Nomogram for predicting survival after first-line anti-PD-1-based immunotherapy in unresectable stage IV melanoma: a multicenter international study.

BACKGROUND: The introduction of anti-programmed cell death protein 1 (PD-1) immunotherapy has revolutionized the treatment landscape for melanoma, enhancing both response rates and survival outcomes in patients with advanced stages of the disease. Despite these remarkable advances, a noteworthy subset of patients (40%-60%) does not derive advantage from this therapeutic approach. This study aims to identify key predictive factors and create a user-friendly predictive nomogram for stage IV melanoma patients receiving first-line anti-PD-1-based immunotherapy, improving treatment decisions. MATERIALS AND METHODS: In this retrospective study, we included patients with unresectable stage IV melanoma who received first-line treatment with either anti-PD-1 monotherapy or anti-PD-1 plus anti-cytotoxic T-lymphocyte associated protein 4 between 2014 and 2018. We documented clinicopathological features and blood markers upon therapy initiation. By employing the random survival forest model and backward variable selection of the Cox model, we identified variables associated with progression-free survival (PFS) after the first-line anti-PD-1-based treatment. We developed and validated a predictive nomogram for PFS utilizing the identified variables. We assessed calibration and discrimination performance metrics as part of the evaluation process. RESULTS: The study involved 719 patients, divided into a training cohort of 405 (56%) patients and a validation cohort of 314 (44%) patients. We combined findings from the random survival forest and the Cox model to create a nomogram that incorporates the following factors: lactate dehydrogenase (LDH), S100, melanoma subtype, neutrophil-to-lymphocyte ratio (NLR), body mass index, type of immune checkpoint inhibitor, and presence of liver or brain metastasis. The resultant model had a C-index of 0.67 in the training cohort and 0.66 in the validation cohort. Performance remained in different patient subgroups. Calibration analysis revealed a favorable correlation between predicted and actual PFS rates. CONCLUSIONS: We developed and validated a predictive nomogram for long-term PFS in patients with unresectable stage IV melanoma undergoing first-line anti-PD-1-based immunotherapy.

Development of a PROMIS multidimensional cancer-related fatigue (mCRF) form using modern psychometric techniques.

PURPOSE: To develop a PRO assessment of multidimensional cancer-related fatigue based on the PROMIS fatigue assessments. METHOD: Cancer patients reporting fatigue were recruited from a comprehensive cancer care center and completed a survey including 39 items from the PROMIS Cancer Item Bank-Fatigue. Component and factor structures of the fatigue items were explored with Monte Carlo parallel factor and Mokken analyses, respectively. Psychometric properties were determined using item response theory, ensuring unidimensionality, scalability, and item independence. RESULTS: Fatigue scores from a sample of 333 fatigued cancer patients (mean age = 59.50, SD = 11.62, 67% women) were used in all scale development analyses. Psychometric analyses yielded 3 dimensions: motivational fatigue (15 items), cognitive fatigue (9 items), and physical fatigue (9 items). The subscales showed strong unidimensionality, were scalable, and were free of differential item function. Confirmatory factor analyses in a new sample of 182 patients confirmed the findings. CONCLUSION: The resulting 33-item PROMIS multidimensional cancer-related fatigue (mCRF) form provides a novel measure for the assessment of the different dimensions of cancer-related fatigue. It is the only multidimensional scale specific for cancer patients that has been developed using modern psychometric approaches. With its 3 dimensions (motivational, cognitive, and physical fatigue), this scale accurately captures the fatigue experienced by cancer patients, allowing clinicians to optimize fatigue management and improve patient care. The scale could also advance research on the nature and experience of cancer-related fatigue.

Generalization of food devaluation following food-specific go/no-go training.

