The tumor microenvironment (TME) is increasingly recognized as a dynamic regulator of cancer progression and therapeutic resistance. Far from being a passive scaffold, the TME comprises diverse immune and stromal components, including cancer-associated fibroblasts, myeloid-derived suppressor cells, tumor-associated macrophages, dysfunctional vasculature, and metabolic stressors, that collectively shape tumor evolution and modulate treatment response. In this review, we explore how spatial immune exclusion, immune cell dysfunction, hypoxia, and metabolic reprogramming create barriers to effective therapy, particularly in tumors refractory to immune checkpoint inhibition. We detail the molecular and cellular mechanisms by which the TME enforces immune suppression and dampens the efficacy of chemotherapy, radiotherapy, and immunotherapy. Moreover, we highlight emerging strategies to therapeutically reprogram the TME, including anti-fibrotic therapies, vascular normalization, myeloid reprogramming, metabolic modulation, and novel platforms such as oncolytic viruses, nanoparticles, and bispecific antibodies. By dissecting both established and innovative approaches, we emphasize the importance of combinatorial and context-specific interventions aimed at increasing immune accessibility and functional competence in selected contexts, thereby improving the likelihood of therapy responsiveness. A deeper understanding of the TME’s complexity offers critical opportunities to overcome resistance and improve outcomes across cancer types.

Background/Objectives: Chronic spontaneous urticaria (CSU) is an immune-mediated skin disorder, with increasing evidence suggesting its association with autoimmune thyroid diseases. The presence of antithyroid antibodies (anti-TPO and anti-TG) and autoimmune thyroid disease indicates shared immunological mechanisms in the pathogenesis of both conditions. This study examines the prevalence of autoimmune thyroid changes in patients with CSU. Methods: The study was conducted as a combined retrospective-prospective observational analysis. It included 43 patients with CSU and 50 healthy participants in the control group. Thyroid hormone levels (TSH, T3, T4), anti-TPO and anti-TG antibodies, as well as ultrasound characteristics of the thyroid gland, were analyzed. Results: In patients with CSU, a higher prevalence of hypothyroidism (27.9% vs. 4% in the control group), hypertension, asthma, and diabetes were observed. Elevated levels of anti-TPO antibodies were found in 51.2% of CSU patients, compared to only 6% in the control group (p < 0.001). Similarly, anti-TG antibodies were increased in 41.9% of CSU patients, compared to 4% in the control group. Additionally, ultrasound analysis revealed significant differences in thyroid morphology, with a heterogeneous structure observed in 72.1% of CSU patients, compared to only 14% in the control group (p < 0.001). Nodular changes were present in 34.88% of CSU patients, whereas the prevalence in the control group was only 6% (p < 0.001). Conclusions: Our results confirm a significant association between CSU and autoimmune thyroid diseases, including a high prevalence of anti-TPO and anti-TG antibodies, hypothyroidism, diffuse heterogeneity, and nodular changes. Additionally, elevated T3 hormone levels were common among CSU patients, while T4 levels did not differ significantly from those in the control group.

Background/Objectives: Adequate knowledge and correct attitudes about the HPV vaccine influence awareness of the importance of preventing HPV-related diseases, which is particularly important for future healthcare professionals. We aim to examine the share of correct answers and the prevalence of different attitudes about the HPV vaccine among active regular students of the Faculty of Medicine in Novi Sad. Methods: A cross-sectional study was conducted from 1 to 30 November 2023 using a structured survey questionnaire. Results: A total of 1760 students were included, of which 78% were female, with an average age of 21 years. Students who participated in prior HPV education) demonstrated significantly higher knowledge (81.92% vs. 65.60%, p < 0.001) and were more likely to recommend the vaccine to patients (89.91% vs. 82.99%, p < 0.001). Almost all vaccinated students (99.41%) would recommend the vaccine, compared to 82.91% of unvaccinated students (p < 0.001). Students who actively sought HPV information also showed a higher likelihood of recommending the vaccine (93.05% vs. 83.02%, p < 0.001). Moreover, those with sufficient self-assessed knowledge were more inclined to recommend the vaccine (89.88%) than those with insufficient knowledge (81.66%, p < 0.001). The analysis demonstrated that an increase in the number of correct answers in the knowledge evaluation corresponds to higher odds of recommending the HPV vaccine to patients (OR = 1.23, 95% CI 1.17–1.28). Positive attitudes prevailed, with 68.89% supporting more education on HPV vaccination. Conclusions: Students who previously attended education on HPV infection/vaccination and those who would recommend the vaccine have significantly higher levels of knowledge. The study highlights the importance of HPV-related education in shaping future healthcare professionals’ attitudes and knowledge.

