Miracle-dz/UniFAR-FTUs huggingface dataset:
Lung Stereotactic Body Radiation Therapy: Regional Nodal Failure Is Not Predicted by Tumor Size

Introduction: To examine regional nodal failure patterns with respect to lesion size in medically inoperable early-stage non–small cell lung cancer (NSCLC) patients treated with definitive lung stereotactic body radiation therapy (SBRT). Methods: Between 2004 and 2012, 342 medically inoperable early-stage NSCLC patients treated with definitive SBRT were identified in our institutional review board–approved prospective registry. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance. Kaplan–Meier analysis was performed with the log-rank test used to detect differences between lesion size and nodal failure patterns. Cox-proportional hazard regression analysis was performed to identify predictors of nodal failure. Results: Median follow-up was 17.6 months (range, 0–84 months). Median tumor size, positron emission tomography maximum standardized uptake value, and dose/fractionation were 2.2 cm (range, 0.8–7.2 cm), 6.7 (range, 1–59), and 50 Gray (Gy)/five fractions, respectively. Of the 342 lesions evaluated, 14.6% (50 of 342) experienced nodal failure. Nodal failure rates were 17.45% (26 of 149), 10.3% (11 of 107), 14.1% (10 of 71), and 20% (3 of 15) for lesions less than or equal to 2 cm, 2.1 to 3 cm, 3.1 to 5 cm, and greater than 5 cm, respectively. Rates of nodal failure were not significantly different between the four different size groups (p = 0.15). On univariate analysis, 2.1 to 3 cm lesions versus less than or equal to 2 cm exhibited less nodal failure after SBRT (hazard ratio = 0.406; 95% confidence interval = 0.189–0.87; p = 0.0205). No other patient, tumor, or treatment factor significantly affected nodal failure. Conclusion: For early-stage NSCLC treated with SBRT, tumor size does not influence the rates of regional nodal failure. This finding warrants further investigation on the possible mechanisms of SBRT by which loco-regional control is improved.
Attenuation of doxorubicin-induced cardiotoxicity and genotoxicity by an indole-based natural compound 3,3′-diindolylmethane (DIM) through activation of Nrf2/ARE signaling pathways and inhibiting apoptosis

Abstract The most crucial complication related to doxorubicin (DOX) therapy is nonspecific cytotoxic effect on healthy normal cells. The clinical use of this broad-spectrum chemotherapeutic agent is restricted due to development of severe form of cardiotoxicity, myelosuppression, and genotoxicity which interfere with therapeutic schedule, compromise treatment outcome and may lead to secondary malignancy. 3,3′-diindolylmethane (DIM) is a naturally occurring plant alkaloid formed by the hydrolysis of indolylmethyl glucosinolate (glucobrassicin). Therefore, the present study was undertaken to investigate the protective role of DIM against DOX-induced toxicity in mice. DOX was administered (5 mg/kg b.w., i.p.) and DIM was administered (25 mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results showed that DIM significantly attenuated DOX-induced oxidative stress in the cardiac tissues by reducing the levels of free radicals and lipid peroxidation, and by enhancing the level of glutathione (reduced) and the activity of antioxidant enzymes. The chemoprotective potential of DIM was confirmed by histopathological evaluation of heart and bone marrow niche. Moreover, DIM considerably mitigated DOX-induced clastogenicity, DNA damage, apoptosis, and myeloid hyperplasia in bone marrow niche. In addition, oral administration of DIM significantly (p < .05) stimulated the Nrf2-mediated activation of antioxidant response element (ARE) pathway and promoted expression of ARE-driven cytoprotective proteins, HO-1, NQO1, and glutathione-S-transferase (GST). In connection with that, DIM significantly attenuated DOX-induced apoptosis by upregulation of Bcl-2 expression and downregulation of Bax and caspase-3 expression. Thus, this study suggests that DIM has promising chemoprotective efficacy against DOX-induced toxicity and indicates its future use as an adjuvant in chemotherapy.
When negative is positive.

