Search Results (22)

Crop simulation models and irrigation decision support systems (IDSS) are essential tools for improving water use efficiency, particularly in Mediterranean and semi-arid regions where water scarcity is a major constraint. However, many platforms are either too complex for widespread adoption or too simplified to capture the combined effects of temperature, water stress, and elevated CO₂ on crop responses. This paper presents the Easy Simulator Crop Model (EaSiCroM), a modular, low-parameterisation system designed to simulate daily crop growth, soil water dynamics, and irrigation requirements. Canopy development follows a beta-function LAI trajectory with Beer–Lambert canopy cover, progressively constrained by temperature (T_lim) and water stress (K_stress, KS_cc). Biomass accumulation combines a water productivity (WP) approach with an optional radiation-use efficiency (RUE) pathway, both scaled by a Michaelis–Menten CO₂ fertilisation sub-model. The soil water balance includes a two-stage bare-soil evaporation formulation and multiple irrigation triggering strategies. EaSiCroM is implemented as a Docker-containerised web application supporting single-crop, multi-plot, and near-real-time irrigation modes, with optional assimilation of user-provided canopy observations from field or remote sensing sources. A proof-of-concept evaluation across four Mediterranean crops (processing tomato, biomass sorghum, sunflower, and durum wheat) yielded RRMSE values between 13.8% and 26.1%, comparable to AquaCrop and CropSyst on the same datasets. Its modular architecture makes it suitable for both research and operational irrigation management in water-scarce environments. Full article

Marinesco–Sjögren syndrome (MSS) is a rare autosomal recessive neuromuscular disorder marked by ataxia, muscle weakness, cataracts, and often intellectual and skeletal abnormalities. It is commonly caused by loss-of-function variants in the SIL1 gene, which impair binding immunoglobulin protein (BiP) function, leading to protein misfolding and activation of the unfolded protein response. In a 2-year-old patient with typical MSS symptoms, we identified a previously unreported c.1024G>A (p.E342K) variant in SIL1 via whole-exome sequencing. The pathogenicity of this Sil1 variant was supported by evidence of structural changes revealed through in silico predictions, circular dichroism, and native gel electrophoresis. Patient-derived fibroblasts exhibited reduced Sil1 protein levels, likely due to misfolding and degradation, which was partially rescued by proteasome inhibition. Proteomics revealed a profile similar to known MSS cases and a distinctive MSS transcriptional signature. Ultrastructural analysis confirmed typical MSS features, such as autophagic vacuoles and lipid droplets. Although the p.E342K phenotype appears milder than the reference pathogenic variant R111X, our findings support the reclassification of this novel variant as pathogenic, in accordance with the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) 2015 guidelines and the refinements proposed by the Clinical Genome Resource Sequence Variant Interpretation (ClinGen SVI) recommendations. Furthermore, the overall evidence also provides important insights into the genotype–phenotype correlation and the underlying pathogenic mechanism of the p.E342K variant. Full article

Purpose/Objectives: Salvage radiotherapy (SRT) after a radical prostatectomy is a curative approach for patients with biochemical recurrence (BR). However, outcomes are often less favorable when imaging reveals macroscopic local recurrence. In such cases, dose escalation through stereotactic salvage radiotherapy (SSRT) may offer improved disease control. The STARR trial (NCT05455736) is a prospective, multicenter study evaluating the efficacy and safety of SSRT in patients with macroscopic prostate bed recurrence. This interim analysis reports early findings from the initial patient cohort. Materials and Methods: Patients with BR (PSA > 0.2 ng/mL) post-prostatectomy and PET-confirmed macroscopic recurrence (PSMA or Choline PET, confirmed by MRI) were eligible. Treatment involved CyberKnife^®-based SSRT delivering 35 Gy in five fractions to the visible lesion. Androgen deprivation therapy (ADT) was not permitted. Complete biochemical response (CBR) was defined as PSA < 0.2 ng/mL, and biochemical response (BR) as a ≥50% PSA reduction. Additional outcomes included biochemical, radiological, and ADT-free survival (bPFS, rPFS, aPFS). Results: As of analysis, 51 patients were enrolled, with a median follow-up of 16 months (95% CI: 16–22). CBR and BR were achieved in 45.1% and 80.4% of patients, respectively. Events affecting bPFS, rPFS, and aPFS occurred in 12, 5, and 6 patients, with median values not yet reached. Toxicity was minimal, with two cases each of acute grade 2 GI and GU events, and one late grade 2 GI event. No grade ≥ 3 toxicities were reported. Conclusion: Early data support SSRT as a safe and a promising option for macroscopic local recurrence, with encouraging response rates and minimal toxicity. Full article