The benefit of food-specific inhibition training on modulating food valuation and eating behaviors has been established, but generalization to untrained foods is seldomly examined. This study investigated whether stimulus variability and practice order, found to effect generalization in motor learning, can improve generalization following food-specific inhibition training. Ninety-three young adults practiced the Go/No-Go task online in three training conditions: 1) Constant (N = 30): inhibition practiced on one food stimulus; 2) Variable-Blocked (N = 32): inhibition practiced on 6 food stimuli, each in a separate block; and 3) Variable-Random (N = 31): inhibition practiced on 6 food stimuli in random order. Consistent with our hypothesis, the Variable-Random group showed better generalization of inhibition to untrained foods than the Constant and the Variable-Blocked groups immediately after training, demonstrating the benefit of stimulus variability and random practice order. This effect was not present 24 h after training. The Variable-Random group also showed decreased desire to eat untrained foods, exhibiting generalization of food devaluation. However, this effect was only present 24 h after training. The Constant group showed increased desire to eat untrained foods immediately and 24 h after training. The Variable-Blocked group did not differ from either group in the desire to eat to untrained foods, suggesting that random order is important for exposing the benefit of variability. The findings illustrate that presenting various training items in random order can improve generalization of food-specific inhibition training. However, inconsistencies found in the timing of generalization effects and modest effect sizes warrant additional investigation into generalization principles of food-specific inhibition training.

H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

'A kindergarten teacher must have 100 eyes and 100 ears!': Kindergarten teachers' experiences coping with child sexual abuse and problematic sexual behavior.

BACKGROUND: Child sexual abuse (CSA) and problematic sexual behavior (PSB) are worldwide phenomena that occur across all ages. Kindergarten teachers' proactive involvement can be crucial to the prevention, disclosure and intervention of CSA and PSB. However, research on their experiences of contending with CSA and PSB remains limited. OBJECTIVE: This study examines kindergarten teachers' experiences in Israel with the CSA and PSB of their students. PARTICIPANTS AND SETTING: Semi-structured interviews were conducted with 31 teachers: 11 secular Jewish, seven religious Jewish, nine Druze Arab, and four Muslim Arab. METHODS: A qualitative analysis was conducted using the interview transcripts as data. RESULTS: The analysis revealed three themes illustrating teachers' professional transformations regarding their knowledge of these phenomena: 1) initial shock, uncertainty and sense of responsibility when exposed to CSA and PSB due to missing knowledge, 2) implementation of prevention and intervention strategies regarding CSA and PSB, and 3) embracing a social role to disseminate CSA and PSB knowledge. The findings indicated that the majority of the teachers went from overwhelming shock and fear due to a lack of knowledge in coping with CSA and PSB to a sense of responsibility as a community leader. CONCLUSIONS: The fragmentation of the Israeli education system isolates kindergartens, and the lack of training and education for the teachers left them alone when contending with the CSA and PSB of their students. Nevertheless, the participants exhibited remarkable agency and resourcefulness, gaining the necessary knowledge and acting as knowledge agents within their communities.

Stimulus variability improves generalization following response inhibition training.

The present study examined the effect of stimulus variability and practice order on generalization to novel stimuli following a single session of response inhibition training. Ninety-six young adults practiced the Go/No-go task online in three training conditions: (1) constant (N = 32)-inhibition practiced on one stimulus; (2) variable-blocked (N = 32)-inhibition practiced on 6 stimuli, each in a separate block; and (3) variable-random (N = 32)-inhibition practiced on 6 stimuli in random order. Generalization was measured by comparing groups on inhibition of novel stimuli and a trained stimulus immediately and 24 h after training. Consistent with our hypothesis, the variable-random and the variable-blocked groups showed better generalization to the novel items than the constant group, demonstrating the benefit of stimulus variability. The variable-random group also showed better generalization than the variable-blocked group, demonstrating the benefit of presenting stimuli in random order. Participants' capacity for working memory maintenance was found to modulate the effect of practice order. While the benefit of variability was retained 24 h after training, the effect of order was not. Results also show generalization to (1) different type of stimuli using the same task and (2) the same stimuli on a different response inhibition task (the Stop-Signal Task), however, the effect of variable practice and order were not evident in these cases. The study findings illustrate the advantage of using variable stimuli presented in random order for generalization and suggest that these principles of motor learning can be applied to learning of cognitive skills.

