Miracle-dz/UniFAR-FTUs huggingface dataset:
Breast cancer: biological characteristics in postmenopausal type 2 diabetic women. Identification of therapeutic targets.

HYPOTHESIS Epidemiological data have suggested a possible relationship between diabetes mellitus and cancer risk, particularly breast cancer. We set out to investigate the effect of diabetes mellitus on the expression of estrogen and progesteron receptors and on the proliferative activity of primary breast cancer. METHODS We selected 77 diabetic women and 578 control patients all in post-menopause and diagnosed with primary breast cancer. All patients underwent surgical excision of the tumor and on the specimens were performed an assessment of estrogen receptor and progesteron receptor and proliferative activity assay by (3)H-Thymidine incorporation. RESULTS Diabetic women showed a decreased proliferative activity, while having the same estrogen receptor and progesteron receptor status and mean cytoplasmic concentration of their receptors than control group. Insulin treated women had a lower proliferative activity than non-insulin treated ones. CONCLUSION Hyperinsulinemia and hyperglicemia influence in negative way the proliferative activity of diabetic women, likely inducing the expression of transforming growth factor beta, despite the high serum levels of Insulin-like growth factor and estrogen.
Serum angiogenin is not elevated in patients with early B‐cell chronic lymphocytic leukemia but is prognostic factor for disease progression

Abstract: The association between angiogenin and cancer progression and poor outcome in solid tumors has been documented, but its significance in leukemias has not been evaluated. Using an ELISA technique (Quantikine Human Angiogenin Immunoassay; R&D Systems), we measured serum angiogenin levels in 77 previously untreated Binet stage A B‐cell chronic lymphocytic leukemia (CLL) patients. No difference in angiogenin serum levels could be found between patients (median: 295 ng/mL; range: 74–1700) and 15 age‐ and sex‐matched healthy controls (median: 264 ng/mL; range: 29–1835) (P = NS; Mann–Whitney test). Increased angiogenin serum level was associated with higher LDH (P = 0.03) and β2‐m (P = 0.007) concentrations. However, angiogenin did not reflect the extent of bone marrow (BM) angiogenesis as evaluated by microvessel area (P = 0.611), circulating levels of vascular endothelial growth factor (VEGF) (P = 0.873) and basic fibroblastic growth factor (FGF‐2) (P = 0.421). When the 25 patients with available data were stratified into the four major cytogenetic categories (normal karyotype, 13q as a sole aberration, 12q trisomy, 11q or 17p deletion) and aberrations were compared with angiogenin serum levels, no correlation was found (P = 0.651; Kruskall–Wallis test). A cut‐off of angiogenin serum level corresponding to median (i.e. 330 ng/mL) or higher identified later upstaging and longer progression‐free survival (PFS). The 5‐yr PFS was 51.5% for patients with angiogenin levels lower than median and 85% for patients with higher values [P = 0.03; hazard ratio (HR) = 2.86; 95% CI: 1.08–6.72]. Although in multivariate analysis only Rai substages (P = 0.00001) and peripheral blood lymphocytosis (P = 0.009) retained their prognostic significance, angiogenin could be incorporated into the Rai substages thus leading to the identification of the following risk categories: (i) stage 0 (angionenin >330 ng/mL); (ii) stage 0 (angiogenin <330 ng/mL) + stage I–II (angiogenin >330 ng/mL); and (iii) stage I–II (angiogenin <330 ng/mL). The 40‐month PFS were as follows: 85%, 65%, 25% (χ2 for trend = 6.33; d.f. = 1; P = 0.01). In conclusion, serum angiogenin levels although not increased in comparison with healthy controls, may predict clinical outcome of patients with early CLL and help to refine Rai's stratification.
Intermittent Fasting Promotes Bacterial Clearance and Intestinal IgA Production in Salmonella typhimurium‐Infected Mice

