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Normal fusion for three-dimensional integrated visualization of SPECT and magnetic resonance brain images.

UNLABELLED: Multimodality visualization aims at efficiently presenting integrated information obtained from different modalities, usually combining a functional modality (SPECT, PET, functional magnetic resonance imaging) with an anatomical modality [CT, magnetic resonance imaging (MRI)]. This paper presents a technique for three-dimensional integrated visualization of SPECT and magnetic resonance brain images, where MRI is used as a framework of reference for the display of the SPECT data. METHODS: A novel technique for three-dimensional integrated visualization of functional and anatomical information, called normal fusion, is presented. With this technique, local functional information is projected onto an anatomic structure. RESULTS: The normal fusion technique is applied to three cases of SPECT/MRI integration. The results are presented, discussed and evaluated for clinical relevance. CONCLUSION: The results for three-dimensional integrated display of SPECT and MR brain images indicate that the normal fusion technique provides a potentially comprehensive and diagnostically valuable presentation of cerebral blood perfusion in relation to the anatomy of the brain.

Autistic Disorder↗

[Multimodal evoked potentials and heart rate variability in comatose patients. 2. Visual evoked potentials and computed tomographic findings].

Visual evoked potentials (VEPs) were examined as an integrated parameter in a multimodal EP study of brain bioelectrical activity in 33 comatose patients (Glasgow Coma Score 3-6) after craniocerebral trauma. Recordings were performed not only from the occipital (01-02) but also from the central (Cz-C3, Cz-A1, Cz-C4) and frontal (F3-F4) areas. The results show an attenuation of the vertex VEP (SNR 3.2 +/- 1.7) and an increase in the occipital VEP (SNR 4.8 +/- 2.3) as compared to the control group (SNR vertex 7.0 +/- 3.0/SNR occipital 3.9 +/- 2.0). In addition, 16 of the comatose patients showed a very considerable loss of the normally polyphasic character of the occipital VEP in favour of a potential that looked almost monophasic; this was either left or right dominant, and was recorded as a negative or positive potential, respectively, in bipolar recording (01-02). Comparison of the electrophysiological and computer tomography findings showed a laterally correlated change in the occipital VEP: contralateral to the injured hemisphere, the VEP was dominant, ipsilateral it was reduced or extinguished.

Adolescent↗

AI-Supported, Integrative Prediction of Postoperative Delirium: Protocol for the CONFUSED Study.

BACKGROUND: Postoperative delirium (POD) is a frequent and serious complication in older surgical patients, characterized by acute cognitive dysfunction and fluctuating levels of consciousness. POD is associated with prolonged hospitalization, long-term cognitive decline, reduced quality of life, and increased mortality. Despite its clinical relevance, the underlying pathophysiological mechanisms remain poorly understood, and reliable biomarkers for early prediction and prevention are lacking. OBJECTIVE: The CONFUSED study aims to identify molecular and clinical predictors of POD by integrating clinical data with proteomic, transcriptomic, and epigenetic analyses. The primary objective is to develop predictive models for POD using multimodal data. Secondary objectives include the identification of delirium-associated genes, proteins, and epigenetic signatures, as well as the exploration of patient subgroups at increased risk for POD. METHODS: CONFUSED is a prospective observational cohort study conducted at a German university hospital. Adult patients undergoing major surgery under general anesthesia will be enrolled until 100 cases of POD have been observed, which is expected to require a total sample size of approximately 200 to 300 patients. Blood samples are collected at 4 predefined time points: before premedication, immediately after surgery, and on postoperative days 2 and 5. Samples undergo comprehensive proteomic profiling, transcriptomic analysis using RNA microarrays, DNA methylation analysis, and genotyping of selected polymorphisms. Clinical data, including demographics, comorbidities, perioperative variables, medications, and delirium assessments using the Confusion Assessment Method (CAM) and CAM for the intensive care unit, are systematically recorded. Statistical analyses include univariate and multivariate methods, as well as machine learning approaches such as random forests and support vector machines, to identify relevant biomarkers and develop predictive models. The study protocol follows STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) guidelines and was approved by the responsible ethics committees. RESULTS: The study was registered in the German Clinical Trials Register (DRKS00033854) on March 18, 2024. Recruitment started in January 2024 and is ongoing at the time of manuscript submission. As of now, 135 patients have been enrolled. Sample collection and laboratory analyses are ongoing. Data analysis began in January 2026, with first results anticipated in July 2026. Final data lock is anticipated after the completion of recruitment. CONCLUSIONS: By integrating multimodal molecular data with clinical parameters and applying advanced machine learning techniques, the CONFUSED study aims to improve the prediction and understanding of POD. The results are expected to support the development of personalized preventive strategies and contribute to improved perioperative care for patients at risk of POD.