Excito-repellent and Pesticide-Likeness Properties of Essential Oils on Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae).

Carpophilus dimidiatus (Fabricius) (Nitidulidae) and Oryzaephilus mercator (L.) (Silvanidae) are insect pests that cause severe damage in important walnut growing regions in the northwest of Argentina. The current management approaches for these pests involve the use of unsafe phosphorus pesticides whose overuse have led to farmworker poisoning, pest resistance issues, and environmental contamination. Plant extracts, particularly essential oils, are an alternative source of insect control agents. Excito-repellent essential oils can be used to develop ecofriendly tools for managing the pest population without affecting quality and visual appearance of the stored walnuts. Laboratory studies were conducted to assess the excito-repellent effects of C. dimidiatus and O. mercator of 12 essential oils derived from aromatic plants used as food additives and traditional medicine in Argentina: Aloysia citrodora (AC), Aloysia gratissima (AG), Aloysia gratissima var. Gratissima (AGG), Blepharocalyx salicipholius (BS), Hyptis mutabilis (HM), Lippia junelliana (LJ), Lippia turbinata (LT), Mentha x piperita (MP), Minthostachys mollis (MM), Minthostachys verticillata (MV), Origanum vulgare(OV), and Rosmarinus officinalis (RO). The most bioactive EOs (ERijk ≥ 70%) were Aloysia gratissima var. Gratissima (AGG), Minthostachys verticillata, and Lippia junelliana. Their bioactivity profile and chemical space, characterized from GC-MS measures, Generalized Estimating Equations, and Hierarchical Cluster Analysis, revealed that they are mixtures of very functionalized molecules with physicochemical properties similar to those of insecticides with low residual property that enter the insect body through the respiratory system by inhalation. The AGG, MV, and LJ oils are promising as protective agents of walnut products. In our laboratory, studies of their formulations for use in integrated pest management programs are still ongoing.

Teaching Chest Tube Insertion by Blended Learning: A Multi-Dimensional Analysis.

BACKGROUND: Emerging technologies are being incorporated in surgical education. The use of such technology should be supported by evidence that the technology neither distracts nor overloads the learner and is easy to use. To teach chest tube insertion, we developed an e-learning module, as part of a blended learning program delivered prior to in-person hands-on simulation. This pilot study was aimed to assess learning effectiveness of this blended learning, and cognitive load and the usability of e-learning. METHODS: The interactive e-learning module with multimedia content was created following learning design principles. In advance of the standard simulation, 13 first-year surgical residents were randomized into two groups: 7 received the e-learning module and online reading materials (e-learning group); 6 received only the online reading materials (controls). Knowledge was evaluated by pre-and post-tests; technical performance was assessed using a Global Rating Scale by blinded assessors. Cognitive load and usability were evaluated using rating scales. RESULTS: The e-learning group showed significant improvement from baseline in knowledge (P = .047), while controls did not (P = .500). For technical skill, 100% of residents in the e-learning group reached a predetermined proficiency level vs 60% of controls (P = .06). The addition of e-learning was associated with lower extrinsic and greater germane cognitive load (P = .04, .03, respectively). Usability was evaluated highly by all participants in e-learning group. CONCLUSION: Interactive e-learning added to hands-on simulation led to improved learning and desired cognitive load and usability. This approach should be evaluated in teaching of other procedural skills.

Co-learning and co-teaching in a newly introduced research learning community.

BACKGROUND: Research clerkships are usually designed as individual learning projects focusing on research skills training, such as research design, data analysis and reporting. When the COVID-19 pandemic triggered an urgent need for digital education, we redesigned a research clerkship with the challenging aim to maintain original quality for more students than usual with limited teaching staff. APPROACH: We introduced the concept of a research learning community (RLC) with co-teaching and co-learning to a group of 14 students and seven teaching faculty using digital platforms. Small groups of students participated in the RLC, which was supervised weekly by the teachers. Research experts were continuously involved and led workshops. EVALUATION: Using a qualitative design, we analysed experiences from the perspectives of students and faculty. We performed an inductive thematic content analysis of three focus group interviews and used 14 student reports for triangulation. The results indicate that apart from developing research skills, students valued peer assistance, attention to uncertainty and learning beyond individual research projects. The teachers/research experts reported that co-teaching and co-learning had contributed to their professional development. In terms of organisation, students and faculty recognised that the RLC model allowed for interdisciplinary learning, facilitated by a digital platform. IMPLICATIONS: To develop students' research skills, embedding a clerkship in an RLC is an attractive alternative to individual research clerkships. The obligatory learning goals are met. Co-learning and co-teaching foster faculty's and students' professional development. When translating to other curricula, we recommend stating common goals in addition to individual objectives.

