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The present study aims to assess the tectonic activity in the South Setifian allochthonous complex, providing insights into the evolution of the landscape. A morphometric analysis of Jebel Youcef Mountain (JYM) in Eastern Algeria was conducted to assess neotectonic activity. Six quantitative parameters were analyzed: stream length-gradient index, asymmetric factor, hypsometric integral, valley floor width-to-valley height ratio, index of drainage basin shape, and index of mountain front sinuosity across the 16 river basins in the region. The geomorphic indices are combined into a single index of relative tectonic activity (IRTA), categorized into four classes: very high, high, moderate, and low. The results identified two major lineament sets. The NE-SW lineament set is the dominant structural feature, playing a key role in driving recent geological processes and deformation in the study area. In contrast, the E-W and NW-SE lineament sets exert a more localized influence, primarily affecting the Jurassic formations at Kef El Ahmar’s central peak in Jebel Youcef, though they exhibit relatively lower tectonic activity compared to the NE-SW lineament set. Based on the relative active tectonic classes, significant neotectonic activity is evident in the study area, as shown by distinctive basement fracturing. The findings contribute to understanding the structural processes in the study area. Furthermore, the study establishes a systematic framework for analyzing tectonic activity and landscape morphology evolution, enhancing our perception of the convergence between the North African Alpine zones and the Atlas range.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease that is heterogenous in nature with various drivers and modifiers such as metabolic dysfunction and genetic factors. MASLD and the progressive subtype, metabolic dysfunction-associated steatohepatitis (MASH) represent the most rapidly increasing cause of liver-related mortality. There are limited treatment options for patients living with MASLD and MASH, various treatments with an array of different targets are under investigation and one therapeutic has been approved since the initiation of this study. Clinical trials investigating treatments for MASLD and MASH are associated with a high screen failure rate, driven largely by the regulatory required histological inclusion criteria for clinical trial eligibility. Other available clinically utilized biomarkers, typically referred to as non-invasive tests (NITs), can assess both the presence of steatosis and the severity of liver fibrosis in patients with MASLD and MASH in the clinic but are not yet approved over histological changes as endpoints for pivotal trials. However, the use of NITs have been demonstrated to increase the likelihood of meeting clinical trial entry criteria. All-Liver Interventional Global Network (ALIGN) is the first described multi-centre global observational screening study aimed at identifying individuals with a high likelihood of MASLD/MASH interested in participating in therapeutic clinical trials using non-invasive methodologies and genetic testing. This study represents a valuable prototype for industry and academic groups looking to evaluate large populations for MASH eligibility and interest in clinical trial participation.

Objective: To analyze data available in the literature regarding a possible prognostic value of the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) in prostate cancer (PCa) patients stratified in non-metastatic and metastatic diseases. Methods: A literature search process was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. In our meta-analysis, the pooled event rate estimated and the pooled hazard ratio were calculated using a random effect model. Results: Forty-two articles were selected for our analysis. The pooled risk difference for non-organ confined PCa between high and low NLR cases was 0.06 (95% confidence interval [CI]: −0.03–0.15) and between high and low PLR cases increased to 0.30 (95% CI: 0.16–0.43). In non-metastatic PCa cases, the pooled hazard ratio for overall mortality between high and low NLR was 1.33 (95% CI: 0.78–1.88) and between high and low PLR was 1.47 (95% CI: 0.91–2.03), whereas in metastatic PCa cases, between high and low NLR was 1.79 (95% CI: 1.44–2.13) and between high and low PLR was 1.05 (95% CI: 0.87–1.24). Conclusion: The prognostic values of NLR and PLR in terms of PCa characteristics and responses after treatment show a high level of heterogeneity of results among studies. These two ratios can represent the inflammatory and immunity status of the patient related to several conditions. A higher predictive value is related to a high NLR in terms of risk for overall mortality in metastatic PCa cases under systemic treatments.

