Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic Discrimination of Alternative Lymph Node Classification Systems for Patients with Radically Resected Non-Metastatic Colorectal Cancer: A Cohort Study from a Single Tertiary Referral Center

Simple Summary We compared the predictive and prognostic performance of different lymph node classification systems regarding overall survival in patients with colorectal cancer (CRC). Distinct lymph node ratio (LNR) and Log odds of positive lymph nodes (LODDS) classifications demonstrated prognostic superiority over the N category only in patients with Stage III CRC. Abstract Background: Lymph node ratio (LNR) and the Log odds of positive lymph nodes (LODDS) have been proposed as a new prognostic indicator in surgical oncology. Various studies have shown a superior discriminating power of LODDS over LNR and lymph node category (N) in diverse cancer entities, when examined as a continuous variable. However, for each of the classification systems various cut-off values have been defined, with the question of the most appropriate for patients with CRC still remaining open. The present study aimed to compare the predictive impact of different lymph node classification systems and to define the best cut-off values regarding accurate evaluation of overall survival in patients with resectable, non-metastatic colorectal cancer (CRC). Methods: CRC patients who underwent surgical resection from 1996 to 2018 were extracted from our medical data base. Cox proportional hazards regression models and C-statistics were performed to assess the discriminative power of 25 LNR and 26 LODDS classifications. Regression models were adjusted for age, sex, extent of the tumor, differentiation, tumor size and localization. Results: Our study group consisted of 654 consecutive patients with non-metastatic CRC. C-statistic revealed 2 LNR and 5 LODDS classifications that demonstrated superior prognostic performance in patients with UICC III CRC, compared to the N category. No clear advantage of one classification over another could be demonstrated in any other patient subgroup. Conclusions: Distinct LNR and LODDS classifications demonstrate a prognostic superiority over the N category only in patients with Stage III radically resected CRC.
Heterogeneous Myeloid Cells in Tumors

Simple Summary It is well known that lymphocytes play a key role in the immunosurveillance for tumors. Accumulating evidence indicates that myeloid cells also have a large impact on tumor development. The tumor-associated myeloid cells (TAMCs) are heterogeneous and exert distinct and even opposing effects on tumor cells and tumor microenvironment (TME). In addition, myeloid cells play a critical role in modulating the behavior of lymphocytes, resulting in immunostimulatory or immunosuppressive TME cues that stimulate or suppress tumor development. Based on the function of myeloid cells in tumors, there are pro-tumor and anti-tumor myeloid cells. They are involved in pleiotropic processes, including growth, survival, differentiation, stemness, invasiveness, dissemination and metastasis of tumor cells, angiogenesis, remodeling of TME, immunomodulation, and response to cancer therapy. Understanding the function and mechanism of TAMCs in tumors will shed light on uncovering novel therapy. Abstract Accumulating studies highlight a critical role of myeloid cells in cancer biology and therapy. The myeloid cells constitute the major components of tumor microenvironment (TME). The most studied tumor-associated myeloid cells (TAMCs) include monocytes, tumor-associated macrophages (TAMs), dendritic cells (DCs), cancer-related circulating neutrophils, tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). These heterogenous myeloid cells perform pro-tumor or anti-tumor function, exerting complex and even opposing effects on all stages of tumor development, such as malignant clonal evolution, growth, survival, invasiveness, dissemination and metastasis of tumor cells. TAMCs also reshape TME and tumor vasculature to favor tumor development. The main function of these myeloid cells is to modulate the behavior of lymphocytes, forming immunostimulatory or immunosuppressive TME cues. In addition, TAMCs play a critical role in modulating the response to cancer therapy. Targeting TAMCs is vigorously tested as monotherapy or in combination with chemotherapy or immunotherapy. This review briefly introduces the TAMC subpopulations and their function in tumor cells, TME, angiogenesis, immunomodulation, and cancer therapy.
Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients

