Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.

Lung cancer (LC) is a highly invasive malignancy and the leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) as its most prevalent histological subtype. Despite all breakthroughs achieved in drug development, the prognosis of NSCLC remains poor. The mitogen-activated protein kinase signaling cascade (MAPKC) is a complex network of interacting molecules that can drive oncogenesis, cancer progression, and drug resistance when dysregulated. Over the past decades, MAPKC components have been used to design MAPKC inhibitors (MAPKCIs), which have shown varying efficacy in treating NSCLC. Thus, recent studies support the potential clinical use of MAPKCIs, especially in combination with other therapeutic approaches. This article provides an overview of the MAPKC and its inhibitors in the clinical management of NSCLC. It addresses the gaps in the current literature on different combinations of selective inhibitors while suggesting two particular therapy approaches to be researched in NSCLC: parallel and aggregate targeting of the MAPKC. This work also provides suggestions that could serve as a potential guideline to aid future research in MAPKCIs to optimize clinical outcomes in NSCLC.

A Comprehensive View on the Impact of Chlorogenic Acids on Colorectal Cancer.

Chlorogenic acids are plant secondary metabolites, chemically-polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress.

Genetic Profiling and Survival Outcomes in Romanian Colorectal Cancer Patients.

BACKGROUND: The increasing incidence of colorectal cancer is one of the most frequently addressed medical topics worldwide. It represents the third most commonly diagnosed cancer in both men and women globally, with significant implications for public health. Mortality for this type of malignancy remains high, second only to lung cancer. Given their clinical relevance, the identification and understanding of KRAS and BRAF mutations have become crucial components of personalized medicine approaches in colorectal cancer. Hence, our desire is to carry out a research that analyzes the impact of these mutations in terms of survival and mortality on patients diagnosed with colorectal cancer. METHODS: We conducted a retrospective study spanning from 2018 to 2022, which involved 118 patients diagnosed with colorectal cancer. The patients were selected from the databases of the Oradea County Emergency Clinical Hospital and Pelican Oradea Hospital. Genetic testing was performed at the "Resident Laboratory" clinic. Subsequently, patients were divided into two groups of equal size based on the presence or absence of mutations. RESULTS: The survival rate one year after the diagnosis of colorectal cancer is 84.74% (N=50/59) for the mutant group versus 67.96% (N=40/59) for the wild-type group. The survival rate at five years from the diagnosis of colorectal cancer is 25.93% (N=15/59) for patients with wild-type tumors compared to 33.54% (N=20/59) for patients with tumors with mutant status (p=0.483, HR=1.153, CI 95% 0.7661-1.735). The five-year survival rate, depending on the mutation present, highlights the fact that the average overall survival for those with the KRAS mutation is 38.6 months (CI 95% 35.22-41.97) and for those with the BRAF mutation is 8.3 months (CI 95% 5.42-11.17) (p=0.039). The mortality rate for mutant KRAS is 44.89% (N=22/50), while for those with mutant BRAF, it is 100% (N=6/6). CONCLUSIONS: We observed no statistically significant difference in overall survival rate and disease-free interval between the two studied groups, but the overall survival was better for those with mutations present (38.64 months versus 31.07 months for wild-type tumors). The mortality rate is higher among tumors with wild-type status (p=0.005), in the first year after the diagnosis of colorectal cancer. The BRAF mutation confers a much worse prognosis than the KRAS mutation, from both the survival analysis and the mortality rate.

Family resilience in a social-ecological context - emotional difficulties and coping strategies.