The impact of intermittent fasting versus ad libitum feeding during Salmonella typhimurium infection was evaluated in terms of duodenum IgA levels, bacterial clearance and intestinal and extra‐intestinal infection susceptibility. Mice that were intermittently fasted for 12 weeks or fed ad libitum were infected with S. typhimurium and assessed at 7 and 14 days post‐infection. Next, we evaluated bacterial load in the faeces, Peyer's patches, spleen and liver by plate counting, as well as total and specific intestinal IgA and plasmatic corticosterone levels (by immunoenzymatic assay) and lamina propria IgA levels in plasma cells (by cytofluorometry). Polymeric immunoglobulin receptor, α‐ and J‐chains, Pax‐5 factor, pro‐inflammatory cytokine (tumour necrosis factor‐α and interferon‐γ) and anti‐inflammatory cytokine (transforming growth factor‐β) mRNA levels were assessed in mucosal and liver samples (by real‐time PCR). Compared with the infected ad libitum mice, the intermittently fasted infected animals had (1) lower intestinal and systemic bacterial loads; (2) higher SIgA and IgA plasma cell levels; (3) higher mRNA expression of most intestinal parameters; and (4) increased or decreased corticosterone levels on day 7 and 14 post‐infection, respectively. No contribution of liver IgA was observed at the intestinal level. Apparently, the changes following metabolic stress induced by intermittent fasting during food deprivation days increased the resistance to S. typhimurium infection by triggering intestinal IgA production and presumably, pathogen elimination by phagocytic inflammatory cells.
Prediction of instability in distal radial fractures.

BACKGROUND Effective methods of treating an unstable distal radial fracture are described in the literature, but there is no reliable method of identifying an unstable fracture in time to initiate appropriate treatment. The purposes of this study were to identify the predictors of fracture instability and to construct a method of prospectively predicting the radiographic outcome. METHODS Data on approximately 4000 distal radial fractures were prospectively recorded over a 5.5-year period. The database was validated by reexamining a sample of it. Demographic data on the patients and mode of injury, as well as the fracture classification and measurements, were recorded at the time of presentation. Outcome measures consisted of radiographic measurements made at one week and six weeks and assessment of carpal alignment at six weeks. Univariate and multiple logistic regression analyses were performed to identify the significance of the data obtained at presentation in the prediction of early and late instability as well as the risk of malunion and carpal malalignment. RESULTS The predictors of early and late instability and malunion differed according to the displacement of the fracture at presentation. Patient age, metaphyseal comminution of the fracture, and ulnar variance were the most consistent predictors of radiographic outcome. Dorsal angulation was not found to be significant in the prediction of radiographic outcome for displaced fractures. The degree to which the patient was independent was predictive of malunion in minimally displaced and displaced fractures. Formulas that are predictive of each of the seven radiographic outcome measurements were constructed. CONCLUSIONS The study succeeded in identifying the factors that are prognostic of the radiographic outcome for distal radial fractures. Formulas to predict the radiographic outcome were constructed as the independent prognostic significance of these factors was quantified. These formulas can be used to inform the surgeon's decision about the nature of primary treatment of fractures of the distal aspect of the radius. However, they must be validated by further studies before they are used to impact the management of distal radial fractures. LEVEL OF EVIDENCE Prognostic Level I.
A Fast Noniterative Algorithm for Compressive Sensing Using Binary Measurement Matrices

In this paper, we present a new algorithm for compressive sensing that makes use of <italic>binary</italic> measurement matrices and achieves <italic>exact</italic> recovery of ultrasparse vectors in a single pass and without any iterations. Due to its noniterative nature, our algorithm is hundreds of times faster than <inline-formula> <tex-math notation="LaTeX">$\ell _1$</tex-math></inline-formula>-norm minimization and methods based on expander graphs, both of which require multiple iterations. Our algorithm can accommodate nearly sparse vectors, in which case, it recovers an index set of the largest components, and can also accommodate burst noise measurements. Compared to compressive sensing methods that are guaranteed to achieve exact recovery of <italic>all</italic> sparse vectors, our method requires fewer measurements. However, methods that achieve <italic>statistical</italic> recovery, that is, recovery of <italic>almost</italic> all but not all sparse vectors, can require fewer measurements than our method.
Phosphorylation of SNAP-23 Regulates Exocytosis from Mast Cells*