Simple Summary Current treatment protocols for pediatric patients with T-Lymphoblastic lymphoma (T-LBL) allow the achievement of a complete remission in around 85% of T-LBL pediatric patients; however the overall survival rate of second-line treatments for patients with progressive disease or relapse is around 14%. Thus, the major issues to be addressed are the identification of a valuable predictor marker to foresee the disease risk and new therapeutic targets to improve relapsed/resistant patients’ outcome. We identified JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target for patients with progressive disease or relapse and suggest that its inhibition by ruxolitinib, a JAK1/2 FDA approved inhibitor, could represent a novel therapeutic approach to overcome therapy resistance and meliorate the outcome of pediatric T-LBL patients. Abstract Lymphoblastic lymphoma (LBL) is the second most common type of non-Hodgkin lymphoma in childhood, mainly of T cell origin (T-LBL). Although current treatment protocols allow a complete remission in 85% of cases, the second-line treatment overall survival for patients with progressive or relapsed disease is around 14%, making this the major issue to be confronted. Thus, we performed a Reverse Phase Protein Array study in a cohort of 22 T-LBL patients to find reliable disease risk marker(s) and new therapeutic targets to improve pediatric T-LBL patients’ outcome. Interestingly, we pinpointed JAK2 Y1007-1008 as a potential prognosis marker as well as a therapeutic target in poor prognosis patients. Hence, the hyperactivation of the JAK1/2-STAT6 pathway characterizes these latter patients. Moreover, we functionally demonstrated that STAT6 hyperactivation contributes to therapy resistance by binding the glucocorticoid receptor, thus inhibiting its transcriptional activity. This was further confirmed by specific STAT6 gene silencing followed by dexamethasone treatment. Finally, JAK1/2-STAT6 pathway inhibition by ruxolitinib, an FDA approved drug, in cell line models and in one T-LBL primary sample led to cell proliferation reduction and increased apoptosis. Globally, our results identify a new potential prognostic marker and suggest a novel therapeutic approach to overcome therapy resistance in pediatric T-LBL patients.
Permafrost condition determines plant community composition and community‐level foliar functional traits in a boreal peatland

Abstract Boreal peatlands are critical ecosystems globally because they house 30%–40% of terrestrial carbon (C), much of which is stored in permafrost soil vulnerable to climate warming‐induced thaw. Permafrost thaw leads to thickening of the active (seasonally thawed) layer and alters nutrient and light availability. These physical changes may influence community‐level plant functional traits through intraspecific trait variation and/or species turnover. As permafrost thaw is expected to cause an efflux of carbon dioxide (CO2) and methane (CH4) from the soil to the atmosphere, it is important to understand thaw‐induced changes in plant community productivity to evaluate whether these changes may offset some of the anticipated increases in C emissions. To this end, we collected vascular plant community composition and foliar functional trait data along gradients in aboveground tree biomass and active layer thickness (ALT) in a rapidly thawing boreal peatland, with the expectation that changes in above‐ and belowground conditions are indicative of altered resource availability. We aimed to determine whether community‐level traits vary across these gradients, and whether these changes are dominated by intraspecific trait variation, species turnover, or both. Our results highlight that variability in community‐level traits was largely attributable to species turnover and that both community composition and traits were predominantly driven by ALT. Specifically, thicker active layers associated with permafrost‐free peatlands (i.e., bogs and fens) shifted community composition from slower‐growing evergreen shrubs to faster‐growing graminoids and forbs with a corresponding shift toward more productive trait values. The results from this rapidly thawing peatland suggest that continued warming‐induced permafrost thaw and thermokarst development alter plant community composition and community‐level traits and thus ecosystem productivity. Increased productivity may help to mitigate anticipated CO2 efflux from thawing permafrost, at least in the short term, though this response may be swamped by increase CH4 release.
Changes in perceptions of the alcohol environment among participants in a Photovoice project conducted in two districts with different socio-economic status

Perceptions of the alcohol environment may influence alcohol consumption patterns. The purpose of this study was to describe changes in perceptions of the urban alcohol environment as experienced by residents of two districts with different socio-economic status after taking part in a Photovoice study. The study was conducted in Madrid, Spain, in a district with a high socio-economic status (HSES) and another district with a low socio-economic status (LSES). A Photovoice project was conducted with 26 participants divided into four groups based on sex and district. Groups met over five sessions in which they discussed photographs taken by the participants themselves on the subject of alcohol in their neighbourhood. A qualitative, descriptive and thematic analysis of participants’ discourses was performed to explore changes in their perceptions of the alcohol environment over the project sessions. Changes in perceptions of the alcohol environment were observed in all groups over the project. The process of change varied by districts’ socio-economic characteristics and gender. Greater changes in perceptions of the alcohol environment were observed in HSES, especially among women, as the participants had a much more positive initial view of their alcohol environment. In LSES, participants showed a more critical perception of the alcohol environment from the beginning of the study, and this broadened and intensified over the course of the sessions. Changes in perceptions also varied by thematic categories, including some categories that were discussed from the start (e.g. socialising and alcohol consumption) and categories that only emerged in later sessions (e.g. alcohol advertising). Involvement in a Photovoice project has favoured a shift in the participant’s perceptions of their alcohol environment towards more critical positions, widening their scope of perceived elements and raising their awareness of specific problems, such as alcohol advertising and social role of alcohol consumption in relation to alcohol exposure.
The Role of RNA Secondary Structure in Regulation of Gene Expression in Bacteria

