Miracle-dz/UniFAR-FTUs huggingface dataset:
Relationship between histologic features, DNA flow cytometry, and clinical behavior of squamous cell carcinomas of the larynx

Flow cytometric analysis of DNA content was done on 133 primary squamous cell carcinomas of the larynx. Overall, 76 tumors (57.1%) were not diploid (aneuploid or tetraploid). The DNA index (DI) was calculated and grouped into three levels. Fiftyseven cases had a DI in a range of 1.85 to 2.15 (44 diploid and 13 tetraploid). The cases were grouped in relation to ploidy, proliferative index, and the tumor‐nodemetastasis (TNM) system. Every group was analyzed with respect to survival rate. Ploidy was related to histocytologic grade. In well‐differentiated tumors (G1) survival rates at 48 months were 41.7% in diploid cases and 27.7% in nondiploid ones (relative risk [RR], 2.01; 95% confidence interval [CI], 0.89, 4.52). In NO cases that underwent surgery, survival rates at 48 months were, respectively, 81.8% and 49.2% (RR, 5.07; 95% CI, 0.76, 33.93). These results suggest that ploidy may be a new independent parameter of prognosis in squamous cell carcinoma of the larynx. This is useful in clinical practice because it allows the clinician to recognize those cases with poorer prognosis among the early tumors at a stage where other prognostic parameters are not yet available.
Quantitative measurement of translesion replication in human cells: Evidence for bypass of abasic sites by a replicative DNA polymerase

Mutations in oncogenes and tumor suppressor genes are critical in the development of cancer. A major pathway for the formation of mutations is the replication of unrepaired DNA lesions. To better understand the mechanism of translesion replication (TLR) in mammals, a quantitative assay for TLR in cultured cells was developed. The assay is based on the transient transfection of cultured cells with a gapped plasmid, carrying a site-specific lesion in the gap region. Filling in of the gap by TLR is assayed in a subsequent bioassay, by the ability of the plasmid extracted from the cells, to transform an Escherichia coli indicator strain. Using this method it was found that TLR through a synthetic abasic site in the adenocarcinoma H1299, the osteogenic sarcoma Saos-2, the prostate carcinoma PC3, and the hepatoma Hep3B cell lines occurred with efficiencies of 92 ± 6%, 32 ± 2%, 72 ± 4%, and 26 ± 3%, respectively. DNA sequence analysis showed that 85% of the bypass events in H1299 cells involved insertion of dAMP opposite the synthetic abasic site. Addition of aphidicolin, an inhibitor of DNA polymerases α, δ, and ɛ, caused a 4.4-fold inhibition of bypass. Analysis of two XP-V cell lines, defective in DNA polymerase η, showed bypass of 89%, indicating that polymerase η is not essential for bypass of abasic sites. These results suggest that in human cells bypass of abasic sites does not require the bypass-specific DNA polymerase η, but it does require at least one of the replicative DNA polymerases, α, δ, or ɛ. The quantitative TLR assay is expected to be useful in the molecular analysis of lesion bypass in a large variety of cultured mammalian cells.
Ablation of Focally Induced Atrial Fibrillation:

Introduction: Focally induced atrial fibrillation (AF) often is due to ectopic activity in the pulmonary veins (PV). Although initial approaches were aimed at ablating only the ectopic foci, more extensive ablation approaches have evolved that isolate all PVs empirically and/or create circumferential ablation lines in the left atrium (LA). These techniques last longer and may be associated with more risks. We retrospectively evaluated the outcome and risks of ablation for focally induced AF in a single‐center patient population.
Itaconic acid production from glycerol using Escherichia coli harboring a random synonymous codon‐substituted 5′‐coding region variant of the cadA gene

Aspergillus terreus cadA, encoding cis‐aconitate decarboxylase, is an essential gene for itaconic acid (IA) biosynthesis, but it is primarily expressed as insoluble aggregates in most industrial hosts. This has been a hurdle for the development of recombinant strategies for IA production. Here, we created a library of synonymous codon variants (scv) of the cadA gene containing synonymous codons in the first 10 codons (except ATG) and screened it in Escherichia coli. Among positive clones, E. coli scvCadA_No8 showed more than 95% of expressed CadA in the soluble fraction, and in production runs, produced threefold more IA than wild‐type E. coli in Luria‐Bertani broth supplemented with 0.5% glucose. In M9 minimal media containing 0.85 g/L citrate and 1% glycerol, E. coli scvCadA_No8 produced 985.6 ± 33.4 mg/L IA during a 72‐h culture after induction with isopropyl β‐D‐1‐thiogalactopyranoside. In a 2‐L fed‐batch fermentation consisting of two stages (growth and nitrogen limitation conditions), we obtained 7.2 g/L IA by using E. coli by introducing only the scv_cadA gene and optimizing culture conditions for IA production. These results could be combined with metabolic engineering and generate an E. coli strain as an industrial IA producer. Biotechnol. Bioeng. 2016;113: 1504–1510. © 2015 Wiley Periodicals, Inc.
Staging of malignant pleural mesothelioma: comparison of CT and MR imaging.

