Miracle-dz/UniFAR-FTUs huggingface dataset:
Sorafenib: a clinical and pharmacologic review

Importance of the field: Sorafenib is an oral receptor tyrosine kinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases (vascular endothelial growth factor receptors 1, 2, 3 and platelet-derived growth factor-β, Flt-3 and c-kit) that are implicated in tumorigenesis and tumor progression. Sorafenib is approved for the treatment of advanced inoperable hepatocellular cancer and advanced renal cell cancer. Areas covered in this review: The findings from the major Phase III studies that led to FDA approval of this drug for the above indications are reviewed. Key aspects of sorafenib pharmacology, dosing in the presence of organ dysfunction, toxicities and weaknesses of the research done so far are summarized. What will the reader gain: The reader will have the knowledge of the major studies that form the basis of the clinical use of sorafenib, information on the upcoming Phase III trials that could lead to changes in clinical practice and some insights on aspects of the drugs' mechanism of action and toxicity that still remain unclear. Take home message: Sorafenib is a well-tolerated oral antiangiogenic agent approved for treatment of two angiogenesis-driven cancers. Studies to broaden the clinical indications and increase understanding of the clinical and laboratory biomarkers of response are needed.
Diagnosis of Swimming Induced Pulmonary Edema—A Review

Swimming induced pulmonary edema (SIPE) is a complication that can occur during exercise with the possibility of misdiagnosis and can quickly become life threatening; however, medical literature infrequently describes SIPE. Therefore, the aim of this review was to analyse all individual cases diagnosed with SIPE as reported in scientific sources, with an emphasis on the diagnostic pathways and the key facts resulting in its diagnosis. Due to a multifactorial and complicated pathophysiology, the diagnosis could be difficult. Based on the actual literature, we try to point out important findings regarding history, conditions, clinical findings, and diagnostic testing helping to confirm the diagnosis of SIPE. Thirty-eight cases from seventeen articles reporting the diagnosis of SIPE were selected. We found remarkable differences in the individual described diagnostic pathways. A total of 100% of the cases suffered from an acute onset of breathing problems, occasionally accompanied by hemoptysis. A total of 73% showed initial hypoxemia. In most of the cases (89%), an initial chest X-Ray or chest CT was available, of which one-third (71%) showed radiological signs of pulmonary edema. The majority of the cases (82%) experienced a rapid resolution of symptoms within 48 h, the diagnostic hallmark of SIPE. Due to a foreseeable increase in participation in swimming competitions and endurance competitions with a swimming component, diagnosis of SIPE will be important, especially for medical teams caring for these athletes.
Effect of Glyburide in Type II Diabetes Mellitus: Studies of Monocyte Membrane Fluidity, Lipid Composition, and Insulin Binding

Monocyte membrane lipid composition, fluidity, and insulin binding were studied in 10 previously untreated obese type II (non-insulin-dependent) diabetic subjects before and 2-7 days, 1 mo, and 3 mo after glyburide therapy. A significant reduction in fasting blood glucose levels occurred within 1 wk after initiation of therapy in all subjects. Serum insulin levels did not change significantly. After a transient increase at 2-7 days, insulin binding and receptor number decreased to less than pretreatment levels after 3 mo of therapy despite continued improved glycemic control. Molar cholesterol-phospholipid ratios increased significantly at 2-7 days and then reverted to pretreatment levels. A significant positive correlation between insulin binding and cholesterol-phospholipid ratios was seen at all durations of treatment. Membrane microviscosity as measured by fluorescence polarization of the probe diphenylhexatriene was significantly decreased after 3 mo of therapy. The results indicate that the glycemic effect of glyburide represents enhancement of insulin action and occurs independently of membrane insulin receptors.
The relationship between personal philosophy and effectiveness in counsellors

