How to measure quality of surgery as a component of multimodality treatment of gastric cancer.

Gastric cancer (GC) is one of the most frequent reasons for cancer-related death worldwide. The multimodal therapeutic strategies are now pragmatically tailored to each patient, especially in advanced GC. A radical but safe gastrectomy remains the cornerstone of the GC treatment. Moreover, the quality-of-life (QoL) outcome measures are now routinely utilized in order to select optimal type of gastrectomy, as well as reconstruction method. Postoperative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. The postoperative complications prolong hospital stay and may result in poor QoL, thus eliminating the completion of perioperative adjuvant therapy. Therefore, avoiding morbidity is not only relevant for the immediate postoperative course, but can also affect long-term oncological outcome. Measuring outcome enables surgeons to: monitor their own results; compare quality of treatment between centres; facilitate improvement both for surgery alone and combined treatment; select optimal procedure for an individual patient. Textbook oncological outcome is a composite quality measure representing the ideal hospitalization for gastrectomy, as well as stage-appropriate (perioperative) adjuvant chemotherapy. Standardized system for recording complications and adherence to multimodality treatment guidelines are crucial for achieving the ultimate goal of surgical quality-improvement that can benefit patients QoL and long-term outcomes after fast and uneventful hospitalization for gastrectomy.

A Clinician's perspective on the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer management.

The prevention of intraperitoneal spread is of utmost importance in the management of advanced ovarian cancer (OC), thus demanding the exploration of innovative treatment techniques. The propensity of OC to spread to the peritoneum has highlighted the potential of local therapy as a promising approach. Among the proposed treatments thus far are several local intraperitoneal therapies, with hyperthermic intraperitoneal chemotherapy (HIPEC) being one of them. The application of HIPEC may potentially enhance the survival rates of patients with OC, as indicated by a recent publication of high-quality prospective data. The incorporation of HIPEC in conjunction with primary cytoreductive surgery (CRS) does not have a significant impact on either overall survival (OS) or disease-free survival (DFS). However, the incorporation of HIPEC alongside interval CRS, followed by systemic chemotherapy (CTH), markedly enhances both OS and DFS. The most recent data also substantiates the effectiveness of HIPEC in recurrent ovarian cancer (ROC), resulting in an improvement of survival outcomes. Additional research will contribute to the improvement of the HIPEC regimen and technique, as well as the precise identification of patients who will gain the most advantage from this treatment approach. It is recommended to discuss and update (inter)national clinical guidelines for managing patients with advanced OC and peritoneal involvement.

The role of biomolecular condensates in protein aggregation.

There is an increasing amount of evidence that biomolecular condensates are linked to neurodegenerative diseases associated with protein aggregation, such as Alzheimer's disease and amyotrophic lateral sclerosis, although the mechanisms underlying this link remain elusive. In this Review, we summarize the possible connections between condensates and protein aggregation. We consider both liquid-to-solid transitions of phase-separated proteins and the partitioning of proteins into host condensates. We distinguish five key factors by which the physical and chemical environment of a condensate can influence protein aggregation, and we discuss their relevance in studies of protein aggregation in the presence of biomolecular condensates: increasing the local concentration of proteins, providing a distinct chemical microenvironment, introducing an interface wherein proteins can localize, changing the energy landscape of aggregation pathways, and the presence of chaperones in condensates. Analysing the role of biomolecular condensates in protein aggregation may be essential for a full understanding of amyloid formation and offers a new perspective that can help in developing new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning.

BACKGROUND: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. METHODS: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. RESULTS: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. CONCLUSION: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.

Gut Microbiota-Adversary or Ally? Its Role and Significance in Colorectal Cancer Pathogenesis, Progression, and Treatment.

In 2022, colorectal cancer (CRC) was the third most prevalent malignancy worldwide. The therapeutic approach for CRC typically involves a multimodal regimen. The human gut microbiota comprises over 35,000 bacterial species. The composition of the gut microbiota is influenced by dietary intake, which plays a crucial role in food absorption, nutrient extraction, and the development of low-grade inflammation. Dysbiosis in the gut microbiota is a key driver of inflammation and is strongly associated with CRC development. While the gut microbiome influences CRC initiation and progression, emerging evidence suggests a role for the gut microbiome in modulating the efficacy and toxicity of cancer treatments. Therapeutic strategies targeting the gut microbiome, such as probiotics, hold promise as effective interventions in the modern therapeutical approach to CRC. For example, Microbiota Implementation to Reduce Anastomotic Colorectal Leaks (MIRACLe) implementation has resulted in improvements in clinical outcomes, including reduced incidence of anastomotic leakage (AL), surgical site infections (SSIs), reoperation, as well as shorter recovery times and hospital stays compared with the control group. Therefore, this review aims to describe the current state of knowledge regarding the involvement of the gut microbiota in CRC pathogenesis and its potential therapeutic implications to treat CRC.