OBJECTIVE This article compares the accuracy of CT with that of MR imaging in staging of malignant pleural mesothelioma. SUBJECTS AND METHODS Ninety-five patients were enrolled in a prospective staging protocol based on the International Mesothelioma Interest Group staging system. Sixty-five patients underwent CT and MR imaging and a surgical procedure (excluding percutaneous needle biopsy) to stage and resect the tumor. Receiver operating characteristic analyses were performed. CT and MR scans were interpreted independently by observers who were unaware of the results of the other imaging study; these imaging findings were compared with the results of surgery and pathologic examination. RESULTS The areas under the receiver operating characteristic curves for eight of 10 features revealed by imaging showed no statistically significant differences between CT and MR imaging. However, MR imaging was superior to CT in revealing invasion of the diaphragm (A(z) = . 55 for CT versus . 82 for MR imaging) and in revealing invasion of endothoracic fascia or solitary resectable foci of chest wall invasion (A(z) = . 46 for CT; A(z) = . 69 for MR imaging). Several anatomic regions could not be evaluated because positive findings at surgery were rare. CONCLUSION CT and MR imaging are of nearly equivalent diagnostic accuracy in staging malignant pleural mesothelioma. MR imaging is superior to CT in revealing solitary foci of chest wall invasion and endothoracic fascia involvement and in showing diaphragmatic muscle invasion; however, this advantage does not affect surgical treatment. For cost reasons, CT should be considered the standard diagnostic study before therapy.
Organochlorine pesticides and polychlorinated biphenyls in 12 edible marine organisms from the Adriatic Sea, Italy, Spring 1997

Edible portions of 12 marine organisms from several areas of the Adriatic Sea, Italy, were collected during Spring 1997 and analysed for 32 organochlorine pesticides residues and 27 polychlorobiphenyl congeners. Only eight organochlorine pesticides—hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) isomers, diphenyl-dichloro-trichloroethane (DDT) group, dieldrin—were determined at levels in the range <0.01–19.88 ng g-1 wet weight, with 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene (DDE) being the more relevant single organochlorine. The contamination by organochlorine pesticides was comparable in organisms from the North, Centre and South Adriatic. Polychlorinated biphenyls (PCBs) were determined at levels in the range <0.05–14.46 ng g-1, with CB 101, 118, 138, 153, 180 and 187 being more relevant (penta-, hexa- and hepta-chlorinated congeners). The sum of PCBs congeners determined were in the range 1.18–69.05 ng g-1. The contamination by PCBs is more relevant in organisms from the North Adriatic Sea owing to the antropic discharge from major rivers such as Po and Adige that flow through highly industrialized and densely populated areas.
Effectiveness of manual therapy for chronic tension-type headache: A pragmatic, randomised, clinical trial

Objective: To evaluate the effectiveness of manual therapy (MT) in participants with chronic tension-type headache (CTTH). Subjects and Methods: We conducted a multicentre, pragmatic, randomised, clinical trial with partly blinded outcome assessment. Eighty-two participants with CTTH were randomly assigned to MT or to usual care by the general practitioner (GP). Primary outcome measures were frequency of headache and use of medication. Secondary outcome measures were severity of headache, disability and cervical function. Results: After 8 weeks (n = 80) and 26 weeks (n = 75), a significantly larger reduction of headache frequency was found for the MT group (mean difference at 8 weeks, −6.4 days; 95% CI −8.3 to −4.5; effect size, 1.6). Disability and cervical function showed significant differences in favour of the MT group at 8 weeks but were not significantly different at 26 weeks. Conclusions: Manual therapy is more effective than usual GP care in the short- and longer term in reducing symptoms of CTTH. Dutch Trial Registration no. TR 1074.
Curcumin Enhances the Anti-Trypanosoma cruzi Activity of Benznidazole-Based Chemotherapy in Acute Experimental Chagas Disease

