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Exploring a novel approach to mental health technology, this study illuminates the intricate interplay between exteroception (the perception of the external world), and interoception (the perception of the internal world). Drawing on principles of sensory substitution, we investigated how interoceptive signals, particularly respiration, could be conveyed through exteroceptive modalities, namely vision and hearing. To this end, we developed a unique, immersive multisensory environment that translates respiratory signals in real-time into dynamic visual and auditory stimuli. The system was evaluated by employing a battery of various psychological assessments, with the findings indicating a significant increase in participants' interoceptive sensibility and an enhancement of the state of flow, signifying immersive and positive engagement with the experience. Furthermore, a correlation between these two variables emerged, revealing a bidirectional enhancement between the state of flow and interoceptive sensibility. Our research is the first to present a sensory substitution approach for substituting between interoceptive and exteroceptive senses, and specifically as a transformative method for mental health interventions, paving the way for future research.

Current advancements in both technology and science allow us to manipulate our sensory modalities in new and unexpected ways. In the present study, we explore the potential of expanding what we perceive through our natural senses by utilizing a visual-to-auditory sensory substitution device (SSD), the EyeMusic, an algorithm that converts images to sound. The EyeMusic was initially developed to allow blind individuals to create a spatial representation of information arriving from a video feed at a slow sampling rate. In this study, we aimed to use the EyeMusic for the blind areas of sighted individuals. We use it in this initial proof-of-concept study to test the ability of sighted subjects to combine visual information with surrounding auditory sonification representing visual information. Participants in this study were tasked with recognizing and adequately placing the stimuli, using sound to represent the areas outside the standard human visual field. As such, the participants were asked to report shapes’ identities as well as their spatial orientation (front/right/back/left), requiring combined visual (90° frontal) and auditory input (the remaining 270°) for the successful performance of the task (content in both vision and audition was presented in a sweeping clockwise motion around the participant). We found that participants were successful at a highly above chance level after a brief 1-h-long session of online training and one on-site training session of an average of 20 min. They could even draw a 2D representation of this image in some cases. Participants could also generalize, recognizing new shapes they were not explicitly trained on. Our findings provide an initial proof of concept indicating that sensory augmentation devices and techniques can potentially be used in combination with natural sensory information in order to expand the natural fields of sensory perception.

This study explores spatial perception of depth by employing a novel proof of concept sensory substitution algorithm. The algorithm taps into existing cognitive scaffolds such as language and cross modal correspondences by naming objects in the scene while representing their elevation and depth by manipulation of the auditory properties for each axis. While the representation of verticality utilized a previously tested correspondence with pitch, the representation of depth employed an ecologically inspired manipulation, based on the loss of gain and filtration of higher frequency sounds over distance. The study, involving 40 participants, seven of which were blind (5) or visually impaired (2), investigates the intrinsicness of an ecologically inspired mapping of auditory cues for depth by comparing it to an interchanged condition where the mappings of the two axes are swapped. All participants successfully learned to use the algorithm following a very brief period of training, with the blind and visually impaired participants showing similar levels of success for learning to use the algorithm as did their sighted counterparts. A significant difference was found at baseline between the two conditions, indicating the intuitiveness of the original ecologically inspired mapping. Despite this, participants were able to achieve similar success rates following the training in both conditions. The findings indicate that both intrinsic and learned cues come into play with respect to depth perception. Moreover, they suggest that by employing perceptual learning, novel sensory mappings can be trained in adulthood. Regarding the blind and visually impaired, the results also support the convergence view, which claims that with training, their spatial abilities can converge with those of the sighted. Finally, we discuss how the algorithm can open new avenues for accessibility technologies, virtual reality, and other practical applications.

This dissertation presents a selection of ten pieces created over the past seven years. These include scores to musical compositions, description of improvisation and technology based projects, and documentation in the form of audio, photography and video recording. Part I is dedicated to the Charasim series, including: Charasim II: in situ, Charasim III and IV: 4Q321, Charasim V: mirrors only exist to show something of which I was previously unaware, and Charasim VI: stratigraphy. Part II includes three compositions for small ensembles each with its unique setting: strait pursuit, strainer, and disposition: truncate, dispose. Part III is dedicated to improvisation based and installation work, and includes: ÆO trio, with pedals, Friendly Foe, and “concerto”. Each of the works presented explores various issues pertaining to subject, material and artifact as they interact within a musical setting. Preceding the portfolio is a short writing called Thinking Interpretation: Improvisation, Composition, Archaeology which is meant to bind the collection of works philosophically.

