Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal growth factor receptor mutations in lung cancers

In 2004, two groups reported somatic mutations in the gene for the epidermal growth factor receptor (EGFR) in patients with non‐small cell lung cancer (NSCLC), which were highly correlated with the clinical response to the anticancer drug, gefitinib. Since then, a tremendous amount of knowledge has accumulated, and sheds light on significant oncological properties as well as the clinical relevance of this mutation, which could be applicable to other malignancies. The EGFR mutations are distributed throughout the kinase domain, but a deletion in exon 19 and the point mutation L858R in exon 21 account for approximately 90%, which confer a greater response to gefitinib treatment, compared with other types of EGFR mutations. These EGFR mutations in the tyrosine kinase domain are seldom acquired in cancers of the other organs and the mutations preferentially involve a subset of lung cancers, which are clinicopathologically characterized by female sex, non‐smoking, adenocarcinoma histology and East Asian ethnicity. In Japan, the EGFR mutations are detected in approximately 30% of overall NSCLC and approximately 40% of surgically resected adenocarcinomas. The morphological features of adenocarcinomas harboring the mutations were reported to be frequent in those with bronchioloalveolar features, but it is suggested that the cellular lineage of the putative original cells of the cancers refines the subset more clearly. In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research.
The correlation between the endometrial integrins and osteopontin expression with pinopodes development in ovariectomized mice in response to exogenous steroids hormones.

BACKGROUND The ovariectomized animals are good models to evaluate the effect of different steroid hormone treatments on implantation events and the pattern of integrin expression. Therefore, this study was performed to compare the expression of integrins and osteopontin (OPN) in correlation with pinopode development in ovariectomized mice endometrium which was subjected to steroid hormones. METHODS Ovariectomized mice were subjected to estrogen, progesterone and estrogen-progesterone hormones. Their uterine horns were evaluated for integrin expression by immunohistochemistry and real-time RT-PCR and for pinopode development by transmission and scanning electron microscopic studies. RESULTS No immunostaining for integrin and OPN molecules were detected in the endometrium of non-ovariectomized mice except in metestrus phase. The α4 and β1 integrin genes were expressed in all phases of estrous cycle. In ovariectomized mice, no reaction was detected in the endometrium of control, sham and estrogen-treated groups, but in both progesterone-treated groups, all examined genes were expressed. There was not any correlation between pinopodes and integrin expression in ovariectomized mice. CONCLUSION The progesterone is more effective on endometrial integrin expression than estrogen and differences in the expression pattern of integrins reflect their important and different roles in embryo implantation. The pinopodes may have minor effect in mice implantation or have some delay in their expressions in ovariectomized mice which were subjected to exogenous hormones.
Safety of Peritoneal Dialysis after Nonrenal Solid-Organ Transplantation

Background: End-stage renal disease is a well-known complication after solid-organ transplantation, mostly as a result of calcineurin-inhibitor therapy. Among recipients of solid-organ transplants other than kidneys, peritoneal dialysis (PD) has been considered an accessory technique as an increased risk of infectious complications has been reported. The aim of our study was to evaluate the outcome of patients with a liver, heart, or lung transplant who underwent PD for replacement therapy. Methods: This was a retrospective, monocentric study. Every adult patient starting PD between January 1, 2001, and December 31, 2016, at our center was included. The history of previous solid-organ transplantation was determined. For the statistical analysis, we considered 2 groups of patients: 1 group having a history of transplantation of an organ other than the kidney (lung, heart, liver), and 1 group that was starting dialysis without any prior history of organ transplantation. Patients who had previously undergone kidney transplantation were excluded. The events of interest were the first peritonitis episode, death, and PD failure, defined as transfer to hemodialysis. Results: A total of 383 patients started PD during this period, 13 of whom had a history of organ transplantation. We found no significant difference between the solid-organ transplantation patients and those without a history of transplantation in terms of the occurrence of peritonitis (HR [hazard ratio] 0.91 [0.37 – 2.22]), death (HR 0.83 [0.26 – 2.63]), and PD failure (HR 1.01 [0.32 – 3.22]). Conclusion: Peritoneal dialysis appears to be an effective replacement therapy for patients with a previous history of solid-organ transplantation.
The role of antisecretory drugs in the treatment of Helicobacter pylori infection

