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Background: Human glioblastoma multiforme (GBM) is a highly aggressive tumor with insufficient therapies available. Especially, novel concepts of immune therapies fail due to a complex immunosuppressive microenvironment, high mutational rates, and inter-patient variations. The intratumoral heterogeneity is currently not sufficiently investigated.

Methods: Biopsies from six different locations were taken in a cohort of 16 GBM patients who underwent surgery. The tissue slides were analyzed utilizing high-content imaging microscopy and algorithm-based image quantification. Several immune markers for macrophage and microglia subpopulations were investigated. Flow cytometry was used to validate key results. Besides the surface marker, cytokines were measured and categorized based on their heterogenicity and overall expression.

Results: M2-like antigens, including CD204, CD163, Arg1, and CSF1R, showed comparatively higher expression, with GFAP displaying the least intratumoral heterogeneity. In contrast, anti-tumor-macrophage-like antigens, such as PSGL-1, CD16, CD68, and MHC-II, exhibited low overall expression and concurrent high intratumoral heterogeneity. CD16 and PSGL-1 were the most heterogeneous antigens. High expression levels were observed for cytokines IL-6, VEGF, and CCL-2. VILIP-a was revealed to differentiate most in principle component analysis. Cytokines with the lowest overall expression, such as TGF-β1, β-NGF, TNF-α, and TREM1, showed low intratumoral heterogeneity, in contrast to βNGF, TNF-α, and IL-18, which displayed high heterogeneity despite low expression.

Conclusion: The study showed high intratumoral heterogeneity in GBM, emphasizing the need for a more detailed understanding of the tumor microenvironment. The described findings could be essential for future personalized treatment strategies and the implementation of reliable diagnostics in GBM.

When clinician-educators and medical education researchers use and discuss medical education research, they can advance innovation in medical education as well as improve its quality. To facilitate the use and discussions of medical education research, we created a prefatory visual representation of key medical education research topics and associated experts. We conducted one-on-one virtual interviews with medical education journal editorial board members to identify what they perceived as key medical education research topics as well as who they associated, as experts, with each of the identified topics. We used content analysis to create categories representing key topics and noted occurrences of named experts. Twenty-one editorial board members, representing nine of the top medical education journals, participated. From the data we created a figure entitled, Medical Education Research Library. The library includes 13 research topics, with assessment as the most prevalent. It also notes recognized experts, including van der Vleuten, ten Cate, and Norman. The key medical education research topics identified and included in the library align with what others have identified as trends in the literature. Selected topics, including workplace-based learning, equity, diversity, and inclusion, physician wellbeing and burnout, and social accountability, are emerging. Once transformed into an open educational resource, clinician-educators and medical education researchers can use and contribute to the functional library. Such continuous expansion will generate better awareness and recognition of diverse perspectives. The functional library will help to innovate and improve the quality of medical education through evidence-informed practices and scholarship.

India has been historically challenged by an insufficient and heterogeneously clustered distribution of healthcare infrastructure. While resource-limited healthcare settings, such as major parts of India, require multidisciplinary approaches for improvement, one key approach is the recruitment and training of a healthcare workforce representative of its population. This requires overcoming barriers to equity and representation in Indian medical education that are multi-faceted, historical, and rooted in inequality. However, literature is lacking regarding the financial or economic barriers, and their implications on equity and representation in the Indian allopathic physician workforce, which this review sought to describe. Keyword-based searches were carried out in PubMed, Google Scholar, and Scopus in order to identify relevant literature published till November 2023. This state-of-the-art narrative review describes the existing multi-pronged economic barriers, recent and forthcoming changes deepening these barriers, and how these may limit opportunities for having a diverse workforce. Three sets of major economic barriers exist to becoming a specialized medical practitioner in India - resources required to get selected into an Indian medical school, resources required to pursue medical school, and resources required to get a residency position. The resources in this endeavor have historically included substantial efforts, finances, and privilege, but rising barriers in the medical education system have worsened the state of inequity. Preparation costs for medical school and residency entrance tests have risen steadily, which may be further exacerbated by recent major policy changes regarding licensing and residency selection. Additionally, considerable increases in direct and indirect costs of medical education have recently occurred. Urgent action in these areas may help the Indian population get access to a diverse and representative healthcare workforce and also help alleviate the shortage of primary care physicians in the country. Discussed are the reasons for rural healthcare disparities in India and potential solutions related to medical education.

CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines in vitro. Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.

Academics in medicine are frequently asked to serve on panels to discuss their clinical, research, education, administrative or personal expertise. While panel discussions are often the highlight of a conference or event, in the medical literature, there is very little published on how an individual can effectively prepare and present as an expert panelist. This paper offers guidelines that will enable academics to prepare, deliver, and engage in active dialogue during a panel discussion. Specific tactics include how to accept invitations to serve on a panel, conducting pre-panel conference meetings and background research, preparing concise opening statements and new insights, connecting with the audience, answering questions in a collaborative spirit, and debriefing after the panel. These guidelines will be valuable to any individual invited to serve on a panel discussion and will promote future panelists in engaging in constructive and fulfilling dialogue, with the ultimate goal of leaving the audience with a greater understanding of the topic of discourse.

Introduction: People who identify as lesbian, gay, bisexual, transgender, queer/questioning, intersex, and other sexual/gender minorities (LGBTQ+) may experience discrimination when seeking healthcare. Medical students should be trained in inclusive and affirming care for LGBTQ+ patients. This narrative literature review explores the landscape of interventions and evaluations related to LGBTQ+ health content taught in medical schools in the USA and suggests strategies for further curriculum development.

Methods: PubMed, ERIC, and Education Research Complete databases were systematically searched for peer-reviewed articles on LGBTQ+ health in medical student education in the USA published between 1 January 2011-6 February 2023. Articles were screened for eligibility and data was abstracted from all eligible articles. Data abstraction included the type of intervention or evaluation, sample population and size, and key outcomes.

Results: One hundred thirty-four articles met inclusion criteria and were reviewed. This includes 6 (4.5%) that evaluate existing curriculum, 77 (57.5%) study the impact of curriculum components and interventions, 36 (26.9%) evaluate student knowledge and learning experiences, and 15 (11.2%) describe the development of broad learning objectives and curriculum. Eight studies identified student knowledge gaps related to gender identity and affirming care and these topics were covered in 34 curriculum interventions.

Conclusion: Medical student education is important to address health disparities faced by the LGBTQ+ community, and has been an increasingly studied topic in the USA. A variety of curriculum interventions at single institutions show promise in enhancing student knowledge and training in LGBTQ+ health. Despite this, multiple studies indicate that students report inadequate education on certain topics with limitations in their knowledge and preparedness to care for LGBTQ+ patients, particularly transgender and gender diverse patients. Additional integration of LGBTQ+ curriculum content in areas of perceived deficits could help better prepare future physicians to care for LGBTQ+ patients and populations.

