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Background & Aims: Transmural healing is a long-term target for patients with Crohn's disease. Factors contributing to its promotion are poorly understood. This study assessed factors correlating with transmural healing based on intestinal ultrasound, in patients in long-term clinical remission on anti-TNF., Methods: 68 consecutive Crohn's patients on adalimumab (50) or infliximab (18) therapy with clinical remission ≥1 year were recruited and assessed for clinical features, trough serum levels of anti-TNF and intestinal ultrasound findings. Univariate analysis and multivariate binary logistic regression analysis identified variables independently associated with bowel wall thickening behavior., Results: Sixty eight patients were in remission for a mean of 4.1 years. Thirty-six patients (52.9 %) showed anti-TNF trough levels below the normal threshold. Twenty-two patients (38.4 %) showed transmural healing, 32 (47.1 %) transmural response, and 26 (38.2 %) no treatment response. Transmural healing correlated with higher BMI and lower baseline bowel wall thickening; transmural response correlated with short Crohn's disease duration, high drug levels, and with non-stricturing phenotype. Treatment non-response correlated with lower BMI, lower drug levels, higher baseline bowel wall thickening, and stricturing phenotype., Conclusions: Lack of transmural healing in stable remission Crohn's patients on anti-TNF therapy is multifactorial, mainly due to low anti-TNFs trough levels, development of strictures, and higher baseline bowel wall thickening at treatment initiation., Competing Interests: Declaration of competing interest Giovanni Maconi consulted for Alfa Sigma, Arena Pharmaceuticals, Fresenius Kabi, Galapaos, Janssen Cilag, Gilead, Riche, Takeda. Simone Saibeni received lecture fees and was an advisory board member for Takeda and Janssen. Cristina Bezzio received lecture fees from Takeda, AbbVie, and Janssen. Sandro Ardizzone served as a speaker, consultant, and/or advisory board member for the following organizations: AbbVie, MSD, Takeda, Janssen, Pfizer, Sandoz, and Enthera. Bincy Abraham has received research funding from Takeda; consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Medtronic, Pfizer, Samsung Bioepis, Celltrion, and Takeda; lectured for AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, and Takeda. Remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Pancreatic ductal adenocarcinoma (PDAC) still has a poor response to therapies, partly due to their cancer-associated fibroblasts (CAFs). Here, we investigate the synergistic impact of a combinatory approach between a known chemotherapy agent, such as gemcitabine (GEM), and gene-modified human mesenchymal stromal/stem cells (MSCs) secreting the pro-apoptotic soluble (s)TRAIL (sTRAIL MSCs) on both PDAC cells and CAFs. The combo significantly impacts on PDAC survival in 2D and 3D models. In orthotopic xenograft models, GEM and sTRAIL MSCs induce tumor architecture shredding with a reduction of CK7- and CK8/18-positive cancer cells and the abrogation of spleen metastases. A cytotoxic effect on primary human CAFs is also observed along with an alteration of their transcriptome and a reduction of the related desmoplasia. Collectively, we demonstrate a promising therapeutic profile of combining GEM and sTRAIL MSCs to target both tumoral and stromal compartments in PDAC., Competing Interests: Declaration of interests M. Dominici and G.G. hold patents in the field of cell and gene therapy. EIR Biotherapies srl holds patents related to the presented technologies. M. Dall’Ora and O.C. are employees of EVOTEC Modena Srl., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Our goal was to evaluate persisting deficits in gait and executive functioning in asymptomatic athletes with a history of concussion using a novel approach combining a dual-task paradigm and post-exercise exertion. Thirty-eight athletes aged 17 to 25 years old participated in the study, including 18 with a history of concussion. The dual-task paradigm required walking continuously at a predetermined self-paced target speed of 6.5 km/h while executing a complex switch task. Athletes completed two conditions, each on separate days: (1) dual task alone and (2) dual task following 20 min of running on a non-motorized treadmill. The statistical analyses revealed a significant reduction in gait speed exclusively for athletes with a history of concussion and only following the post-exercise condition ( p = 0.008). These findings suggest that although asymptomatic concussed athletes maintain a cognitive performance comparable to non-concussed athletes, this appears to be achieved at the expense of gait speed. Our results underscore the importance of incorporating gait assessments and post-exercise exertion into concussion evaluation protocols in both research and clinical settings.

Background: The number of accidents due to distracted pedestrian is on the rise and many governments and institutions are enacting public policies which restrict texting while walking. However, pedestrians do more than just texting when they use their mobile devices on the go., Objective: Exploring pedestrian multitasking, this paper aims to examine the effects of mobile device task type on pedestrian performance outcomes., Method: We performed two studies in lab simulations where 78 participants were asked to perform different tasks on a mobile device (playing a game, reading, writing an email, texting one person, group texting) while performing a pedestrian visual discrimination task while either standing or walking on a treadmill. Behavioral performance as well as neurophysiological data are collected., Results: Results show that compared to a no-phone control, multitasking with any of the tasks on a mobile device leads to poor performance on a pedestrian visual discrimination task. Playing a game is the most cognitively demanding task and leads to the greatest performance degradation., Conclusion: Our studies show that multitasking with a mobile device has the potential to negatively impact pedestrian safety, regardless of task type. However, the impacts of different mobile device tasks are not all equivalent. More research is needed to tease out the different effects of these various tasks and to design mobile applications which effectively and safely capture pedestrians' attention., Application: Public policy, infrastructure, and smart technologies can be used to mitigate the negative effects of mobile multitasking. A more thorough understanding of mobile device task-specific factors at play can help tailor these counter-measures to better aid distracted pedestrians.