A Qualitative Study of Knowledge of Metabolic Syndrome, Attitudes about Lifestyle Modifications, and Preferences for Lifestyle Interventions among Patients with Cancer and Metabolic Syndrome.

Background: Nearly 60% of patients with cancer have metabolic syndrome, which increases the risk of mortality, but there is no clear guidance for oncology providers about its management. Here, we report on the qualitative component of a larger mixed methods study that aimed to understand cancer patients' knowledge, attitudes, and preferences regarding metabolic syndrome. Methods: Adult cancer patients with metabolic syndrome were recruited during 2022-2023 in the MD Anderson General Internal Medicine clinic and participated in semistructured interviews focused on metabolic syndrome and lifestyle interventions. Interviews were audio-recorded and transcribed verbatim. Participants' demographic information was collected. Interviews were analyzed using hybrid thematic analysis and constant comparison involving deductive and inductive coding. Researcher triangulation and debriefing were used to ensure rigor. Results: There were 19 participants, 12 female and 12 White. Eighteen had solid tumors, including gynecologic (n = 5), genitourinary (n = 4), colorectal (n = 3), and breast (n = 2). Analysis yielded 5 major themes: 1) patients' understanding of metabolic syndrome; 2) attitudes about and approaches to managing metabolic syndrome; 3) capacity and limitations regarding managing metabolic syndrome; 4) patient-led care; and 5) tailored intervention plans. Participants had limited knowledge of metabolic syndrome and its cancer-related consequences; most desired additional education. Many participants reported that their cancer or diabetes diagnosis motivated them to prioritize lifestyle Modifications. Participants expressed strong interest in personalized care plans focused on healthy lifestyle rather than simply weight loss. As part of their tailored intervention plans, participants desired clear communication with their medical team, coordination of care among team members, and collaboration with providers about treatment decisions. Conclusion: Cancer patients with metabolic syndrome want collaborative, patient-centered care. Shared decision-making based on respect for patients' distinctive needs and preferences is an essential component of the development of such collaborative care. Tailored interventions, practical implementation strategies, and personalized care plans are needed for cancer patients with metabolic syndrome. The study findings contribute to filling the gap in knowledge regarding clear guidance for oncology providers on managing metabolic syndrome and will inform the development of future lifestyle interventions for patients diagnosed with metabolic syndrome.

Efficient Narrowband Photoconductivity of the Excitonic Resonance in Two-Dimensional Ruddlesden-Popper Perovskites Due to Exciton Polarons.

Filter-less, wavelength-selective photodetectors made of perovskite usually rely on the charge collection narrowing mechanism, which intrinsically limits the response times. Using the narrow excitonic peak of, e.g., two-dimensional (2D) Ruddlesden-Popper perovskites as direct absorbers to realize color-selective photodetectivity promises faster responses. However, one major challenge in realizing such devices remains the separation and charge carrier extraction of the tightly bound excitons. Here, we report on filter-less color-selective photoconductivity in 2D perovskite butylammonium lead iodide thin film devices, exhibiting a distinct resonance in the photocurrent spectrum with a full width at half-maximum of 16.5 nm that correlates to the excitonic absorption. Our devices exhibit unexpectedly efficient charge carrier separation with an external quantum efficiency of ≤8.9% at the excitonic resonance, which we trace back to the involvement of exciton polarons. Our photodetector achieves response times of 150 µs and a maximum specific detectivity of 2.5 × 1010 Jones at the excitonic peak.

