Poppy Seeds Signal Limitations of Urine Drug Testing Protocols.

Appropriate care for patients with chronic pain is complex, requiring a thoughtful and holistic approach to pharmacologic intervention, as well as appropriate monitoring when opioids are employed as part of a multimodal regimen. The urine drug test has become an expected standard when longterm opioids are prescribed, but it should be remembered that this test is not intended to be punitive. It is ordered to promote patient safety (Dowell et al., 2022). Recent literature and events surrounding the effect of poppy seeds on urine drug test results have drawn attention to the risks of misinterpreting this test (Bloch, 2023; Lewis et al., 2021; Reisfield et al., 2023; Temple, 2023). Misinterpretation of urine drug tests creates a potential for unfounded accusations from health care workers toward patients, thus, undermining therapeutic relationships and intensifying stigma. Such circumstances may also preclude chances to offer patients needed interventions. Therefore, a valuable opportunity exists for nurses to mitigate untoward consequences by developing a robust understanding of urine drug testing, destigmatizing chronic pain and opioid use, advocating for patients, and enacting change at both an individual and a systems-level.

Assessing the mobility of Bronze Age societies in East-Central Europe. A strontium and oxygen isotope perspective on two archaeological sites.

European Bronze Age societies are generally characterised by increased mobility and the application of isotopic methods to archaeology has allowed the rate and range of human travels to be quantified. However, little is known about the mobility of the people inhabiting East-Central Europe in the late Early and Middle Bronze Age (1950-1250 BC) whose primary subsistence strategy was herding supported by crop cultivation. This paper presents the results of strontium (87Sr/86Sr) and oxygen (δ18O) isotope analyses in the enamel of people buried in collective graves at the cemeteries in Gustorzyn and Zerniki Górne. These sites are located in Kujawy and the Nida Basin, a lowland and an upland region with clearly different environmental conditions, respectively. Both sites are classified as belonging to the Trzciniec cultural circle and were used between 16th and 13th centuries BC. Among the 34 examined individuals only an adult female from Gustorzyn can be assessed as non-local based on both 87Sr/86Sr and δ18O signatures in her first molar. This may indicate the practice of exogamy in the studied population but more generally corresponds with the hypothesis of limited mobility within these societies, as has previously been inferred from archaeological evidence, anthropological analysis, and stable isotope-based diet reconstruction. New and existing data evaluated in this paper show that the 87Sr/86Sr variability in the natural environment of both regions is relatively high, allowing the tracking of short-range human mobility. A series of oxygen isotope analyses (conducted for all but one individuals studied with strontium isotopes) indicates that δ18O ratios measured in phosphate are in agreement with the predicted modern oxygen isotope precipitation values, and that this method is useful in detecting travels over larger distances. The challenges of using both 87Sr/86Sr and δ18O isotopic systems in provenance studies in the glacial landscapes of temperate Europe are also discussed.

Interpersonal contrast avoidance as a mechanism for the maintenance of worry.

Despite consistent links between interpersonal problems and worry, mechanisms explaining this relationship remain unknown. The Contrast Avoidance Model (CAM; Newman & Llera, 2011) posits that individuals at risk for chronic worry and generalized anxiety disorder (GAD) fear sudden negative mood shifts, using worry to perpetuate negative moods and avoid these negative emotional contrasts. We propose interpersonal (IP) contrast avoidance (e.g., acting friendly to prevent others from causing mood shifts) as a novel explanation for interpersonal dysfunction in worriers. This study investigated IP contrast avoidance and worry in two samples. A nonclinical sample ranging in GAD symptoms (Study 1; N = 92) reported IP problems at baseline then IP contrast avoidance and worry over eight weeks (637 diaries). As expected, baseline IP problems prospectively predicted worry indirectly through chronic IP contrast avoidance. Affiliative, submissive, cold, and total IP contrast avoidance strategies predicted same-week and lagged next-week worry increases; affiliative, submissive, and total strategies also predicted maintenance of worry over eight weeks in growth models. Lastly, Study 2 showed the relevance of IP contrast avoidance strategies in a treatment-seeking clinical sample (N = 40), correlating with interpersonal problems and worry. Overall, results provide proof-of-concept for extending the CAM to the interpersonal domain.