Purpose: Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS., Methods: This case-control study included 12 patients with ulcerative colitis or Crohn's colitis with extensive left colon pseudopolyposis and 18 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition., Results: Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis. The detection of both these findings were able to detect extensive pseudopolyposis a sensitivity of 75% (CI 95%: 42.8-94.5%) and a specificity of 100% (CI 95%: 81.5-100%)., Conclusion: This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition., (© 2024. The Author(s).)

Sensory deprivation, especially hearing loss (HL), offers a valuable model for studying neuroplasticity in the human brain and adaptive behaviours that support the daily lives of those with limited or absent sensory input. The study of olfactory function is particularly important as it is an understudied aspect of sensory deprivation. This study aimed to compare the effects of congenital HL on olfactory capacity by using psychophysical tasks. Methodological concerns from previous studies regarding the onset of HL and cognitive assessments were addressed. We recruited 11 individuals with severe-to-profound sensorineural HL (SNHL) since birth and 11 age- and sex-matched typical hearing non-signers. We used standardized neuropsychological tests to assess typical cognition among participants with SNHL. We evaluated olfactory functions by assessing olfactory detection threshold, odour discrimination and odour identification. Hearing-impaired participants outperformed their typical hearing counterparts in olfactory tasks. We further evaluated the accuracy and response time in identifying and localizing odours to disentangle olfactory sensitivity from trigeminal system sensitivity. Participants with SNHL demonstrated higher sensitivity to both the identification and localization tasks. These findings suggest that congenital SNHL is associated with enhanced higher-level olfactory processing and increased trigeminal sensitivity., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Animal models are currently used in several fields of biomedical research as useful alternatives to human-based studies. However, the obtained results do not always effectively translate into clinical applications, due to interspecies anatomical and physiological differences. Detailed comparability studies are therefore required to verify whether the selected animal species could be a representative model for the disease or for cellular process under investigation. This has proven to be fundamental to obtaining reliable data from preclinical studies. Among the different species, swine is deemed an excellent animal model in many fields of biological research, and has been largely used in respiratory medicine, considering the high homology between human and swine airways. In the context of in vitro studies, the validation of porcine airway epithelial cells as an alternative to human epithelial cells is crucial. In this paper, porcine and human tracheal and bronchial epithelial cells are compared in terms of in vivo tissue architecture and in vitro cell behaviour under standard and airlifted conditions, analyzing the regenerative, proliferative and differentiative potentials of these cells. We report multiple analogies between the two species, validating the employment of porcine airway epithelial cells for most in vitro preclinical studies, although with some limitations due to species-related divergences., (© 2023. Springer Nature Limited.)

Our ability to consciously perceive information from the visual scene relies on a myriad of intrinsic neural mechanisms. Functional neuroimaging studies have sought to identify the neural correlates of conscious visual processing and to further dissociate from those pertaining to preconscious and unconscious visual processing. However, delineating what core brain regions are involved in eliciting a conscious percept remains a challenge, particularly regarding the role of prefrontal-parietal regions. We performed a systematic search of the literature that yielded a total of 54 functional neuroimaging studies. We conducted two quantitative meta-analyses using activation likelihood estimation to identify reliable patterns of activation engaged by i. conscious (n = 45 studies, comprising 704 participants) and ii. unconscious (n = 16 studies, comprising 262 participants) visual processing during various task performances. Results of the meta-analysis specific to conscious percepts quantitatively revealed reliable activations across a constellation of regions comprising the bilateral inferior frontal junction, intraparietal sulcus, dorsal anterior cingulate, angular gyrus, temporo-occipital cortex and anterior insula. Neurosynth reverse inference revealed conscious visual processing to be intertwined with cognitive terms related to attention, cognitive control and working memory. Results of the meta-analysis on unconscious percepts revealed consistent activations in the lateral occipital complex, intraparietal sulcus and precuneus. These findings highlight the notion that conscious visual processing readily engages higher-level regions including the inferior frontal junction and unconscious processing reliably recruits posterior regions, mainly the lateral occipital complex., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

It is well documented that early sensory loss typically alters brain morphology in the areas associated with the lost sense. However, much less is known about the impact of early sensory loss on the remainder of the sensory regions. Therefore, we investigated whether congenitally blind (CB) individuals show brain alterations in the olfactory system by comparing cortical morphology and olfactory bulb (OB) volume between 16 congenitally blind individuals and 16 sighted matched controls. Our results showed that not only CB blind individuals exhibited smaller OB but also alterations of cortical density in some higher olfactory processing centres, but unchanged cortical thickness. Our current findings suggest that a lifelong absence of visual input leads to morphological alterations in olfactory processing areas., (© 2022 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The brain operates through the synaptic interaction of distant neurons within flexible, often heterogeneous, distributed systems. Histological studies have detailed the connections between distant neurons, but their functional characterization deserves further exploration. Studies performed on the corpus callosum in animals and humans are unique in that they capitalize on results obtained from several neuroscience disciplines. Such data inspire a new interpretation of the function of callosal connections and delineate a novel road map, thus paving the way toward a general theory of cortico-cortical connectivity. Here we suggest that callosal axons can drive their post-synaptic targets preferentially when coupled to other inputs endowing the cortical network with a high degree of conditionality. This might depend on several factors, such as their pattern of convergence-divergence, the excitatory and inhibitory operation mode, the range of conduction velocities, the variety of homotopic and heterotopic projections and, finally, the state-dependency of their firing. We propose that, in addition to direct stimulation of post-synaptic targets, callosal axons often play a conditional driving or modulatory role, which depends on task contingencies, as documented by several recent studies., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)