Regulated exocytosis is a process in which a physiological trigger initiates the translocation, docking, and fusion of secretory granules with the plasma membrane. A class of proteins termed SNAREs (including SNAP-23, syntaxins, and VAMPs) are known regulators of secretory granule/plasma membrane fusion events. We have investigated the molecular mechanisms of regulated exocytosis in mast cells and find that SNAP-23 is phosphorylated when rat basophilic leukemia mast cells are triggered to degranulate. The kinetics of SNAP-23 phosphorylation mirror the kinetics of exocytosis. We have identified amino acid residues Ser95 and Ser120 as the major phosphorylation sites in SNAP-23 in rodent mast cells. Quantitative analysis revealed that ∼10% of SNAP-23 was phosphorylated when mast cell degranulation was induced. These same residues were phosphorylated when mouse platelet degranulation was induced with thrombin, demonstrating that phosphorylation of SNAP-23 Ser95 and Ser120 is not restricted to mast cells. Although triggering exocytosis did not alter the absolute amount of SNAP-23 bound to SNAREs, after stimulation essentially all of the SNAP-23 bound to the plasma membrane SNARE syntaxin 4 and the vesicle SNARE VAMP-2 was phosphorylated. Regulated exocytosis studies revealed that overexpression of SNAP-23 phosphorylation mutants inhibited exocytosis from rat basophilic leukemia mast cells, demonstrating that phosphorylation of SNAP-23 on Ser120 and Ser95 modulates regulated exocytosis by mast cells.
Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food‐derived carcinogen

Several molecular changes in colorectal adenomas provide the basis of the adenoma–carcinoma sequence. We investigated the expression of xenobiotic ATP‐binding cassette (ABC) transporters in humans and in ApcMin mice and conducted functional studies estimating the importance of the expression changes. Twenty‐nine adenomas from 21 patients and eight adenomas from four ApcMin mice were analyzed using Western blotting and quantitative Real‐time polymerase chain reaction (RT‐PCR). Adjacent healthy tissue served as control for each polyp. Breast cancer resistance protein (BCRP) was significantly downregulated in human colorectal adenomas (to 28 ± 35% of adjacent healthy tissue). This was in line with data from ApcMin mice adenomas, where downregulation was significant as well (to 58 ± 34%). In parallel, quantitative RT‐PCR showed BCRP mRNA downregulation in human adenomas (to 17 ± 31%). Basal multidrug resistance‐associated protein 2 expression was low and did not change in adenomas; multidrug resistance transporter 1 expression also did not differ between adenomas and healthy tissue. In a functional study, ApcMin mice received radioactively labelled 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐β] pyridine (PhIP), a food colon carcinogen and substrate of BCRP, by oral gavage with analysis of PhIP accumulation and DNA adduct formation 48 hr later. In this setting, we could demonstrate a higher carcinogen concentration in adenomas of ApcMin mice (181 ± 113% of normal tissue) including immunohistochemical detection of PhIP–DNA adducts. We conclude that significant transcriptional downregulation of BCRP/Bcrp leads to higher carcinogen concentrations in colorectal adenomas of mice and men. This might promote the adenoma–carcinoma sequence by higher genotoxic effects. The results indicate a possible role of transporter deficiencies in susceptibility for colon carcinoma.
GABA Agonist "Muscimol" Is Neuroprotective in Repetitive Transient Forebrain Ischemia in Gerbils