Informed by a strong theoretical framework, El-Sheikh, Kouros, Erath, Cummings, Keller, and Staton have produced a rich empirical description of children’s physiological and behavioral profiles as a function of marital conflict in their families. The findings from three related studies contribute to an emerging understanding of processes that may explain why some children adapt negatively and some children adapt positively to family environments characterized by conflict between parents. Conflict in families has traditionally been considered to be an unambiguous risk factor for children’s development, largely based on research that has assessed one measure in one domain (e.g., attachment relationships, externalizing behaviors, vagal functioning). The approach of studying profiles of joint parasympathetic and sympathetic nervous system (PNS and SNS) functioning is a promising move away from this research tradition and has generated intriguing findings that require a shift in perspective of marital conflict as a universally negative experience for children. In fact, El-Sheikh and colleagues’ findings show that certain physiological phenotypes in some cases have more positive outcomes under conditions of high marital conflict than they do under conditions of low marital conflict, leading to the speculation that for some children negative environments can be positive and for other children with the same autonomic nervous system (ANS) profiles positive environments can be negative. The rich set of findings reported in this monograph leaves open several crucial questions, the discussion of which extends to theories beyond those in which the authors have positioned their research, highlighting the significance and innovation of this work. In this commentary I identify and discuss these crucial questions in the context of theories that focus on
Mediating role of peritraumatic dissociation and depression on post‐MVA distress: path analysis

Background: The aim of this study was to examine the role of pre‐trauma, traumatic event, and peri‐traumatic psychological characteristics on post‐motor vehicle accident (MVA) Posttraumatic Stress Disorder (PTSD) and depression. Methods: The sample comprised 333 (54% female) hospital accident and emergency attendees who completed a self‐report postal screening survey approximately 1‐month post‐accident and 128 (62% female) participants who completed a follow‐up survey at 3‐months. Results: Path analysis (Model 1) showed that dissociation partially mediated the relationship between past emotional problems and initial post‐MVA distress, as well as between fear of dying and levels of distress. Level of alertness and perceived accident severity had no direct effects on post‐MVA distress. However, higher levels of exposure contributed to distress predominantly in the presence of high levels of fear and subsequent dissociative experiences. When ongoing PTSD and depression symptoms were included (Model 2), feeling depressed/sad at 1‐month was the strongest predictor of both PTSD and depression symptom severity at 3‐months post‐MVA, explaining 53% and 40% of the variance, respectively. Dissociation remained an important mediating variable at both time points. Conclusions: These models show the influence of previous emotional vulnerability factors and the important mediating role of peri‐traumatic experiences (in the presence of fear due to increased levels of accident severity) on post‐MVA morbidity. Additionally, MVA survivors who report feeling depressed/sad 1‐month after their accident are at greater risk of developing both PTSD and depression. Depression and Anxiety 28:218–226, 2011. © 2011 Wiley‐Liss, Inc.
CATALYTIC MODELS IN EPIDEMIOLOGY

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Telomere Length and Recurrence Risk after Curative Resection in Patients with Early-Stage Non–Small-Cell Lung Cancer: A Prospective Cohort Study

Background: We hypothesized that telomere length in peripheral blood would have significant predictive value for risk of recurrence after curative resection in non–small-cell lung cancer (NSCLC). Methods: This prospective study included 473 patients with histologically confirmed early stage NSCLC who underwent curative therapy at MD Anderson Cancer Center between 1995 and 2008. Relative telomere length (RTL) of peripheral leukocytes was measured by real-time polymerase chain reaction. The risk of recurrence was estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) using a multivariable Cox proportional hazard regression model. Results: Median duration of follow-up was 61 months, and 151 patients (32%) had developed recurrence at time of analysis. Patients who developed recurrence had significantly longer mean RTL compared with those without recurrence (1.13 versus 1.07, p = 0.046). A subgroup analysis indicates that women had longer RTL compared with men (1.12 versus 1.06, p = 0.025), and the patients with adenocarcinoma demonstrated longer RTL compared with those with other histologic types (1.11 versus 1.05, p = 0.042). To determine whether longer RTL in women and adenocarcinoma subgroup would predict risk of recurrence, multivariate Cox analysis adjusting for age, sex, stage, pack year and treatment regimens was performed. Longer telomeres were significantly associated with higher risk of developing recurrence in women (hazard ratio [HR], 2.25; 95% confidence interval [CI], 1.02–4.96, p = 0.044) and adenocarcinoma subgroups (HR, 2.19; 95% CI, 1.05–4.55, p = 0.036). The increased risk of recurrence due to long RTL was more apparent in women with adenocarcinoma (HR, 2.67; 95% CI, 1.19–6.03, p = 0.018). Conclusions: This is the first prospective study to suggest that long RTL is associated with recurrence in early stage NSCLC after curative resection. Women and adenocarcinoma seem to be special subgroups in which telomere biology may play an important role.
Phase II Study of Afatinib, an Irreversible ErbB Family Blocker, in EGFR FISH-Positive Non–Small-Cell Lung Cancer