Abstract This study investigates the relationship between the effectiveness of counsellors and their personal philosophy, beliefs and attitudes. There is a review of the relevant literature concerning the qualities and attributes of effective counsellors, with a detailed examination of studies of counsellor philosophy. Two groups (n = 14 and n = 19) of counsellors on training courses were studied. Each participant wrote an account of a ‘Helping Relationship Incident’ which was rated on the 12 dimensions of counsellor ‘perceptual organization’ developed by Combs & Soper (1963). Course tutors gave ratings of the counselling effectiveness of their students. Rank order correlations between judgements of counsellor effectiveness and ratings of perceptual organization/philosophy were made. In both groups statistically significant results were found, adding weight to the hypothesis that a ‘person-centred’ perceptual organization or belief system is an important factor in counsellor effectiveness. The implication.
Assessment of the transition from junior-to-senior sports in Swedish athletes

The objectives of this study were (1) to explore the Transition Monitoring Survey (TMS) for assessing athletes' transition from junior-to-senior sports, (2) to describe the transition from junior-to-senior sports in Swedish athletes based on the TMS data, and (3) to explore how the transition variables contribute to the athletes' perceived degree of adjustment to the senior level and to their sport and life satisfaction. The TMS was developed based on career development/transition frameworks and previous qualitative research on the transition from junior-to-senior sports. Altogether 416 participants organized in three samples were involved in this exploratory study. The study illuminated the strong points of the TMS as a theoretically based and culturally adapted instrument, but it also shed a light on some deficits of the TMS that should be eliminated in its further use in transition research.
‘Proper museum’ or branding platform? Club museums in England

This paper examines to what extent English football club museums live up to the International Council of Museums (ICOM) definition of a museum. This definition, amongst other things, describes a museum as an institution in the service of society and its development, whilst exhibiting heritage for the purposes of education, study and enjoyment. Using the National Football Museum as a benchmark, this paper investigates to what extent club museums manage to exhibit their heritage in a way that enables learning and links the story of the club to wider society. Club museums are shown to have moved in the direction of halls of fame, with a historical descriptions of the ‘essence’ of the club, rather than fulfilling their potential as platforms for reflection on club identity. In contrast to sport museums more broadly, this shift signifies their role as branding platforms for profit-making purposes rather than as museums by ICOM’s definition.
When knowledge matters—differential effects of available knowledge in standard and basic anchoring tasks

The present research examines whether anchoring effects—the assimilation of a numeric estimate towards a previously considered standard—depend on judges' available knowledge in the target domain. Based on previous research, I distinguish two types of anchoring effects. Standard anchoring is obtained if judges are explicitly asked to compare the anchor to the target. Basic anchoring results if the accessibility of the anchor is increased prior to judgments about the target. I expected that only basic but not standard anchoring is reduced by providing judges with judgment-relevant knowledge. Using a standard versus basic anchoring paradigm, 112 participants were confronted with a high versus low anchor before estimating the average price of a German midsize car. Prior to this task, participants were provided with information about prices of cars (relevant knowledge) versus kitchens (irrelevant knowledge). Results demonstrate that this knowledge only influenced the magnitude of basic but not standard anchoring effects. This finding demonstrates that knowledge has differential effects in different types of anchoring. Copyright © 2007 John Wiley & Sons, Ltd.
Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer

Objective Loss of ARID1A is related to oncogenic transformation of ovarian clear cell adenocarcinoma. The present study was conducted in epithelial ovarian cancer of all tissue types to investigate whether an increased or decreased expression level of ARID1A can be a prognostic factor for ovarian cancer or can influence the sensitivity to anticancer drugs. Methods The expression level of ARID1A was investigated in 111 patients with epithelial ovarian cancer who received initial treatment at the Hirosaki University Hospital between 2006 and 2011. The expression level of ARID1A was immunohistochemically graded using staining scores, which were calculated by multiplying the staining intensity of the nuclei by the stain-positive area. Results The level of ARID1A was significantly lower in clear cell adenocarcinoma than in other histologic types. Among the patients with stage III, IV cancer (n=46), the level of ARID1A was significantly lower (p=0.026) in patients who did not achieve complete response (CR; n=12) than in patients who achieved CR (n=34). The level of ARID1A was relatively lower (p=0.07) in patients who relapsed after achieving CR (n=21) than in patients who did not relapse (n=13). When the staining score of 0 was defined as ARID1A-negative and other staining scores were defined as ARID1A-positive, there was significant difference in progression-free survival between ARID1A-negative (n=11) and ARID1A-positive (n=35) patients in stage III, IV disease. Conclusion The result suggests that decreased ARID1A expression is correlated with chemoresistance and may be a predictive factor for the risk of relapse of advanced cancer after achieving CR.
Towards a Computational Narration of Inner