ABSTRACT Although curcumin can increase the effectiveness of drugs against malaria, combination therapies using the molecule have never been investigated in Chagas disease (ChD). Therefore, we evaluated the efficacy of curcumin as a complementary strategy to benznidazole (Bz)-based chemotherapy in mice acutely infected with Trypanosoma cruzi. Eighty-four 12-week-old Swiss mice were equally randomized into seven groups: uninfected (NI), T. cruzi infected and untreated (INF), infected and treated with 100 mg/kg of body weight Bz (B100), 50 mg/kg Bz (B50), 100 mg/kg curcumin (C100), 100 mg/kg Bz plus 100 mg/kg curcumin (B100 plus C100), and 50 mg/kg Bz plus 100 mg/kg curcumin (B50 plus C100). After microscopic identification of blood trypomastigotes (4 days after inoculation), both drugs were administered by gavage once a day for 20 days. Curcumin showed limited antiparasitic, anti-inflammatory, and antioxidant effects when administered alone. When curcumin and Bz were combined, there was a drastic reduction in parasitemia, parasite load, mortality, anti-T. cruzi IgG reactivity, circulating levels of cytokines (gamma interferon [IFN-γ], interleukin 4 [IL-4], and MIP1-α), myocardial inflammation, and morphological and oxidative cardiac injury; these results exceeded the isolated effects of Bz. The combination of Bz and curcumin was also effective at mitigating liver toxicity triggered by Bz, increasing the parasitological cure rate, and preventing infection recrudescence in noncured animals, even when the animals were treated with 50% of the recommended therapeutic dose of Bz. By limiting the toxic effects of Bz and enhancing its antiparasitic efficiency, the combination of the drug with curcumin may be a relevant therapeutic strategy that is possibly better tolerated in ChD treatment than Bz-based monotherapy.
Necrotizing soft tissue infections: obstacles in diagnosis.

BACKGROUND This study was done to identify obstacles in the early diagnosis and treatment of necrotizing soft tissue infections. STUDY DESIGN A ten-year retrospective case series was analyzed. RESULTS Data from 29 patients were analyzed. Among patients undergoing early operation within 24 hours of admission (n = 17) there was one death (6 percent mortality rate); survivors averaged 2.9 operations per patient. By comparison, of patients with delayed operation (n = 12) three died (25 percent mortality rate) and there were 3.6 operations per patients. Positive fine-needle aspiration (FNA) of suspicious lesions, demonstrating either pus or bacteria by Gram's stain, led to early operation in 80 percent of patients tested. Patients with soft tissue gas on radiographs were more likely to undergo early operation (58 percent). Delayed operation was more common in the absence of radiographic findings. All patients admitted to nonsurgical services had delayed operations. CONCLUSIONS Suspected necrotizing soft tissue infections require prompt surgical evaluation and early operative exploration. Early operation with definitive surgical therapy initiated within 24 hours of admission is associated with decreased mortality rates. Negative FNA findings, nondiagnostic radiographs, and admission to a nonsurgical service correlate with delay in definitive operative intervention.
Optimization of culture media to enhance the growth of tissue engineered cartilage

Tissue engineering is a promising option for cartilage repair. However, several hurdles still need to be overcome to develop functional tissue constructs suitable for implantation. One of the most common challenges is the general low capacity of chondrocytes to synthesize cartilage‐specific extracellular matrix (ECM). While different approaches have been explored to improve the biosynthetic response of chondrocytes, several studies have demonstrated that the nutritional environment (e.g., glucose concentration and media volume) can have a profound effect on ECM synthesis. Thus, the purpose of this study was to optimize the formulation of cell culture media to upregulate the accumulation of cartilaginous ECM constituents (i.e., proteoglycans and collagen) by chondrocytes in 3D culture. Using response surface methodology, four different media factors (basal media, media volume, glucose, and glutamine) were first screened to determine optimal media formulations. Constructs were then cultured under candidate optimal media formulations for 4 weeks and analyzed for their biochemical and structural properties. Interestingly, the maximal accumulation of proteoglycans and collagen appeared to be elicited by different media formulations. Most notably, proteoglycan accumulation was favored by high volume, low glucose‐containing DMEM/F12 (1:1) media whereas collagen accumulation was favored by high volume, high glucose‐containing F12 media. While high glutamine‐containing media elicited increased DNA content, glutamine concentration had no apparent effect on ECM accumulation. Therefore, optimizing the nutritional environment during chondrocyte culture appears to be a promising, straight‐forward approach to improve cartilaginous tissue formation. Future work will investigate the combined effects of the nutritional environment and external stimuli.
Safety and efficacy of silicone rod frontalis suspension surgery for childhood ptosis repair.