Purpose/Objective: The clinical implementation of MR-guided radiotherapy on MR-linacs (MRL) hasrapidly increased in recent years. The advantages represented by the MR-based daily online plan adaptation and real-time monitoring have been exploited for different tumor sites. Nevertheless, some concerns remain, mainly related to the longer treatment time and limited patient eligibility. We report here the experience of our center, where a 1.5T MRL was clinically implemented in 2019 and, since then, more than 1200 patients have been treated. Material and Methods: The first 1000 patients treated at the MRL in our department were selected. Technical information such as treatment time and adaptive technic have been prospectively recorded, while toxicity data were retrospectively collected. Results: Between October 2019 and June 2024, 1000 patients for a total of 1061 treatment courses were included. Prostate and prostate bed were irradiated in 57.1% and 10.2% of the cases, respectively, including regional pelvic lymphnodes in 4.7%. Other frequent treated sites were lymph node metastases, pancreas and liver. The most frequent prescribed doses were 36.25 Gy (31%), 35 Gy (28.3%) and 30 Gy (9.4%) in five fractions. On a total of 9076 administered fractions, 80.8% were performed with adapt-to-shape and 19.2% with adapt-to-position method. The mean in-room time was 38 min (range, 18–103), with 74.4% of patients completing the session within 40 min. Acute grade (G) 3 toxicity was recorded in 1.6% of the cases, while, on a total of 858 patients available for late toxicity, G3 was recorded in 0.3% of the cases, with no >G3. Conclusions: Our real-world experience of an early-adopter center confirms that MRL treatments are feasible for different tumor entities in several anatomical sites. We showed that most of the patients could be treated within 40 min and showed low toxicity rates. Protocols for dose escalation and margin reduction, by adopting new comprehensive motion monitoring strategies, are under development. Full article

Background: Phenylketonuria (PKU) poses significant challenges for maternal and neonatal outcomes, requiring strict adherence to dietary protocols to maintain optimal maternal phenylalanine (Phe) levels during pregnancy. This study retrospectively analyzed outcomes of pregnancies in PKU-affected women and conducted a systematic review on the timing of dietary management and its impact on outcomes. Methods: This retrospective study included data from nine PKU-affected women and 14 pregnancies followed at the Regional Reference Center for Metabolic Diseases in Catania. Women were categorized based on the timing of dietary intervention: preconception (pcD), during pregnancy (pD), or never (nD). Maternal Phe levels were classified as in-target (tP+) or non-target (tP−). A systematic review of the literature was conducted using PRISMA methodology, including 77 studies reporting maternal Phe levels, dietary timing, and clinical/auxological offspring outcomes. Results: In the retrospective study, pcD and tP+ groups had significantly better neonatal outcomes, with lower rates of congenital heart disease (CHD), facial dysmorphisms, intrauterine growth restriction (IUGR), and microcephaly. Systematic review data from 1068 PKU-affected women and 2094 pregnancies revealed that pcD with tP+ resulted in the lowest rates of miscarriage (0.14%) and adverse neonatal outcomes, while tP− and nD groups showed the highest rates of CHD, microcephaly, and intellectual disability. Conclusions: Early dietary intervention, ideally preconceptionally, and achieving target maternal Phe levels are critical in reducing adverse outcomes in pregnancies of PKU-affected women. These findings emphasize the importance of metabolic control and adherence to dietary protocols in maternal PKU management. Full article