The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches to the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a “protein corona” composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced. We developed the design of an experimental prospective single-center study with patients allocated in a 1:1:1 ratio of one of three arms: untreated patients with benign prostatic hyperplasia (BPH), untreated patients with non-metastatic prostate cancer (PCa), and metastatic prostate cancer patients starting systemic therapies with new androgen-targeted agents or taxanes. The protocol aims to develop and implement sensitive nanotools with two distinct objectives: First, to design NPs capable of selectively binding and detecting biomarkers in order to build a predictive diagnostic model to effectively discriminate between patient sera affected by BPH and PCa. Secondly, within the population with PCa, in the case of initial advanced metastatic diagnosis, the objective is to find biomarkers capable of predicting the response to systemic treatments to improve the precision and efficiency of monitoring treatment outcomes. For protein and metabolite corona experiments, we developed a cross-reactive sensor array platform with cancer detection capacity made of three liposomal formulations with different surface charges. For proteomic-NP studies, proteins were identified and quantified using nano-high-performance LC (nanoHPLC) coupled with MS/MS (nanoHPLC−MS/MS). Metabolites were instead analyzed using an untargeted metabolomic approach. Compared with previous review articles, the novelty of this review is represented by the analysis of the possible clinical applications of protein corona NPs focused on PCa and the presentation of a new clinical protocol in the metastatic phase of PCa.

Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

The increasing diffusion of genetic analysis regarding the pathogenetic variants (PVs) of genes involved in DNA Damage Repair (DDR) mechanisms and the development of Poly ADP ribose polymerase (PARP) inhibitors (PARPis) led to the first valid precision medicine option tailored toward metastatic prostate cancer (mPC). The concept of anticipation in the systemic treatment of mPC was initially adopted for androgen receptor signaling inhibitors (ARSIs) to describe the expansion of their indications, from the setting of the late-stage second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) to first-line therapy in selected cases. There is already mounting evidence in favor of the anticipation of PARPis in the first line of mCRPC therapy, and further evidence in favor of mHSPC is emerging. Many studies have demonstrated the synergism between ARSIs and PARP inhibitors. Recent discoveries regarding the crosstalk between the androgen receptor (AR) and DNA repair mechanisms are disconnecting the use of PARPis from genetic analysis. The new message emerging is that the combination of PARPis with ARSIs may work independently of DDR mutational status. As a matter of fact, most of the recent trials analyzing the combination of PARPis with abiraterone or enzalutamide as a first-line therapy enrolled mCRPC patients irrespective of their mutational status. The PROPEL trial concluded that the advantage of the combination was independent of PV status, despite a higher advantage being reported in the BRCA1/2 mutated subgroup. The MAGNITUDE trial, however, showed a significant advantage only in the DDR mutated subgroup, and the DDR non-mutated cohort was closed for further enrollment. The combination of PARPis with ARSIs represents a significant strategy with a view to the anticipation and intensification of care in mPC. However, it should not nullify the advantages of precision medicine linked to the genetic analysis of DDR genes.

Exosomes are extracellular nanovesicles (EV), that is, carriers of different biomolecules such as lipids, proteins, nucleic acids. Their composition and the fact that their release dramatically increases in cases of tumorigenesis open up different scenarios on their possible application to research into new biomarkers. The first purpose of the present review was to specifically analyze and compare different methodologies available for the use of exosomes in prostate cancer (PC). The most widely applied methodologies include ultracentrifugation techniques, size-based techniques, immunoaffinity capture-based techniques (mainly ELISA), and precipitation. To optimize the acquisition of exosomes from the reference sample, more techniques can be applied in sequence for a single extraction, thereby determining an increase in labor time and costs. The second purpose was to describe clinical results obtained with the analysis of PSA-expressing exosomes in PC; this provides an incredibly accurate method of discriminating between healthy patients and those with prostate disease. Specifically, the IC-ELISA alone method achieved 98.57% sensitivity and 80.28% specificity in discriminating prostate cancer (PC) from benign prostatic hyperplasia (BPH). An immunocapture-based ELISA assay was performed to quantify and characterize carbonic anhydrase (CA) IX expression in exosomes. The results revealed that CA IX positive exosomes were 25-fold higher in plasma samples from PC patients than in those from healthy controls. The analysis of PC-linked exosomes represents a promising diagnostic model that can effectively distinguish patients with PC from those with non-malignant prostatic disease. However, the use of exosome analysis in clinical practice is currently limited by several issues, including a lack of standardization in the analytical process and high costs, which are still too high for large-scale use.