Structural basis of the Integrator complex assembly and association with transcription factors.

Integrator is a multi-subunit protein complex responsible for premature transcription termination of coding and non-coding RNAs. This is achieved via two enzymatic activities, RNA endonuclease and protein phosphatase, acting on the promoter-proximally paused RNA polymerase Ⅱ (RNAPⅡ). Yet, it remains unclear how Integrator assembly and recruitment are regulated and what the functions of many of its core subunits are. Here, we report the structures of two human Integrator sub-complexes: INTS10/13/14/15 and INTS5/8/10/15, and an integrative model of the fully assembled Integrator bound to the RNAPⅡ paused elongating complex (PEC). An in silico protein-protein interaction screen of over 1,500 human transcription factors (TFs) identified ZNF655 as a direct interacting partner of INTS13 within the fully assembled Integrator. We propose a model wherein INTS13 acts as a platform for the recruitment of TFs that could modulate the stability of the Integrator's association at specific loci and regulate transcription attenuation of the target genes.

Exploring the Survival Determinants in Recurrent Ovarian Cancer: The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Recurrent ovarian cancer (ROC) significantly challenges gynecological oncology due to its poor outcomes. This study assesses the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) on ROC survival rates. MATERIALS AND METHODS: Conducted at the Medical University of Lublin from April 2011 to November 2022, this retrospective observational study involved 71 patients with histologically confirmed ROC who underwent CRS and subsequent HIPEC. RESULTS: The median overall survival (OS) was 41.1 months, with 3-year and 5-year survival rates post-treatment of 0.50 and 0.33, respectively. Patients undergoing radical surgery for primary ovarian cancer had a median OS of 61.9 months. The key survival-related factors included the Peritoneal Carcinomatosis Index (PCI) score, AGO score, platinum sensitivity, and ECOG status. CONCLUSIONS: The key factors enhancing ROC patients' survival include radical surgery, optimal performance status, platinum sensitivity, a positive AGO score, and a lower PCI. This study highlights the predictive value of the platinum resistance and AGO score in patient outcomes, underlining their role in treatment planning. Further prospective research is needed to confirm these results and improve patient selection for this treatment approach.

Textbook Neoadjuvant Outcome-Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment.

The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.

Current Status of Treatment among Patients with Appendiceal Tumors-Old Challenges and New Solutions?

The 5th edition of the World Health Organization (WHO) classification of tumors of the digestive system distinguishes four categories of appendiceal tumors (ATs): serrated lesions and polyps, mucinous neoplasms, adenocarcinomas, and neuroendocrine neoplasms (NENs). The differential diagnosis of ATs can be challenging in medical practice, due to their rarity and lack of data from randomized controlled trials on a large, diverse group of patients. ATs are usually noted in specimens obtained during appendectomies due to clinical acute appendicitis. In the European population, most ATs (65%) occur over the age of 50 and among women (56.8%). According to histological type, 54.6% are neuroendocrine tumors (NETs); 26.8% cystic, mucinous, and serous neoplasms; and 18.6% adenocarcinoma not otherwise specified (NOS). On pathologic analysis, most AT findings are benign lesions or small NENs that do not require further therapeutic measures. The presence of appendiceal mucinous neoplasm (AMN) can lead to pseudomyxoma peritonei (PMP). While the multimodal treatment for abdominal malignancies has evolved over the past several decades, the clinical workup and treatment of ATs remain a challenge. Therefore, this review aims to describe the diagnostic possibilities, molecular-based diagnosis, staging, differences in the treatment process, and prognostic factors associated with ATs.

Structure of the human 20S U5 snRNP.

The 20S U5 small nuclear ribonucleoprotein particle (snRNP) is a 17-subunit RNA-protein complex and a precursor of the U4/U6.U5 tri-snRNP, the major building block of the precatalytic spliceosome. CD2BP2 is a hallmark protein of the 20S U5 snRNP, absent from the mature tri-snRNP. Here we report a high-resolution cryogenic electron microscopy structure of the 20S U5 snRNP, shedding light on the mutually exclusive interfaces utilized during tri-snRNP assembly and the role of the CD2BP2 in facilitating this process.

Examination of Transmission Zeros in the MIMO Sensor-Based Propagation Environment Using a New Geometric Procedure.

