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Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second most common cause of cancer deaths. Initial clinical presentation as metastatic CRC (mCRC) occurs in approximately 20% of patients. Moreover, up to 50% of patients with localized disease eventually develop metastases. Appropriate clinical management of these patients is still a challenging medical issue. Major ef-forts have been made to unveil the molecular landscape of mCRC. This has resulted in the identification of several druggable tumor molecular targets with the aim of developing personalized treatments for each patient. This review summarizes the im-provements in the clinical management of patients with mCRC in the emerging era of precision medicine. In fact, molecular stratification, on which the current treatment algorithm for mCRC is based, although it does not completely represent the complex-ity of this disease, has been the first significant step toward clinically informative genetic profiling for implementing more effective therapeutic approaches. This has resulted in a clinically relevant increase in mCRC disease control and patient survival. The next steps in the clinical management of mCRC will be to integrate the compre-hensive knowledge of tumor gene alterations, of tumor and microenvironment gene and protein expression profiling, of host immune competence as well as the applica-tion of the resulting dynamic changes to a precision medicine- based continuum of care for each patient. This approach could result in the identification of individual prognostic and predictive parameters, which could help the clinician in choosing the most appropriate therapeutic program(s) throughout the entire disease journey for each patient with mCRC.

Translational research has revolutionized how we develop new treatments for cancer patients. The change from an organ-centric concept guiding treatment choice towards deep molecular analysis, driving a personalized approach, is one of the most important advances of modern oncology. Several tools such as next generation sequencing and RNA sequencing have greatly improved the capacity to detect predictive and prognostic molecular alterations. Detection of gene mutations, amplifications, and fusions has therefore altered the history of several diseases in both a localized and metastatic setting. This shift in perspective, in which attention is focused on the specific molecular alterations of the tumor, has opened the door to personalized treatment. This situation is reflected in the increasing number of basket trials selecting specific molecular targets. Nonetheless, some weaknesses need to be addressed. The complexity of cancer cells enriched with concomitant molecular alterations complicates identification of the driver. Moreover, tumor heterogeneity could be responsible for the lack of benefit when targeted agents are used. In light of this, there is growing interest in the role of multidisciplinary committees or molecular tumor boards to try to enhance selection. The aim of this review is to critically analyze the evolution of cancer treatment towards a precision approach, underlining some recent successes and unexpected failures.

A substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment. Standard platinum-based chemotherapy is the basis of treatment of many cancers, however a proportion of patients do not derive benefit. Here the authors show that the platinum-based drug oxaliplatin accumulates in cancer-associated fibroblasts, activating pathways associated with cancer progression and resistance to therapy.

Bacterial expansin-like proteins have synergistically increased cellulose hydrolysis by cellulolytic enzymes during the initial stages of biofuel production, but they have not been tested on livestock feeds. The objectives of this study were to: isolate and express an expansin-like protein (BsEXLX1), to verify its disruptive activity (expansion) on cotton fibers by immunodetection (Experiment 1), and to determine the effect of dose, pH and temperature for BsEXLX1 and cellulase to synergistically hydrolyze filter paper (FP) and carboxymethyl cellulose (CMC) under laboratory (Experiment 2) and simulated ruminal (Experiment 3) conditions. In addition, we determined the ability of BsEXLX1 to synergistically increase hydrolysis of corn and bermudagrass silages by an exogenous fibrolytic enzyme (EFE) (Experiment 4) and how different doses of BsEXLX1 and EFE affect the gas production (GP), in vitro digestibility and fermentation of a diet for dairy cows (Experiment 5). In Experiment 1, immunofluorescence-based examination of cotton microfiber treated without or with recombinant expansin-like protein expressed from Bacillus subtilis (BsEXLX1) increased the surface area by > 100% compared to the untreated control. In Experiment 2, adding BsEXLX1 (100 μg/g FP) to cellulase (0.0148 FPU) increased release of reducing sugars compared to cellulase alone by more than 40% (P < 0.01) at optimal pH (4.0) and temperature (50°C) after 24 h. In Experiment 3 and 4, adding BsEXLX1 to cellulase or EFE, synergistically increased release of reducing sugars from FP, corn and bermudagrass silages under simulated ruminal conditions (pH 6.0, 39°C). In Experiment 5, increasing the concentration of BsEXLX1 linearly increased (P < 0.01) GP from fermentation of a diet for dairy cows by up to 17.8%. Synergistic effects between BsEXLX1 and EFE increased in vitro NDF digestibility of the diet by 23.3% compared to the control. In vitro digestibility of hemicellulose and butyrate concentration were linearly increased by BsEXLX1 compared to the control. This study demonstrated that BsEXLX1 can improve the efficacy of cellulase and EFE at hydrolyzing pure substrates and dairy cow feeds, respectively.