Groundwater contamination in the Mediterranean Basin is a severe problem that has a significant impact on environmental ecosystems and human health. The unconventional uranium and the potentially toxic elements (PTEs) of phosphate rocks are the principal contaminants in the phosphate mining industry in Tunisia. Phosphogypsum (PG) results from the valorization of phosphate to fertilizers and phosphoric acid. PG stocks can be used in cement production, brick manufacturing, and soil amendments in desertic land, and can be resolved by using nanomaterial adsorbents. In the flat area of the study area, the increase in radioactivity (40K) is due to abusive fertilizer use. Geochemical and radiological analyses in the northern part of Tunisia and its karst shallow aquifer indicate significant contamination levels. The northern part exhibits moderate contamination, whereas the karst shallow aquifer shows higher contamination levels, particularly with elevated nitrate concentrations. In the phosphate basin, both washing phosphate and phosphogypsum reveal high levels of radioactive elements, with the latter showing especially high concentrations of radium. The shallow aquifer in this region has moderate contamination levels, while the deep geothermal aquifer also shows noticeable contamination but to a lesser degree compared to the shallow aquifer. The shallow groundwater is characterized by a higher value of radioactivity than the groundwater due to the contamination impact from the phosphate industry and the cumulative radioactivity disintegration. Finally, the nanoparticles and the electrostatic adsorption can decrease the PTEs and radionuclides from the contaminated water in the study area. Moreover, other key issues for advancing research on groundwater contamination are proposed in this study. It is time to valorize this PG and the other mines of (Fe, Pb, and Zn) in the socioeconomic sector in Tunisia and to minimize the environmental impact of the industrial sector’s extraction on groundwater and human health in the study area.

Background: Congenital prepubic sinus (CPS) is a rare congenital variant of urethral duplication, with less than 50 cases documented in the scientific literature since it was first reported by Campbell et al., in 1987. Case presentation: An 8-year-old male patient complained of an inflammatory secretion from a sinus opening on the dorsal base of his penis. Physical examination revealed an accessory orifice in the midline of the dorsal proximal penis without any penile curvature. An ultrasound (US) examination found an 8-mm collection of cutaneous and subcutaneous tissue at the dorsal base of the penis. The renal US, however, showed no abnormalities. Additionally, micturating cystourethrogram (MCUG), was negative for vesicoureteral reflux (VUR). Retrograde sinusography (RS) and urethrogram showed no communication between the urinary tract, and the sinus was found to end blindly at the level of the pubic symphysis. A surgical excision was decided, to avoid potential future complications. A 3-cm-long intact sinus was dissected and excised entirely. Histological examination confirmed the diagnosis of a urethral duplication. The postoperative course was uneventful. To date, at six-month of follow-up, the patient remains asymptomatic. Conclusions: The histological findings in this case support the theory that CPS is a variant of dorsal urethra. Urethral duplication should always be suspected in the case of accessory dorsal openings. Surgical excision is recommended at an early age, even in the absence of symptoms, to improve aesthetics, prevent recurrent infections and avoid the development of future malignant tumors.

Purpose: To prospectively evaluate the albumin/globulin ratio (AGR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) diagnostic and prognostic predictive value in a stratified population of prostate cancer (PC) cases. Methods: Population was divided based on the clinical and histologic diagnosis in: Group A: benign prostatic hyperplasia (BPH) cases (494 cases); Group B: all PC cases (525 cases); Group B1: clinically significant PC (426 cases); Group B2: non-metastatic PC (416 cases); Group B3: metastatic PC (109 cases). NLR, PLR, and AGR were obtained at the time of the diagnosis, and only in cases with PC considered for radical prostatectomy, determinations were also repeated 90 days after surgery. For each ratio, cut-off values were determined by receiver operating characteristics curve (ROC) analysis and fixed at 2.5, 120.0, and 1.4, respectively, for NLR, PLR, and AGR. Results: Accuracy in predictive value for an initial diagnosis of clinically significant PC (csPC) was higher using PLR (0.718) when compared to NLR (0.220) and AGR (0.247), but, despite high sensitivity (0.849), very low specificity (0.256) was present. The risk of csPC significantly increased only according to PLR with an OR = 1.646. The percentage of cases with metastatic PC significantly increased according to high NLR and high PLR. Accuracy was 0.916 and 0.813, respectively, for NLR and PLR cut-off, with higher specificity than sensitivity. The risk of a metastatic disease increased 3.2 times for an NLR > 2.5 and 5.2 times for a PLR > 120 and at the multivariate analysis. Conclusion: PLR and NLR have a significant predictive value towards the development of metastatic disease but not in relation to variations in aggressiveness or T staging inside the non-metastatic PC. Our results suggest an unlikely introduction of these analyses into clinical practice in support of validated PC risk predictors.