Narrative, as it evolves with technological developments, constantly reinvents itself in order to better capture new social orders and individual experiences. As an emerging cultural expression, however, most computergenerated narrative works are still restricted to an action-based, goal-driven aesthetics, leaving little space for characters’ inner world. This paper proposes to expand the range of computer-generated narrative by addressing this imbalance between the “physical” and the “internal. ” It presents our approach for algorithmically narrating characters’ inner world by leveraging the synergy between modernist stream of consciousness literature and contemporary research in artificial intelligence and cognitive science. The Riu system, a text-based computational narrative system inspired by Woolf’s novel Mrs. Dalloway, is provided as a case study towards this new direction.
Predictive validity of the PCL-R in offenders with intellectual disability in a high secure hospital setting: Institutional aggression

Abstract Psychopathy has emerged as one of the constructs most predictive of violence risk in the forensic field. The Psychopathy Checklist-Revised (PCL-R) has previously been found to have acceptable reliability and validity in a sample of offenders with intellectual disability, but its predictive validity in this group has yet to be established. This prospective study examined the relative ability of the PCL-R and two other instruments, the Historical Clinical Risk-20 (HCR-20) and the Emotional Problem Scales' Behaviour Ratings Scale, to predict officially recorded institutional aggression. A sample of 60 offenders with intellectual disability in a high security forensic psychiatric setting was followed up for a period of 12 months. The PCL-R 20-item total, the PCL-R 13-item total, and PCL-R Factor 1 and Factor 2 scores did not significantly predict any type of aggressive behaviour. In contrast, the two more clinically based measures significantly predicted both interpersonal physical and verbal/property aggression. A primary justification for using the PCL-R in forensic settings is the evidence for its association with violence. Further studies examining the relationship between psychopathy, aggression, and violent recidivism in broader samples of offenders with ID are therefore imperative.
Two-Processor Scheduling with Start-Times and Deadlines

Given a set $\mathcal{T} = \{ T_1 ,T_2 , \cdots ,T_n \} $ of tasks, each $T_i$ having execution time 1, an integer start-time $s_i \geqq 0$ and a deadline $d_i > 0$, along with precedence constraints among the tasks, we examine the problem of determining whether there exists a schedule on two identical processors that executes each task in the time interval between its start-time and deadline. We present an $O(n^3)$ algorithm that constructs such a schedule whenever one exists. The algorithm may also be used in a binary search mode to find the shortest such schedule or to find a schedule that minimizes maximum “tardiness”. A number of natural extensions of this problem are seen to be $NP$ complete and hence probably intractable.
Nitrogen mustards in the treatment of neoplastic disease.