The efficacy of antibiotics against Helicobacter pylori is enhanced by the co‐administration of antisecretory drugs. While proton pump inhibitors appear to have some direct effect on H. pylori and extreme hypochlorhydria has a deleterious effect on the organism, the most likely mechanism by which antisecretory drugs as a class provide this effect is by improving the efficacy of the antibiotics themselves. Although proton pump inhibitors are the most widely used antisecretory agents, H2 receptor antagonists also enhance antibiotic effects.
Role of 3 Lipoprotein Lipase Variants in Triglycerides in Children Receiving Highly Active Antiretroviral Therapy

Background: Lipoprotein lipase is a key enzyme in lipid metabolism, especially for plasma triglycerides (TGs). Genetic variants have been associated with lipid levels in healthy individuals, cardiovascular disease, obesity and diabetes. Our aim was to evaluate the influence of 3 polymorphisms: Hind III, Pvu II and S447X in plasma TG levels in human immunodeficiency virus-1-infected children under highly active antiretroviral therapy (HAART). Methods: Fifty-two children diagnosed with human immunodeficiency virus-1 between 2005 and 2009 were retrospectively selected with at least 1 plasma TG level assessment. TG levels were examined before and after 1 year of HAART. Hypertriglyceridemia was defined as TG > 150 mg/dL. Hind III (H+/H−), Pvu II (P+/P−) and S447X (S/X) were determined by polymerase chain reaction and restricted fragment length polymorphism. The Wilcoxon sum-rank test was used to compare median plasma TG among groups. Also, allelic frequencies were estimated for these variants in an Argentinean population. Results: Allelic frequencies for human immunodeficiency virus-1-infected children were: H−, 0.21; P−, 0.53; and X, 0.05 with no significant differences to controls. After 1 year of HAART, median TG levels were significantly lower in P−/P− (98.5 mg/dL) when compared with P+/P+ (180 mg/dL) (P = 0.039). The presence of the P− allele was associated with an 11-fold lower risk of hypertriglyceridemia. Hind III and S447X were not associated with TG at the selected time points. Conclusions: Our findings suggest a protective effect of lipoprotein lipase polymorphisms against hypertriglyceridemia in children after 1 year of HAART. These results could endorse a prompt nutritional or pharmacological intervention in patients lacking the P− allele.
Self-aligned growth of single-walled carbon nanotubes using optical near-field effects

Self-aligned growth of ultra-short single-walled carbon nanotubes (SWNTs) was realized by utilizing optical near-field effects in a laser-assisted chemical vapor deposition (LCVD) process. By introducing the optical near-field effects, bridge structures containing single suspended SWNT channels were successfully fabricated through the LCVD process at a relatively low substrate temperature. Raman spectroscopy and I–V analyses have been carried out to characterize the SWNT-bridge structures. Numerical simulations using a high-frequency structure simulator revealed that significant enhancement of local heating occurs at metallic electrode tips under laser irradiation; it is about one order of magnitude higher than that in the rest of the electrodes. This technique suggests a novel approach to in situ low-temperature fabrication of SWNT-based devices in a precisely controlled manner, based on the nanoscale heating enhancement induced by the optical near-field effects.
Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma.