Why we need a Public Understanding of Social Science.

Who is licensed to make knowledge claims about society? A more diffuse group of individuals are afforded the status of legitimate speakers on society in the public sphere than is the case when the questions relate to the expertise of the natural sciences. We draw on the concept of the 'locus of legitimate interpretation' and the sensibilities of Collins and Evans' Studies of Expertise and Experience programme to help make sense of these issues. The social sciences are not the natural sciences, and one key difference is their relationship with publics. The social sciences are intrinsically entangled, at both the level of the research question and the research subject/object, with public knowledge, the knowledges of publics and public interests. We therefore outline what these differences might mean for a serious, distinct and purposive Public Understanding of Social Science programme and how this differs from current work in the Public Understanding of Science.

An Evaluation of the Clinical Tools Used to Monitor Illicit Methamphetamine Use Among Chronic Pain Patients: A Cross Sectional Retrospective Study.

Purpose: Illicit drug use continues to be a concern for adults on opioid therapy for chronic pain. Prescribers use tools such as urine screening and confirmatory testing with mass spectrometry to monitor adherence to chronic opioid therapy contracts. Design: A cross sectional retrospective study was conducted using electronic medical records. Methods: Data was analyzed from 6558 urine samples of adult outpatients receiving opioid therapy at an urban pain specialty clinic who consented to urine drug tests. Results: From October 18, 2021, to October 21, 2022, 569 were positive amphetamine with immunoassay testing. 310 (54%) of those samples were absent amphetamine with or without methamphetamine while 259 (45.5%) were true positive amphetamine proven by confirmation testing. Analysis of confirmatory testing results identified 281 samples positive for amphetamine with or without methamphetamine. 71 samples confirmed positive for methamphetamine with or without amphetamine. 37 (52.1%) of those methamphetamine samples screened positive for amphetamine and 34 (47.9%) samples screened negative for amphetamine. 48 of the methamphetamine samples were sent for chiral confirmation testing. 45 (93.8%) samples were positive for D-methamphetamine while 3 (6.2%) samples were positive for L-methamphetamine. Only 5 (11.1%) of the 45 patients whose samples were positive for d-methamphetamine reported the use of illicit drugs before their urine sample was tested. Discussion: Confirmatory testing with mass spectrometry can detect illicit drugs, such as methamphetamine, with high sensitivity and specificity and should be used with all samples given the low sensitivity of screening immunoassay. It is of utmost importance that opioid pain medicine prescribers know the many possible interpretations of these results so that they are equipped to make appropriate clinical decisions to ensure the safety of the patient, prescriber, and practice.

Exploring the K isotope composition of Göttingen minipig brain regions, and implications for Alzheimer's disease.

Natural stable metal isotopes have shown utility in differentiation between healthy and diseased brain states (e.g. Alzheimer's disease, AD). While the AD brain accumulates some metals, it purges others, namely K (accompanied by increased serum K, suggesting brain-blood transferal). Here, K isotope compositions of Göttingen minipig brain regions for two AD models at midlife are reported. Results indicate heavy K isotope enrichment where amyloid beta (Aß) accumulation is observed, and this enrichment correlates with relative K depletion. These results suggest preferential efflux of isotopically light K+ from the brain, a linkage between brain K concentrations and isotope compositions, and linkage to Aß (previously shown to purge cellular brain K+). Brain K isotope compositions differ from that for serum and brain K is much more abundant than in serum, suggesting that changes in brain K may transfer a measurable K isotope excursion to serum, thereby generating an early AD biomarker.

Rotavirus Strain Trends in United States, 2009-2016: Results from the National Rotavirus Strain Surveillance System (NRSSS).