Introduction: Afatinib, an oral irreversible ErbB Family Blocker, has demonstrated efficacy and safety in epidermal growth factor receptor (EGFR) mutation-positive advanced lung adenocarcinoma. It is unknown whether such activity also occurs in patients with EGFR gene overexpression, regardless of mutation status. This phase II study investigated the activity and safety of afatinib in advanced non–small-cell lung cancer with increased EGFR gene copy number and/or gene amplification by fluorescence in situ hybridization (FISH), with or without EGFR mutation. Methods: EGFR gene overexpression was assessed by FISH analysis; patients with high polysomy or gene amplification were considered FISH positive. Patients received daily afatinib less than or equal to 50 mg (monotherapy). Endpoints included objective response rate (ORR; primary), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Of 223 patients screened, 69 patients were FISH-positive and met eligibility criteria for treatment. The ORR was 13.0% overall (n =9 of 69). Higher ORRs were observed in patients with gene amplification (20.0%; n =5 of 25) and EGFR mutation-positive tumors (25.0%; n =3 of 12). The DCR was 50.7% overall (n = 35 of 69; median duration: 24.9 weeks) with higher DCRs observed in patients with gene amplification 64.0%; (n = 16 of 25), and in patients with EGFR mutation-positive tumors 66.7% (n = 8 of 12). In the overall population, median PFS was 8.4 weeks and median OS was 50.4 weeks. The most common afatinib-related adverse events were rash/acne (83%) and diarrhea (78%). Conclusions: First- or second-line afatinib demonstrated preliminary activity and manageable safety in EGFR FISH-positive patients with advanced non–small-cell lung cancer.
An Integrative Framework of the Information Systems Development Process

Despite more than 25 years of research on the processes and outcomes of information systems development in organizations, deficiencies exist in our knowledge about the effective management of complex systems development processes. Although individual studies have generated a wealth of findings, there is a need for a cumulative framework that facilitates interpretation of what has been learned and what needs to be learned about the process of information systems development. This paper reviews prior research on ISD processes and identifies the different types of contributions that have been made to our growing knowledge. More important, it generates a cumulative framework for understanding the process of ISD that could provide a valuable template for future research and practice.
Modeling the Audit Opinions Issued to Bankrupt Companies: A Two-stage Empirical Analysis

Many observers are dissatisfied with the accounting profession? s ability to warn the public of upcoming bankruptcy filings. The Chairman of the SEC recently reminded auditors that "they are the public? s watchdog in the financial reporting process" and that "we rely on auditors to put something like the Good Housekeeping seal of approval on the information investors receive" (Levitt, 1998). Since regulators and users tend to treat an unmodified audit opinion as a "clean bill of health", they do not expect the business to fail in the near future. Research has shown that more often than not, auditors end up letting users down when it comes to predicting bankruptcy filings with audit opinions. Although auditors assert they are not responsible for predicting future events, it is very clear that their opinion decision is evaluated, at least in part, based on events that occur after the audit report date. The interesting and logical next step is to find out how companies exit bankruptcy. Do they liquidate or reorganize? Successful reorganization may, in the end, exonerate auditors and preserve their role as an early warning device. Is there any evidence to suggest that auditors end up being correct? The opinion prediction model developed in the paper introduces a new bankruptcy resolution variable that proxies for the auditor? s prognosis of the ultimate disposition of the soon-to-be-bankrupt company. Using a sample of bankruptcy filings between 1982 and 1992, we find that auditors do not seem to be able to predict filings or resolution. Instead, the model suggests that auditors are less likely to issue a modified opinion when the financial prospects of the company are not clear and when auditors are faced with incentives to delay or avoid a modified opinion. Our tests of bankruptcy resolution support what auditors have been arguing for years: that they are not clairvoyant with respect to a client? s future. The results of the research are not encouraging for those who rely on audit opinions as an early warning device.
Cost-Effectiveness of Multiplexed Predictive Biomarker Screening in Non-Small-Cell Lung Cancer

Journal of Thoracic Oncology ® • Volume 10, Number 4, April 2015 Introduction: Population-wide screening for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements to inform cancer therapy in non-small-cell lung cancer (NSCLC) is recommended by guidelines. We estimated costeffectiveness of multiplexed predictive biomarker screening in metastatic NSCLC from a societal perspective in the United States. Methods: We constructed a microsimulation model to compare the life expectancy and costs of multiplexed testing and molecularly guided therapy versus treatment with cisplatin-pemetrexed (CisPem). All testing interventions included a two-step algorithm of concurrent EGFR mutation and ALK overexpression testing with immunohistochemistry followed by ALK rearrangement confirmation with a fluorescence in situ hybridization assay for immunohistochemistry-positive results. Three strategies were included: “Test-treat” approach, where molecularly guided therapy was initiated after obtainment of test results; “Empiric switch therapy,” with concurrent initiation of CisPem and testing and immediate switch to test-result conditional treatment after one cycle of CisPem; and “Empiric therapy” approach in which CisPem was continued for four cycles before start of a tyrosine kinase inhibitor. Results: The incremental cost-effectiveness ratio for “Test-treat” compared with treatment with CisPem was $136,000 per qualityadjusted life year gained. Both empiric treatment approaches had less favorable incremental cost-effectiveness ratios. “Test-treat” and “Empiric switch therapy” yielded higher expected outcomes in terms of quality-adjusted life years and life-years than “Empiric therapy. ” These results were robust across plausible ranges of model inputs. Conclusion: From a societal perspective, our cost-effectiveness results support the value of multiplexed genetic screening and molecularly guided therapy in metastatic NSCLC.
Docosahexaenoic acid–mediated, targeted and sustained brain delivery of curcumin microemulsion

