using the pyrosequencing test. Relative quantification data derived from pyrosequencing matched the approximate wild-type/mutant ratios found by Sanger sequencing. Serial dilution experiments show sensitivity to 5% mutant allele. The authors also quantitatively assessed the influence of untranslocated ABL1 in the sample background on the assay and found that it occurred at levels not likely to influence performance. Conclusion The described test is useful for detection and relative quantification of the T315I point mutation in chronic myelogenous leukaemia in a sensitive, specific and reproducible manner.
Socioeconomic variations in women’s diets: what is the role of perceptions of the local food environment?

Objectives: To test the contribution of perceived environmental factors (food availability, accessibility and affordability) to mediating socioeconomic variations in women’s fruit, vegetable and fast food consumption. Methods: A community sample of 1580 women from 45 neighbourhoods provided survey data on their socioeconomic position (SEP) (education and income); diet (fruit, vegetable and fast food consumption); and the perceived availability of, access to and cost of healthy food in their local area. Results: Once perceived environmental variables were considered, the associations between SEP and diet were weak and non-significant, suggesting that socioeconomic differences in diet were almost wholly explained by perceptions of food availability, accessibility and affordability. Conclusions: Strategies to decrease socioeconomic inequalities in diet could involve promoting inexpensive ways to increase fruit and vegetable consumption, and ensuring that people of low SEP are aware that many healthy foods are available at relatively low cost. Future research should also confirm if perceptions match objective measures of food availability, accessibility and affordability, in order to address the real and/or perceived lack of healthy options in low SEP neighbourhoods.
High levels of polybrominated diphenyl ethers in vacuum cleaner dust from California fire stations.

Firefighters are exposed to chemicals during fire events and may also experience chemical exposure in their fire stations. Dust samples from used vacuum cleaner bags were collected from 20 fire stations in California and analyzed for polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) using gas chromatography-mass spectrometry. Median dust concentrations were higher for PBDEs (e.g., 47 000 ng/g for BDE-209) than for PAHs (e.g., 220 ng/g for benzo[a]pyrene) or PCBs (e.g., 9.3 ng/g for PCB-180). BDE-209 concentrations in dust from California fire stations were among the highest of any previously documented homes or occupational settings in the world. We examined factors such as the frequency of emergency responses, the number of fire vehicles on site, and building age, but we could not account for the high levels of BDE-209 observed in fire station dust. Based on the findings of our pilot study, we hypothesize that possible sources of BDE-209 in fire stations include contaminated ash tracked back from fire events via boots, clothing, and other equipment as well as specialized equipment treated with BDE-209, including turnout gear and fire vehicles. We suggest possible follow-up studies to confirm these hypotheses.
High agreement on family affluence between children’s and parents’ reports: international study of 11-year-old children

Objective: To examine the agreement between parents’ and children’s reports on four items of family affluence: number of cars, own bedroom, number of family holidays and number of computers, and to analyse predictors of disagreement. Design: Cross-sectional child–parent validation study of selected items from an internationally standardised questionnaire. Setting: Survey conducted in schools in Denmark, Germany, Hungary, Italy, Poland and Scotland. Participants: 972 11-year-old children and their parents responded to the questionnaires. Results: The child item response rates were high (above 93%). The per cent agreement was low for holidays spent with family (52.5%), but high for the other three items of family affluence (76.2–88.1%). The kappa coefficients were good or excellent for all items (between 0.41 and 0.74) and the gamma coefficients were strong for all items (between 0.56 and 0.96). Children from single-parent families were more likely to over-report family affluence (OR 2.67; CI 1.83 to 3.89). Conclusions: Young adolescents’ self-reports of family affluence are fairly valid across the six countries. This finding suggests that the variables measured can be used in epidemiological studies that aim at ranking children according to socioeconomic position.
Are neighbourhood characteristics associated with depressive symptoms? A review of evidence

A review of published observational studies of neighbourhoods and depression/depressive symptoms was conducted to inform future directions for the field. Forty-five English-language cross-sectional and longitudinal studies that analysed the effect of at least one neighbourhood-level variable on either depression or depressive symptoms were analysed. Of the 45 studies, 37 reported associations of at least one neighbourhood characteristic with depression/depressive symptoms. Seven of the 10 longitudinal studies reported associations of at least one neighbourhood characteristic with incident depression. Socioeconomic composition was the most common neighbourhood characteristic investigated. The associations of depressive symptoms/depression with structural features (socioeconomic and racial composition, stability and built environment) were less consistent than with social processes (disorder, social interactions, violence). Among the structural features, measures of the built environment were the most consistently associated with depression but the number of studies was small. The extent to which these associations reflect causal processes remains to be determined. The large variability in studies across neighbourhood definitions and measures, adjustment variables and study populations makes it difficult to draw more than a few general qualitative conclusions. Improving the quality of observational work through improved measurement of neighbourhood attributes, more sophisticated consideration of spatial scale, longitudinal designs and evaluation of natural experiments will strengthen inferences regarding causal effects of area attributes on depression.
Antenatal depression in socially high-risk women in Canada

Background: Antenatal depression is potentially deleterious to the mother and baby. Canadian Aboriginal women have an increased risk for living in poverty, family violence, and substance use; however, little is known about antenatal depression in this group. The aim of this study was to determine the prevalence and correlates of depression in socially high-risk, mostly Aboriginal pregnant women. Methods: Women (Aboriginal and non-Aboriginal), in two prenatal outreach programmes were approached and depressive symptoms between the two groups were compared, using the Edinburgh Postnatal Depression Scale (EPDS). Results: Sixty per cent (n = 402) of potential participants were recruited for the study. The prevalence of depression was 29.5% (n = 402). Depression was associated with a history of depression, mood swings, increased stressors, current smoker, and lack of social support. Aboriginal women were more likely to be depressed, but this was not significantly higher than non-Aboriginal women; however, they did experience significantly more self-harm thoughts. Exercise was a significant mediator for depression. Conclusion: The prevalence of antenatal depression confirms rates in other high-risk, ethnic minority groups of women. A previous history of depression and mood problems were associated with depression, thus prenatal care should include a careful mental health assessment. On a positive note, the present study suggests that exercise may mediate antenatal depression.