Seeing the Other: How Residents Expand Their Perspective by Learning With the Arts.

Background: Engaging with the arts can enrich medical education by fostering transformative learning, reflection, and a holistic view of the patient. Objective: To explore the development of professional competence of residents in prolonged arts-based medical education. Methods: We followed residents (n=99) of various specialties as they engaged in arts-based learning through creative and reflective assignments such as painting, sculpting, and formal analysis. Participants were interviewed about their learning process and experiences, one-on-one and in small groups, by independent researchers using short, semistructured interviews. We used grounded theory to inform an iterative process for data collection and analysis over the course of 3 years (2016-2018). Results: Seven themes were constructed, which showed that (1) slowing down education provides room for reflection; (2) absence of judgment and rules sparks experimentation; (3) engaging with emotions fostered reflection and motivation; (4) the artists' methods provided a perspective change; (5) a holistic view on the patient emerged; (6) residents understood the need to take control over their professional development; and (7) there were barriers to overcome in terms of hierarchy and expectations. Our investigation shows that interns and residents undergo a perspective transformation. Key to the development of the physicians in training is the open and affective nature of the arts in education. Conclusions: Arts-based learning results in a new perspective for physicians in training in line with patient-centered health care and self-directed learning.

Community paramedic hospital reduction and mitigation program: study protocol for a randomized pragmatic clinical trial.

BACKGROUND: New patient-centered models of care are needed to individualize care and reduce high-cost care, including emergency department (ED) visits and hospitalizations for low- and intermediate-acuity conditions that could be managed outside the hospital setting. Community paramedics (CPs) have advanced training in low- and high-acuity care and are equipped to manage a wide range of health conditions, deliver patient education, and address social determinants of health in the home setting. The objective of this trial is to evaluate the effectiveness and implementation of the Care Anywhere with Community Paramedics (CACP) program with respect to shortening and preventing acute care utilization. METHODS: This is a pragmatic, hybrid type 1, two-group, parallel-arm, 1:1 randomized clinical trial of CACP versus usual care that includes formative evaluation methods and assessment of implementation outcomes. It is being conducted in two sites in the US Midwest, which include small metropolitan areas and rural areas. Eligible patients are ≥ 18 years old; referred from an outpatient, ED, or hospital setting; clinically appropriate for ambulatory care with CP support; and residing within CP service areas of the referral sites. Aim 1 uses formative data collection with key clinical stakeholders and rapid qualitative analysis to identify potential facilitators/barriers to implementation and refine workflows in the 3-month period before trial enrollment commences (i.e., pre-implementation). Aim 2 uses mixed methods to evaluate CACP effectiveness, compared to usual care, by the number of days spent alive outside of the ED or hospital during the first 30 days following randomization (primary outcome), as well as self-reported quality of life and treatment burden, emergency medical services use, ED visits, hospitalizations, skilled nursing facility utilization, and adverse events (secondary outcomes). Implementation outcomes will be measured using the RE-AIM framework and include an assessment of perceived sustainability and metrics on equity in implementation. Aim 3 uses qualitative methods to understand patient, CP, and health care team perceptions of the intervention and recommendations for further refinement. In an effort to conduct a rigorous evaluation but also speed translation to practice, the planned duration of the trial is 15 months from the study launch to the end of enrollment. DISCUSSION: This study will provide robust and timely evidence for the effectiveness of the CACP program, which may pave the way for large-scale implementation. Implementation outcomes will inform any needed refinements and best practices for scale-up and sustainability. TRIAL REGISTRATION: ClinicalTrials.gov NCT05232799. Registered on 10 February 2022.