IntroductionAdolescent obesity is markedly increasing worldwide and bariatric surgery is emerging as an effective treatment option. However, a subset of patients fails to achieve significant weight loss or show post-surgical weight regain. Efforts have been made to identify different post-surgical weight trajectories and their possible predictors. Furthermore, the role of pre-surgical intervention programs in optimizing post-surgical results has been a subject of debate.ObjectivesThis study aimed to evaluate the impact of a 3-month lifestyle-oriented pre-surgical program for adolescent candidates for bariatric surgery on pre-surgical weight loss (body mass index (BMI) on completion − BMI at admission), and to identify predictors of different post-surgical weight loss trajectories.MethodsForty-eight adolescent bariatric surgery candidates were enrolled in a lifestyle- and behavior-oriented bariatric program consisting of a 3-month pre-surgical outpatient intervention and a 6-month post-surgical follow-up.ResultsMean BMI decreased by 1.82 points (SD = 1.83) during the program’s pre-surgical intervention phase, a 3.8% average drop in participants’ BMI; post-surgical weight loss trajectories were significantly associated in a curvilinear model with pre-surgical weight loss; optimal post-surgical results were associated with moderate pre-surgical weight loss, and inversely associated with maternal history of obesity, early-life weight loss attempts, and comorbid learning disorders.ConclusionsModerate weight loss in a pre-surgical lifestyle-oriented intervention program predicts optimal post-surgical weight loss. Additionally, by assessing risk factors and pre-surgical weight loss patterns, it may be possible to identify sub-populations of adolescents undergoing bariatric surgery at risk of achieving sub-optimal long-term results.

Primary sclerosing cholangitis (PSC) is a rare, progressive disease, characterized by inflammation and fibrosis of the bile ducts, lacking reliable prognostic biomarkers for disease activity. Machine learning applied to broad proteomic profiling of sera allowed for the discovery of markers of disease presence, severity, and cirrhosis and the exploration of the involvement of CCL24, a chemokine with fibro-inflammatory activity. Sera from 30 healthy controls and 45 PSC patients were profiled with proximity extension assay, quantifying the expression of 2870 proteins, and used to train an elastic net model. Proteins that contributed most to the model were tested for correlation to enhanced liver fibrosis (ELF) score and used to perform pathway analysis. Statistical modeling for the presence of cirrhosis was performed with principal component analysis (PCA), and receiver operating characteristics (ROC) curves were used to assess the useability of potential biomarkers. The model successfully predicted the presence of PSC, where the top-ranked proteins were associated with cell adhesion, immune response, and inflammation, and each had an area under receiver operator characteristic (AUROC) curve greater than 0.9 for disease presence and greater than 0.8 for ELF score. Pathway analysis showed enrichment for functions associated with PSC, overlapping with pathways enriched in patients with high levels of CCL24. Patients with cirrhosis showed higher levels of CCL24. This data-driven approach to characterize PSC and its severity highlights potential serum protein biomarkers and the importance of CCL24 in the disease, implying its therapeutic potential in PSC.

Patients with ulcerative colitis (UC) undergoing proctocolectomy and ileal pouch-anal anastomosis (IPAA) may eventually require biologic therapy. Factors associated with biologic therapy after IPAA have not been previously studied. All patients with UC after total proctocolectomy and IPAA who were followed at Rabin Medical Center comprehensive pouch clinic and who consented to prospective observational follow-up were included. The primary outcome was the initiation of biologic therapy after IPAA. Cox proportional hazard models were used to evaluate potential associations. Out of 400 patients receiving their care at the pouch clinic, 148 patients consented to prospective observational follow-up and constituted the study cohort. The median age at diagnosis was 21 years and the age at IPAA was 30 years. Median time-to-biologic therapy initiation post-IPAA was 9.2 years, with 34 patients (23%) initiating biologic therapy: Associated factors for initiating biologic therapy post-IPAA were preoperative treatment with biologic therapy and immunomodulatory therapy (hazard ratio [HR] 6.1 and 3.6, respectively, P < .001); Arab descent (HR 5.3, P < .001); heterozygosity of NOD2 variant rs2066845 (HR 5.1, P = .03); past smoking status (HR 2.3, P = .03); 3-stage IPAA (HR 2.3, P = .02); immediate postoperative complications (HR 2.1, P = .033); and pediatric-onset UC (HR 2.1, P = .03). None of the patients undergoing IPAA due to dysplasia (n = 27) required biologic therapy. Several demographic, disease-related, surgery-related, and genetic factors associated with post-IPAA biologic therapy were identified. Physicians treating patients with UC undergoing colectomy should incorporate these factors into their decision-making process. These patients may benefit from closer postoperative follow-up, and earlier initiation of biologic therapy should be considered.