Before the introduction of vaccines, group A rotaviruses (RVA) were the leading cause of acute gastroenteritis in children worldwide. The National Rotavirus Strain Surveillance System (NRSSS) was established in 1996 by the Centers for Disease Control and Prevention (CDC) to perform passive RVA surveillance in the USA. We report the distribution of RVA genotypes collected through NRSSS during the 2009-2016 RVA seasons and retrospectively examine the genotypes detected through the NRSSS since 1996. During the 2009-2016 RVA seasons, 2134 RVA-positive fecal specimens were sent to the CDC for analysis of the VP7 and VP4 genes by RT-PCR genotyping assays and sequencing. During 2009-2011, RVA genotype G3P[8] dominated, while G12P[8] was the dominant genotype during 2012-2016. Vaccine strains were detected in 1.7% of specimens and uncommon/unusual strains, including equine-like G3P[8] strains, were found in 1.9%. Phylogenetic analyses showed limited VP7 and VP4 sequence variation within the common genotypes with 1-3 alleles/lineages identified per genotype. A review of 20 years of NRSSS surveillance showed two changes in genotype dominance, from G1P[8] to G3P[8] and then G3P[8] to G12P[8]. A better understanding of the long-term effects of vaccine use on epidemiological and evolutionary dynamics of circulating RVA strains requires continued surveillance.

Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report.

Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products. Case Summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2. Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma. Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis's effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day. Conclusion and Relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.

Leadership assessments: A history and overview of empirical and practical considerations.

Assessment instruments are critical to assist in the selection and development of strong, effective leaders. Developing a strong understanding of what makes a tool empirically sound, based on solid scientific concepts, can mean the difference between choosing an assessment that provides targeted, actionable, and accurate information versus an instrument that yields information that is biased, unhelpful, or even harmful to individuals and organizations. This article discusses the history of leadership assessments and how to critically evaluate available leadership instruments in order to enhance decision-making about what tool to use.

Project Vienna: A Novel Precell Mass Filter for Collision/Reaction Cell MC-ICPMS/MS.

The last decade has seen widespread adoption of triple quadrupole-based inductively coupled plasma-tandem mass spectrometry (ICPMS/MS) technique using a collision/reaction cell in combination with a precell bandpass mass analyzer to measure isotopes otherwise masked by spectral interferences. High-precision isotope ratio analysis containing such isotopes would benefit from a similar capability on a multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) platform, but using a quadrupole-based precell mass analyzer for MC-ICPMS/MS has several limitations. To overcome these limitations, we developed a novel precell mass analyzer for MC-ICPMS/MS using sector field technology. The new precell mass analyzer, comprising two Wien filters and a selection aperture, and a hexapole collision/reaction cell were integrated together in a single module and added to the commercially available Thermo Scientific Neptune XT MC-ICPMS to create a prototype MC-ICPMS/MS we named Vienna. Vienna was proven to retain the same performance of the base MC-ICPMS in terms of sensitivity, accuracy, and precision. Using the Vienna mass filter to eliminate Ar-based species, the abundance sensitivity achievable was equivalent to TIMS at mass 237.05, which was used to accurately determine the low 236U/238U isotope ratio of the uranium reference material IRMM184 (certified value, 1.2446 × 10-7). The performance of Vienna was then tested for a variety of geoscience applications that were expected to benefit from MC-ICPMS/MS technique, including Ca, K, Si, and in situ Rb/Sr dating by laser ablation.

In situ Rb-Sr dating by collision cell, multicollection inductively-coupled plasma mass-spectrometry with pre-cell mass-filter, (CC-MC-ICPMS/MS).

