Assessment of four dose calculation algorithms using IAEA-TECDOC-1583 with medium dependency correction factor (Kmed) application.

PURPOSE: This study discusses the measurement of dose in clinical commissioning tests described in IAEA-TECDOC-1583. It explores the application of Monte Carlo (MC) modelled medium dependency correction factors (Kmed) for accurate dose measurement in bone and lung materials using the CIRS phantom. METHODS: BEAMnrc codes simulate radiation sources and model radiation transport for 6 MV and 15 MV photon beams. CT images of the CIRS phantom are converted to an MC compatible phantom. The PTW 30013 farmer chamber measures doses within modeled CIRS phantom. Kmed are determined by averaging values from four central voxels within the sensitive volume of the farmer chamber. Kmed is calculated for Dm.m and Dw.w algorithm types in bone and lung media for both photon beams. RESULTS: Average modelled correction factors for Dm.m calculations using the farmer chamber are 0.976 (±0.1 %) for 6 MV and 0.979 (±0.1 %) for 15 MV in bone media. Correspondingly, correction factors for Dw.w calculations are 0.99 (±0.3 %) and 0.992 (±0.4 %), respectively. For lung media, average correction factors for Dm.m calculations are 1.02 (±0.3 %) for 6 MV and 1.022 (±0.4 %) for 15 MV. Correspondingly, correction factors for Dw.w calculations are 1.01 (±0.3 %) and 1.012 (±0.2 %), respectively. CONCLUSIONS: This study highlights the significant impact of applying Kmed on dose differences between measurement and calculation during the dose audit process.

Treating Tobacco Dependency in National Health Service Workers in Greater Manchester: An Evaluation of a Bespoke Digital Service.

Introduction: Treating tobacco dependency in National Health Service (NHS) workers delivers substantial benefits at an individual, population, and health care system level. We report the outcomes from the Greater Manchester Integrated Care Partnership's tobacco dependency treatment program for NHS workers which includes 6-months' access to behavioral support and 12 weeks of treatment through a digital application. Methods: Aggregate results for all participants across the program from January 1, 2022, to September 1, 2023, are reported including a deep-dive evaluation of 300 participants recruited to provide chemically validated outcomes. Results: A total of 1567 NHS workers participated in the program within the evaluation period, completing 24,048 sessions with specialist advisors within the application, ordering 18,710 nicotine vape liquids, 6927 nicotine patches, and 297 short-acting nicotine products. Users reported achieving 89,464 smoke-free days, 1,258,069 less cigarettes smoked, and a financial saving of £622,231. The deep-dive evaluation revealed a CO-verified 12-week abstinence rate of 37% (111 of 300). Conclusion: This evaluation provides assurance of clinical effectiveness within a bespoke digital tobacco dependency treatment program for NHS workers across an Integrated Care Partnership.

Nicotine Dependency Levels Among Adult Electronic Cigarette Smokers in Jeddah, Saudi Arabia: An Analytical Cross-Sectional Study.

BACKGROUND: Electronic cigarettes (ECs) are a recent method to deliver nicotine with less harmful effects than traditional cigarettes. Studying nicotine dependence in adult EC users is a crucial area, but few measures are available to evaluate nicotine dependence induced by EC. Our study aims to estimate the levels of nicotine dependency among adult EC smokers using a modified Fagerström Test of Nicotine Dependence (e-FTND) in Jeddah, Saudi Arabia, and to identify EC-associated sociodemographic and smoking-related factors affecting nicotine dependency. METHODS: An analytical cross-sectional study was conducted on adults 18 years of age and older in Jeddah, Saudi Arabia, from December 2023 to March 2024. Data were collected from the participants using a pre-tested structured self-administered questionnaire, and nicotine dependence was assessed using the modified e-FTND. Descriptive statistics such as frequency, mean, and standard deviation were applied. Chi-square was used to assess the association between categorical variables. Ordinal regression was used to predict the nicotine dependency levels with different variables. RESULTS: A total of 344 participants were included in the study. The mean e-FTND score for EC users was 4.14 ± 2.45. Females had a lower likelihood of experiencing higher dependence compared to males (OR = 0.52, 95% CI: 0.32, 0.85). Using ECs for more than three years was associated with higher odds of increased dependence (OR = 3.18, 95% CI: 1.28, 7.98; p < 0.001). The use of Pod system devices lowered the odds of developing high nicotine dependence (OR = 0.32, 95% CI: 0.13, 0.75; p = 0.01) compared to Iqos device users, while mechanical Mod device users exhibited a trend towards higher dependence, although it was not statistically significant. Nicotine concentration in ECs had a significant impact on the degree of nicotine dependence. Higher concentrations were associated with increased odds of higher dependence (12-18 mg: OR = 3.26, 95% CI: 1.55, 6.91; >18 mg: OR = 4.53, 95% CI: 2.37, 8.75; p < 0.001). CONCLUSION: Most exclusive EC users in the study developed a moderate nicotine dependence level. The EC device type and nicotine concentration were significant drivers of nicotine dependence. Additionally, the personal characteristics of the users, such as male gender and duration of use, were associated with a higher risk of dependence. An in-depth understanding of the magnitude of nicotine dependence among EC users will enhance the opportunity for tailored health-enhancing interventions and policies.