Abstract We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHA-rich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size <20 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher C max than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8- and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher C max and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood–brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentration-dependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to >66-fold(intranasal) and >21–fold (intravenous) the IC50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.
Impact of an Interactive On-line Tool on Therapeutic Decision-Making for Patients with Advanced Non–Small-Cell Lung Cancer

Background: Treatment guidelines provide recommendations but cannot account for the wide variability in patient-tumor characteristics in individual patients. We developed an on-line interactive decision tool to provide expert recommendations for specific patient scenarios in the first-line and maintenance settings for advanced non–small-cell lung cancer. We sought to determine how providing expert feedback would influence clinical decision-making. Method: Five lung cancer experts selected treatment for 96 different patient cases based on patient and/or tumor-specific features. These data were used to develop an on-line decision tool. Participant physicians entered variables for their patient scenario with treatment choices, and then received expert treatment recommendations for that scenario. To determine the impact on decision-making, users were asked whether the expert feedback impacted their original plan. Results: A total of 442 individual physicians, of which 88% were from outside the United States, entered 653 cases, with report on impact in 389 cases. Expert feedback affected treatment choice in 73% of cases (23% changed and 50% confirmed decisions). For cases with epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion, all experts selected targeted therapy whereas 51% and 58% of participants did not. Greater variability was seen between experts and participants for cases involving EGFR or ALK wild-type tumors. Participants were 2.5-fold more likely to change to expert recommended therapy for ALK fusions than for EGFR mutations (p = 0.017). Conclusion: This online tool for treatment decision-making resulted in a positive influence on clinician’s decisions. This approach offers opportunities for improving quality of care and meets an educational need in application of new therapeutic paradigms.
Anticonvulsant potential of some medicinal plants and their beneficial properties

Epilepsy has now become the most serious brain disorder. A number of synthetic antiepileptic drugs are available in practice, however their effectiveness does not grip true with the entire population suffering from epilepsy. Traditional systems of medicine are popular in developing countries and most of the population relies on traditional medicines for their primary health care need. Medicinal plants to be an important source of traditional medicines. Various plants are used for the treatment of epilepsy in traditional system of medicines and various plants are yet to be scientifically investigated. Phytoconstituents have been the basis of treatment of human diseases including epilepsy. Herbal products are extensively used for the treatment of many diseases worldwide and where allopathic fails or has severe side effects. Psycho neural drugs are also have very serious side effects like physical dependence, tolerance, deterioration of cognitive function and effect on respiratory, digestive and immune system. So the treatments through herbal medicines are widely used across the world due to their wide applicability and therapeutic efficacy with least side effects, which in turn has accelerated the research regarding natural therapy. In this review we have summarized some herbal antiepileptics.
The protective effect of lipid emulsion in preventing bupivacaine-induced mitochondrial injury and apoptosis of H9C2 cardiomyocytes

Abstract Lipid emulsion (LE) has been shown to be effective in the resuscitation of bupivacaine-induced cardiac arrest, but the precise mechanism of this action has not been fully elucidated. Pursuant to this lack of information on the mechanism in which LE protects the myocardium during bupivacaine-induced toxicity, we explored mitochondrial function and cell apoptosis. H9C2 cardiomyocytes were used in study. Cells were randomly divided in different groups and were cultivated 6 h, 12 h, and 24 h. The mitochondria were extracted and mitochondrial ATP content was measured, as was mitochondrial membrane potential, the concentration of calcium ion (Ca2+), and the activity of Ca2+-ATP enzyme (Ca2+-ATPase). Cells from groups Bup1000, LE group, and Bup1000LE were collected to determine cell viability, cell apoptosis, and electron microscopy scanning of mitochondrial ultrastructure (after 24 h). We found that LE can reverse the inhibition of the mitochondrial function induced by bupivacaine, regulate the concentration of calcium ion in mitochondria, resulting in the protection of myocardial cells from toxicity induced by bupivacaine.