Aim: Functional gastrointestinal (GI) disorders are recognized as a major public health concern worldwide. These disorders involve persistent digestive symptoms indicative of digestive tract dysfunction.Materials and Methods: A survey examining the utilisation of probiotics and medicinal plants as supplementary treatments was conducted on 160 patients with GI disorders at healthcare institutions in Saïda from March to April 2023 using questionnaires that had been previously adapted and tested for reliability with Cronbach's alpha test. Raw data collected through the questionnaires were transferred to a database and analysed using SPSS software.Results: Overall, 49.38% of participants possessed knowledge of or actively utilised probiotics; such awareness was strongly associated with the participants' educational attainment (p = 0.029). The noteworthy probiotic supplements were Biocharbon (36.09%), Lactocil (15.38%), Smebiocta (13.61%), Ultrabiotic Adult (12.43%), Effidigest (12.43%), and Ultralevure (7.69%). During crisis, individuals tended to consume natural goods rich in probiotics, including yoghurt (13.26%) and fermented milk (8.60%), as well as foods rich in prebiotic fibre, including vegetables (18.99%), fruits (13.26%), wheat (9.67%), bran (7.52%), rye (6.81%), and oat flakes (6.45%). Additionally, 77.56% of patients used medicinal plants during crises, with Mentha spicata (12.2%), Thymus vulgaris (11.3%), Pimpinella anisum (8.5%), Cuminum cyminum (8.0%), Punica granatum (7.8%), Trachyspermum ammi (7.5%), and Senna acutifolia (7.0%) being the more commonly favoured options in phytotherapy. The main focus of these herbs was to alleviate bloating (57%), constipation (30.12%), and diarrhoea (12.87%) (p < 0.001). The most frequently utilised plant parts were leaves (47.30%), seeds (25.21%), and bark (13.21%). Most patients (82.91%) favoured infusion as their preferred consumption method, and approximately 85.43% believed in phytotherapy's ability to extend symptomatic relief.Conclusion: The understanding of probiotics is still in its infancy, whereas phytotherapy is more widely accepted by patients. Nonetheless, patients are open to the exploration of natural alternatives to conventional medicines.

Innovation is of fundamental importance for improving food production, as well as sustainability food production. Since 1960, food production has benefited from innovations in plant breeding technologies, fertilizer, chemicals and equipment. These innovations have dramatically increased food production, while the amount of land used has minimally increased. However, future food production increases are jeopardized from widening knowledge gaps between rural food producers and large urban food consuming populations. Over time, that gap has fueled disinformation. The development of disinformation business models contributes to urban consumers receiving inaccurate information about the importance of inputs essential to food production, resulting in political pressures being applied that are targeted at reductions in the use of many food production inputs. The use of chemicals are a frequent target of disinformation campaigns. This article examines how the lack of government clarity about the safe use of chemicals contributes to a lack of public information.

Background: The impact of heat waves and atmospheric oxidising pollutants on residential mortality within the framework of global climate change has become increasingly important.

Objective: In this research, the interactive effects of heat waves and oxidising pollutants on the risk of residential mortality in Fuzhou were examined. Methods We collected environmental, meteorological, and residential mortality data in Fuzhou from 1 January 2016, to 31 December 2021. We then applied a generalised additive model, distributed lagged nonlinear model, and bivariate three-dimensional model to investigate the effects and interactions of various atmospheric oxidising pollutants and heat waves on the risk of residential mortality.

Results: Atmospheric oxidising pollutants increased the risk of residential mortality at lower concentrations, and O3 and Ox were positively associated with a maximum risk of 2.19% (95% CI: 0.74-3.66) and 1.29% (95% CI: 0.51-2.08). The risk of residential mortality increased with increasing temperature, with a strong and long-lasting effect and a maximum cumulative lagged effect of 1.11% (95% CI: 1.01, 1.23). Furthermore, an interaction between atmospheric oxidising pollutants and heat waves may have occurred: the larger effects in the longest cumulative lag time on residential mortality per 10 µg/m3 increase in O3, NO2 and Ox during heat waves compared to non-heat waves were [-3.81% (95% CI: -14.82, 8.63)]; [-0.45% (95% CI: -2.67, 1.81)]; [67.90% (95% CI: 11.55, 152.71)]; 16.37% (95% CI: 2.43, 32.20)]; [-3.00% (95% CI: -20.80, 18.79)]; [-0.30% (95% CI: -3.53, 3.04)]. The risk on heat wave days was significantly higher than that on non-heat wave days and higher than the separate effects of oxidising pollutants and heat waves.

Conclusions: Overall, we found some evidence suggesting that heat waves increase the impact of oxidising atmospheric pollutants on residential mortality to some extent.