Impact of nicotine dependence on self-efficacy and readiness to quit among tobacco consumers in rural areas.

Aim and Objectives: The aim of the present study was to determine the impact or effect of nicotine dependence on self-efficacy and readiness to quit. Materials and Method: The current study was performed using a cross-sectional descriptive questionnaire design among tobacco users visiting primary health care facilities in the rural Jaipur district. Jaipur district is divided into four directions: east, west, north, and south. From each direction, two PHCs were selected randomly based on suitable accessibility to patients. Sample size of study is 465. Out of 465 tobacco consumers, 238 were consuming a smoked form of tobacco, and 227 study participants were consuming a smokeless form of tobacco. Results: It was observed that the majority of study participants (145 (31%)) need smoke/smokeless tobacco within 5 minutes of waking up. With regards to internal stimuli, the majority of study participants (179 (38%)) and (203 (44%)) were not very sure that they would refrain from smoking when they were nervous and depressed. It was determined that quitting tobacco products was not at all important for 159 (34%) study participants. In regards to confidence in tobacco product quitting, only 79 (16%) of tobacco consumers were extremely confident. Conclusion: It was concluded that nicotine dependence impacts both self-efficacy and readiness to quit. It was determined that the higher the nicotine dependence, the less self-efficacy and the less would be the readiness to quit.

Health status, care dependency and oral care utilization among older adults: a register-based study.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine oral care utilisation among older Danes and to describe the extent to which oral care use is associated with the co-existence of challenges relating to general health and care dependency. MATERIALS AND METHODS: The study used registry data covering the entire population of older adults (≥65 years) in seven municipalities in Denmark (N = 178 787 individuals). Oral care services utilisation was computed from administrative data on oral care contacts up to and including 2019, including both private oral care and a municipal oral care programme (MOCP). Various registry data sources were used to compute risk factors to describe oral care utilisation across indicators of general health and care dependency. RESULTS: Indicators for poorer health were associated with larger proportions of individuals enrolled in the MOCPs and larger proportions of non-users of any type of oral care. Higher degrees of care dependency were associated with larger proportions of individuals enrolled in MOCPs and individuals with no use of any oral care services, with the exception of nursing home residents, who comprised a lower proportion of non-users than individuals receiving at-home care. Municipal oral care mainly enrolled older adults who were nursing home residents (60% of nursing home residents were enrolled). CONCLUSION: Our findings support existing evidence on the link between oral care utilisation and general health and frailty. While the municipal care programmes assisted in covering oral care for those with the highest level of care dependency, future preventive strategies for ensuring care continuity for older adults that are increasing in frailty may want to focus on the earlier stages of frailty and of general health deterioration.

Repercussions of Smokeless Tobacco on Buccal Mucosa: A Community Based Observational Study at a Tertiary Care Centre in Western Rajasthan.

Background: Tobacco is consumed mainly as smoking or smokeless tobacco [SLT]. "Smokeless tobacco" (SLT) term is used for the consumption of tobacco mixed with other constituents in form of chewing, spitting and dipping. Consumers of smokeless tobacco chew the products and spit out the juice that builds up in oral cavity which leads to various malignant and pre malignant lesions of oral cavity. Methods: Descriptive observational study was conducted in the city of Jodhpur through department of ENT, Head & Neck Surgery, Dr. SN medical college, Jodhpur. Results: Male to female ratio of smokeless tobacco usage was almost same. Increasing age was associated with occurrence of oral lesions and 43% patients developed oral lesions in the group > 64 yrs of age. Duration was another associating factor and 66% developed symptoms within < 10 years of usage. Oral submucous fibrosis is the most common lesion. Malignant lesions were seen in 0.3% cases. Around 78% cases developed dependency. Diabetic patients were seen more prone to development of oral lesions. Conclusions: Development of lesions in the oral cavity by smokeless tobacco depends on various factors such as quantity of tobacco usage per day, place of putting tobacco and duration. Awareness regarding its fatal effects and timely diagnosis and management can save many lives.

STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer.

Oncogenic mutations in KRAS are among the most common in cancer. Classical models suggest that loss of epithelial characteristics and the acquisition of mesenchymal traits are associated with cancer aggressiveness and therapy resistance. However, the mechanistic link between these phenotypes and mutant KRAS biology remains to be established. Here, we identify STAT3 as a genetic modifier of TGF-beta-induced epithelial to mesenchymal transition. Gene expression profiling of pancreatic cancer cells identifies more than 200 genes commonly regulated by STAT3 and oncogenic KRAS. Functional classification of the STAT3-responsive program reveals its major role in tumor maintenance and epithelial homeostasis. The signatures of STAT3-activated cell states can be projected onto human KRAS mutant tumors, suggesting that they faithfully reflect characteristics of human disease. These observations have implications for therapeutic intervention and tumor aggressiveness.

Characterization of PRAME immunohistochemistry reveals lower expression in pediatric melanoma compared to adult melanoma.

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next-generation immunotherapies including T-cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18-30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0-18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age-dependent expression could be observed. An analysis of event-free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor-associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age-dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients.

Dependence of Positive Bias Stress Instability on Threshold Voltage and Its Origin in Solution-Processed Aluminum-Doped Indium Oxide Thin-Film Transistors.

The initial electrical characteristics and bias stabilities of thin-film transistors (TFTs) are vital factors regarding the practical use of electronic devices. In this study, the dependence of positive bias stress (PBS) instability on an initial threshold voltage (VTH) and its origin were analyzed by understanding the roles of slow and fast traps in solution-processed oxide TFTs. To control the initial VTH of oxide TFTs, the indium oxide (InOx) semiconductor was doped with aluminum (Al), which functioned as a carrier suppressor. The concentration of oxygen vacancies decreased as the Al doping concentration increased, causing a positive VTH shift in the InOx TFTs. The VTH shift (∆VTH) caused by PBS increased exponentially when VTH was increased, and a distinct tendency was observed as the gate bias stress increased due to a high vertical electric field in the oxide dielectric. In addition, the recovery behavior was analyzed to reveal the influence of fast and slow traps on ∆VTH by PBS. Results revealed that the effect of the slow trap increased as the VTH moved in the positive direction; this occured because the main electron trap location moved away from the interface as the Fermi level approached the conduction band minimum. Understanding the correlation between VTH and PBS instability can contribute to optimizing the fabrication of oxide TFT-based circuits for electronic applications.

Antineuropathic Pain Management After Orthopedic Surgery: A Systematic Review.

Background: The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids. Objective: This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery. Methods: During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic. Results: Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency. Conclusion: Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort.

BACKGROUND & AIMS: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

Patient dependency in the Oncology Emergency Room. Reliability and validity of the Jones Dependency Tool.

BACKGROUND: Patients' dependency has significant nursing implications. Nurse skill mix and staffing levels may be addressed more successfully when dependency can be measured. In the oncology emergency room, a valid and reliable tool that measures patients' dependency on nursing care is necessary. AIM: This study aimed to evaluate the psychometric properties of the Jones Dependency Tool in Adult Oncology Emergency Setting at a Cancer Center in Jordan. METHODS: A prospective cross-sectional design was used to test the Reliability and Validity of the Jones Dependency Tool among patients with cancer visiting the ED. A sample of 79 patients were assessed using the JDT and Conner's tool. RESULTS: Jones Dependency Tool showed a high level of validity and reliability. In terms of reliability, which was tested by test-re-test, Intra-class correlation (ICC) = 0.902 which indicates good to excellent. The tool demonstrates a high validity evidenced by its correlation with a criterion (p < 0.001). CONCLUSION: The study demonstrated that the JDT tool is a valid and reliable tool that can be used to quantify a patient's dependency level and the level of nursing care they need, assisting in the selection of the ideal staffing level in terms of quantity and skill mix.

Discovery of a proliferation essential gene signature and actin-like 6A as potential biomarkers for predicting prognosis and neoadjuvant chemotherapy response in triple-positive breast cancer.