Background and Aims: This study aims at determining the demographic profile and extra-intestinal manifestations of Ulcerative Colitis in the Nepalese patients treated in a tertiary referral centre. Methods : The study was conducted between February 1, 2014 and January 31, 2015 at the Department of Gastroenterology Tribhuvan University Teaching Hospital, Kathmandu, Nepal. The clinical and epidemiologic data from patients diagnosed to have Ulcerative Colitis were obtained and analysed. Results : During the study period, 60 patients were identified as having ulcerative colitis. Mean age at diagnosis was 34.6 years. The mean duration of illness at diagnosis was 3.7 years. Extra-intestinal manifestations (EIM) were seen in 16.6% of the patients. Sacroilitis was the most common EIM seen in11.6% followed by peripheral arthritis in 6.6% of the patients. Episcleritis, Primary Sclerosing Cholangitis and Erythema Nodosum were seen only in 1.6% each. At the time of presentation, 38.3% (n=23) had proctosigmoiditis , 50% (n=30) left sided colitis and pancolitis was seen in 11.7% (n=7). 53.3% patients had mild disease, 38.3% and 8.3 % presented with moderate to severe disease respectively. Conclusion : Peak age of onset for UC in the study was third and fourth decade which was similar to the various studies from Asia and West. Musculoskeletal manifestation was the most common extra- intestinal manifestation of UC in Nepalese population. As Nepal is perhaps the most diverse country in terms of ethnicity, cultural variation, socio-economic status and health care facilities, a comprehensive nationwide data bank involving ethnicity and geographical variation is needed for a better definition of the disease characteristics. Journal of Advances in Internal Medicine 2015;04(01):1-5.
Momentary affective states predicting substance use events in depressed youth

The relationship between mood and substance use in depressed adolescents has been well established, but the precise mechanisms need elucidation. We sought to characterize 24-h momentary affective antecedents of alcohol and marijuana use in depressed youth. Thirty-eight participants (84% females, 15–22 years old), all clinically depressed and substance users, completed four to six daily momentary reports for two weeks using a hand-held device. The reports included participants' momentary positive and negative affect (PA and NA) and their recent consumption of alcohol and/or marijuana. Statistical models compared affect characteristics during 24-h periods preceding substance use with affect at other times. Because most participants were females, we also examined data for girls alone. Participants reported 394 total substance use events. Prior to use, participants displayed narrower ranges of PA and NA compared with times distant from use, especially for marijuana use. Girls had lower maximum PA prior to mar.
Perioperative Rofecoxib Improves Early Recovery After Outpatient Herniorrhaphy

Non-opioid analgesics have become increasingly popular as part of a multimodal regimen for pain management in the ambulatory setting. We designed this randomized, double-blind, placebo-controlled study to evaluate the effect of perioperative administration of the cyclooxygenase-2 inhibitor rofecoxib on patient outcome after inguinal herniorrhaphy procedures. Sixty consenting outpatients undergoing elective hernia repair surgery were randomly assigned to one of two treatment groups: control (vitamin C, 500 mg) or rofecoxib (rofecoxib, 50 mg). The first oral dose of the study medication was administered 30–40 min before entering the operating room, and a second dose of the same medication was given on the morning of the first postoperative day. Recovery times, postoperative pain scores, the need for “rescue” analgesics, and side effects were recorded at 1- to 10-min intervals before discharge from the recovery room. Follow-up evaluations were performed at 36 h, 7 days, and 14 days after surgery to assess postdischarge pain, analgesic requirements, resumption of normal activities, as well as patient satisfaction with their postoperative pain management. Rofecoxib significantly decreased the early recovery times, leading to an earlier discharge home after surgery (88 ± 30 vs 126 ± 44 min, P < 0.05). When compared with the control group, the patients’ median [range] quality of recovery score was also significantly higher in the rofecoxib group (18 [14–18] vs 16 [13–18], P < 0.05). In the predischarge period, a significantly larger percentage of patients required rescue pain medications in the control group (67% vs 37% in the rofecoxib group, P < 0.05). At the 36-h follow-up assessment, rofecoxib-treated patients reported significantly reduced oral analgesic requirements (0 [0–20] vs 9 [1–33] pills, P < 0.05) and lower maximal pain scores, resulting in improved patient satisfaction with their postoperative pain management (3 [1–4] vs 2 [0–3], P < 0.05). However, there were no differences in the times required to resume their activities of daily living. In conclusion, perioperative rofecoxib, 50 mg per os, significantly decreased postoperative pain and the need for analgesic rescue medication, leading to a faster and improved quality of recovery after outpatient hernia surgery. However, perioperative use of rofecoxib failed to improve recovery end points in the postdischarge period.
Mobilizing Social Capital Through Employee Spinoffs