Background: Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, leading to impaired amino acid metabolism. Early diagnosis through newborn screening (NBS) enables prompt treatment, preventing neurological complications. This study aims to describe the genetic and phenotypic spectrum of PKU and mild hyperphenylalaninemia (m-HPA) in patients diagnosed at the Department of Inborn Errors of Metabolism and Newborn Screening, Hospital G. Rodolico-S. Marco, Catania, over four decades (1987–2023). Materials and Methods: The retrospective analysis included 102 patients with elevated blood phenylalanine (Phe) levels born in Sicily and followed at the Institute. The phenotype evaluation comprised the Phe levels at birth/diagnosis, dietary tolerance, and sapropterin dihydrochloride responsiveness. The dietary compliance and Phe/Tyr ratios were assessed and compared across phenotypic classes and age groups. Results: Of 102 patients, 34 were classified as having classic PKU, 9 as having moderate PKU, 26 as having mild PKU, and 33 as having m-HPA, with a median age of 21.72 years. Common PAH variants included c.1066-11G>A (26/204 alleles), c.782G>A (18/204 alleles), and c.165delT (13/204 alleles). The phenotypes sometimes diverged from the genotype predictions, emphasizing dietary tolerance over the initial Phe levels for classification: m-HPA was statistically associated with a higher dietary tolerance (p < 0.001) compared to the classic, moderate, or mild forms of PKU. Conclusions: This study highlights the importance of large databases (e.g., BioPKU) for phenotype prediction and treatment optimization. Regular assessment of Phe/Tyr ratios is crucial for monitoring adherence and health. Phenotype determination, dietary management, and emerging therapies (Pegvaliase and gene therapy) are key to improving outcomes for PKU patients. Full article

Michele Ruggieri (1543–1607) was the first Westerner officially approved to reside in China. He promoted Chinese and Western cultural exchange, and he was especially noted for facilitating dialogue between Confucianism and Catholicism. His writings had an important impact in both China and Europe. During his sojourn preaching in China, Ruggieri not only wrote the Tianzhu shilu—the first catechism written in Chinese—but he was also the first Westerner to translate the Four Books into Western language and introduce them to Europe. Based on Ruggieri’s two translations of the Four Books—one translation into Spanish, and one into Latin—this article analyzes Ruggieri’s views of Confucius. In his translations, Ruggieri identified Confucius as a philosopher and a shengren, or saint, and he highlighted the status of Confucius in the Four Books. After analyzing Ruggieri’s treatments of Confucian concepts, this article discusses how Ruggieri’s translations imply that Confucianism had both rational and religious dimensions. After Ruggieri, other Jesuits who came to China gradually turned to emphasizing the rational aspects of Confucianism. Full article

This article centers around the early translation of the term Li 礼 in the Analects of Confucius (论语). This Latin translation shows that the interpretation of the Confucian term Li 礼 mostly did not include any religious meaning. This article also centers on the personal formation of the Jesuits of that time. Taking Michele Ruggieri as reference, this article details how studies based on the Latin Classics (especially Cicero) provided them with a reference to interpret this term as unrelated to religious worship. When the Jesuits arrived in China, at the end of the Ming dynasty, strong emphasis was given to the proper etiquette towards state officials. This in turn derived from the situation in the imperial court. In this historical environment, the Confucian rites (Li 礼) were interpreted as “good manners”. This article also presents briefly the question of whether for Christians, Li 礼 as a proper social behavior inspired by a particular cultural tradition has any connection with or can be a problem for the rituals of the Christian tradition instituted by Jesus as vehicles of divine grace. Full article

Background and purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. Materials and methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with ⁶⁸Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). Results: a total of 150 NSBM in 95 patients were treated with 30–35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often characterized by a life-threatening interstitial pneumonia requiring hospitalization. The aim of this retrospective cohort study is to identify hallmarks of in-hospital mortality in patients affected by Coronavirus Disease 19 (COVID-19). A total of 150 patients admitted for COVID-19 from March to June 2021 to “F. Perinei” Murgia Hospital in Altamura, Italy, were divided into survivors (n = 100) and non-survivors groups (n = 50). Blood counts, inflammation-related biomarkers and lymphocyte subsets were analyzed into two groups in the first 24 h after admission and compared by Student’s t-test. A multivariable logistic analysis was performed to identify independent risk factors associated with in-hospital mortality. Total lymphocyte count and CD3⁺ and CD4⁺ CD8⁺ T lymphocyte subsets were significantly lower in non-survivors. Serum levels of interleukin-6 (IL-6), lactate dehydrogenase (LDH), C-reactive protein (CRP) and procalcitonin (PCT) were significantly higher in non-survivors. Age > 65 years and presence of comorbidities were identified as independent risk factors associated with in-hospital mortality, while IL-6 and LDH showed a borderline significance. According to our results, markers of inflammation and lymphocytopenia predict in-hospital mortality in COVID-19. Full article