BACKGROUND: Patients with triple-positive breast cancer (TPBC) have a higher risk of recurrence and lower survival rates than patients with other luminal breast cancers. However, there are few studies on the predictive biomarkers of prognosis and treatment responses in TPBC. METHODS: Proliferation essential genes (PEGs) were acquired from clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) technology, and cohorts of patients with TPBC were obtained from public databases and our cohort. To develop a TPBC-PEG signature, Cox regression and least absolute shrinkage and selection operator regression analyses were applied. Functional analyses were performed with gene set enrichment analysis. The relationship between candidate genes and neoadjuvant chemotherapy (NACT) sensitivity was explored via real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) on the basis of clinical samples. RESULTS: Among 900 TPBC-PEGs, 437 showed significant differential expression between TPBC and normal tissues. Three prognostic PEGs (actin-like 6A [ACTL6A], chaperonin containing TCP1 subunit 2 [CCT2], and threonyl-TRNA synthetase [TARS]) were identified and used to construct the PEG signature. Patients with high PEG signature scores exhibited a worse overall survival and lower sensitivity to NACT than patients with low PEG signature scores. RT-qPCR results indicated that ACTL6A and CCT2 expression were significantly upregulated in patients who lacked sensitivity to NACT. IHC results showed that the ACTL6A protein was highly expressed in patients with NACT resistance and nonpathological complete responses. CONCLUSIONS: This efficient PEG signature prognostic model can predict the outcomes of TPBC. Furthermore, ACTL6A expression level was associated with the response to NACT, and could serve as an important factor in predicting prognosis and drug sensitivity of patients with TPBC.

EPidemiology, clinical characteristics and Outcomes of 4546 adult admissions to high-dependency and intensive care units in Kenya (EPOK): a multicentre registry-based observational study.

Objective: to describe clinical, management and outcome features of critically ill patients admitted to intensive care units (ICUs) and high dependency units (HDUs) in Kenya. Design: prospective registry-based observational study. Setting: three HDUs and eight ICUs in Kenya. Patients: consecutive adult patients admitted between January 2021 and June 2022. Interventions: none. Measurements and main results: data was entered in a cloud based platform using a common data model. Study endpoints included case mix variables, management features and patient centred outcomes. Patients with Coronavirus disease 2019 (COVID-19) were reported separately. Of the 3892/4546 patients without COVID-19, 2445 patients (62.8%) were from HDUs and 1447 (37.2%) from ICUs. Patients had a median age of 53 years (interquartile range [IQR] 38-68), with HDU patients being older but with a lower severity (APACHE II 6 [3-9] in HDUs vs 12 [7-17] in ICUs; p<0.001). One out of four patients were postoperative with 604 (63.4%) receiving emergency surgery. Readmission rate was 4.8%. Hypertension and diabetes were prevalent comorbidities, with a 4.0% HIV/AIDS rate. Invasive mechanical ventilation (IMV) was applied in 3.4% in HDUs vs. 47.6% in ICUs (P<0.001), with a duration of 7 days (IQR 3-21). There was a similar use of renal replacement therapy (4.0% vs. 4.7%; P<0.001). Vasopressor use was infrequent while half of patients received antibiotics. Average length of stay was 2 days (IQR 1-5). Crude HDU mortality rate was 6.5% in HDUs versus 30.5% in the ICUs (P<0.001). Of the 654 COVID-19 admissions, most were admitted in ICUs (72.3%) with a 33.2% mortality. Conclusions: We provide the first multicenter observational cohort study from an African ICU national registry. Distinct management features and outcomes characterise HDU from ICU patients. Study registration: Clinicaltrials.gov (reference number NCT05456217, date of registration 07 Nov 2022).

NLRP3 Contributes to Sarcopenia Associated to Dependency Recapitulating Inflammatory-Associated Muscle Degeneration.

Sarcopenia, a complex and debilitating condition characterized by progressive deterioration of skeletal muscle, is the primary cause of age-associated disability and significantly impacts healthspan in elderly patients. Despite its prevalence among the aging population, the underlying molecular mechanisms are still under investigation. The NLRP3 inflammasome is crucial in the innate immune response and has a significant impact on diseases related to inflammation and aging. Here, we investigated the expression of the NLRP3 inflammasome pathway and pro-inflammatory cytokines in skeletal muscle and peripheral blood of dependent and independent patients who underwent hip surgery. Patients were categorized into independent and dependent individuals based on their Barthel Index. The expression of NLRP3 inflammasome components was significantly upregulated in sarcopenic muscle from dependent patients, accompanied by higher levels of Caspase-1, IL-1ß and IL-6. Among older dependent individuals with sarcopenia, there was a significant increase in the MYH3/MYH2 ratio, indicating a transcriptional shift in expression from mature to developmental myosin isoforms. Creatine kinase levels and senescence markers were also higher in dependent patients, altogether resembling dystrophic diseases and indicating muscle degeneration. In summary, we present evidence for the involvement of the NLRP3/ASC/NEK7/Caspase-1 inflammasome pathway with activation of pro-inflammatory SASP in the outcome of sarcopenia in the elderly.