PURPOSE The purpose of this study was to evaluate the impact of carboplatin and paclitaxel in patients with advanced previously untreated thymoma and thymic carcinoma. PATIENTS AND METHODS We conducted a prospective multicenter study in patients with unresectable thymoma (n = 21) or thymic carcinoma (n = 23). Patients were treated with carboplatin (area under the curve, 6) plus paclitaxel (225 mg/m(2)) every 3 weeks for a maximum of six cycles. The primary end point of this trial was to evaluate the objective response rate. RESULTS From February 2001 through January 2008, 46 patients were enrolled. Thirteen patients had grade 4 or greater toxicity, mostly neutropenia. Using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria, three complete responses (CRs) and six partial responses (PRs; objective response rate [ORR], 42.9%; 90% CI, 24.5% to 62.8%) were observed in the thymoma cohort; 10 patients had stable disease. For patients with thymic carcinoma, no CRs and five PRs (ORR, 21.7%; 90% CI, 9.0% to 40.4%) were observed; 12 patients had stable disease. Progression-free survival (PFS) was 16.7 (95% CI, 7.2 to 19.8) and 5.0 (95% CI, 3.0 to 8.3) months for thymoma and thymic carcinoma cohorts, respectively. To date, only seven patients (33.3%) with thymoma have died, compared with 16 patients (69.6%) with thymic carcinoma. Median survival time was 20.0 months (95% CI, 5.0 to 43.6 months) for patients with thymic carcinoma, but it has not been reached for patients with thymoma. CONCLUSION Carboplatin plus paclitaxel has moderate clinical activity for patients with thymic malignancies, but this seems less than expected with anthracycline-based therapy. Patients with thymic carcinoma have poorer PFS and overall survival than patients with thymoma.
Unraveling Process Evolution by Handling Concept Drifts in Process Mining

Business processes change over time in response to changing circumstances, it is crucial for process managers to discover and understand such changes from event logs. While existing techniques in process mining cannot efficiently detect and locate concept drifts in uncompleted event logs. Hence, an appropriate method, which could prompt to unravel the process evolution, may greatly assist organizations to manage the flexibility and change of business processes in the context of business process management (BMP). In this paper, we first proposed an extensible feature and employed it with the sliding window technique and heuristic miner for detecting and locating concept drifts in uncompleted event logs. Then, Genetic Process Mining (GPM) was improved by the Weight Heuristic Miner (WHM) and Differential Evolution (DE) for mining the new process model of an evolving process. Finally, experimental results on four event logs which are created based on a real-world business process have validated the proposed method.
III-V heterostructure based three terminal thermal rectifier

A novel three terminal nano-rectifier which utilizes dissipated thermal energy to produce electrical signals is designed and analyzed. The device is simulated using different models including standard mobility model, negative differential mobility model and energy balance model. The electrical (DC and RF) performances of the rectifier have been obtained at room temperature in push-fixed configuration at the input terminals. Due to the planar architecture, device exhibits less parasitic capacitance enabling very high speed operation. The results demonstrate velocity saturation effect at nanoscale affecting the device performances.
Cemented or uncemented hemiarthroplasty for the treatment of femoral neck fractures?

Sir—We read with interest the article by Yli-Kynyy et al. (2014) on the use of cemented versus cementless hemiarthroplasty in the treatment of femoral neck fractures. However, we would like to know some aspects of the study which would be of help to orthopedic surgeons. The authors found an increased mortality rate directly related to the use of cemented hemiarthroplasty and fat embolus syndrome in their study. However, the mortality after hip fracture is multifactorial including operative delay (Ratcliff et al. 2008). In the present study the time of the fracture event and start of the surgical intervention were not presented. The second point is that hip fracture is associated with a substantial increase in mortality with co-existing chronic renal failure (Karaeminogullari et al. 2007). We found no information about the co-existence of renal disease.
Evaluating Cellular Impedance Assays for Detection of GPCR Pleiotropic Signaling and Functional Selectivity

G-protein—coupled receptors can couple to different signal transduction pathways in different cell types (termed cell-specific signaling) and can activate different signaling pathways depending on the receptor conformation(s) stabilized by the activating ligand (functional selectivity). These concepts offer potential for developing pathway-specific drugs that increase efficacy and reduce side effects. Despite significant interest, functional selectivity has been difficult to exploit in drug discovery, in part due to the burden of multiple assays. Cellular impedance assays use an emerging technology that can qualitatively distinguish Gs, Gi/o, and Gq signaling in a single assay and is thereby suited for studying these pharmacological concepts. Cellular impedance confirmed cell-specific Gs and Gq coupling for the melanocortin-4 receptor and dual Gi and Gs signaling with the cannabinoid-1 (CB1) receptor. The balance of Gi versus Gs signaling depended on the cell line. In CB1-HEKs, Giand Gs-like responses combined to yield a novel impedance profile demonstrating the dynamic nature of these traces. Cellspecific signaling was observed with endogenous D1 receptor in U-2 cells and SK-N-MC cells, yet the pharmacological profile of partial and full agonists was similar in both cell lines. We conclude that the dynamic impedance profile encodes valuable relative signaling information and is sufficiently robust to help evaluate cell-specific signaling and functional selectivity. (Journal of Biomolecular Screening 2009:246-255)
Daily Singing Practice as a Means of Improving Pulmonary Function and Quality of Life in Emphysema Patients