Humans↗

The role of circulating tumor DNA (ctDNA) to detect minimal residual disease in locally advanced gastroesophageal carcinoma: the BUTTERFLY study.

BACKGROUND: Despite advances in perioperative and neoadjuvant strategies, patients with locally advanced gastroesophageal cancers remain at high risk of recurrence after curative intent treatment. No validated biomarkers are available to detect minimal residual disease (MRD) or to guide post-operative risk-adapted management. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool for disease monitoring; single-parameter or tumor-informed assays, however, may lack sensitivity in low-tumor burden settings. Multimodal, tumor-agnostic approaches may overcome these limitations. METHODS: The BUTTERFLY study is a prospective, multicenter observational study enrolling patients with stage II-III gastric, gastroesophageal junction, or esophageal cancer treated with perioperative chemotherapy or neoadjuvant chemoradiotherapy followed by surgery. It evaluates the diagnostic performance and prognostic value of an academic, tumor-agnostic, multimodal ctDNA assay for MRD detection and prognostic stratification. Serial plasma samples are collected from baseline through post-operative follow-up and at relapse. Cell-free DNA is analyzed using the Agnostic Liquid Biopsy Multimodal Advancement (ALMA) platform, integrating tumor fraction estimation, somatic copy number alterations, fragmentomic features, single-nucleotide variants, and whole-genome methylation profiling. Multimodal features are combined with clinical variables using machine learning-based models to enhance MRD detection and relapse risk stratification. The primary endpoint includes sensitivity and specificity of ALMA-defined ctDNA/MRD status at the 4-8 weeks after surgery landmark, whereas secondary endpoints assess diagnostic performance at other time points and associations between ctDNA status and dynamics with disease-free survival, overall survival, treatment response, and lead time to recurrence. FUTURE PERSPECTIVES: If validated, this tumor-agnostic, multimodal ctDNA approach may enable earlier molecular relapse detection and support personalized post-operative management strategies.

circulating tumor DNA (ctDNA)↗

Corticocortical connections of visual, sensorimotor, and multimodal processing areas in the parietal lobe of the macaque monkey.

We studied the corticocortical connections of architectonically defined areas of parietal and temporoparietal cortex, with emphasis on areas in the intraparietal sulcus (IPS) that are implicated in visual and somatosensory integration. Retrograde tracers were injected into selected areas of the IPS, superior temporal sulcus, and parietal lobule. The distribution of labeled cells was charted in relation to architectonically defined borders throughout the hemisphere and displayed on computer-generated three-dimensional reconstructions and on cortical flat maps. Injections centered in the ventral intraparietal area (VIP) revealed a complex pattern of inputs from numerous visual, somatosensory, motor, and polysensory areas, and from presumed vestibular- and auditory-related areas. Sensorimotor projections were predominantly from the upper body representations of at least six somatotopically organized areas. In contrast, injections centered in the neighboring ventral lateral intraparietal area (LIPv) revealed inputs mainly from extrastriate visual areas, consistent with previous studies. The pattern of inputs to LIPv largely overlapped those to zone MSTdp, a newly described subdivision of the medial superior temporal area. These results, in conjunction with those from injections into other parietal areas (7a, 7b, and anterior intraparietal area), support the fine-grained architectonic partitioning of cortical areas described in the preceding study. They also support and extend previous evidence for multiple distributed networks that are implicated in multimodal integration, especially with regard to area VIP.