PURPOSE To evaluate the safety and efficacy of silicone rod frontalis suspension surgery for childhood ptosis. METHODS The authors retrospectively studied 89 consecutive children (110 eyelids) who had silicone rod frontalis suspension surgery for ptosis at Duke University Eye Center from 1983 to 2004. Marginal reflex distance1 (MRD1) elevation of 2 mm or more (vs preoperative MRD1) was considered satisfactory. MRD1 was measured as the vertical distance from the corneal light reflex in primary gaze to the upper eyelid margin. The postoperative eyelid symmetry (< or = 1 mm = satisfactory) was the difference between the MRD1 of the surgical and fellow eyelid. RESULTS Median age at surgery was 45 months (range: 3 to 223 months) and median follow-up was 17 months (range: 1 to 88 months). Ptosis types (number of eyelids) were unilateral congenital (53), bilateral congenital (30), third nerve palsy (16), Marcus Gunn jaw wink (7), trauma (2), and myasthenia gravis (2). Median MRD1 elevation was 2 mm or greater for all ptosis types, whereas satisfactory postoperative symmetry occurred in 60% of unilateral and 100% of bilateral congenital ptosis cases (last follow-up). Complications occurred in 10 eyelids (9%) and reoperation occurred in 10 eyelids (9%). CONCLUSION The use of silicone rod frontalis suspension surgery for ptosis repair in pediatric patients is modestly effective, with few complications and easy removal and adjustment.
Efficacy of Mannheim Peritonitis Index (MPI) Score in Patients with Secondary Peritonitis.

BACKGROUND Despite advances in diagnosis, management and critical care of patients with peritonitis due to hollow viscus perforation, prognosis remains poor. Early assessment by scoring systems will influence the management and prognosis. AIM Evaluation of Mannheim Peritonitis Index (MPI) score for predicting the outcome in patients with peritonitis. MATERIALS AND METHODS Prospective study of 50 patients admitted and operated for peritonitis in JSS Medical College Hospital. The structured scoring system i.e. MPI was applied along with other clinical and biochemical parameters recorded in pre-structured proforma. Data was analysed for predicting mortality and morbidity using EPI info and SPSS software. RESULTS The overall mortality and morbidity was 14% and 38% respectively. MPI scores of ≤ 20, 21-29, and ≥ 30 had a mortality of 5%, 14%, and 50% respectively. MPI score of 25 had highest sensitivity of 72.09% and specificity of 71.43% in predicting mortality, 80.65% sensitivity and 57.89% specificity for morbidity. MPI score of > 25 were associated with 6.45 times higher risk of mortality (p=0.03), 5.72 times higher risk of morbidity (p=0.005) compared to patients with MPI score ≤ 25. CONCLUSION MPI is disease specific, easy scoring system for predicting the mortality in patients with secondary peritonitis. Increasing scores are associated with poorer prognosis, needs intensive management and hence it should be used routinely in clinical practice.
Guidelines in cardiac clinical practice: evaluation of their methodological quality using the AGREE II instrument

Although clinical guidelines have an influential role in healthcare practice, their development process and the evidence they cite has been subject to criticism. This study evaluates the quality of guidelines in cardiac clinical practice by examining how they adhere to validated methodological standards in guideline development. A structured review of cardiac clinical practice guidelines published in seven cardiovascular journals between January 2001 and May 2011 was performed. The AGREE II assessment tool was used by two researchers to evaluate guideline quality. A total of 101 guidelines were identified. Assessment of guidelines using AGREE II found methodological quality to be highly variable (median score, 58.70%; range, 45.34–76.40%). ‘Scope and purpose’ (median score, 86.1%) and ‘clarity of development’ (median score, 83.3 %) were the two domains within AGREE II that received the highest scores. Applicability (median score, 20.80%; range, 4.20–54.20%) and editorial independence (median score, 33.30%; range, 0–62.50%) had the lowest scores. There is considerable variability in the quality of cardiac clinical practice guidelines and this has not improved over the last 10 years. Incorporating validated guideline assessment tools, such as AGREE II, may improve the quality of guidelines.
Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage caused by liver and cerebral ischaemia‐reperfusion in rats