Introduction: This research explored how crises such as the pandemic influence the family dynamic and the way that the parents and the children face new difficulties and challenges. The present study investigates children's and young people's emotional states, the dimensions of family resilience, and the types of coping strategies and parents' emotional states during the coronavirus pandemic. The final sample for the research was represented by 1,010 parents from Romania. Methods: The present scientific research is a transversal study with the scope to understand the emotional difficulties that parents and children/ young people face and the coping strategies that they adopt in a crisis, such as the time of the coronavirus pandemic. Results: Parents with maladaptive coping strategies are more affected by the pandemic. Also, the results indicate that there is a significant correlation between parental coping strategies and the children's emotional states, and the adaptability level. Therefore, the high scores on the subscales which measure maladaptive coping indicate high scores of the levels of depression, anxiety, and stress of the parents. Family resilience, through the dimension of 'communication and problem-solving in the family' has a moderation role in the relationship between parental depression and the maladaptive coping strategy of rumination. Family resilience through 'maintaining a positive attitude' has a moderation role in the relationship between catastrophizing and the teenagers' level of adaptability. Discussion: The results of the study pointed out the role and place of family resilience within the family system and how a period of crisis can affect this system.

Premature Mortality Excess Rates Before and During the COVID-19 Pandemic: A Comparative Analysis Conducted in Bihor County, Romania.

BACKGROUND: Estimating the excess of premature deaths (before the age of 75 years) and Potential Years of Life Lost allows ranking causes of death as an expression of the burden of disease in a population. We statistically analysed the impact of the coronavirus disease 2019 (COVID-19) pandemic on excess premature mortality in the total population and specifically, by sexes, compared to the pre-pandemic period, through Potential Years of Life Lost. MATERIAL AND METHOD: In this retrospective descriptive observational study, we counted excess of premature mortality in the years 2020, 2021, and 2022 by cause of death (cardiovascular diseases, cancer, digestive diseases, injury, COVID-19, and other causes) and by sexes compared to the period average from 2017-2019, based on the deaths registered in Bihor County (48,948 people). RESULTS: Premature deaths due to COVID-19 (1,745 people of both sexes) contributed 71.3% to excess mortality, the population being similar for both sexes (71.4% in men and 71.2% in women). The Potential Years of Life Lost/death due to COVID-19 was 11.84 years for both sexes (11.76 years in men and 12.02 years in women). Potential Years of Life Lost/all-cause heath was lower during the pandemic (13.42 years for both sexes, 14.06 years for men and 12.32 years for women) compared to the pre-pandemic period (14.6 years for both sexes, 15.1 years for men and 13.5 years for women). CONCLUSIONS: The excess of premature mortality and decreased Potential Years of Life Lost/death during the pandemic, shows an increase in the proportion of deaths at ages closer to the established limit for premature mortality (75 years) compared to the pre-pandemic period.

The Impact of SARS-CoV-2 Pandemic on Antibiotic Prescriptions and Resistance in a University Hospital from Romania.

This paper aimed to evaluate the effects of the COVID-19 pandemic on prescription rates and antibiotic resistance in a university hospital. A retrospective study was conducted on the medical records of patients admitted to the Bihor Emergency Clinical County Hospital in Romania in 2019 (pre-pandemic) and 2021 (during the pandemic period). We evaluated the antibiotic consumption index (ACI) and susceptibility rates. The overall percentage of antibiotic prescribing increased in 2021, while the total number of patients decreased. Genito-urinary, digestive, respiratory infections, heart diseases and wounds were the most common conditions for antibiotic prescriptions, but the number of them decreased in 2021. There was a decrease in the proportion of antibiotics from the Watch and Reserve class and an increase in the proportion of antibiotics from the Access class. Antibiotic use has been reduced despite an increase in the number of patients, with a high consumption in the Watch group in the ICU wards. By contrast, surgical wards had the highest rate of antibiotic prescriptions, but a decrease in the number of patients. The patients who were administered antibiotics were hospitalized for diagnoses other than COVID-19. Almost all prescribed antibiotics displayed decreasing sensitivity rates. The number of isolated ESKAPE pathogens, except for Staphylococcus aureus methicillin-resistant strains, were increased. Strategies to control antibiotic prescriptions and the spread of resistant pathogens should be improved.

Histopathology Features of H. pylori Gastritis Associated With Altered Lipid Profile: An Observational Study from a Tertiary Healthcare Center in North West Romania.