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42–81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC. Full article

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52–84). The median total dose delivered was 35 Gy (35–36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3–20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted. Full article

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia. Full article

There is disagreement regarding the description of the patellofemoral ligaments (PFLs), considered by some authors as capsular thickening and by others as independent ligaments. It was hypothesised that the PFLs and retinacula are structures with different histological features. The aim of this study was to describe the stabilising structures of the patella in detail and to determine if the PFLs and retinacula are different and separable structures from a macroscopic, microscopic and imaging viewpoint. An anatomical study was performed on eight knees from five cadavers (mean age, 56.2 years; range, 35–63 years), and a histological study was conducted on specimens from nine patients having a mean age of 65 years (range 35–84 years) who had undergone surgical knee procedures. The imaging study was based on 100 MRIs (96 patients). The mean age was 46 years (range 16–88), and the study analysed the capsular-ligamentous structures. In the medial compartment, the layers and structures were as follows: superficial layer, medial retinaculum; intermediate layer, Medial Collateral Ligament (MCL), Posterior Oblique Ligament (POL) and Medial Patellofemoral Ligament (MPFL); deep layer, deep part of the MCL and joint capsule. In the lateral compartment, the layers and structures were the following: superficial layer, lateral retinaculum; intermediate layer, Lateral Collateral Ligament (LCL) and Lateral Patellofemoral Ligament (LPFL); deep layer, joint capsule. All of the knees examined presented a clearly distinguishable MPFL and LPFL separable from the capsular layer. Histological study: there was a higher density of nerve fibres in retinacula compared to ligaments (p = 0.0034) and a higher content of elastic fibres in retinacula (p < 0.0005). In imaging, there was no difference between medial and lateral retinaculum thickness (p > 0.05). In conclusion, both the lateral and medial compartment can be described using the three-layer scheme. PFLs and retinacula are separate structures both macroscopically and according to imaging analysis. The retinacula respond to their specific function with a higher nerve fibre content and higher number of elastic fibres compared to the ligaments. Full article

Marinesco–Sjogren syndrome (MSS) is a rare multisystem pediatric disorder, caused by loss-of-function mutations in the gene encoding the endoplasmic reticulum cochaperone SIL1. SIL1 acts as a nucleotide exchange factor for BiP, which plays a central role in secretory protein folding. SIL1 mutant cells have reduced BiP-assisted protein folding, cannot fulfil their protein needs, and experience chronic activation of the unfolded protein response (UPR). Maladaptive UPR may explain the cerebellar and skeletal muscle degeneration responsible for the ataxia and muscle weakness typical of MSS. However, the cause of other more variable, clinical manifestations, such as mild to severe mental retardation, hypogonadism, short stature, and skeletal deformities, is less clear. To gain insights into the pathogenic mechanisms and/or adaptive responses to SIL1 loss, we carried out cell biological and proteomic investigations in skin fibroblasts derived from a young patient carrying the SIL1 R111X mutation. Despite fibroblasts not being overtly affected in MSS, we found morphological and biochemical changes indicative of UPR activation and altered cell metabolism. All the cell machineries involved in RNA splicing and translation were strongly downregulated, while protein degradation via lysosome-based structures was boosted, consistent with an attempt of the cell to reduce the workload of the endoplasmic reticulum and dispose of misfolded proteins. Cell metabolism was extensively affected as we observed a reduction in lipid synthesis, an increase in beta oxidation, and an enhancement of the tricarboxylic acid cycle, with upregulation of eight of its enzymes. Finally, the catabolic pathways of various amino acids, including valine, leucine, isoleucine, tryptophan, lysine, aspartate, and phenylalanine, were enhanced, while the biosynthetic pathways of arginine, serine, glycine, and cysteine were reduced. These results indicate that, in addition to UPR activation and increased protein degradation, MSS fibroblasts have profound metabolic alterations, which may help them cope with the absence of SIL1. Full article