Search Results (1,643)

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

Background/Objective: The most effective strategy for addressing users’ prosthetic needs is a comprehensive clinical assessment that provides a holistic understanding of the individual’s symptoms, health, function, and environmental barriers and facilitators. A standardized evaluation form would provide guidance for a structured approach to comprehensive clinical assessments of people with LLA. The objective of this study was to determine a list of relevant elements to be included in prosthetic evaluation for adults with lower limb amputation. Methods: Three independent focus group discussions were conducted with prosthetists (n = 15), prosthesis users (n = 11), and decision makers (n = 4) to identify all relevant elements that should be included in the clinical assessment of prosthetic services. The final content was then determined using the Delphi technique, with 35 panelists (18 prosthetists and decision makers, and 17 prosthesis users) voting in each round. Results: A total of 91 elements were identified through the focus group, of which 78 were included through the Delphi process. The identified elements are mostly related to the physical health of the prosthesis user (e.g., mobility, pain, and medical information), while others address personal or psychosocial aspects (e.g., activities of daily living, goals, and motivation) or technical aspects (prosthesis-related). Conclusions: Through a Delphi consensus, a list of relevant elements to be included in a prosthetic evaluation was generated. These results will inform the development of a standardized clinical prosthetic assessment form. This form has the potential to improve the quality of clinical evaluations, guide interventions, and enhance the well-being of prosthetic users. Full article

This study explored the potential of reusing eggshell powders as a renewable activating agent for producing porous carbon materials from coffee husk. Carbonization and activation experiments were conducted by heating the samples at a rate of 10 °C/min up to 850 °C under a nitrogen atmosphere. A custom-designed double steel-mesh sample holder was used to hold approximately 2.0 g coffee husk on the top, with varying masses of eggshell at the bottom to achieve eggshells to coffee husk mass ratios of 2:1, 4:1, 6:1 and 8:1. The results demonstrated that CO₂ released from the thermal decomposition of the eggshell powder significantly enhanced pore development at 850 °C. Compared to the pore properties of carbon material produced without eggshell (e.g., BET surface area of 321 m²/g), the activated carbon samples exhibited substantially improved pore properties (e.g., BET surface area in the range of 592 to 715 m²/g). Furthermore, the pore characteristics improved consistently with increasing eggshell content. Observations by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and Fourier-transform infrared spectroscopy (FTIR) confirmed the structural and chemical transformations of the resulting carbon materials. Under optimal carbonization-activation conditions, the resulting carbon materials derived from coffee husk exhibited microporous structures and slit-shaped pores, as indicated by the Type I isotherms and H4 hysteresis loops. Full article

DNA polymerase epsilon (POLe) is the leading strand replicative polymerase. POLe mutations located primarily in the proofreading domain cause replication errors and increase mutation burden in cancer cells. Consequently, POLe has been classified as a cancer driver gene. Certain POLe frameshift mutations that affect the proofreading domain are purified in cancer cells, but point mutations in other domains have also been reported. Here we use an artificial intelligence algorithm to determine what other mutations co-occur with POLe mutations in colorectal cancers. We partitioned POLe mutations into driver, passenger, and WT (no mutation), then assessed mutations in other genes in these three groups. We found that a driver POLe mutation is not likely to associate with driver mutations in other genes. Thus, driver mutations in colorectal cancers appear to purify in a manner that is independent of POLe. Mutations that affect POLe function do not necessarily increase the frequency of driver mutations in other genes. Structural analysis shows that many POLe driver mutations affect coordination of the Mg²⁺ ion in the active site. Our data show that the accumulation of colorectal cancer mutations is driven by complex factors. Full article

Background/Objectives: Radicular pain is a frequent pathology, and disc herniation is the commonest aetiology. A meta-analysis summarising international guidelines for radicular pain, published in 2021, showed that lumbar traction’s place is still a topic of debate. In this study, our aim was to evaluate the effectiveness of lumbar tractions in treating radicular pain of discal origin in association with medical treatment versus medical treatment alone. We performed a randomised, controlled, interventional, prospective, superiority trial in Reims Hospital Rheumatology Unit. Methods: We included participants with radicular pain and concordant disc herniation with ambulatory treatment failure. Participants were randomised into two groups: medical group (analgesics, anti-inflammatories treatments, at least two epidural injections); tractions group with this medical treatment associated with lumbar tractions. The primary outcome was the difference in the proportion of participants experiencing a minimum of 25% improvement in radicular pain at one month follow-up between the two groups. Results: We included 424 participants: 211 in the tractions group and 213 in the medical group. We analysed 388 participants (194 in each group). We collected demographic and clinical data, lumbar and radicular Numeric Pain Scale at baseline, one and three months. A statistical difference was found for the primary outcome: 120/194 participants (62%) in tractions group and 98/194 participants (51%) in medical group (p = 0.024). Conclusions: To our knowledge, this is the first randomised and controlled study on this topic with these results. We can assert the superiority of lumbar tractions in association with medical treatment over medical treatment alone for radicular pain with concordant disc herniation. Full article

Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterologous fusion proteins assembled from interchangeable building blocks is of high importance. The V5 tag, a 14-residue epitope tag, offers promising characteristics for these applications but has only rarely been used in this context. Thus, we have systematically evaluated the murine anti-V5 tag antibody mu_SV5-Pk1 as well as its humanized version, hu_SV5-Pk1, to analyze cells expressing V5-tagged receptors in samples from various in vitro and in vivo experiments. We found that the V5 tag signal on cells is affected by certain fixation and detachment reagents. Immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) mouse tissue samples was performed to sensitively detect cells in tissue. We improved IHC by applying the hu_SV5-Pk1 monoclonal antibody (mAb) to avoid cross-reactivity within and unspecific background signals arising on fixed mouse tissue. Conversely, the absence of unspecific binding by the mu_SV5-Pk1 mAb was evaluated on 46 human normal or cancer tissues. Our findings present a robust toolbox for utilizing the V5 tag and cognate antibodies in synthetic biology applications. Full article

Malignant cutaneous melanoma is among the most aggressive forms of skin cancer, characterized by high metastatic potential and frequent resistance to standard therapies. Hydroxytyrosol, a phenolic compound derived from extra virgin olive oil, has shown promising anticancer properties in various models, yet its effects in 3D melanoma systems remain poorly understood. In this study, we used paired 3D spheroid models of non-tumorigenic (HEMa) and melanoma (C32) to assess the therapeutic potential of hydroxytyrosol. To evaluate the anti-tumoral effect of hydroxytyrosol, we performed cytotoxicity, metastasis, invasiveness, cell cycle arrest, apoptotic, and proteomic assays. Hydroxytyrosol treatment significantly impaired spheroid growth, reduced cell viability, and induced cell cycle arrest and apoptosis in C32 spheroids, with minimal cytotoxicity observed in HEMa models. Proteomic profiling further demonstrated that hydroxytyrosol selectively downregulated a network of oncogenic proteins, including ERBB2, ERBB3, ERBB4, VEGFR-2, and WIF-1, along with suppression of downstream PI3K-Akt and MAPK/ERK signaling pathways. In conclusion, compared to dabrafenib, hydroxytyrosol exerted a broader range of molecular effects and was more selective toward tumor cells. These findings support the use of hydroxytyrosol as a multi-targeted agent capable of attenuating melanoma progression through suppression of kinase signaling and tumor-stromal interactions. Full article

Long-COVID (LC) is characterized by diverse and persistent symptoms, potentially mirroring different molecular pathways. Recent data might offer that one of them is mediated by functional autoantibodies (fAAb) targeting G protein-coupled receptors (GPCR). Thus, the aim of this study was to investigate the clinical phenotype of patients with LC in relation to their GPCR-fAAb seropositivity. The present study recruited 194 patients with LC and profiled them based on self-reported symptoms. GPCR-fAAb seropositivity was identified by using a cardiomyocyte bioassay, testing the presence and functionality of the AAbs. Logistic regression, clustering, and decision tree analyses were applied to examine associations between GPCR-fAAb profiles and self-reported symptoms considering age and gender. The most prevalent GPCR-fAAbs in patients with LC were fAAB targeting the β2 adrenergic receptor (β2-fAAb, 92.8%), the muscarinergic M2 receptor (M2-fAAb, 87.1%), the Angiotensin II type 1 receptor (AT1-fAAb, 85.6%), and angiotensin (1–7) Mas receptor (MAS-fAAb, 85.6%). β2-fAAb showed a significant relation with dizziness, lack of concentration, and POTS, while Endothelin Type A receptor functional autoantibody (ET-A-fAAb) was significantly related to deterioration of pre-existing neurological disorders. Statistical analysis indicated a strong positive correlation between M2- and β2-fAAb; as in addition, an association of β2-fAAb and gender was observed to one of the major clinical symptoms (fatigue/PEM), a critical impact of GPCR-fAAb on LC-pathogenesis can be assumed. Summing up, the present data show that specific GPCR-fAAb are associated with distinct clinical phenotypes. Especially, the combination of M2- and β2-fAAb seemed to be essential for the LC-phenotype with a combination of fatigue/PEM and lack of concentration as major clinical symptoms. Full article