Genetic consequences of Last Glacial-Holocene changes in snowfall regime in Arnica mallotopus populations: A plant confined to heavy-snow areas of Japan.

PREMISE: Snow is an important environmental factor affecting plant distribution. Past changes in snowfall regimes may have controlled the demographies of snow-dependent plants. However, our knowledge of changes in the distribution and demographies of such plants is limited because of the lack of fossil records. METHODS: Population genetic and landscape genetic analyses were used to investigate the response of population dynamics of Arnica mallotopus (Asteraceae)-a plant confined to heavy-snow areas of Japan-to changes in snowfall regimes from the Last Glacial Period to the Holocene. RESULTS: The population genetic analysis suggested that the four geographic lineages diverged during the Last Glacial Period. The interaction between reduced snowfall and lower temperatures during this period likely triggered population isolation in separate refugia. Subpopulation differentiation in the northern group was lower than in the southern group. Our ecological niche model predicted that the current distribution was patchy in the southern region; that is, the populations were isolated by topologically flat and climatically unsuitable lowlands. The landscape genetic analysis suggested that areas with little snowfall acted as barriers to the Holocene expansion of species distribution and continued limiting gene flow between local populations. CONCLUSIONS: These findings indicate that postglacial population responses vary among regions and are controlled by environmental and geographic factors. Thus, changes in snowfall regime played a major role in shaping the distribution and genetic structure of the snow-dependent plant.

Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma.

A hallmark of high-risk childhood medulloblastoma is the dysregulation of RNA translation. Currently, it is unknown whether medulloblastoma dysregulates the translation of putatively oncogenic non-canonical open reading frames (ORFs). To address this question, we performed ribosome profiling of 32 medulloblastoma tissues and cell lines and observed widespread non-canonical ORF translation. We then developed a stepwise approach using multiple CRISPR-Cas9 screens to elucidate non-canonical ORFs and putative microproteins implicated in medulloblastoma cell survival. We determined that multiple lncRNA-ORFs and upstream ORFs (uORFs) exhibited selective functionality independent of main coding sequences. A microprotein encoded by one of these ORFs, ASNSD1-uORF or ASDURF, was upregulated, associated with MYC-family oncogenes, and promoted medulloblastoma cell survival through engagement with the prefoldin-like chaperone complex. Our findings underscore the fundamental importance of non-canonical ORF translation in medulloblastoma and provide a rationale to include these ORFs in future studies seeking to define new cancer targets.

Elucidating survival and functional outcomes in patients with primary head and neck malignancies treated in academic versus community settings.

BACKGROUND: Differences in treatment outcomes between community or academic centers are incompletely understood. METHODS: Retrospective review of head and neck cancer patients between 2010 and 2020 in a rural health region. Kaplan-Meier curves and log-rank tests were used to evaluate survival outcomes, along with bivariate and multivariable Cox proportional hazards models. Linear regression was used for functional outcomes of tracheotomy and gastrostomy tube dependence. RESULTS: Two hundred and forty-eight patients treated at an academic center were compared with 94 patients treated in community centers. In multivariable analysis, the risk of death (HR = 0.60, p = 0.019), and risk of recurrence were lower (HR = 0.29, p < 0.001) for patients treated in academic centers. Patients treated in community centers had longer gastrostomy tube dependence (p = 0.002). CONCLUSION: Our findings suggest that treatment at an academic center was associated with a lower risk of recurrence and shorter gastrostomy tube dependence compared to treatment in the community.

Dose-dependent effect on skin permeation of polar and non-polar compounds.

The study of the relationship between the amount of drug applied to the skin and fraction of drug absorbed can improve our understanding of finite-dose percutaneous absorption in the development of topical products and risk assessment of hazardous chemical exposure. It has been previously shown that an increase in the dose applied to the skin leads to a decrease in the fraction of drug permeated the skin (dose-dependent effect). The objective of this research was to examine the dose-dependent effect using permeants of varying physiochemical properties. The dose-dependent effect was studied using human epidermal membrane under finite dose conditions in Franz diffusion cell with model permeants at doses ranging from 0.1 to 200 µg. The dose-dependent effect was evident with model permeants caffeine, corticosterone, dexamethasone, and estradiol, consistent with the relationship of decreasing fraction of dose permeated the skin at increasing the applied dose. However, no significant dose-dependent effect was observed for the polar model permeants urea, mannitol, tetraethyl ammonium, and ethylene glycol, suggesting different transport mechanisms for these permeants. It was also found that, at relatively high doses, estradiol, dexamethasone, and corticosterone could increase the permeation of polar and lipophilic permeants, which could counter the dose-dependent effect under the conditions studied.