The Holism of Doxastic Justification

I argue against the orthodox view of doxastic justification, according to which a belief of a given subject is justified for her just in case the subject has a good reason for the belief and she also bases the belief on that reason. The orthodox view is false, I maintain, because there might be unjustified beliefs that are based on the good reasons that support them. The fault lies with the ‘particularism’ of the orthodox view, which is why it cannot handle those cases where certain ‘holistic’ considerations render an otherwise justified belief unjustified. Accordingly, I argue for a holistic constraint on doxastic justification: whether a subject that bases a particular belief on a reason that supports it is justified in having that belief depends on what she does, cognitively speaking, with that reason vis-à-vis a considerable portion of her other beliefs

A Hybrid Account of Structural Rationality

In this paper, I will present and defend a hybrid account of structural rationality, simultaneously accommodating what two rival accounts, wide-scopism and narrow-scopism, get right. Wide-scopism holds that moving from an incoherent state to a coherent state is always a structurally rational thing to do. Narrow-scopism holds that there are cases in which the particular way in which coherence is achieved matters to structural rationality. The hybrid account I offer here holds that these two claims are compatible and true

Monitoraggio in area sismica di beni monumentali: tecniche NDT e procedure di verifica

Negli ultimi anni il concetto di vulnerabilità sismica è tristemente entrato a far parte delle conoscenze anche dei non addetti ai lavori. Infatti, gli eventi sismici che hanno interessato dagli inizi del ‘900 il territorio Italiano, hanno sistematicamente messo in risalto l’elevata vulnerabilità sismica del nostro patrimonio edilizio, ivi compresi i beni monumentali, nonché, l’inesistenza di qualsiasi attività di programmazione della manutenzione periodica ordinaria e straordinaria delle strutture sismo-resistenti, che garantiscono nel tempo la conservazione delle loro capacità di risposta alle perturbazioni esterne.Il progetto PON sul Monitoraggio in Area Sismica di SIstemi MOnumentali nasce con la prerogativa di produrre uno strumento dedicato alla tutela di strutture a valenza storico – artistica, attraverso un percorso di catalogazione, di analisi del bene inteso come elemento costituito da elementi resistenti e da materiali, di studio del sito dove la struttura è ubicata e di attività di monitoraggio

Textural, chemical and sensory properties of döners produced from beef, chicken and ostrich meat

In this study, the chemical, textural and sensory properties of beef, chicken, or ostrich meat döners empirically produced were compared. Ostrich döner samples had lower (P<0.0001) cholesterol content than beef or chicken döners but higher calori values. It is observed that beef döners had higher (P<0.0001) Warner-Bratzler shear force (WBSF) than chicken and ostrich döners. According to the texture analyses results it is concluded that hardness measured by Texture Profile Analyzer was found to be a better predictor of sensory tenderness than WBSF. Panelists rated ostrich döner meat with highest point in terms of sensory properties. Ostrich döners had better overall acceptance than beef or chicken döners. Therefore it is concluded ostrich döner can be taken into consideration as an alternative protein source to beef or chicken döners

Subclinical immune reactions to viral infections may correlate with child and adolescent diagnosis of attention-deficit/hyperactivity disorder: A preliminary study from Turkey

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common neuro-developmental disorders of childhood and  adolescence. Studies focusing on the relationship of infectious agents and ADHD are scarce. It is also known that cerebellar injury may lead to  hyperactive behavior. This study aimed to evaluate the relationship  between viral agents of cerebellitis and the diagnosis of ADHD.Methods: The study group was formed of 60 consecutive ADHD patients and 30 healthy children. IgG levels for VZV; HSV-1, CMV, Measles, Mumps, Rubella and EBV were evaluated.Results: Males were significantly higher among patients with ADHD (65% vs. 40%, p=0.025). Patients with ADHD displayed significantly higher positivity for measles IgG (80% vs. 60%, p=0.044). When patients with ADHD were classified according to their pubertal status, adolescents with ADHD displayed higher positivity for mumps (100% vs. 74.4%, p=0.043). Most of the patients were diagnosed with ADHD-Combined or  Hyperactive/Impulsive Subtypes (56.6%) while 43.3% were diagnosed with ADHD-predominantly inattentive type. When patients with subtypes of ADHD were compared in terms of seropositivity, it was found that patients with ADHD-Combined/ Hyperactive-Impulsive subtypes had significantly elevated reactions for Rubella (100% vs. 88.5%, p=0.044).Conclusion: Although limited to a single center and may be prone to sampling biases, our results may support the notion that immune reactions may be related with ADHD among children and adolescents. Further,  prospective studies from multiple centers are needed to support our  findings and establish causality.Key words: ADHD, infection, immunology, measles, rubella, mumps, Ig

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII

Purpose: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. Methods: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. Result: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. Conclusion: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. Critical relevance statement: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. Key points: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score (https://metricsscore.github.io/metrics/METRICS.html) and a repository created to collect feedback from the radiomics community (https://github.com/metricsscore/metrics). Graphical Abstract: [Figure not available: see fulltext.

Oncofetal reprogramming drives phenotypic plasticity in WNT-dependent colorectal cancer

Targeting cancer stem cells (CSCs) is crucial for effective cancer treatment, yet resistance mechanisms to LGR5(+) CSC depletion in WNT-driven colorectal cancer (CRC) remain elusive. In the present study, we revealed that mutant intestinal stem cells (SCs) depart from their canonical identity, traversing a dynamic phenotypic spectrum. This enhanced plasticity is initiated by oncofetal (OnF) reprogramming, driven by YAP and AP-1, with subsequent AP-1 hyperactivation promoting lineage infidelity. The retinoid X receptor serves as a gatekeeper of OnF reprogramming and its deregulation after adenomatous polyposis coli (APC) loss of function establishes an OnF ‘memory’ sustained by YAP and AP-1. Notably, the clinical significance of OnF and LGR5(+) states in isolation is constrained by their functional redundancy. Although the canonical LGR5(+) state is sensitive to the FOLFIRI regimen, an active OnF program correlates with resistance, supporting its role in driving drug-tolerant states. Targeting this program in combination with the current standard of care is pivotal for achieving effective and durable CRC treatment

RAS-Mutant Leukaemia Stem Cells Drive Clinical Resistance to Venetoclax

Cancer driver mutations often show distinct temporal acquisition patterns, but the biological basis for this, if any, remains unknown. RAS mutations occur invariably late in the course of acute myeloid leukaemia, upon progression or relapsed/refractory disease1-6. Here, by using human leukaemogenesis models, we first show that RAS mutations are obligatory late events that need to succeed earlier cooperating mutations. We provide the mechanistic explanation for this in a requirement for mutant RAS to specifically transform committed progenitors of the myelomonocytic lineage (granulocyte-monocyte progenitors) harbouring previously acquired driver mutations, showing that advanced leukaemic clones can originate from a different cell type in the haematopoietic hierarchy than ancestral clones. Furthermore, we demonstrate that RAS-mutant leukaemia stem cells (LSCs) give rise to monocytic disease, as observed frequently in patients with poor responses to treatment with the BCL2 inhibitor venetoclax. We show that this is because RAS-mutant LSCs, in contrast to RAS-wild-type LSCs, have altered BCL2 family gene expression and are resistant to venetoclax, driving clinical resistance and relapse with monocytic features. Our findings demonstrate that a specific genetic driver shapes the non-genetic cellular hierarchy of acute myeloid leukaemia by imposing a specific LSC target cell restriction and critically affects therapeutic outcomes in patients