The Setifian high-plains region, Northeast of Algeria, grapples with challenges in water resource management. As the water demand intensifies across a diverse range of sectors, assessing groundwater quality becomes indispensable. This article responds to the critical need for a thorough assessment of groundwater quality in the Wadi Boussellam sub-watershed. Employing a GIS-based method, we evaluate groundwater geochemistry by estimating the Water Quality Index (WQI), offering a comprehensive overview of water consumption. The analysis of groundwater samples reveals distinct facies, including calcic bicarbonate, calcic chloride, calcic sulfate, and magnesium sulfate, contributing to an enhanced understanding of the hydrochemical composition in the Setif region. Hydrochemical indices, specifically the WQI, Sodium Adsorption Ratio (SAR), and Na% are applied to assess groundwater suitability for various applications. The results indicate that most crops are generally suitable for irrigation, though they advise exercising caution with regard to human consumption. This study underscores the significance of regular monitoring to avert groundwater contamination and ensure sustainable use in the Setif region, providing insights that emphasize the ongoing necessity for efforts in water resource management and the preservation of this vital resource’s quality.

Fires are a growing problem even in temperate climate areas, such as those in Central Italy, due to climate change leading to longer and longer periods of drought. Thus, knowing the fire susceptibility of an area is crucial for good planning and taking appropriate countermeasures. In this context, it was decided to use only causal factors of a geomorphological and environmental nature in order to obtain a fire susceptibility analysis that can also be applied to climatically under-sampled areas. Vector data of fires in Central Italy from 2005 to 2023 were collected, and the correct areal extent was calculated for each. At the same time, six factors were selected that could have an influence on fire development, such as ecological units, topographic wetness index (TWI), geology, slope, exposure, and altitude. The model was obtained by means of the weight of evidence statistical method, which takes into account past data by reinterpreting them in a future-oriented way on the basis of the identified factors and classes. The model was validated with a test sample and shows an area under the curve (AUC) value of 0.72 with a reliability that can be described as good considering the total absence of climatic factors that are known to play a major role in fire development. Furthermore, the identified causal factors were divided into classes, and these were carefully weighted in order to define their relative influence in the study area. Particularly Ecological Units with characteristic and well-defined contrast (C) values, which could lead to a more complete definition of forests that tend to increase fire susceptibility and those that tend to decrease it, allowing the latter to be exploited as a hazard mitigation agent.

Background: Radical removal of the ureter is not routinary performed during nephrectomy/hemineprectomy, distal ureteral stump syndrome may follow. Case summary: A 17-year-old male with urinary malformation history came to the emergency department for abdominal pain and tenesmus. Imaging revealed a huge abdominal mass, compatible with a massively dilated residual ureteral stump resulting from heminephrectomy operation performed 7 years before for a complete right duplex system with hypoplasia of the upper right system. A robotic procedure was planned and the stump, which was ectopic and drained into the seminal vesicles, was successfully removed. The patient was discharged after recovery; he was followed up for one year after surgery without any complications. Conclusion: Ureteral stumps rarely require reoperation, but our case suggests a need for long-term follow-up. Robotic-assisted excision showed to be a safe and effective technique for surgical management of a massively dilated ectopic stump in the pediatric population.

Simple Summary: Recent research suggests that once nanoparticles (NPs) come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a "protein corona" composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced. Our experimental design makes a significant contribution to the field of specific protein corona nanoparticles as molecular biomarkers differentiating between benign and malignant prostatic pathology. Above all, these can be used as an indicator of the response to systemic therapy for metastatic PCa in a sector where the therapeutic choices are numerous and require increasingly valid precision medicine. The National Cancer Institute (NCI) recognizes the potential of technologies based on the use of nanoparticles (NPs) in revolutionizing clinical approaches to the diagnosis and prognosis of cancer. Recent research suggests that once NPs come into contact with the biological fluid of cancer patients, they are covered by proteins, forming a "protein corona" composed of hundreds of plasma proteins. The concept of a personalized, disease-specific protein corona, demonstrating substantial differences in NP corona profiles between patients with and without cancer, has been introduced. We developed the design of an experimental prospective single-center study with patients allocated in a 1:1:1 ratio of one of three arms: untreated patients with benign prostatic hyperplasia (BPH), untreated patients with non-metastatic prostate cancer (PCa), and metastatic prostate cancer patients starting systemic therapies with new androgen-targeted agents or taxanes. The protocol aims to develop and implement sensitive nanotools with two distinct objectives: First, to design NPs capable of selectively binding and detecting biomarkers in order to build a predictive diagnostic model to effectively discriminate between patient sera affected by BPH and PCa. Secondly, within the population with PCa, in the case of initial advanced metastatic diagnosis, the objective is to find biomarkers capable of predicting the response to systemic treatments to improve the precision and efficiency of monitoring treatment outcomes. For protein and metabolite corona experiments, we developed a cross-reactive sensor array platform with cancer detection capacity made of three liposomal formulations with different surface charges. For proteomic-NP studies, proteins were identified and quantified using nano-high-performance LC (nanoHPLC) coupled with MS/MS (nanoHPLC−MS/MS). Metabolites were instead analyzed using an untargeted metabolomic approach. Compared with previous review articles, the novelty of this review is represented by the analysis of the possible clinical applications of protein corona NPs focused on PCa and the presentation of a new clinical protocol in the metastatic phase of PCa. [ABSTRACT FROM AUTHOR]