Many founding teams of new firms form at a common employer. We model team formation and the entry of employee spinoffs by extending the Jovanovic (1979) theory of job matching and employer learning. In our social-capital model employees learn about their colleagues' characteristics at a faster rate than the employer and recruit suitable colleagues to join the spinoff firm. For spinoff firms, our model predicts that the separation hazard is lower among founding team members than among workers hired from outside at founding, and that this difference shrinks with worker tenure at the firm. For parent firms, our model predicts that a worker's departure hazard to join a spinoff initially increases with worker tenure at the parent, whereas the separation hazard for conventional quits and layoffs decreases with worker tenure as in Jovanovic (1979). All these predictions are clearly supported in Brazilian data for the period 1995-2001. Calibration of our dynamic model indicates that employee spinoffs raise the share of workers in Brazil's private sector known to be of high match quality by 3.2 percent.
Efficient decellularization of whole porcine kidneys improves reseeded cell behavior

Combining patient-specific cells with the appropriate scaffold to create functional kidneys is a promising technology to provide immunocompatible kidneys for the 100 000+ patients on the organ waiting list. For proper recellularization to occur, the scaffold must possess the critical microstructure and an intact vascular network. Detergent perfusion through the vasculature of a kidney is the preferred method of decellularization; however, harsh detergents could be damaging to the microstructure of the renal tissue and may undesirably solubilize the endogenous growth and signaling factors. In this study, automated decellularization of whole porcine kidneys was performed using an improved method that combined physical and chemical steps to efficiently remove cellular materials while producing minimal damage to the collagenous extracellular matrix (ECM). Freezing/thawing, incremental increases in flow rate under constant pressure, applying osmotic shock to the cellular membranes, and low concentrations of the detergent sodium dodecyl sulfate (SDS) were factors used to decrease SDS exposure time during the decellularization process from 36 to 5 h, which preserved the microstructure while still removing 99% of the DNA. The well-preserved glycosaminoglycans (GAGs) and collagen fibers enhanced cell-ECM interactions. Human renal cortical tubular epithelium (RCTE) cells grew more rapidly when cultured on the ECM obtained from the improved decellularization process and also demonstrated more in vivo-like gene expression patterns. The optimized, automated process that resulted from this work is now used routinely in our laboratory to rapidly decellularize porcine kidneys and could be adapted to other large organs (e.g. heart, liver, and lung).
Exploring the Disjuncture Between the Politics of Trauma and Everyday Realities of Women in Afghanistan

This article makes a case for public recognition of the quotidian and everyday realities of Afghan women. It argues that it is within these spaces that war-related trauma and social suffering can be understood as part of the body politic, as opposed to the medicalized and individualized model of care. Body politics entails recognizing the emerging agency of subjects as global actors. Based on ethnographic research in Afghanistan in late 2008, the article maintains that the starting point of any work on trauma and recovery must acknowledge the initiatives taken by the people themselves, a task that requires exploration of spaces that we do not otherwise tread. Only then can social and health policies resonate with the lived realities of people.
Joint Application of Concentration and δ18O to Investigate the Global Atmospheric CO Budget

Abstract: Most previous top-down global carbon monoxide (CO) budget estimates have used only concentration information and shown large differences in individual source estimates. Since CO from certain sources has a specific isotopic signature, coupling the concentration and isotope fraction information can provide a better constraint on CO source strength estimates. We simulate both CO concentration and its oxygen isotopologue C 18 O in the 3-D global chemical transport model MOZART-4 and compare the results with observations. We then used a Bayesian inversion to calculate the most probable global CO budget. In the analysis, δ 18 O information is jointly applied with concentration. The joint inversion results should provide more accurate and precise inversion results in comparison with CO-only inversion. Various methods combining the concentration and isotope ratios were tested to maximize the benefit of including isotope information. The joint inversion of CO and δ 18 O estimated total global CO production at 2951 Tg-CO/yr in 1997, 3084 Tg-CO/yr in 1998, and 2583 Tg-CO/yr in 2004. The updated CO budget improved both the modeled CO and δ