We present a detailed examination of the absorption coefficients in the THz region for different water models using different types of potentials: the non-polarizable SPC/E, the Drude-polarizable SWM4-NDP and OPC3-pol, IPOL-0.13 and the multipole AMOEBA14 water. The primary focus is on understanding the interplay between permanent and induced dipole moments and their influence on the THz spectrum. Although the induced dipoles strongly contribute to the peak at 200 cm⁻¹, merely increasing the induced dipole moments does not improve the agreement with experiments. We aim to investigate the behavior of the intensity at 200 cm⁻¹ depending on the water model. Furthermore, we dissect the THz spectra of the water models into distinct contributions to gain more insight into the inter- and intramolecular interactions. Intermolecular interactions significantly contribute to the low-frequency peak, while the peak observed at 600 cm⁻¹ can be adequately attributed to intramolecular dipole–dipole interactions. Full article

Arterial aneurysms are vascular conditions associated with life-threatening consequences in patients, such as dissection and rupture. Understanding their genetic basis is an evolving field, driven by the robust reporting of genetic variants associated with aneurysms in patients. In this study, we present clinical and genetic data from nine unrelated subjects with arterial aneurysms who were identified to harbor rare variants in the TNXB gene, mainly affecting fibronectin type III (FNIII) domains. The cohort included three female and six male subjects with a mean age of 53.5 years (SD = 14.4). The most frequently affected vascular territory was the thoracic ascending aorta (n = 7). A range of pathogenic impacts was predicted via multiple in silico tools that analyze evolutionary conservation and biochemical properties. Computational protein structure modeling with AlphaFold 3 predicted domain-specific alterations across multiple FNIII regions for four unique missense variants and one in-frame deletion, and premature protein truncation resulting from two frameshift variants. To our knowledge, this study is one of the first and largest to associate TNXB variants with arterial aneurysmal disease. Our findings demonstrate the potential of computational genomics and structural modeling to advance the understanding of extracellular matrix gene alterations in aneurysm pathogenesis. Full article

Rice (Oryza sativa L.), a staple food for over half of the global population, plays a pivotal role in food security. Among its two primary groups, japonica and indica, temperate japonica varieties are particularly valued for their high-quality grain and culinary uses. Although some of these varieties are adapted to cooler climates, they often suffer from reduced productivity or increased disease susceptibility when cultivated in warmer productive environments. These limitations underscore the need for breeding programs to incorporate biotechnological tools that can enhance the adaptability and resilience of the plants. However, New Genomic Techniques (NGTs), including CRISPR-Cas9, require robust in vitro systems, which are still underdeveloped for temperate japonica genotypes. In this study, we developed a reproducible and adaptable protocol for protoplast isolation and regeneration from the temperate japonica cultivars ‘Ónix’ and ‘Platino’ using somatic embryos as the starting tissue. Protoplasts were isolated via enzymatic digestion (1.5% Cellulase Onozuka R-10 and 0.75% Macerozyme R-10) in 0.6 M AA medium over 18–20 h at 28 °C. Regeneration was achieved through encapsulation in alginate beads and coculture with feeder extracts in 2N6 medium, leading to embryogenic callus formation within 35 days. Seedlings were regenerated in N6R and N6F media and acclimatized under greenhouse conditions within three months. The isolated protoplast quality displayed viability rates of 70–99% within 48 h and supported transient PEG-mediated transfection with GFP. Additionally, the transient expression of a gene editing CRISPR-Cas9 construct targeting the DROUGHT AND SALT TOLERANCE (OsDST) gene confirmed genome editing capability. This protocol offers a scalable and genotype-adaptable system for protoplast-based regeneration and gene editing in temperate japonica rice, supporting the application of NGTs in the breeding of cold-adapted cultivars. Full article

The emergence of antifungal-resistant Aspergillus fumigatus (A. fumigatus) became a serious public health concern, underscoring the need for new effective antifungal agents. Here, we present a strategy based on the in situ generation of radical species that are toxic to the pathogen. The synthesis of an alkoxyamine linked to a peptide substrate recognized by A. fumigatus-secreted dipeptidyl peptidase is described. Kinetic experiments show a stable prodrug prior to enzymatic activation. Ensuing peptide cleavage and spontaneous homolysis resulted in the generation of a stable nitroxide and a reactive alkyl radical moiety. Next, the exposure of A. fumigatus spores to the prodrug lead to pathogen growth inhibition in a compound concentration-dependent fashion (e.g., 42% inhibition at 10 µg/L). Importantly, the designed alkoxyamine inhibited not only the growth of a clinical voriconazole-susceptible A. fumigatus strain, but also the growth of a strain resistant to this azole. To determine the antifungal importance of the reactive alkyl radical, its substitution with a non-radical structure did not prevent A. fumigatus growth. Furthermore, the introduction of succinic group in the peptide substrate resulted in the loss of alkoxyamine antifungal properties. Our work reports a novel chemical strategy for antifungal therapy against A. fumigatus based on the pathogen enzyme-mediated generation of toxic radicals. Significantly, these findings are timely since they could overcome the emerged resistance to conventional drugs that are known to target defined pathogen biologic mechanisms such as ergosterol synthesis. Full article