A detailed description of the distress trajectory from pre- to post-treatment in breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: To characterize the distress trajectory in patients with newly diagnosed, non-metastatic breast cancer from pre-neoadjuvant chemotherapy until 12 months after onset of treatment and to identify demographic and clinical predictors of distress in these patients. METHODS: In a retrospective, longitudinal study, chart review data were abstracted for 252 eligible patients treated at a comprehensive cancer care center. The center screens for distress at least monthly with the distress thermometer; the highest distress score per month was included in the analyses. The growth trajectory was established using mixed modeling and predictors were added to the initial growth model in subsequent models. RESULTS: Distress showed a cubic growth trajectory with highest distress prior to treatment onset followed by a steep decline in the first three months of treatment. A slight increase in distress was apparent over months 6-10. Being Hispanic was associated with a stronger increase in distress in the second half of the year (p = 0.012). NACT was associated with lower distress and surgery with higher distress (both: p < 0.001). CONCLUSION: Distress is at its peak prior to treatment onset and rapidly decreases once treatment has started. Oncologist should be aware that both completion of NACT and undergoing surgery are associated with increases in distress and Hispanic patients may be more at risk for an increase in distress at these times; this suggests that careful monitoring of distress during the treatment trajectory and in Hispanic patients in particular in order to provide timely support.

Measurement and Management of Cognitive Load in Surgical Education: A Narrative Review.

BACKGROUND: Cognitive load should be considered in designing optimal educational programs in health care. Despite the highly demanding nature of surgery and surgical education, a consensus on how to manage cognitive load has not been established. The objective of this review is to map out how recent surgical education research incorporates cognitive load. METHODS: A literature search was performed using keywords related to cognitive load and digital education up to December 2021. Studies published in English relevant to assessment and management of cognitive load in surgical education were included. Terminology, assessment tools, association with different surgical procedures and training modalities, and programs considering cognitive load were reported. RESULTS: We identified several terms to describe cognitive load. Cognitive load was measured by subjective, self-reported questionnaires and by objective measurements, such as physiological parameters or estimated by reaction time to secondary tasks. Subjective measurements reported cognitive load in one or multiple dimensions. Correlations between subjective and objective measurements were shown in multiple studies. Overall, higher cognitive load was observed in training for more complex tasks and high-fidelity modalities, and among less experienced trainees. Cognitive load theory has been lately incorporated into designing teaching programs. CONCLUSIONS: A broad range of terms and assessment tools were identified for cognitive load. To maximize the learning outcome, management of cognitive load is necessary in surgical education. This review summarizes the current knowledge in assessment and management of cognitive load in surgical education and provides suggestions for future studies.

Development of spatially variant photonic crystals to control light in the near-infrared spectrum.

Spatially Variant Photonic Crystals (SVPCs) have shown the ability to control the propagation and direction of light in the near-infrared spectrum. Using a novel approach for simplified modeling and fabrication techniques, we designed unique, spatially-varied, unit-cell structures to develop photonic crystals that maintain self-collimation and direction of light for desired beam tuning applications. The finite-difference time-domain technique is used to predict the self-collimation and beam-bending capabilities of our SVPCs. These SVPC designs and the simulation results are verified in laboratory testing. The experimental evidence shows that two-dimensional SVPCs can achieve self-collimation and direct light through sharp bends. The simplicity and quality of these designs show their potential for widespread implementation in modern devices. These SVPCs will serve as a unique solution to optical systems for optical computing, multiplexing, data transfer, and more.

Non-tumorigenic epithelial breast cells and ionizing radiation cooperate in the enhancement of mesenchymal traits in tumorigenic breast cancer cells.

AIMS: Radioresistance and recurrences are crucial hindrances in cancer radiotherapy. Fractionated irradiation can elicit a mesenchymal phenotype in irradiated surviving cells and a deep connection exists between epithelial mesenchymal transition, radioresistance, and metastasis. The aim of this study was to analyze the effect of the secretoma of irradiated non-tumorigenic mammary epithelial cells on surviving irradiated breast tumor cells regarding the gain of mesenchymal traits and migratory ability. MAIN METHODS: MDA-MB-231 and MCF-7 breast cancer cells, irradiated or not, were incubated with conditioned media from MCF-10A non-tumorigenic epithelial breast cells, irradiated or not. After five days, we evaluated the expression and localization of epithelial and mesenchymal markers (by western blot and indirect immunofluorescence), cell migration (using transwells) and metalloproteinases activity (by zymography). We also assessed TGF-ß1 content in conditioned media by immunoblot, and the effect of A83-01 (a selective inhibitor of TGF-ß receptor I) and PP2 (a Src-family tyrosine kinase inhibitor) on nuclear Slug and cell migration. KEY FINDINGS: Conditioned media from MCF-10A cells caused phenotypic changes in breast tumor cells with attainment or enhancement of mesenchymal traits mediated at least in part by the activation of the TGF-ß type I receptor and a signaling pathway involving Src activation/phosphorylation. The effects were more pronounced mostly in irradiated tumor cells treated with conditioned media from irradiated MCF-10A. SIGNIFICANCE: Our results suggest that non-tumorigenic epithelial mammary cells included in the irradiation field could affect the response to irradiation of post-surgery residual cancer cells enhancing EMT progression and thus modifying radiotherapy efficacy.