We document the utility for in situ Rb-Sr dating of a one-of-a-kind tribrid mass spectrometer, 'Proteus', coupled to a UV laser ablation system. Proteus combines quadrupole mass-filter, collision cell and sector magnet with a multicollection inductively-coupled plasma mass spectrometer (CC-MC-ICPMS/MS). Compared to commercial, single collector, tribrid inductively-coupled plasma mass spectrometers (CC-ICPMS/MS) Proteus has enhanced ion transmission and offers simultaneous collection of all Sr isotopes using an array of Faraday cups. These features yield improved precision in measured 87Sr/86Sr ratios, for a given mass of Sr analysed, approximately a factor of 25 in comparison to the Thermo Scientific™ iCAP TQ™ operated under similar conditions. Using SF6 as a reaction gas on Proteus, measurements of Rb-doped NIST SRM (standard reference material) 987 solutions, with Rb/Sr ratios from 0.01-100, yield 87Sr/86Sr that are indistinguishable from un-doped NIST SRM 987, demonstrating quantitative 'chemical resolution' of Rb from Sr. We highlight the importance of mass-filtering before the collision cell for laser ablation 87Sr/86Sr analysis, using an in-house feldspar standard and a range of glass reference materials. By transmitting only those ions with mass-to-charge ratios 82-92 u/e into the collision cell, we achieve accurate 87Sr/86Sr measurements without any corrections for atomic or polyatomic isobaric interferences. Without the pre-cell mass-filtering, measured in situ 87Sr/86Sr ratios are inaccurate. Combining in situ measurements of Rb/Sr and radiogenic Sr isotope ratios we obtain mineral isochrons. We utilise a sample from the well-dated Dartmoor granite (285 ± 1 Ma) as a calibrant for our in situ ages and, using the same conditions, produce accurate Rb-Sr isochron ages for samples of the Fish Canyon tuff (28 ± 2 Ma) and Shap granite pluton (397 ± 1 Ma). Analysing the same Dartmoor granite sample using identical laser conditions and number of spot analyses using the Thermo Scientific™ iCAP TQ™ yielded an isochron slope 5× less precise than Proteus. We use an uncertainty model to illustrate the advantage of using Proteus over single collector CC-ICPMS/MS for in situ Rb-Sr dating. The results of this model show that the improvement is most marked for samples that have low Rb/Sr (<10) or are young (<100 Ma). We also report the first example of an in situ, internal Rb-Sr isochron from a single potassium-feldspar grain. Using a sample from the Shap granite, we obtained accurate age and initial 87Sr/86Sr with 95% confidence intervals of ±1.5% and ±0.03% respectively. Such capabilities offer new opportunities in geochronological studies.

A Profile of Point of Care Coordinators: Roles, Responsibilities and Attitudes.

BACKGROUND: Point of care (POC) testing is rapidly evolving. POC testing is often managed by POC coordinators (POCC), but this role is relatively new and has not been characterized. OBJECTIVES: To characterize the background, responsibilities, and job satisfaction of POCCs. METHODS: Structured interviews were conducted with 15 POCCs. On the basis of these interviews, a 38-item questionnaire was developed and administered as a web-based survey. RESULTS: The respondents (N = 98) were mostly female (87%) and had a bachelor's degree (79%). About half the respondents were older than 55 years and were in supervisory positions. Overall, respondents indicated high job satisfaction, but women were significantly less satisfied than men. POCCs were infrequently involved in decisions regarding the implementation of new tests. The number of tests managed by each POCC varied widely (median, 6.0; range, 1-30). CONCLUSIONS: The POCC role is in flux. There is consensus regarding some aspects of the job, but there are significant differences in the way that hospitals organize the POCC function.

Terrorism, geopolitics, and oil security: Using remote sensing to estimate oil production of the Islamic State.

As the world's most traded commodity, oil production is typically well monitored and analyzed. It also has established links to geopolitics, international relations, and security. Despite this attention, the illicit production, refining, and trade of oil and derivative products occur all over the world and provide significant revenues outside of the oversight and regulation of governments. A prominent manifestation of this phenomenon is how terrorist and insurgent organizations-including the Islamic State group, also known as ISIL/ISIS or Daesh-use oil as a revenue source. Understanding the spatial and temporal variation in production can help determine the scale of operations, technical capacity, and revenue streams. This information, in turn, can inform both security and reconstruction strategies. To this end, we use satellite multi-spectral imaging and ground-truth pre-war output data to effectively construct a real-time census of oil production in areas controlled by the ISIL terrorist group. More broadly, remotely measuring the activity of extractive industries in conflict-affected areas without reliable administrative data can support a broad range of public policy and decisions and military operations.