The present study aims to assess the tectonic activity in the South Setifian allochthonous complex, providing insights into the evolution of the landscape. A morphometric analysis of Jebel Youcef Mountain (JYM) in Eastern Algeria was conducted to assess neotectonic activity. Six quantitative parameters were analyzed: stream length-gradient index, asymmetric factor, hypsometric integral, valley floor width-to-valley height ratio, index of drainage basin shape, and index of mountain front sinuosity across the 16 river basins in the region. The geomorphic indices are combined into a single index of relative tectonic activity (IRTA), categorized into four classes: very high, high, moderate, and low. The results identified two major lineament sets. The NE-SW lineament set is the dominant structural feature, playing a key role in driving recent geological processes and deformation in the study area. In contrast, the E-W and NW-SE lineament sets exert a more localized influence, primarily affecting the Jurassic formations at Kef El Ahmar's central peak in Jebel Youcef, though they exhibit relatively lower tectonic activity compared to the NE-SW lineament set. Based on the relative active tectonic classes, significant neotectonic activity is evident in the study area, as shown by distinctive basement fracturing. The findings contribute to understanding the structural processes in the study area. Furthermore, the study establishes a systematic framework for analyzing tectonic activity and landscape morphology evolution, enhancing our perception of the convergence between the North African Alpine zones and the Atlas range. [ABSTRACT FROM AUTHOR]

Integrins are heterodimeric cell-surface receptors that regulate cell–cell adhesion and cellular functions through bidirectional signaling. On the other hand, anomalous trafficking of integrins is also implicated in severe pathologies as cancer, thrombosis, inflammation, allergies, and multiple sclerosis. For this reason, they are attractive candidates as drug targets. However, despite promising preclinical data, several anti-integrin drugs failed in late-stage clinical trials for chronic indications, with paradoxical side effects. One possible reason is that, at low concentration, ligands proposed as antagonists may also act as partial agonists. Hence, the comprehension of the specific structural features for ligands’ agonism or antagonism is currently of the utmost interest. For α4β1 integrin, the situation is particularly obscure because neither the crystallographic nor the cryo-EM structures are known. In addition, very few potent and selective agonists are available for investigating the mechanism at the basis of the receptor activation. In this account, we discuss the physiological role of α4β1 integrin and the related pathologies, and review the few agonists. Finally, we speculate on plausible models to explain agonism vs. antagonism by comparison with RGD-binding integrins and by analysis of computational simulations performed with homology or hybrid receptor structures.

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of liver‐related events (LREs). Here, we have assessed the ability of a composite score based on clinical features, metabolic comorbidities, and genetic variants to predict LREs. A total of 546 consecutive patients with NAFLD were recruited and stratified according to the fibrosis‐4 (FIB‐4) index. LREs were defined as occurrence of hepatocellular carcinoma or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LREs. The UK Biobank was used as the validation cohort, and severe liver disease (incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma, and/or liver transplantation) was used as the outcome. LREs were experienced by 58 patients, only one of whom was in the cohort of patients with a FIB‐4 score

Laparoscopic Appendectomy (LPSA) is the first choice for appendectomy in pediatric surgery. Trans-Umbilical Laparoscopic Assisted Appendicectomy (TULAA) is another used technique. We compared both these procedures used for the treatment of acute appendicitis. The study was conducted between January 2019 to December 2020. Patients were divided into two groups: LPSA and TULAA groups. The collected data were: operative time, number of conversions, time of canalization and hospital stay. A total of 181 patients were included: 73 were kept in the LPSA and 108 in the TULAA group. Mean operative time was 70.9 minutes (range 45-130 min) for LPS and 56.4 (30-145 min) for TULAA group (p