Background: Splenectomy remains necessary in selected oncologic and hematologic indications but is associated with significant postoperative morbidity and mortality. The data on outcomes in this high-risk population remain limited, particularly in mixed cohorts. Methods: We conducted a retrospective cohort study including all patients undergoing splenectomy for oncologic or hematologic causes between 2009 and 2022 at a cancer referral center. The primary outcomes were the occurrence of major complications at day 90 and the 1-year all-cause mortality. Multivariate logistic regression was used to identify independent predictors. Results: Among the 8503 ICU admissions from surgical wards, 204 splenectomies were performed; 179 patients were analyzed. The median age was 64 years, and 100 patients (55.9%) were female. Splenectomy was performed for hematologic malignancies in 76 cases (42.5%) and for oncologic causes in 103 cases (57.5%). Laparotomy was used in 154 cases (86.0%), and metastasectomy was performed in 54 patients (30.2%). At day 90, 86 patients (48.0%) developed a major complication: 12 deaths (6.7%), 44 surgical complications (24.6%), and 71 episodes of sepsis (39.7%). In a multivariate analysis, weight loss (OR 3.39, 95% CI [1.32–8.70], p = 0.011), laparotomy (OR 4.38 [1.09–17.60], p = 0.038), and a higher SAPS II score (OR 1.08 per point [1.03–1.13], p = 0.003) were associated with complications, while metastasectomy was protective (OR 0.23 [0.08–0.67], p = 0.007). At one year, the mortality reached 22.4%. Independent predictors of death were sepsis at one year (OR 5.04, 95% CI [1.30–25.96], p = 0.029), the Charlson Comorbidity Index (OR 1.30 per point, 95% CI [1.04–1.68], p = 0.030), invasive mechanical ventilation (OR 14.94, 95% CI [2.83–118.93], p = 0.003), and a performance status >1 (OR 7.84, 95% CI [2.38–27.75], p < 0.001). Encapsulated bacteria were not isolated; sepsis was mainly due to Gram-negative and enterococcal organisms. Conclusions: Splenectomy in onco-hematologic patients is associated with high rates of sepsis and mortality. In addition to surgical factors, frailty, immune status, and infection independently contribute to the patients’ outcomes. These results support risk-adapted perioperative strategies and long-term infectious surveillance in immunocompromised patients. Full article

Background: Polluted soils represent a major problem in many industrialized countries that urgently requires appropriate health risk assessment. The One Health concept that considers a close relationship between human and animal health and ecosystems relies, among other techniques, on continuous monitoring through the use of animal species as bioindicators. In this context, terrestrial gastropods, already recognized as relevant indicators due to their anatomo-physiology, provide a reliable model to study the pneumotoxic effects of pollutants. On the other hand, risk assessment is based on multi-biomarker studies. Therefore, omic approaches seem particularly useful since they can simultaneously detect numerous early biological changes. Methods: In this study, Helix aspersa maxima was exposed to naphthalene, a highly volatile aromatic hydrocarbon responsible for numerous respiratory disorders. Pulmonary membrane extracts and hemolymph samples were analyzed by ¹H-NMR spectroscopy after single or repeated exposures to naphthalene. Results: Numerous metabolic changes were observed, which could be related to membrane lesions, energy, anti-inflammatory, and tumorigenesis pathways. Conclusions: Our findings highlight the potential of combining animal indicator and omics techniques to predict respiratory health risks in cases of exposure to polluted soils. Full article

(1) Introduction: Precise femoral component rotation is critical for achieving symmetric flexion-gap balance and physiologic patellofemoral tracking in mechanically aligned total knee arthroplasty (TKA). Surgeons often infer an appropriate rotational target from the patient’s coronal limb alignment, yet the strength of this relationship remains uncertain. (2) Methods: We identified 695 consecutive patients undergoing primary TKA with a preoperative planning CT scan. The surgical transepicondylar axis (sTEA) and posterior condylar axis (PCAxis) were identified and the angle between them was measured. The angle between the mechanical axis of the femur and tibia was used to measure the coronal alignment of the limb. (3) Results: The mean sTEA was 3.0° externally rotated to the PCAxis (range 3.1° internal to 9.2° external). The mean coronal alignment was 4.3° varus (range −12.5° valgus to 24.5° varus). There were 465 patients with >2° varus and 101 patients with >2° valgus. The mean sTEA was 2.9 ± 1.9° externally rotated relative to the PCAxis in the valgus group and 2.8 ± 2.0° in the varus group, with no statistically significant difference (p = 0.7). (4) Conclusions: There is significant variation in the femoral rotation axes between patients, but no significant relationship between overall limb coronal alignment and the magnitude of femoral rotation axes variation. This reinforces the need for independent assessment of rotational landmarks when performing mechanically aligned TKA. Full article