ˆCCL24 is a pro-fibrotic, pro-inflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation, and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease. Multidrug resistance gene 2-knockout (Mdr2-/-) mice demonstrated CCL24 expression in liver macrophages and were used as a relevant experimental PSC model. CCL24-neutralizing monoclonal antibody, CM-101, significantly improved inflammation, fibrosis, and cholestasis-related markers in the biliary area. Moreover, using spatial transcriptomics, we observed reduced proliferation and senescence of cholangiocytes following CCL24 neutralization. Next, we demonstrated that CCL24 expression was elevated under pro-fibrotic conditions in primary human cholangiocytes and macrophages, and it induced proliferation of primary human hepatic stellate cells and cholangiocytes, which was attenuated following CCL24 inhibition. Correspondingly, CCL24 was found to be highly expressed in liver biopsies of patients with PSC. CCL24 serum levels correlated with Enhanced Liver Fibrosis score, most notably in patients with high alkaline phosphatase levels. These results suggest that blocking CCL24 may have a therapeutic effect in patients with PSC by reducing liver inflammation, fibrosis, and cholestasis.

Primary sclerosing cholangitis (PSC) is an inflammatory and fibrotic biliary disease lacking approved treatment. We studied CCL24, a chemokine shown to be overexpressed in damaged bile ducts, and its involvement in key disease-related mechanisms. Serum proteomics of PSC patients and healthy controls (HC) were analyzed using the Olink® proximity extension assay and compared based on disease presence, fibrosis severity, and CCL24 levels. Disease-related canonical pathways, upstream regulators, and toxicity functions were elevated in PSC patients compared to HC and further elevated in patients with high CCL24 levels. In vitro, a protein signature in CCL24-treated hepatic stellate cells (HSCs) differentiated patients by disease severity. In mice, CCL24 intraperitoneal injection selectively recruited neutrophils and monocytes. Treatment with CM-101, a CCL24-neutralizing antibody, in an α-naphthylisothiocyanate (ANIT)-induced cholestasis mouse model effectively inhibited accumulation of peribiliary neutrophils and macrophages while reducing biliary hyperplasia and fibrosis. Furthermore, in PSC patients, CCL24 levels were correlated with upregulation of monocyte and neutrophil chemotaxis pathways. Collectively, these findings highlight the distinct role of CCL24 in PSC, influencing disease-related mechanisms, affecting immune cells trafficking and HSC activation. Its blockade with CM-101 reduces inflammation and fibrosis and positions CCL24 as a promising therapeutic target in PSC.

INTRODUCTION:The gut microbiome in Crohn's disease (CD) shows variability and conflicting associations with disease activity. We aimed to assess microbial and clinical trajectories in newly diagnosed CD (ndCD) over 1 year.METHODS:This prospective longitudinal inception cohort study followed treatment-naive patients with ndCD for 1 year. The primary outcome was sustained corticosteroid-free clinical remission (CSFR) after 1 year. Paired fecal samples were collected at diagnosis and 1 year later, analyzed using bacterial 16S rRNA gene high-throughput sequencing. Microbial composition changes were compared between baseline and 1-year follow-up and between biologics-treated and conservatively managed patients. Fecal samples from healthy volunteers served as controls.RESULTS:Seventy-three patients participated; 64.4% achieved sustained CSFR after 1 year. During follow-up, 60.3% had moderate-to-severe disease activity and received biologics (95.5% anti-tumor necrosis factor), whereas 39.7% were managed conservatively. Significant microbial improvements, including increased Shannon diversity and decreased microbial dysbiosis index, were observed only in patients achieving sustained CSFR (both P < 0.001). Biologic-treated patients had more disrupted baseline microbiome composition than conservatively managed ones (Shannon, P = 0.04; microbial dysbiosis index, P = 0.03); they showed significant microbial improvement regardless of clinical success, shifting toward a healthier microbiome profile. Changes in clinical outcomes over 1 year correlated with microbial alterations.DISCUSSION:Over 1 year, treatment-naive patients with ndCD showed microbial improvements paralleling clinical outcomes, with shifts toward a healthier state. Biologic therapy enhanced microbial profiles, likely due to greater baseline disruption in these patients. These findings suggest that the microbiome is a marker of inflammation and a modifiable factor in CD management.