Moisture Damage in Ancient Masonry: A Multidisciplinary Approach for In Situ Diagnostics

San Nicola in Carcere, one of the minor basilicas in the historical center of Rome, was the location of a wide investigation campaign of the water-related deterioration causes, present in the lower sector of the apse and adjacent pillars, affected by water infiltrations, mould and salt efflorescence. The results obtained identify the presence of water content and related effects mainly on the sides of the apsidal wall. This work focuses on the use of five Non-Destructive Techniques (NDT) and intends to show the gains obtained by integrating widely interdisciplinary methods, namely the Infrared Thermography (IRT), the Unilateral Nuclear Magnetic Resonance (Unilateral NMR), the Acoustic Tomography (AT), the Acoustic Imaging (AI) and the Laser-Induced Fluorescence (LIF). All the techniques contribute to the rapid, non-invasive and early identification of the moisture distribution, while some of them (LIF and AI) also address the determination of some moisture effects. The integrated use of different techniques helps to take the multidisciplinary point of view necessary to formulate an effective restoration intervention based on a sound scientific rationale; nonetheless, it allows to experiment a holistic approach, verifying the potential of a wide range of NDTs available within the context of a restoration yard

IDH-wild type glioblastomas featuring at least 30% giant cells are characterized by frequent RB1 and NF1 alterations and hypermutation

: Giant cell glioblastoma (GC-GBM) is a rare variant of IDH-wt GBM histologically characterized by the presence of numerous multinucleated giant cells and molecularly considered a hybrid between IDH-wt and IDH-mutant GBM. The lack of an objective definition, specifying the percentage of giant cells required for this diagnosis, may account for the absence of a definite molecular profile of this variant. This study aimed to clarify the molecular landscape of GC-GBM, exploring the mutations and copy number variations of 458 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability (MSI) in 39 GBMs dichotomized into having 30-49% (15 cases) or\u2009 65\u200950% (24 cases) GCs. The type and prevalence of the genetic alterations in this series was not associated with the GCs content (<\u200950% or 65\u200950%). Most cases (82% and 51.2%) had impairment in TP53/MDM2 and PTEN/PI3K pathways, but a high proportion also featured TERT promoter mutations (61.5%) and RB1 (25.6%) or NF1 (25.6%) alterations. EGFR amplification was detected in 18% cases in association with a shorter overall survival (P\u2009=\u20090.004). Sixteen (41%) cases had a TMB\u2009>\u200910 mut/Mb, including two (5%) that harbored MSI and one with a POLE mutation. The frequency of RB1 and NF1 alterations and TMB counts were significantly higher compared to 567 IDH wild type (P\u2009<\u20090.0001; P\u2009=\u20090.0003; P\u2009<\u20090.0001) and 26 IDH-mutant (P\u2009<\u20090.0001; P\u2009=\u20090.0227; P\u2009<\u20090.0001) GBMs in the TCGA PanCancer Atlas cohort. These findings demonstrate that the molecular landscape of GBMs with at least 30% giant cells is dominated by the impairment of TP53/MDM2 and PTEN/PI3K pathways, and additionally characterized by frequent RB1 alterations and hypermutation and by EGFR amplification in more aggressive cases. The high frequency of hypermutated cases suggests that GC-GBMs might be candidates for immune check-point inhibitors clinical trials

Recurrent oligodendroglioma with changed 1p/19q status

: We report a case of oligodendroglioma that had consistent histopathological features as well as a distinct change in 1p/19q status in the second recurrence, after temozolomide chemotherapy and radiotherapy. The first tumor recurrence had oligodendroglial morphology, IDH1 R132H and TERT promoter mutations, and 1p/19q codeletion detected by fluorescent in situ hybridization (FISH). Copy number analysis, assessed by next-generation sequencing, confirmed 1p/19q codeletion, and disclosed loss of heterozygosity (LOH) of chromosomes 4 and 9 and chromosome 11 gain. The second recurrence featured not only oligodendroglial morphology but also the appearance of admixed multinucleated giant cells or neoplastic cells having oval nuclei and mitoses and showing microvascular proliferation; it maintained IDH1 R132H and TERT promoter mutations, acquired TP53 mutation, and showed 19q LOH, but disomic 1p, detected by FISH. Copy number analysis depicted LOH of chromosomes 3p, 13, and 19q, 1p partial deletion (1p chr1p34.2-p11), and gain of chromosomes 2p25.3-p24.1, 8q12.2-q24.3, and 11q13.3-q25. B-allele frequency analysis of polymorphic sites disclosed copy-neutral LOH at 1p36.33-p34.2, supporting the initial deletion of 1p, followed by reduplication of 1p36.33-p34.2 alone. These findings suggest that the two tumor recurrences might have originated from an initial neoplastic clone, featuring 1p/19q codeletion and IDH1 and TERT promoter mutations, and have independently acquired other copy number alterations. The reduplication of chromosome 1p might be the result of temozolomide treatment, and gave rise to false negative 1p deletion detected by FISH. The possibility of 1p copy-neutral LOH should be considered in recurrent oligodendrogliomas with altered 1p/19q status detected by FISH