Due to the high exposition to changing environmental conditions, bacteria have developed many mechanisms enabling immediate adjustments of gene expression. In many cases, the required speed and plasticity of the response are provided by RNA-dependent regulatory mechanisms. This is possible due to the very high dynamics and flexibility of an RNA structure, which provide the necessary sensitivity and specificity for efficient sensing and transduction of environmental signals. In this review, we will discuss the current knowledge about known bacterial regulatory mechanisms which rely on RNA structure. To better understand the structure-driven modulation of gene expression, we describe the basic theory on RNA structure folding and dynamics. Next, we present examples of multiple mechanisms employed by RNA regulators in the control of bacterial transcription and translation.
Assessing the Educational and Supportive Care Needs of Canadian Metastatic Melanoma Patients and Survivors Attending an Outpatient Clinic

The rapid development of metastatic melanoma treatment options has significantly improved overall survival, but paralleled patient educational and supportive care resources have fallen behind. Particularly, the need for grassroots programs targeting environments outside urban centers has grown. Accordingly, an environmental scan of the Durham region in Ontario, Canada, showed the lack of melanoma-specific resources for outpatients. The goal of this study was to identify the needs of metastatic melanoma patients and survivors attending a large outpatient clinic in Durham, and then develop a patient-reviewed intervention plan. Needs were assessed in 5 domains through a melanoma-specific supportive care needs assessment survey. Among 75 surveyed melanoma patients and survivors, high-level needs were identified in 3 domains: psychological, health system information, and melanoma-specific information. Furthermore, domain-specific needs were heightened in specific sociodemographic groups. Based on these survey results, a multifaceted intervention plan was developed to mitigate future needs. The intervention plan was patient-reviewed in focus groups prior to implementation, refining the developed intervention plan.
Depletion of Psoas Muscle Mass after Systemic Chemotherapy Is Associated with Poor Prognosis in Patients with Unresectable Pancreatic Cancer

Simple Summary The psoas muscle mass index (PMI) is a simplified tool used in the quantification of skeletal muscle. The aim of our study was to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The median overall survival (OS) was 278.0 (95% confidence interval (CI), 199.1–356.9) days in the high-PMI group, and 221.0 (95% CI, 90.9–351.1) days in the low-PMI group (p = 0.329). The median OS was 347.0 (95% CI, 289.1–404.9) days in the group without PMI decrease and 172.0 (95% CI, 129.8–214.2) days in the group with PMI decrease (p = 0.001). We determined that the PMI at diagnosis was not associated with OS in patients with unresectable pancreatic cancer receiving systemic chemotherapy, whereas PMI decrease during chemotherapy influenced the OS. Abstract The impact of the psoas muscle mass index (PMI) on survival is still poorly understood in unresectable pancreatic cancer. Thus, we aimed to investigate whether the PMI at diagnosis or its decrease during chemotherapy can influence the prognosis of unresectable pancreatic cancer. The data of 100 patients were analyzed, and they were divided into two groups according to the median PMI in each sex. Subsequently, 72 patients undergoing computed tomography (CT) within 30–100 days from CT at diagnosis were evaluated in terms of PMI change rate, and divided into two groups based on the median. We evaluated the clinical characteristics and outcomes in terms of the PMI at diagnosis or its decrease during chemotherapy. The median PMI was 5.00 in males, and 3.66 in females. The median overall survival (OS) was 278.0 days in the high-PMI group and 221.0 days in the low-PMI group (p = 0.329). The median PMI change rate was −2.4%. The median OS was 347.0 days in the group without PMI decrease and 172.0 days in the group with PMI decrease (p = 0.001). We determined that a pivotal prognostic factor was not the PMI at diagnosis, but rather PMI decrease during chemotherapy in unresectable pancreatic cancer.
Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and “prion-like disease”, amyotrophic lateral sclerosis, Huntington’s disease, Friedreich’s ataxia, and depression.
Glutamatergic Signaling a Therapeutic Vulnerability in Melanoma