Prospective Investigation of the Contrast Avoidance Model of Generalized Anxiety and Worry.

The factors that maintain generalized anxiety disorder (GAD) symptoms and worry over time are not entirely clear. The Contrast Avoidance Model (CAM) postulates that individuals at risk for pathological worry and GAD symptoms uniquely fear emotional shifts from neutral or positive emotions into negative emotional states, and consequently use worry to maintain negative emotion in order to avoid shifts or blunt the effect of negative contrasts. This model has received support in laboratory experiments, but has not been investigated prospectively in the naturalistic context of daily life. The present study tested the CAM in a longitudinal experience sampling study with a subclinical sample. Participants selected to represent a broad range of symptoms (N = 92) completed baseline measures of GAD and depression symptoms, and eight weekly assessments of worry, experiences of negative emotional contrasts during their worst event of the week, and situation-specific negative emotion. Consistent with the CAM, GAD symptoms prospectively predicted higher endorsement of negative contrast experiences as worst events, independent of depression symptoms. Unsurprisingly, higher negative contrasts predicted higher negative emotion. However, both higher baseline GAD symptoms and weekly worry uniquely moderated (reduced) this relationship, providing consistent support for the idea that worry may blunt the emotional effects of contrasts. Depression symptoms did not have the same moderating effect. These findings support the CAM in an ecologically valid context.

Acute Responses to the 7-Minute Workout.

Riegler, M, Stotz, G, Fitzgerald, K, Munoz, CK, Lewis, J, Ring, S, and Astorino, TA. Acute responses to the 7-minute workout. J Strength Cond Res 31(9): 2572-2578, 2017-A popular smartphone application called the 7-Minute Workout (7Min) claims to be scientifically proven to promote weight loss and improve cardiovascular function. The application has 10 million downloads and has been reviewed by 350,000 users. However, changes in metabolic and perceptual variables in response to 7Min are unknown. Our study compared acute responses between 7Min and a time-matched session of cycling-based high-intensity interval exercise (HIIE). Fourteen active men and women (age and V[Combining Dot Above]O2max = 25.4 ± 8.3 years and 40.5 ± 6.4 ml·kg·min) initially underwent V[Combining Dot Above]O2max testing. During 2 subsequent sessions separated by ≥48 hours, they completed 7Min or HIIE. During exercise, oxygen uptake (V[Combining Dot Above]O2), heart rate (HR), blood lactate concentration (BLa), and rating of perceived exertion were measured. Peak V[Combining Dot Above]O2 was higher (p < 0.001) in HIIE vs. 7Min, and HIIE yielded greater (p < 0.001) mean V[Combining Dot Above]O2 (1.83 ± 0.41 L·min vs. 1.44 ± 0.32 L·min) and HR (159.0 ± 10.7 b·min vs. 140.7 ± 18.3 b·min, p < 0.001) vs. 7Min. Blood lactate concentration increased (p < 0.001) during exercise but was similar between bouts (p = 0.07). Rating of perceived exertion was higher (p = 0.008) in response to HIIE vs. 7Min. Although 7Min yields lower peak V[Combining Dot Above]O2 and HR than HIIE, it is characterized by bursts approaching 90 %HRmax and causes significant BLa accumulation, representing vigorous exercise. Nevertheless, 7Min is on the low end of the intensity spectrum, which questions whether it represents true HIIE and will confer similar benefits if performed long term.

Bioinformatics: indispensable, yet hidden in plain sight?