BACKGROUND/AIM: H. pylori infection can promote a systemic inflammatory syndrome, eventually leading to intestinal metaplasia and gastric cancer. The aim of our study was to investigate the possible association between dyslipidemia and histopathological features of H. pylori gastritis. PATIENTS AND METHODS: An observational, retrospective study was conducted over the period 2017-2022 on symptomatic patients with a positive rapid urease test. A total of 121 patients who underwent upper gastrointestinal endoscopy with stomach biopsy were enrolled in this study. Based on the updated Sydney System, we investigated the association between neutrophils, mononuclear cells, intestinal metaplasia, or gastric atrophy and altered lipid profiles. RESULTS: A high prevalence of H. pylori infection was noticed in the studied group upon the application of the rapid urease test, being associated with dyslipidemia regardless of patient sex. All the endoscopic diagnoses (acute, chronic, or atrophic chronic gastritis, metaplasia) correlated with the histopathological features. Mononuclear cells and metaplasia were more likely to be found in H. pylori-positive patients with dyslipidemia, which is consistent with acute and chronic inflammation caused by H. pylori in the gastric mucosa. CONCLUSION: Although our study was conducted on a small scale, it offers new insights and details regarding H. pylori infection and histopathological features. Mononuclear cells and metaplasia were associated with an altered lipid profile in H. pylori-positive patients. These findings warrant future investigation, such as the evolution of gastric biopsies and lipid profiles before and after eradication.

Prompt Placental Histopathological and Immunohistochemical Assessment after SARS-CoV-2 Infection during Pregnancy-Our Perspective of a Small Group.

Research indicates compelling evidence of SARS-CoV-2 vertical transmission as a result of placental pathology. This study offers an approach to histopathological and immunohistochemical placental observations from SARS-CoV-2-positive mothers compared to negative ones. Out of the 44 examined placentas, 24 were collected from patients with a SARS-CoV-2 infection during pregnancy and 20 were collected from patients without infection. The disease group showed strong SARS-CoV-2 positivity of the membranes, trophoblasts, and fetal villous macrophages. Most infections occurred during the third trimester of pregnancy (66.6%). Pathology revealed areas consistent with avascular villi (AV) and thrombi in the chorionic vessels and umbilical cord in the positive group, suggesting fetal vascular malperfusion (FVM). This study shows SARS-CoV-2 has an impact on coagulation, demonstrated by fetal thrombotic vasculopathy (p = 0.01) and fibrin deposition (p = 0.01). Other observed features included infarction (17%), perivillous fibrin deposition (29%), intervillous fibrin (25%), delayed placental maturation (8.3%), chorangiosis (13%), chorioamnionitis (8.3%), and meconium (21%). The negative control group revealed only one case of placental infarction (5%), intervillous fibrin (5%), delayed placental maturation (5%), and chorioamnionitis (5%) and two cases of meconium (19%). Our study sheds light on the changes and differences that occurred in placentas from SARS-CoV-2-infected mothers and the control group. Further research is necessary to definitively establish whether SARS-CoV-2 is the primary culprit behind these intricate complications.

Breaking Barriers: AI's Influence on Pathology and Oncology in Resource-Scarce Medical Systems.

The application of artificial intelligence to improve the access of cancer patients to high-quality medical care is one of the goals of modern medicine. Pathology constitutes the foundation of modern oncologic treatment, and its role has expanded far beyond diagnosis into predicting treatment response and overall survival. However, the funding of pathology is often an afterthought in resource-scarce medical systems. The increased digitalization of pathology has paved the way towards the potential use of artificial intelligence tools for improving pathologist efficiency and extracting more information from tissues. In this review, we provide an overview of the main research directions intersecting with artificial intelligence and pathology in relation to oncology, such as tumor classification, the prediction of molecular alterations, and biomarker quantification. We then discuss examples of tools that have matured into clinical products and gained regulatory approval for clinical use. Finally, we highlight the main hurdles that stand in the way of the digitalization of pathology and the application of artificial intelligence in pathology while also discussing possible solutions.