The damaging effects from transient forebrain ischemia may be a result of excessive excitability or loss of inhibitory influences. In the brain, GABA acts as the major inhibitory neurotransmitter and its loss may be an important factor leading to delayed neuronal damage in the substantia nigra reticulata (SNr). In this study, we looked at the protective effects of muscimol, a GABA A agonist in a gerbil model of repetitive forebrain ischemia. For cerebral ischemia, we used three episodes of 2 min with a reperfusion period of 1 h between the insults. Histological evaluations were done 7 days after the insult using silver degeneration staining. Muscimol was infused into the third ventricle continuously for 7 days beginning just prior to the insult. There were a total of 20 animals, 12 treated with muscimol and the other 8 serving as controls. At 7 days, there was significant protection in the cortex (P = 0.007), hippocampus [CA1 (P = 0.01), CA4 (P = 0.015)], substantia nigra reticulata (P = 0.007), striatum (P = 0.049), and thalamus (P = 0.012). All statistical comparisons were done using nonparametric tests (Mann-Whitney U test). Our study shows that potentiation of inhibitory mechanisms may be important mechanisms of neuronal protection from the effects of repetitive ischemia and the effects are not limited to the SNr. Further studies are needed to better understand their mechanism of action.
[Expression of Th1/th2 transcription factors and cytokines in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE To study the differentiation of Th1/Th2 on the levels of transcription factors and cytokines production in patients with laryngeal squamous cell carcinoma in peripheral blood mononuclear cells (PBMC). In addition, the relation of p53 and T-bet, GATA3 expression was discussed for understanding the role of T-bet and GATA3 in metastasis. METHOD The gene expression of Th1/Th2 type transcription factors T-bet, GATA3 and cytokines IFN-gamma, IL-4 were determined by RT-PCR and realtime RT-PCR from 49 patients with laryngeal squamous cell carcinoma and 30 normal controls. The expression of p53 was analyzed by immunohistochemistry. RESULT Predominant expression of Th2 type cytokines was detected in 49 laryngeal squamous cell carcinoma patients. The expression rates of T-bet, GATA3, IFN-gamma and IL-4 was 42.86% (21/49), 71.43% (35/49), 26.53% (13/49), 63.27% (33/49) respectively. The expression rates of T-bet and IFN-gamma in patients were lower than in control group (P < 0.05), but the results of GATA3 and IL-4 were opposite (P < 0.05). The similar results were obtained by realtime PCR. The expression of p53 in patients was accompanied with lower expression of T-betmRNA and higher expression of GATA3mRNA. CONCLUSION There is predominant expression of Th2 type transcription factors and cytokines in PBMC of laryngeal squamous cell carcinoma patients. T-bet and GATA3 can be used as reference indicators for the metastasis of laryngeal squamous cell carcinoma.
Circulating microRNAs, potential biomarkers for drug-induced liver injury

Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for ≈30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.
Prediction of intrauterine growth restriction with customised estimated fetal weight centiles

Objectives 1.To determine the value of third trimester customised estimated fetal weight centile ranking in the prediction of infants born with anthropometric features of intrauterine growth restriction (IUGR). 2. To compare the performance of customised centiles with fetal growth velocity in the prediction of IUGR.
Perinatal outcome of pregnancy after GnRH antagonist (ganirelix) treatment during ovarian stimulation for conventional IVF or ICSI: a preliminary report.

BACKGROUND Gonadotrophin-releasing hormone (GnRH) antagonists have been proven safe and effective, with no adverse effects on offspring in animal studies. Careful study of pregnancy outcome in humans is mandatory. METHODS AND RESULTS This preliminary report includes follow-up data of patients treated with the GnRH antagonist, ganirelix, during ovarian stimulation for IVF or ICSI. In total, 333 patients were randomized in a multicentre, double-blind, dose-finding study of ganirelix, at six different doses ranging from 0.0625 to 2 mg. In total, 68 vital intrauterine pregnancies were established that resulted in the birth of 46 singletons, 12 twins and one triplet. Follow-up of the 67 pregnant patients (one subject was lost to follow-up) revealed six miscarriages (9%). Of the 61 subjects with an ongoing pregnancy, two with a singleton pregnancy did not give birth to a live-born infant (one spontaneous abortion in week 19, and one intrauterine death in week 27). The mean gestational age was 39.4 weeks for singleton pregnancies, and 36.6 weeks for multiple pregnancies. In total, 73 infants (33 boys, 40 girls) were born. A birth weight <2500 g was reported for 8.7% and 54.2% of the infants resulting from singleton and twins delivery respectively. One major congenital malformation was diagnosed; a boy with Beckwith-Wiedemann syndrome (exomphalos and macroglossia). Seven minor malformations were reported among five infants. CONCLUSIONS In this first follow-up study, the incidence of adverse obstetrical and neonatal outcome was comparable with reported incidences for IVF-embryo transfer pregnancies.
Dexmedetomidine ameliorates monitored anaesthesia care