BACKGROUND: Bioinformatics has multitudinous identities, organisational alignments and disciplinary links. This variety allows bioinformaticians and bioinformatic work to contribute to much (if not most) of life science research in profound ways. The multitude of bioinformatic work also translates into a multitude of credit-distribution arrangements, apparently dismissing that work. RESULTS: We report on the epistemic and social arrangements that characterise the relationship between bioinformatics and life science. We describe, in sociological terms, the character, power and future of bioinformatic work. The character of bioinformatic work is such that its cultural, institutional and technical structures allow for it to be black-boxed easily. The result is that bioinformatic expertise and contributions travel easily and quickly, yet remain largely uncredited. The power of bioinformatic work is shaped by its dependency on life science work, which combined with the black-boxed character of bioinformatic expertise further contributes to situating bioinformatics on the periphery of the life sciences. Finally, the imagined futures of bioinformatic work suggest that bioinformatics will become ever more indispensable without necessarily becoming more visible, forcing bioinformaticians into difficult professional and career choices. CONCLUSIONS: Bioinformatic expertise and labour is epistemically central but often institutionally peripheral. In part, this is a result of the ways in which the character, power distribution and potential futures of bioinformatics are constituted. However, alternative paths can be imagined.

Doing laboratory ethnography: reflections on method in scientific workplaces.

Laboratory ethnography extended the social scientist's gaze into the day-to-day accomplishment of scientific practice. Here we reflect upon our own ethnographies of biomedical scientific workspaces to provoke methodological discussion on the doing of laboratory ethnography. What we provide is less a 'how to' guide and more a commentary on what to look for and what to look at. We draw upon our empirical research with stem cell laboratories and animal houses, teams producing robotic surgical tools, musicians sonifying data science, a psychiatric genetics laboratory, and scientists developing laboratory grown meat. We use these cases to example a set of potential ethnographic themes worthy of pursuit: science epistemics and the extended laboratory, the interaction order of scientific work, sensory realms and the rending of science as sensible, conferences as performative sites, and the spaces, places and temporalities of scientific work.

Hidden in the Middle: Culture, Value and Reward in Bioinformatics.

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether.

A positive feedback loop involving the Wnt/ß-catenin/MYC/Sox2 axis defines a highly tumorigenic cell subpopulation in ALK-positive anaplastic large cell lymphoma.

BACKGROUND: We have previously described the existence of two phenotypically distinct cell subsets in ALK-positive anaplastic large cell lymphoma (ALK + ALCL) based on their differential responsiveness to a Sox2 reporter (SRR2), with reporter-responsive (RR) cells being more tumorigenic and chemoresistant than reporter-unresponsive (RU) cells. However, the regulator(s) of RU/RR dichotomy are not identified. In this study, we aim to delineate the key regulator(s) of RU/RR dichotomy. METHODS: JASPER motif match analysis was used to identify the putative factors binding to SRR2 sequence. SRR2 probe pull-down assay and quantitate real-time PCR were performed to analyze the regulation of Sox2 transcriptional activity by MYC. Methylcellulose colony formation assay, chemoresistance to doxorubicin and mouse xenograft study were performed to investigate the biological functions of MYC. PCR array and western blotting were executed to study related signaling pathways that regulate MYC expression. Immunofluorescence and immunohistochemistry assay were initiated to evaluate the expression of MYC and its correlation with its regulator by chi-square test analysis in human primary tumor cells. RESULTS: We identified MYC as a potential regulator of RU/RR dichotomy. In support of its role, MYC was highly expressed in RR cells compared to RU cells, and inhibition of MYC substantially decreased the Sox2/SRR2 binding, Sox2 transcriptional activity, chemoresistance, and methylcellulose colony formation. In contrast, enforced expression of MYC in RU cells conferred the RR phenotype. The Wnt/ß-catenin pathway, a positive regulator of MYC, was highly active in RR but not RU cells. While inhibition of this pathway in RR cells substantially decreased MYC expression and SRR2 reporter activity, experimental activation of this pathway led to the opposite effects in RU cells. Collectively, our results support a model in which a positive feedback loop involving Wnt/ß-catenin/MYC and Sox2 contributes to the RR phenotype. In a mouse xenograft model, RU cells stably transfected with MYC showed upregulation of the Wnt/ß-catenin/MYC/Sox2 axis and increased tumorigenecity. Correlating with these findings, there was a significant correlation between the expression of active ß-catenin and MYC in ALK + ALCL primary tumor cells. CONCLUSIONS: A positive feedback loop involving the Wnt/ß-catenin/MYC/Sox2 axis defines a highly tumorigenic cell subset in ALK + ALCL.