The study applied a targeted metabolomics approach that uses a direct injection and tandem mass spectrometry (DI–MS/MS) coupled with a liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based metabolomics of plasma to evaluate the effects of supplementing clay with or without Saccharomyces cerevisiae fermentation product (SCFP) on the metabolic status of dairy cows challenged with aflatoxin B1. Eight healthy, lactating, multiparous Holstein cows in early lactation (64 ± 11 DIM) were randomly assigned to one of four treatments in a balanced 4 × 4 duplicated Latin square design with four 33 d periods. Treatments were control, toxin (T; 1725 µg aflatoxin B1 (AFB1)/head/day), T with clay (CL; 200 g/head/day), and CL with SCFP (YEA; 35 g of SCFP/head/day). Cows in T, CL, and YEA were dosed with aflatoxin B1 (AFB1) from days 26 to 30. The sequestering agents were top-dressed from day 1 to 33. On day 30 of each period, 15 mL of blood was taken from the coccygeal vessels and plasma samples were obtained from blood by centrifugation and analyzed for metabolites using a kit that combines DI–MS/MS with LC–MS/MS-based metabolomics. The data were analyzed using the GLIMMIX procedure of SAS. The model included the effects of treatment, period, and random effects of cow and square. Significance was declared at p ≤ 0.05. Biomarker profiles for aflatoxin ingestion in dairy cows fed no sequestering agents were determined using receiver–operator characteristic (ROC) curves, as calculated by the ROCCET web server. A total of 127 metabolites such as amino acids, biogenic amines, acylcarnitines, glycerophospholipids, and organic acids were quantified. Compared with the control, T decreased (p < 0.05) plasma concentrations of alanine, leucine, and arginine and tended to decrease that of citrulline. Treatment with CL had no effects on any of the metabolites relative to the control but increased (p ≤ 0.05) concentrations of alanine, leucine, arginine, and that of citrulline (p = 0.07) relative to T. Treatment with YEA resulted in greater (p ≤ 0.05) concentrations of aspartic acid and lysine relative to the control and the highest (p ≤ 0.05) plasma concentrations of alanine, valine, proline, threonine, leucine, isoleucine, glutamic acid, phenylalanine, and arginine compared with other treatments. The results of ROC analysis between C and T groups revealed that the combination of arginine, alanine, methylhistidine, and citrulline had sufficient specificity and sensitivity (area under the curve = 0.986) to be excellent potential biomarkers of aflatoxin ingestion in dairy cows fed no sequestering agents. This study confirmed the protective effects of sequestering agents in dairy cows challenged with aflatoxin B1.