Associations between fatigue and cellular metabolism in breast cancer patients: A longitudinal study.

PURPOSE: Fatigue is frequently experienced during treatment for cancer and persists for months to years after treatment completion in a subset of patients. The underlying mechanisms remain poorly understood. We postulated that reduced cellular energy metabolism may underlie fatigue in cancer patients and survivors and tested this hypothesis in a sample of patients newly diagnosed with early-stage breast cancer (n = 49) followed for approximately 1 year from before the start of neoadjuvant chemotherapy (NACT) till after treatment completion. METHODS: Patient-reported fatigue was assessed with the Checklist Individual Strength, and blood samples were obtained before, during, and shortly after NACT. A final assessment was completed after surgery and radiation therapy, 4-6 months after NACT. At each study time point, mitochondrial oxygen consumption and glycolytic activity were measured in peripheral blood mononuclear cells (PBMC). Associations of these measures of PBMC energy metabolism with fatigue were assessed in multilevel models. RESULTS: Before NACT, higher mitochondrial oxygen consumption and glycolytic activity were associated with higher fatigue, whereas after completion of all primary treatment, these assessments were associated with lower fatigue. CONCLUSION: These findings suggest that lower cellular energy metabolism after treatment may be a novel target for interventions aimed at preventing or reducing persistent fatigue. Earlier studies investigated the use of supplements for maintaining mitochondrial health during treatment, with mixed results; when proven to be safe, such interventions may be more effective after treatment and in individuals with reduced mitochondrial oxygen consumption rates.

Neurenteric Cyst of the Posterior Cranial Fossa: A Case Report and Literature Review.

Neurenteric cysts (NCs) are rare benign endodermal lesions of the central nervous system (CNS), most commonly found in the spinal cord. Intracranial lesions are rare, among which the posterior fossa appears to be the predominant location. We present a case of a 60-year-old man who presented with a suddenly decreased level of consciousness. After a series of radiological studies were done, a multilobulated cystic lesion in the right posterior fossa was observed. Surgical resection was performed and based on its histopathological characteristics, NC diagnosis was confirmed. Because of the wide list of differential diagnoses and low specificity of radiological features, surgical gross total resection remains the most effective treatment, followed by diagnosis confirmation through histopathological techniques.

From Clinic to Classroom: Two Case Studies of Youth With ASD and Anxiety From the School-Based Facing Your Fears Program.

Cognitive behavioral therapy (CBT) is considered best practice for treating anxiety in youth with autism spectrum disorder (ASD) in clinic settings. However, there is significant need to translate CBT into school settings. This paper presents two case illustrations of students who participated in the Facing Your Fears: School-Based program (FYF-SB), a manualized, group CBT intervention for anxiety in ASD, adapted for delivery in schools by interdisciplinary school providers. Students showed improvement in anxiety across multiple domains following intervention, according to clinical interview and parent- and self-report. These outcomes suggest that anxious youth with ASD can benefit from CBT delivered by interdisciplinary school providers. Importantly, decreases in anxiety symptoms were evident in domains that were not explicitly targeted during intervention. Overall, these case illustrations help frame areas of future research, including examining how treatment gains may generalize across anxiety domains as well as whether corresponding improvement in school functioning occurs.