Tissue ischaemia‐reperfusion evokes toxic and harmful biochemical processes such as oxidative stress and inflammation. The aim of this study is to investigate the indices of tissue damage in rat liver and brain after ischaemia‐reperfusion injury of these organs, and to study prospective cytoprotection of molecules such as the novel anti‐inflammatory N‐(2‐thiolethyl)‐2‐{2‐[N′‐(2,6‐dichlorophenyl) amino] phenyl}acetamide (compound 1) and α‐tocopherol. Two experimental models were studied: firstly, 30 min liver ischaemia via hepatoduodenal ligament clamping followed by 60 min reperfusion; and secondly, 45 min cerebral ischaemia via bilateral common carotid artery occlusion followed by 90 min reperfusion. Compound 1 and α‐tocopherol were administered intraperitoneally before induction of ischaemia. We hereby report that compound 1, a molecule that combines potent in‐vitro antioxidant and in‐vivo anti‐inflammatory activity with low gastrointestinal toxicity, offered protection in‐vivo against liver or brain ischaemia‐reperfusion‐induced damage. Both compound 1 and α‐tocopherol prevented changes in lipid peroxidation in the rat liver and brain tissue and in tumour necrosis factor (TNF‐α) levels in brain. Also compound 1 attenuated glutathione depletion, evoked by ischaemia‐reperfusion, in the rat brain but not in the liver. These results could be explained on the basis of the antioxidant/anti‐inflammatory properties of compound 1 and suggest its beneficial effect and potential therapeutic use in post‐ischaemic injury.
Inhibition of Innate Co‐Receptor TREM‐1 Signaling Reduces CD4+ T Cell Activation and Prolongs Cardiac Allograft Survival

The innate receptor “triggering‐receptor‐expressed‐on‐myeloid‐cells‐1” (TREM‐1) enhances downstream signaling of “pattern recognition receptor” (PRR) molecules implicated in inflammatory responses. However the mechanistic role of TREM‐1 in chronic heart rejection has yet to be elucidated. We examined the effect of TREM‐1+ antigen‐presenting cells (APC) on alloreactive CD4+ lymphocytes. Bm12 donor hearts were transplanted into wild‐type MHC‐class‐II‐mismatched C57BL/6J recipient mice. Progressive allograft rejection of bm12‐donor hearts with decreased organ function, severe vasculopathy and allograft fibrosis was evident within 4 weeks. TREM‐1+CD11b+MHC‐II+F4/80+CCR2+ APC and IFNγ‐producing CD4+ cells were detected during chronic rejection. Peptide inhibition of TREM‐1 attenuated graft vasculopathy, reduced graft‐infiltrating leukocytes and prolonged allograft survival, while being accompanied by sustained low levels of CD4+ and CD8+ cell infiltration. Remarkably, temporary inhibition of TREM‐1 during early immune activation was sufficient for long‐term allograft survival. Mechanistically, TREM‐1 inhibition leads to reduced differentiation and proliferation of IFNγ‐producing Th1 cells. In conclusion, TREM‐1 influences chronic heart rejection by regulating the infiltration and differentiation of CD4+ lymphocytes.
Acute effects of smoking on right ventricular function. A tissue Doppler imaging study on healthy subjects.

BACKGROUND Smoking is a risk factor for cardiovascular mortality and morbidity. Besides chronic effects, it has unfavourable effects in the acute period. Although there are plenty of data regarding its effect on left ventricle functions, the effect of cigarette smoking on right ventricular function in the acute period is unknown. The objective of this study was to investigate the effect of cigarette smoking on the right ventricular function. METHODS Twenty healthy young male were evaluated by echocardiography before and after smoking one cigarette. Heart rate, blood pressure, mitral and tricuspid inflow parameters as well as annulus velocity parameters were obtained. Pulmonary artery acceleration time was measured as a surrogate marker for pulmonary artery pressure. Results at baseline and at minutes 5, 15, 30, 60; consecutively after smoking were compared. RESULTS There was not any significant change at left ventricular diastolic function with pulsed wave Doppler echocardiography, however right ventricular diastolic function was significantly impaired. Both right and left ventricle diastolic functions were impaired significantly with tissue Doppler echocardiography though there was no change at systolic functions. Pulmonary artery pressure increased significantly concomitant with impairment of right ventricular diastolic dysfunction. All the changes seen after smoking a cigarette almost returned to baseline levels after 30 minutes. CONCLUSIONS Cigarette smoking does not change right ventricular systolic function however impairs right ventricular diastolic function in the acute period. Its effect on diastolic function may be related to increased afterload due to increase in pulmonary artery pressure.