Simple Summary Out of all the skin cancers, melanoma is the most aggressive and dangerous form due to its high metastatic propensity. Patients with late-stage melanomas have poor prognosis as their five-year survival rate is only 27% while the survival rate for primary melanomas is 99%. Metastatic melanomas are resistant to most therapeutic approaches, progress quickly, and account for the majority of mortalities in melanoma patients. Melanomas like other cancers are driven by the dysregulation of the normal cellular networks that leads to uncontrolled cell proliferation, altered cellular metabolism and dissemination of tumor cells to distal organs. Our lab has described the oncogenic role of a normal neuronal receptor, Metabotropic Glutamate Receptor 1, that when aberrantly expressed in melanocytes leads to deregulated glutamatergic signaling in melanocytes. Activation of this receptor results in a cascade of disorders that promote cell transformation and tumor formation. Here we will explore the contribution of abnormal glutamatergic signaling to melanoma. Abstract Like other cancers, melanomas are associated with the hyperactivation of two major cell signaling cascades, the MAPK and PI3K/AKT pathways. Both pathways are activated by numerous genes implicated in the development and progression of melanomas such as mutated BRAF, RAS, and NF1. Our lab was the first to identify yet another driver of melanoma, Metabotropic Glutamate Receptor 1 (protein: mGluR1, mouse gene: Grm1, human gene: GRM1), upstream of the MAPK and PI3K/AKT pathways. Binding of glutamate, the natural ligand of mGluR1, activates MAPK and PI3K/AKT pathways and sets in motion the deregulated cellular responses in cell growth, cell survival, and cell metastasis. In this review, we will assess the proposed modes of action that mediate the oncogenic properties of mGluR1 in melanoma and possible application of anti-glutamatergic signaling modulator(s) as therapeutic strategy for the treatment of melanomas.
Be Aware of Burnout! The Role of Changes in Academic Burnout in Problematic Facebook Usage among University Students

Most previous research has examined the relationship between FB addiction and burnout level by conducting cross-sectional studies. Little is known about the impact of changes in burnout on FB addiction in an educational context. Through a two-way longitudinal survey of a student population sample (N = 115), this study examined the influence of changes in academic burnout over time and FB motives and importance (measured at the beginning and the end of the semester) on FB intrusion measured at the end of the academic semester. The findings show that: (1) increases in cynicism and in FB motives and importance significantly predicted time2 FB intrusion; (2) FB importance enhanced the prediction power of changes in the academic burnout total score, exhaustion and personal inefficacy, and reduced the regression coefficient of changes in cynicism; (3) the interaction effects between FB social motive use and changes in academic burnout, as well as between FB importance and personal inefficacy and exhaustion, accounted for a significant change in the explained variance of time2 FB intrusion. About 20–30% of the variance in time2 FB intrusion was explained by all the examined variables and by the interactions between them. The results suggest that changes in academic burnout and FB motives and importance are suppressive variables, as including these variables in the regression model all together changed the significance of the relationship between independent variables and FB intrusion.
Precision Medicine and Triple-Negative Breast Cancer: Current Landscape and Future Directions

Simple Summary The implementation of precision medicine will revolutionize cancer treatment paradigms. Notably, this goal is not far from reality: genetically similar cancers can be treated similarly. The heterogeneous nature of triple-negative breast cancer (TNBC) made it a suitable candidate to practice precision medicine. Using TNBC molecular subtyping and genomic profiling, a precision medicine-based clinical trial is ongoing. This review summarizes the current landscape and future directions of precision medicine and TNBC. Abstract Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer associated with a high recurrence and metastasis rate that affects African-American women disproportionately. The recent approval of targeted therapies for small subgroups of TNBC patients by the US ‘Food and Drug Administration’ is a promising development. The advancement of next-generation sequencing, particularly somatic exome panels, has raised hopes for more individualized treatment plans. However, the use of precision medicine for TNBC is a work in progress. This review will discuss the potential benefits and challenges of precision medicine for TNBC. A recent clinical trial designed to target TNBC patients based on their subtype-specific classification shows promise. Yet, tumor heterogeneity and sub-clonal evolution in primary and metastatic TNBC remain a challenge for oncologists to design adaptive precision medicine-based treatment plans.