Covid-19 and Its Impact on Colorectal Cancer Diagnosis in Romania: A Single-Centered 5-year Retrospective Cohort Study.

Background: Colorectal cancer, 3rd in incidence and 2nd in mortality among cancers worldwide, represents the most common malignant tumor of the digestive tract. In Romania, it is the most frequently diagnosed type of cancer (approximately 0.06% of the population/year). During the COVID-19 pandemic the legislation preventing the SARS-CoV-2 viral transmission impairing access to outpatient healthcare services combined with patients fear of SARS-CoV-2 infection had consequences on the diagnosis and treatment of all other pathologies. Methods: A 5-year retrospective cohort study was conducted in a tertiary hospital in Arad, Romania, and included 1329 newly diagnosed colorectal cancer patients. For statistical analysis, Fisher's exact test was used for categorical data and the unpaired test with Welch's correction for continuous data. Results: The age on diagnosis decreased during the early COVID-19 pandemic to 68.50 (95% CI [67.90 69.11]) years, with the highest percentage (7.41%) of early onset colorectal cancer patients, a steady post-pandemic increase in the percentage of male (52.71% in 2019 to 62.20% in 2022) and urban (54.18% in 2018 to 70.10% in 2022) patients, admitted to the hospital due to an emergency presentation (peaking at 83.95% in 2020) and requiring a longer hospitalization period (10.03 [95% CI (8.76-11.30)] days in 2020 to 8.37 [95% CI (7.44-9.30)] days in 2022). The most common colo-rectal cancer diagnosis of patients in our reference population was malignant neoplasm of the rectum (ICD-10 code C20.0), while the most common complications were peritumoral adherence-related disorder, occlusion, and perforation, encountered in patients with comorbidities such as arterial hypertension, ischemic cardiomyopathy, diabetes mellitus, obesity, and non-alcoholic steatohepatitis. Conclusions: Regional particularities should be analyzed to better target the population at risk and to better direct the necessary healthcare resources towards the reference population, especially during crisis periods similar to the COVID-19 pandemic.

Cutaneous metastasis of rectal adenocarcinoma: a case report and literature review.

According to the latest data provided by Globocan 2020, the incidence of colorectal cancer ranks third, after lung cancer and breast cancer, becoming a more and more important global health issue. Of the cases diagnosed with colorectal cancer, more than 25% are diagnosed in the metastatic stage, with the presence of secondary tumors more frequently in the liver, lung and bone. Skin metastases from colorectal cancer are still rare today (< 4%). We want to present a rare, unique case in our department of a 74-year-old patient diagnosed 9 years ago with a malignant rectal tumor who, after a disease-free period of approximately 8 years and a half, developed multiple skin metastases of rectal adenocarcinoma.

A Comprehensive Analysis: Evaluating Security Characteristics of Xbee Devices against Zigbee Protocol.

In recent times, the security of sensor networks, especially in the field of IoT, has become a priority. This article focuses on the security features of the Zigbee protocol in Xbee devices developed by Digi International, specifically in the Xbee 3 (XB3-24) devices. Using the TI LaunchXL-CC26X2R1 kit, we intercepted and analyzed packets in real-time using the Wireshark application. The study encompasses various stages of network formation, packet transmission and analysis of security key usage, considering scenarios as follows: without security, distributed security mode and centralized security mode. Our findings highlight the differences in security features of Xbee devices compared to the Zigbee protocol, validating and invalidating methods of establishing security keys, vulnerabilities, strengths, and recommended security measures. We also discovered that security features of the Xbee 3 devices are built around a global link key preconfigured therefore constituting a vulnerability, making those devices suitable for man-in-the-middle and reply attacks. This work not only elucidates the complexities of Zigbee security in Xbee devices but also provides direction for future research for authentication methods using asymmetric encryption algorithms such as digital signature based on RSA and ECDSA.

A Rare Case of an Occult Primary Tumor With a Profile of Colon Cancer and Synchronous Metastasis in the Lung, Liver, Bone, and Cerebellum: A Case Report and Literature Review.