It is estimated that more than 80% of people are infected with human papilloma virus (HPV) at some point in their lives. Knowledge about HPV infection and methods of its prevention is important for society as a whole. Medical students as future healthcare workers must be thoroughly informed about HPV infection in order to properly participate in the promotion of its prevention. The aim was to examine the knowledge and attitudes in relation to previous education about HPV infection and prevention methods. A cross-sectional study was conducted among undergraduate students at the Faculty of Medicine in Novi Sad (MFNS). The study covered all study programs and was conducted in the period from 1 to 30 November 2023, using a specially created survey questionnaire for the purposes of this research. 1760 surveys were collected, representing 70.4% of the total number of MFNS students. In the past year, only 26% of respondents attended some kind of education about HPV infection/vaccine. Statistical significance was observed in the difference between the responses of students who attended education in comparison to those who did not attend education in the past year (75.5% versus 63.3%, p < 0.001). Students who stated that they plan to get vaccinated in the following period answered the questions correctly in a higher percentage (87.5% versus 80.1%, p = 0.01). Students of the Faculty of Medicine in Novi Sad, as future healthcare workers, demonstrated certain knowledge and demonstrated right attitudes. Students who attended education about HPV infection and methods of prevention had more correct answers, as did students who plan to get vaccinated in the future.

Background: Heart rate variability (HRV) reflects the autonomic nervous system’s (ANS) influence on heart rate control. Daily essential activities, such as water ingestion, affect HRV. This study aims to investigate the effect of cold water intake on HRV in young, healthy females.Materials and Methods: Fourteen healthy young females participated in the study during the luteal phase of their menstrual cycle. R-R intervals were recorded using an ECG, 5 min before and 35 min after the ingestion. We used LabChart to determine HRV parameters from time (HR, rMSSD, pRR50) and frequency (LF, HF) domains. Data were processed in JASP using repeated-measures ANOVA to compare parameters across five different 5-min ECG segments. A post hoc Bonferroni test revealed specific time points where significant differences occurred.Results: Statistically significant differences were found in all HRV parameters. The post hoc test revealed differences between pre-ingestion and post-ingestion intervals, while no significant differences were found among the post-ingestion periods. Both branches of the ANS were activated. A statistically significant increase in LF, indicating sympathetic activation, and in rMSSD and pRR50 components, reflecting parasympathetic activity, was observed immediately after cold water ingestion compared to the pre-ingestion period. HF became statistically significantly higher 10 min after cold water ingestion.Conclusion: In young healthy females, the ANS responds coordinately to cold water ingestion, activating both branches to maintain homeostasis, preventing heat loss through sympathetic activation and limiting excessive increases in blood pressure and heart rate via parasympathetic regulation.

Background: Tumor budding is an adverse histopathological feature in colorectal cancer, but its role in colorectal liver metastases (CRLM) remains insufficiently defined. This study explored the association between tumor budding density and clinical outcomes in resected synchronous and metachronous CRLM. Methods: This single-center ambispective cohort included 77 patients who underwent R0 resection of CRLM between 2007 and 2017. Tumor budding density was assessed in liver metastases and classified as low (0–9 buds per field) or high (≥10 buds per field). Outcomes were analyzed according to tumor budding density, metastatic timing, and preoperative regimen. Results: Forty-one patients had synchronous and 36 had metachronous CRLM. Overall, 64 patients received preoperative systemic therapy, including FOLFOX4 in 38 and FOLFOX4 plus bevacizumab in 26. Low tumor budding density was associated with better 2-year overall survival in synchronous CRLM, both in the pooled cohort (95.2% vs. 65.0%, p = 0.015) and in patients treated with FOLFOX4 (90.9% vs. 55.6%, p = 0.049) or FOLFOX4 plus bevacizumab (100.0% vs. 66.7%, p = 0.048). No significant association was observed in metachronous CRLM. Kaplan-Meier analyses of time to progression and 5-year overall survival did not show significant differences by tumor budding density. Conclusion: Tumor budding density showed an exploratory association with 2-year overall survival in patients with synchronous resected colorectal liver metastases, but this association was not consistently observed in metachronous disease or in long-term time-to-event analyses. These findings suggest that tumor budding may reflect aggressive metastatic biology, but larger standardized studies are required before it can be considered an independent prognostic marker.