In this paper, we propose the application of a new geometric procedure in order to calculate a set of transmission zeros of a propagation environment. Since the transmission zeros play a crucial role in modern communication systems, there is a need to apply the efficient solutions characterized by a maximum speed operation. It turns out that the classical method based on the Smith-McMillan factorization is time-consuming, so its contribution to the detection of transmission zeros could be unsatisfactory. Therefore, in order to fill the gap, we present a new algorithm strictly dedicated to the multivariable telecommunications systems described by the transfer-function approach. Consequently, a set of new achievements resulted, particularly in terms of computational efforts. Indeed, the proposed procedure allows us to overcome obstacles derived from technological limitations. The representative simulation examples confirm the great potential of this new method. Finally, it has been pointed out that the newly introduced geometric-originated approach has significantly reduced the computational burden. Indeed, for the randomly selected matrix of the 5×5 dimension describing the sensor-related propagation environment, two representative scenarios were performed in order to manifest the crucial properties. In the first scenario, the sets of multiple transmission zeros were analyzed, ultimately leading to intriguing results. The Smith-McMillan solution took three times longer to discover the mentioned sets. On the other hand, the second instance brought us the same result. Naturally, the discussed difference has increased as a function of the number of matrix elements. For the square matrices involving 100 components, we have observed the respective differences, both over QI=100 and QII=60. It should be emphasized that the finding derived from the Smith-McMillan factorization corresponds to the geometric-related approach in the context of some mechanisms. This is particularly visible when appointing the greatest common divisors.

Impact of different severity hyperglycemia on erythrocyte rheological properties1.

BACKGROUND: The triad "insulin resistance, prediabetes, diabetes" is three independent neologies with characteristic features and development. In addition, each are characterized by progression and the possibility of transition from one form to other. Due to the fact that diabetes is one of the common diseases associated with high rates of disability, it is necessary to improve diagnostic methods and educational regimens for successful prevention and treatment of the disease. OBJECTIVE: We investigated Band 3 protein (B3p) level, osmotic resistance of erythrocytes, the total antioxidant activity (TAA) of blood serum, level of HbA1 in group patients with insulin resistance (IR), prediabetes, and Type 2 Diabetes Mellitus (T2DM) and comparative with health control group. METHODS: We used original, accurate research methods that measure the essence of the studied quantities. RESULTS: Disruptions of glucose and insulin homeostasis ay lead to the initiation of oxidative stress (in our study demonstrated by a decrease of TAA of blood serum) increased redox-sensitive PTP activity and aberrant band 3 phosphorylation, potentially leading to reduced erythrocyte deformability. At the same time glycation of Hb during T2DM may affect its cross-link with membrane proteins, in particular with B3p, and although appears to limit its cross-linking and decrease its clusterization ability, induces alterations in the cytoskeletal matrix, and thereby decrease erythrocytes' osmotic resistance making them more susceptible to hemolysis. CONCLUSIONS: The osmotic resistance of the erythrocytes can be used as a sensitive marker for the detection of the early stages of hyperglycemia (prediabetes). This set of clinical trials will make it possible to identify diseases that make up the triad at an early stage. Early detection of disorders and continued research in this direction will help in the development of a diagnostic scheme for the prevention of such patients. Based on our data, research into anti-oxidation drugs is very important. With the help of the array of studies described in the article and antioxidant treatment, the likelihood of successful treatment will increase.

The unique monoclonal antibodies and immunochemical assay for comprehensive determination of the cell-bound and soluble HER2 in different biological samples.

The expression of the HER2 (human epidermal growth factor receptor 2) protein in cancer cells is a well-established cancer marker used for diagnostic and therapeutic purposes in modern treatment protocols, especially in breast cancer. The gold-standard immunohistochemical diagnostic methods with the specific anti-HER2 antibodies are utilized in the clinic to measure expression level of the membrane-bound receptor. However, a soluble extracellular domain (ECD) of HER2 is released to the extracellular matrix, thus the blood assays for HER2 measurements present an attractive way for HER2 level determination. There is a need for accurate and validated assays that can be used to correlate the concentration of the circulating HER2 protein with disease clinical manifestations. Here we describe two monoclonal antibodies binding HER2 with a unique sequence of the complementarity-determining regions that recognize HER2 ECD. Development and validation of the sandwich enzyme-linked immunosorbent assay (ELISA) for quantification of the soluble HER2 in a variety of biological samples is also presented. The assay provides HER2 quantitation within a concentrations range from 1.56 to 100 ng/ml with sensitivity at the level of 0.5 ng/ml that meets the expectations for measurements of HER2 in the blood and tumor tissue samples. The method presents satisfactory intra- and inter-assay precision and accuracy for immunochemical quantification of biomarkers in biological samples. The utility of the generated monoclonal anti-HER2 antibodies has been confirmed for use in the precise measurement of HER2 (both cell-bound and soluble) in several types of biological material, including serum, solid tumor tissue, and cell culture medium. Additionally, the developed immunochemical tools have a potential for HER2 detection, not only in a wide range of sample types but also independently of the sample storage/pre-processing, allowing for comprehensive HER2 analysis in tissue (IHC), cultured cells (immunofluorescence) and blood (ELISA).