Occult primary tumors, or cancers of unknown primary site (CUP), are an oncological pathology characterized by the presence of metastases but without being able to determine the presence of the primary tumor. These types of tumors are very rare, and they pose challenges for diagnosis and treatment. Colorectal cancer is the most common type of malignant tumor worldwide and the second most common cause of death. The most common sites of metastasis in colorectal cancer are hepatic and pulmonary. Relatively rare, patients develop brain and bone metastasis. We reported a rare case of an occult primary tumor with a profile of colon cancer and synchronous metastasis in the lung, liver, bone, and cerebellum developed in a woman who was only 51 years old.

The Glioblastoma CircularRNAome.

Glioblastoma remains one of the most aggressive cancers of the brain, warranting new methods for early diagnosis and more efficient treatment options. Circular RNAs (circRNAs) are rather new entities with increased stability compared to their linear counterparts that interact with proteins and act as microRNA sponges, among other functions. Herein, we provide a critical overview of the recently described glioblastoma-related circRNAs in the literature, focusing on their roles on glioblastoma cancer cell proliferation, survival, migration, invasion and metastasis, metabolic reprogramming, and therapeutic resistance. The main roles of circRNAs in regulating cancer processes are due to their regulatory roles in essential oncogenic pathways, including MAPK, PI3K/AKT/mTOR, and Wnt, which are influenced by various circRNAs. The present work pictures the wide implication of circRNAs in glioblastoma, thus highlighting their potential as future biomarkers and therapeutic targets/agents.

Laser in the Treatment of Atonic Wounds.

Atonic wounds represent a major health problem, being frequently encountered in medical practice with consequences that have a negative impact on the patient's daily life as well as their general condition. In this study, a brand laser with a 12-watt probe was used to stimulate patients' wounds. We involved in this study a group of 65 patients, which was compared with a group of 30 patients, the latter not receiving this laser therapy. The data were accumulated from the questionnaire of subjective assessment of the laser impact on patients' condition as well as from the local evolution. We noticed the improvement of the local symptomatology which was found to be more effective in the patients from the study group compared to the reference group. The beneficial and positive effects, mainly on the symptoms but also on the local evolution of atonic wounds, can be observed in our study. We consider that this therapy is of major importance considering the lower costs both from the shortening of hospitalization and the long-term use of various substances. The early reintegration of patients into daily life is an important benefit for them.

Platelets Rich Plasma (PRP) Procedure in the Healing of Atonic Wounds.

(1) Background: Patients suffering from chronic wounds report physical, mental, and social consequences due to their existence and care. There is a global need for tissue repair strategies and, in our case, for chronic wound healing. PRP therapy is based on the fact that platelet-derived growth factors (PGF) support the three phases of the wound healing and repair cascade (inflammation, proliferation, and remodeling); (2) Methods: A comparative study was carried out on two groups of patients with atonic wounds totaling a total of 80 cases as follows: a study group in which the PRP procedure was applied and a control group in which the biological product was not injected. The study was carried out in the surgery clinic of the Clinical Hospital C.F. Oradea City; (3) Results: A much faster healing was achieved in the case of patients who benefited from the platelet-rich plasma injection therapy compared to the group of patients in whom this therapy was not used. Three weeks after the plasma injection, a considerable reduction of the wound was evident, with some of the patients presenting with a closed wound; (4) Conclusions: The effect of PRP on the healing of chronic wounds is promising in most cases. A positive effect was also highlighted in terms of reducing treatment costs by considerably reducing the materials used as well as the number of hospitalizations for the same pathology.

Hypersensitivity and lymphocyte activation after total hip arthroplasty.