Introduction: The purpose of this study was to determine if 10 minutes of singing every day might lead to improved pulmonary function and quality of life in chronic obstructive pulmonary disease (COPD) patients. Singing requires a controlled and precise use of respiratory musculature suggesting its daily use as a rehabilitation tool could help reduce respiratory symptoms. Materials and Methods: This was a quasi-experimental pre–post test designed study lasting 12 weeks. The Springfield Committee for Research Involving Human Subjects approved the study, and all patients were provided written informed consent. Measurements were taken for actual and perceived respiratory function and quality of life. There were 25 patients who completed the study. All patients were enrolled in a rehabilitation program at a Phase 3 status. Patients were given an instructor-led demonstration as well as a pamphlet that guided them through a series of breathing and vocal warm-ups which, upon completion, they followed with singing a song. This process took approximately five minutes and was done morning and evening. Results: Results for the study showed no mean changes beyond standard deviation in any of the measurements taken both in lung function and in quality of life. However, there was a statistically significant decrease in the Borg fatigue rating with a mean at baseline of 8.88+/-3.76 and 7.60+/-2.61 at follow-up (p=0.04).
Efficacy of the GemOx‐R regimen leads to the identification of Oxaliplatin as a highly effective drug against Mantle Cell Lymphoma

Mantle Cell Lymphoma (MCL) is an aggressive lymphoma subtype that accounts for 6–8% of non‐Hodgkin lymphomas. The disease is mostly incurable and characterized by a continuous pattern of relapse. Major changes have recently been implemented in the management of MCL, but continuous relapses still mark this disease as a challenge for clinicians. We previously reported the efficacy of GemOx‐R (Gemcitabine, Oxaliplatin and Rituximab) in patients with refractory and relapsing MCL. We present results for a larger series with longer follow‐up and including high‐risk frontline patients, showing an overall response rate of 83%. The efficacy of each component of GemOx‐R was evaluated in a panel of MCL cell lines. Also, patient‐derived primary cells were used in ex vivo experiments. The results show that oxaliplatin has a profound effect on cellular viability and is the most effective drug within this regimen. We further present synergistic efficacy of oxaliplatin combined with cytarabine in MCL cells. Interestingly, this synergistic effect was not seen when cisplatin and cytarabine were combined, indicating that among the platinum‐derived agents oxaliplatin may be the preferred approach. Taken together our findings suggest that oxaliplatin alone or combined with cytarabine could constitute an alternative backbone for MCL regimens.
Mast cell chymase and tryptase during tissue turnover: analysis on in vitro mitogenesis of fibroblasts and keratinocytes and alterations in cutaneous scars

Abstract: In order to shed further light on the potential role of mast cells during tissue turnover, we have investigated the number of mast cells containing only tryptase and those storing both tryptase and chymase by enzyme histochemistry in normal versus healing skin. Furthermore, we have studied the in vitro effect of these enzymes on the mitogenesis of subconfluent quiescent fibroblast and HaCaT keratinocyte cultures, using flowcytometric DNA analysis. Chymase‐containing mast cell numbers were markedly decreased in scars (P<0.001), whereas the overall number of tryptase‐containing mast cells was not decreased, although these cells were smaller and stained more faintly in scars. Chymase (5 to 300 mU/ml) induced a marked, dose‐dependent in vitro mitogenic response in 3T3 fibroblasts, whereas the effects of tryptase, at up to 60 nM, were only moderate, compared to the known fibroblast mitogens EGF, TGF‐α, α‐thrombin and trypsin at optimal concentrations. Coincubation of either protease with EGF or α‐thrombin had additive effects. In contrast to fibroblasts, keratinocytes showed only minor mitogenic responses to tryptase and chymase, also in comparison to other known mitogenic stimuli, and responses to EGF and α‐thrombin were inhibited on costimulation of cells with the proteases. These findings document for the first time a potential role of mast cell chymase in connective tissue repair, with tryptase being less active on fibroblasts, and with inhibitory effects of both mast cell proteases on keratinocytes.
A Randomized, Evaluator‐Blinded, Two‐Center Study of the Safety and Effect of Volume on the Diffusion and Efficacy of Botulinum Toxin Type A in the Treatment of Lateral Orbital Rhytides