Prognostic Value of Inflammatory Burden Index in Advanced Gastric Cancer Patients Undergoing Multimodal Treatment.

Since increasing evidence underlines the prominent role of systemic inflammation in carcinogenesis, the inflammation burden index (IBI) has emerged as a promising biomarker to estimate survival outcomes among cancer patients. The IBI has only been validated in Eastern gastric cancer (GC) patients; therefore, the aim of this study was to evaluate the IBI as a prognostic biomarker in Central European GC patients undergoing multimodal treatment. Ninety-three patients with histologically confirmed GC who underwent multimodal treatment between 2013 and 2021 were included. Patient recruitment started with the standardization of neoadjuvant chemotherapy (NAC). Blood samples were obtained one day prior to surgical treatment. The textbook outcome (TO) served as the measure of surgical quality, and tumor responses to NAC were evaluated according to Becker's system tumor regression grade (TRG). A high IBI was associated with an increased risk of postoperative complications (OR 2.95, 95% CI 1.13-7.72). In multivariate analysis, a high IBI (HR = 2.56, 95% CI 1.28-5.13) and a high neutrophil-to-lymphocyte ratio (NLR, HR = 2.55, 95% CI 1.32-4.94) were associated with an increased risk of death, while NAC administration (HR = 0.40, 95% CI 0.18-0.90) and TO achievement (HR = 0.42, 95% CI 0.22-0.81) were associated with a lower risk of death. The IBI was associated with postoperative complications and mortality among GC patients undergoing multimodal treatment.

MalnutritiOn assessment with biOelectrical impedaNce analysis in gastRic cancer patIentS undergoing multimodaltrEatment (MOONRISE)-Study protocol for a single-arm multicenter cross-sectional longitudinal study.

European data suggests that over 30% of gastric cancer (GC) patients are diagnosed with sarcopenia before surgery, while unintentional weight loss occurs in approximately 30% of patients following gastrectomy. Preoperative sarcopenia significantly increases the risk of major postoperative complications, and preoperative body weight loss remains a superior predictor of outcome and an independent prognostic factor for overall survival (OS) in patients with GC. A standardized approach of nutritional risk screening of GC patients is yet to be established. Therefore, the MOONRISE study aims to prospectively analyze the changes in nutritional status and body composition at each stage of multimodal treatment among GC patients from five Western expert centers. Specifically, we seek to assess the association between nutritional status and body composition on tumor response following neoadjuvant chemotherapy (NAC). Secondary outcomes of the study are treatment toxicity, postoperative complications, quality of life (QoL), and OS. Patients with locally advanced gastric adenocarcinoma scheduled for multimodal treatment will be included in the study. Four consecutive nutritional status assessments will be performed throughout the treatment. The following study was registered in ClinicalTrials.gov (Identifier: NCT05723718) and will be conducted in accordance with the STROBE statement. The anticipated duration of the study is 12-24 months, depending on the recruitment status. Results of this study will reveal whether nutritional status and body composition assessment based on BIA will become a validated and objective tool to support clinical decisions in GC patients undergoing multimodal treatment.

Methodology of generation of CFD meshes and 4D shape reconstruction of coronary arteries from patient-specific dynamic CT.

Due to the difficulties in retrieving both the time-dependent shapes of the vessels and the generation of numerical meshes for such cases, most of the simulations of blood flow in the cardiac arteries use static geometry. The article describes a methodology for generating a sequence of time-dependent 3D shapes based on images of different resolutions and qualities acquired from ECG-gated coronary artery CT angiography. The precision of the shape restoration method has been validated using an independent technique. The original proposed approach also generates for each of the retrieved vessel shapes a numerical mesh of the same topology (connectivity matrix), greatly simplifying the CFD blood flow simulations. This feature is of significant importance in practical CFD simulations, as it gives the possibility of using the mesh-morphing utility, minimizing the computation time and the need of interpolation between boundary meshes at subsequent time instants. The developed technique can be applied to generate numerical meshes in arteries and other organs whose shapes change over time. It is applicable to medical images produced by other than angio-CT modalities.

Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome.

Cleavage and formation of phosphodiester bonds in nucleic acids is accomplished by large cellular machineries composed of both protein and RNA. Long thought to rely on a two-metal-ion mechanism for catalysis, structure comparisons revealed many contain highly spatially conserved second-shell monovalent cations, whose precise function remains elusive. A recent high-resolution structure of the spliceosome, essential for pre-mRNA splicing in eukaryotes, revealed a potassium ion in the active site. Here, we employ biased quantum mechanics/ molecular mechanics molecular dynamics to elucidate the function of this monovalent ion in splicing. We discover that the K+ ion regulates the kinetics and thermodynamics of the first splicing step by rigidifying the active site and stabilizing the substrate in the pre- and post-catalytic state via formation of key hydrogen bonds. Our work supports a direct role for the K+ ion during catalysis and provides a mechanistic hypothesis likely shared by other nucleic acid processing enzymes.

Characterization of the SF3B1-SUGP1 interface reveals how numerous cancer mutations cause mRNA missplicing.

The spliceosomal gene SF3B1 is frequently mutated in cancer. While it is known that SF3B1 hotspot mutations lead to loss of splicing factor SUGP1 from spliceosomes, the cancer-relevant SF3B1-SUGP1 interaction has not been characterized. To address this issue, we show by structural modeling that two regions flanking the SUGP1 G-patch make numerous contacts with the region of SF3B1 harboring hotspot mutations. Experiments confirmed that all the cancer-associated mutations in these regions, as well as mutations affecting other residues in the SF3B1-SUGP1 interface, not only weaken or disrupt the interaction but also alter splicing similarly to SF3B1 cancer mutations. Finally, structural modeling of a trimeric protein complex reveals that the SF3B1-SUGP1 interaction "loops out" the G-patch for interaction with the helicase DHX15. Our study thus provides an unprecedented molecular view of a protein complex essential for accurate splicing and also reveals that numerous cancer-associated mutations disrupt the critical SF3B1-SUGP1 interaction.

Temporal changes in regulatory T cell subsets defined by the transcription factor Helios in stroke and their potential role in stroke-associated infection: a prospective case-control study.

BACKGROUND: Regulatory T cells (Tregs) are involved in the systemic immune response after ischemic stroke. However, their role remains unclear, and the effect appears to be both neuroprotective and detrimental. Treg suppressor function may result in immunodepression and promote stroke-associated infection (SAI). Thus we assume that the bidirectional effects of Tregs may be in part attributed to the intracellular transcription factor Helios. Tregs with Helios expression (H+ Tregs) constitute 70-90% of all Treg cells and more frequently than Helios-negative Tregs (H- Tregs) express molecules recognized as markers of Tregs with suppressor abilities. METHODS AND RESULTS: We prospectively assessed the circulating Treg population with flow cytometry in 52 subjects on days 1, 3, 10 and 90 after ischemic stroke and we compared the results with those obtained in concurrent age-, sex- and vascular risk factor-matched controls. At all studied time points the percentage of H+ Tregs decreased in stroke subjects-D1: 69.1% p < 0.0001; D3: 62.5% (49.6-76.6), p < 0.0001; D10: 60.9% (56.5-72.9), p < 0.0001; D90: 79.2% (50.2-91.7), p = 0.014 vs. controls: 92.7% (81.9-97.0) and the percentage of H- Tregs increased accordingly. In patients with SAI the percentage of pro-suppressor H+ Tregs on post-stroke day 3 was higher than in those without infection (p = 0.03). After adjustment for confounders, the percentage of H+ Tregs on day 3 independently correlated with SAI [OR 1.29; CI 95%: 1.08-1.27); p = 0.02]. Although the percentage of H+ Tregs on day 3 correlated positively with NIHSS score on day 90 (rS = 0.62; p < 0.01) and the infarct volume at day 90 (rS = 0.58; p < 0.05), in regression analysis it was not an independent risk factor. CONCLUSIONS: On the first day after stroke the proportion of H+ vs. H- Tregs changes in favor of pro-inflammatory H- Tregs, and this shift continues toward normalization when assessed on day 90. A higher percentage of pro-suppressive H+ Tregs on day 3 independently correlates with SAI and is associated positively with NIHSS score, but it does not independently affect the outcome and stroke area in the convalescent phase of stroke.

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managing these innovative aspects of GC. This study aims to present an in-depth and comprehensive review of the clinical advancements in targeted therapy and immunotherapy for advanced GC.