In the last decades total hip arthroplasty (THA) has become a standard procedure with many benefits but also a few still unsolved complications, which can lead to surgical revision in 19-23% of cases. Thus, aseptic loosening and metal hypersensitivity remain challenges. The phenomenon of wear debris causes chronic inflammation, which produces osteolysis and aseptic loosening. Wear debris promotes osteoclast production and inhibits osteoblasts by secretion of pro-inflammatory cytokines. Micro-abrasions can be induced by abrasive, adhesive and fatigue wear and cause a liberation of metal ions, which lead to another immune response elicited mostly by macrophages. Another reaction in the neocapsule can be a type IV hypersensitivity reaction to various alloys, containing metals such as nickel, cobalt and chromium. Patch testing and the lymphocyte transformation test (LTT) are not the best diagnostic possibilities to exclude a postoperative hypersensitivity reaction, because of the different alignment of the epicutaneous cells compared to the periprosthetic deep tissue. This hypersensitivity reaction is mostly induced by cytokines, which are secreted by macrophages rather than lymphocytes. In cell cultures and in animal studies, multipotent mesenchymal stem cells (MSC) have been shown to play a role in improving initial implant integration, to limit periprosthetic osteolysis and also to reconstitute peri-implant bone stock during implant revision. Thus, MSC might be used in the future to prolong the durability of THA. A better understanding of the interactions between primary chronic inflammation, corrosion, osteolysis and hypersensitivity is mandatory to develop new therapeutic strategies, aiming at the reduction of the incidence of implant failures. In this article the underlying immunological mechanisms to aseptic loosening are presented.

Epidermoid Cyst of the Uterine Cervix, an Unusual Location: Literature Review and Case Report.

Epidermoid cysts are most often benign cystic lesions, with uterine cervical localisation being very unusual. We present the case of a 52-year-old female patient diagnosed with an epidermoid cyst at the level of the uterine cervix. A bioptic and haemostatic uterine curettage was performed, followed by total hysterectomy with bilateral adnexectomy. The histopathologic analysis and immunohistochemical essay of the resection specimens confirmed the cervical epidermoid cyst. The presence of high-risk HPV (human papillomavirus) was only seen in the cervical mucosa. The exact etiopathogenesis is unknown, but postpartum cell implantation of reminiscent embryonic tissue can be involved in the development of these lesions.

Identification and validation of core genes as promising diagnostic signature in hepatocellular carcinoma based on integrated bioinformatics approach.

The primary objective of this investigation was to determine the hub genes of hepatocellular carcinoma (HCC) through an in silico approach. In the current context of the increased incidence of liver cancers, this approach could be a useful prognostic biomarker and HCC prevention target. This study aimed to examine hub genes for immune cell infiltration and their good prognostic characteristics for HCC research. Human genes selected from databases (Gene Cards and DisGeNET) were used to identify the HCC markers. Further, classification of the hub genes from communicating genes was performed using data derived from the targets' protein-protein interaction (PPI) platform. The expression as well as survival studies of all these selected genes were validated by utilizing databases such as GEPIA2, HPA, and immune cell infiltration. Based on the studies, five hub genes (TP53, ESR1, AKT1, CASP3, and JUN) were identified, which have been linked to HCC. They may be an important prognostic biomarker and preventative target of HCC. In silico analysis revealed that out of five hub genes, the TP53 and ESR1 hub genes potentially act as key targets for HCC prevention and treatment.

Exploring the plant-derived bioactive substances as antidiabetic agent: An extensive review.

Diabetes mellitus (DM) is a metabolic syndrome. Diabetes has become more common in recent years. Chemically generated drugs are used to lessen the effects of DM and its following repercussions due to unpleasant side effects such as weight gain, gastrointestinal issues, and heart failure. On the other hand, medicinal plants could be a good source of anti-diabetic medications. This article aims to determine any plant matrix's positive potential. Food restriction, physical activity, and the use of antidiabetic plant-derived chemicals are all being promoted as effective ways to manage diabetes because they are less expensive and have fewer or no side effects. This review focuses on antidiabetic plants, along with their bioactive constituent, chemically characterization, and plant-based diets for diabetes management. There is minimal scientific data about the mechanism of action of the plant-based product has been found. The purpose of this article is to highlight anti-diabetic plants and plant-derived bioactive compounds that have anti-diabetic properties. It also provides researchers with data that may be used to build future strategies, such as identifying promising bioactive molecules to make diabetes management easier.