Does cirrhotic cardiomyopathy exist? 50 years of uncertainty

Subtle abnormalities of cardiac structure or function are often identified in patients with liver cirrhosis and have been termed cirrhotic cardiomyopathy. However, in the absence of a precise definition, its diagnosis remains a challenge. Cardiac dysfunction in patients with cirrhosis can often be attributed to concomitant diseases such as hypertension, ischaemic heart disease or excess alcohol consumption in many patients. Further research is required to identify the existence, origin and importance of abnormal cardiac function due specifically to liver disease. Cardiac dysfunction may be masked by treatments given to cirrhotic patients, such as mineral-corticoid receptor antagonists, or by co-existing conditions, such as anaemia. New imaging tests or plasma biomarkers might be able to detect abnormal cardiac function at an early stage of its development

Moisture Damage in Ancient Masonry: A Multidisciplinary Approach for In Situ Diagnostics

San Nicola in Carcere, one of the minor basilicas in the historical center of Rome, was the location of a wide investigation campaign of the water-related deterioration causes, present in the lower sector of the apse and adjacent pillars, affected by water infiltrations, mould and salt efflorescence. The results obtained identify the presence of water content and related effects mainly on the sides of the apsidal wall. This work focuses on the use of five Non-Destructive Techniques (NDT) and intends to show the gains obtained by integrating widely interdisciplinary methods, namely the Infrared Thermography (IRT), the Unilateral Nuclear Magnetic Resonance (Unilateral NMR), the Acoustic Tomography (AT), the Acoustic Imaging (AI) and the Laser-Induced Fluorescence (LIF). All the techniques contribute to the rapid, non-invasive and early identification of the moisture distribution, while some of them (LIF and AI) also address the determination of some moisture effects. The integrated use of different techniques helps to take the multidisciplinary point of view necessary to formulate an effective restoration intervention based on a sound scientific rationale; nonetheless, it allows to experiment a holistic approach, verifying the potential of a wide range of NDTs available within the context of a restoration yard

Genomic characterization of undifferentiated sarcomatoid carcinoma of the pancreas

Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features. The study cohort included 10 patients with pancreatic USC. Clinicopathological parameters were determined for each patient. The molecular profile was investigated using next-generation sequencing (NGS). Histologically, all tumors were hypercellular neoplasms with spindle-shaped or sarcomatoid cells. All patients showed vascular and perineural invasion. Most patients had a poor prognosis. NGS showed important similarities with conventional PDAC, including frequent alterations in the classic PDAC drivers, KRAS (100% of cases), TP53 (90%), and CDKN2A (60%). There were also some important distinctions from conventional PDAC: 1) SMAD4, a typical PDAC driver gene, was mutated in only one case (10%); 2) Another distinctive molecular feature was the recurrent KRAS amplification (30% of cases), which is very rare in conventional PDAC. It has been previously reported in another subtype of pancreatic undifferentiated carcinoma, the rhabdoid variant, and may be a key event leading to the acquisition of an undifferentiated phenotype in a subgroup of cases; 3) Lastly, in two different cases, we detected two potentially actionable targets, not belonging to the typical PDAC molecular landscape, such as MCL1 amplification and POLQ mutation. Our study sheds light on this rare tumor type, which shows aggressive biological behavior and few druggable alterations. The most distinctive molecular features of pancreatic USC are the paucity of SMAD4 alterations and recurrent KRAS amplification