BACKGROUND There has been considerable discussion about the effect of the degree of dilution of botulinum toxin (BTX) but very few scientific studies. OBJECTIVE The objective was to observe as to whether a fivefold difference in concentration of BTX solution would produce a difference in clinical effect or duration of effect. METHODS AND MATERIALS Twenty individuals were enrolled at two sites and a within-subject paired-comparison study was performed on the lateral orbital area with a single injection of 5 U of BTX (BOTOX Cosmetic, Allergan Inc., Irvine, CA). The results were assessed both clinically and using a computer-assisted estimation of the degree of wrinkling. RESULTS No statistically significant differences were observed between the two sides. CONCLUSIONS This is a small study and it may be that dilution does affect BTX result. We were, however, unable to detect any difference in this study, which suggests that the degree of dilution, at least within a fivefold margin, has only a small effect on the results of BTX injection in the lateral orbital area.
Psychiatric Emergency Services in a Canadian City: I. Prevalence and Patterns of Use *

The patterns of use of psychiatric emergency services in Saskatoon, Saskatchewan were studied. A total of 576 patients who had received psychiatric emergency care from any of the four major health care facilities in Saskatoon during a three month period were included in the study. Visits for psychiatric emergency services during the study period represented 2.32% of the total number of visits to emergency facilities. Most patients with psychiatric emergencies went to hospitals with psychiatric units. The characteristics of patients served by the four facilities and those who visited the psychiatric emergency services on more than one occasion during the study period are reported. The implications of these findings for health care planning are discussed.
A doughnut‐shaped heteromer of human Sm‐like proteins binds to the 3′‐end of U6 snRNA, thereby facilitating U4/U6 duplex formation in vitro

We describe the isolation and molecular characterization of seven distinct proteins present in human [U4/U6·U5] tri‐snRNPs. These proteins exhibit clear homology to the Sm proteins and are thus denoted LSm (like Sm) proteins. Purified LSm proteins form a heteromer that is stable even in the absence of RNA and exhibits a doughnut shape under the electron microscope, with striking similarity to the Sm core RNP structure. The purified LSm heteromer binds specifically to U6 snRNA, requiring the 3′‐terminal U‐tract for complex formation. The 3′‐end of U6 snRNA was also co‐precipitated with LSm proteins after digestion of isolated tri‐snRNPs with RNaseT1. Importantly, the LSm proteins did not bind to the U‐rich Sm sites of intact U1, U2, U4 or U5 snRNAs, indicating that they can only interact with a 3′‐terminal U‐tract. Finally, we show that the LSm proteins facilitate the formation of U4/U6 RNA duplices in vitro, suggesting that the LSm proteins may play a role in U4/U6 snRNP formation.
Pregnancy Outcome in Patients with Insulin Dependent Diabetes Mellitus and Diabetic Nephropathy Treated with ACE Inhibitors before Pregnancy

The preconception and intrapregnancy parameters that are relevant to outcome in women with insulin dependent diabetes mellitus (IDDM) and diabetic nephropathy remain controversial. We analyzed the types and frequencies of maternal and neonatal complications in 24 IDDM patients with diabetic nephropathy (24 pregnancies), all with preserved to mildly impaired renal function. All patients received treatment with captopril for at least six months prior to planned pregnancy and were maintained under strict glycemic control from at least three months before pregnancy to delivery. A successful pregnancy outcome (live, healthy infant without severe handicaps two years after delivery) was observed in 87.5% of the patients. Preexisting hypertension was the only parameter found to be significantly predictive of an unsuccessful outcome (p = 0.0004). We conclude that in patients with IDDM complicated by diabetic nephropathy, pre-pregnancy captopril treatment combined with strict glycemic control offers a prolonged protective effect against possible renal deterioration and probably improves pregnancy outcome.