Background and Aims: Monitored anaesthesia care (MAC) is meant for procedures under local anaesthesia. Various drugs have been used for this purpose. The recently introduced alpha2 agonist, dexmedetomidine provides "conscious sedation" with adequate analgesia and minimal respiratory depression. Hence, the safety and efficacy of two doses of dexmedetomidine for sedation and analgesia were evaluated. Methods: A total of 90 patients were distributed in three groups of 30 each: Dexmedetomidine 0.5 μg/kg (DL), dexmedetomidine 1.0 μg/kg (DH) and normal saline (C). The initial loading dose was followed by maintenance infusion of 0.2-0.7 μg/kg/h of dexmedetomidine or equivalent volume of saline. Study drug was started at least 15 min before placement of local anaesthesia. Drugs were titrated to a target level of sedation (=3 on Ramsay sedation scale [RSS]). Midazolam 0.02 mg/kg for RSS < 3 and fentanyl 0.5 μg/kg were supplemented as required. The statistical analysis was performed using Chi-square test and mean and anova analysis. Results: In groups DL and DH fewer patients required supplemental midazolam, 56.7% (17/30) and 40% (12/30), compared with control, where 86.7% (26/30)needed midazolam supplements. P = 0.000. Both groups DL and DH required significantly less fentanyl (84.8 and 83.9 μg) versus control (144.2 μg). There was significantly increased ease of achieving and maintaining targeted sedation and analgesia in both dexmedetomidine groups when compared with placebo (P = 0.001). Adverse events observed with dexmedetomidine were bradycardia and hypotension. Conclusions: Dexmedetomidine in the doses studied was considered safe and effective sedative and analgesic for patients undergoing procedures under MAC.
A randomized trial of a multicomponent intervention for adolescent sun protection behaviors.

OBJECTIVE To evaluate a multicomponent primary care-based intervention to increase sun protection behaviors among adolescents. Excessive sun exposure in childhood increases the lifetime risk of melanomas and other forms of skin cancer. Interventions to improve sun protection behaviors in childhood have been based primarily in school and community settings, with little attention to the role of primary care physicians. DESIGN A 2-year randomized controlled trial. SETTING Primary care physician offices and participant homes. PARTICIPANTS Eight hundred nineteen adolescents aged 11 to 15 years. INTERVENTIONS At the study onset and the 12-month follow-up, the adolescents engaged in an office-based expert system assessment of sun protection behaviors followed by brief stage-based counseling from the primary care provider. Participants also received up to 6 expert system-generated feedback reports, a brief printed manual, and periodic mailed tip sheets. Participants randomized to the comparison condition received a physical activity and nutrition intervention. MAIN OUTCOME MEASURE A self-reported composite measure of sun protection behavior. RESULTS A random-effects repeated-measures model indicated a greater adoption of sun protection behaviors over time in the intervention group compared with the control group. The intervention effect corresponded to between-group differences at 24 months in avoiding the sun and limiting exposure during midday hours and using sunscreen with a sun protection factor of at least 15. Secondary analysis indicated that, by 24 months, more adolescents in the intervention group had moved to the action or the maintenance stage of change than those in the control group (25.1% vs 14.9%; odds ratio, 1.74; 95% confidence interval, 1.13-2.68). Sun protection behavior was also found to be positively associated with the completion of more intervention sessions (P = .002). CONCLUSION Primary care counseling coupled with a minimal-intensity expert system intervention can improve adolescents' sun protection behaviors.