Small-scale farmers in the southeastern United States face increasing challenges in sustaining forage production due to erratic rainfall, poor soils, and limited access to precision agricultural tools. These constraints demand site-specific solutions that integrate climate resilience with sustainable land use. This study introduces a pioneering Site-Specific Fodder Management Decision Support System (SSFM-DSS) designed to optimize the cultivation of Lespedeza cuneata (sericea lespedeza), a drought-tolerant, nitrogen-fixing legume well-suited for marginal lands. By integrating high-resolution geospatial technologies—Geographic Information Systems (GIS), Global Navigation Satellite Systems (GNSS), and remote sensing—with empirical field data and predictive modeling, we have developed an automated suitability framework for SL cultivation across Alabama, Georgia, and South Carolina. The model incorporates multi-criteria environmental parameters, including soil characteristics, topography, and climate variability, to generate spatially explicit recommendations. To translate these insights into actionable strategies, we also developed a farmer-focused WebGIS Dashboard that delivers real-time, location-based guidance for SL production. Our findings underscore the significant potential of SSFM-DSS to enhance fodder availability, improve system resilience under climate stress, and promote sustainable livestock production. This integrative approach offers a promising pathway for climate-smart agriculture, supporting broader food security objectives in vulnerable agroecosystems.

The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet been validated in patients receiving molecular targeting agents.

Persistent Idiopathic   Dentoalveolar Pain (PIDAP) is an orofacial neuropathic pain, which can be difficult to diagnose and is usually accompanied by increasing anxiety from both the patient and the treating dentist. A case of a 38-year-old female patient is presented, and it is shown the diagnostic process and therapeutic approach. The interdisciplinary management accompanied by several pharmacological lines is highlighted: Botulinum toxin was used as an adjunctive treatment allowing it to decrease systemically administered medications dosing and therefore its possible side effects. This condition usually affects psychosocial aspects of the patient and has a major impact on his quality of life. It is very important before initiating an invasive clinical treatment, obtaining a clear differential diagnosis and assessing in some cases the presence of non-odontogenic pain, such as PIDAP.

The test is based on a four-gene real-time RT-PCR assay, which measures gene-expression levels in formalin-fixed, paraffin-embedded tumour tissues, and consists of two rule-based, single patient classifier algorithms for prognosis and prediction.Genomic alterations detected in primary tumours could differ significantly from those observed in metastatic tumours or cell-free DNA.7 This heterogeneity is one of the main barriers to the development and implementation of precision medicine strategies in gastric cancer, which is also hindered by insufficient knowledge of the molecular characteristics of minimal residual disease.[...]this important research by Cheong and colleagues paves the way for implementation of precision medicine in other clinically relevant settings.

This study provides a comparative analysis of the post-thaw sperm lipidomic profiles of Alpine and Spanish–Creole goat breeds to explore breed-specific differences in fatty acid composition and their implications for sperm function and reproductive efficiency. Lipids were extracted from cryopreserved semen samples of Alpine (n = 7) and Spanish–Creole (n = 4) mature bucks and subsequently analyzed by gas chromatography–mass spectrometry (GC-MS), with 21 fatty acids identified within the two breeds. Eight of these fatty acids, namely 13:0, 16:0, 18:0, 24:0, 14:1, 18:1 (cis-9), 24:1, and 18:2 showed significant differences (p < 0.05). The levels of 16:0, 18:0, 24:0, 18:1 (cis-9), 18:1, and 18:2 were higher in the Alpine breed, whereas the levels of 13:0, 14:1, and 24:1 were higher in the Spanish–Creole breed (p < 0.05). Of those, 16:0, 18:1 (cis-9), and 18:2 were both statistically and biologically significant (p < 0.05, FC > 2). Concentrations of the total fatty acids, total saturated fatty acids (Total-SFA), and total polyunsaturated fatty acids (Total-PUFA) were significantly higher in the Alpine breed, whereas the concentrations of the total cis-monounsaturated fatty acid (Total cis-MUFA) were significantly higher in the Spanish–Creole breed (p < 0.05). Network and pathway analyses revealed that 16:0, 18:1 (cis-9), and 18:2 contributed to the most central nodes of the lipidomic network, which may support membrane stability and cryotolerance. The lipidomic differences observed between breeds may be attributed to both genetic and environmental factors and may provide valuable tools for enhancing breeding strategies, artificial insemination programs, and sperm cryopreservation techniques.