Animals↗

Heterarchical reinforcement-learning model for integration of multiple cortico-striatal loops: fMRI examination in stimulus-action-reward association learning.

The brain's most difficult computation in decision-making learning is searching for essential information related to rewards among vast multimodal inputs and then integrating it into beneficial behaviors. Contextual cues consisting of limbic, cognitive, visual, auditory, somatosensory, and motor signals need to be associated with both rewards and actions by utilizing an internal representation such as reward prediction and reward prediction error. Previous studies have suggested that a suitable brain structure for such integration is the neural circuitry associated with multiple cortico-striatal loops. However, computational exploration still remains into how the information in and around these multiple closed loops can be shared and transferred. Here, we propose a "heterarchical reinforcement learning" model, where reward prediction made by more limbic and cognitive loops is propagated to motor loops by spiral projections between the striatum and substantia nigra, assisted by cortical projections to the pedunculopontine tegmental nucleus, which sends excitatory input to the substantia nigra. The model makes several fMRI-testable predictions of brain activity during stimulus-action-reward association learning. The caudate nucleus and the cognitive cortical areas are correlated with reward prediction error, while the putamen and motor-related areas are correlated with stimulus-action-dependent reward prediction. Furthermore, a heterogeneous activity pattern within the striatum is predicted depending on learning difficulty, i.e., the anterior medial caudate nucleus will be correlated more with reward prediction error when learning becomes difficult, while the posterior putamen will be correlated more with stimulus-action-dependent reward prediction in easy learning. Our fMRI results revealed that different cortico-striatal loops are operating, as suggested by the proposed model.

Association Learning↗

Spectral-Proteomic Integration Analysis (SPIA) Deciphers Molecular Trajectories of Breast Cancer and Enables Multitarget Therapeutic Assessment.

Raman spectroscopy and mass spectrometry-based proteomics offer deeply complementary yet largely disconnected views of cancer biology: the former provides a label-free, real-time biochemical phenotype, while the latter delivers a quantitative inventory of specific protein effectors. Bridging this gap remains a fundamental challenge in analytical biomedicine. Here, we introduce Spectral-Proteomic Integration Analysis (SPIA)─a novel, data-driven integrative framework that systematically links Raman spectroscopic phenotypes with quantitative proteomic profiles through machine learning and statistical correlation. Using a DMBA-induced rat breast cancer model with and without Toremifene (TOR) intervention, SPIA dynamically maps tumor microenvironment remodeling, capturing progressive collagen deposition and lipid metabolic reprogramming. An SVM classifier trained on Raman spectra achieves exceptional diagnostic accuracy (AUC ≥ 99.0%) and successfully predicts TOR therapeutic response. Proteomic analysis identifies 1,350 differentially expressed proteins, with convergent machine learning feature selection (LASSO, Random Forest, XGBoost) pinpointing core regulators including Luc7l2, Nucb1, Cbx3, and Csnk2a1. Crucially, Spearman correlation analysis between key Raman bands and core DEPs reveals strong, statistically robust associations (median ρ ∼ 0.75 in the 1533-1669 cm-1 region), empirically validating SPIA's core integrative logic. Leveraging this multimodal map, we elucidate a multitarget mechanism for TOR involving concurrent suppression of collagen deposition and correction of aberrant lipid metabolism. SPIA establishes a powerful, generalizable paradigm for integrating phenotypic and molecular data, with broad implications for biomarker discovery, drug mechanism elucidation, and precision oncology.

Animals↗

Audio-visual perception of sinewave speech in an adult cochlear implant user: a case study.

OBJECTIVE: The purpose of this case study was to investigate multimodal perceptual coherence in speech perception in an exceptionally good postlingually deafened cochlear implant user. His ability to perceive sinewave replicas of spoken sentences, and the extent to which he integrated sensory information from multimodal sources was compared with a group of adult normal-hearing listeners to determine the contribution of natural auditory quality in the use of electrocochlear stimulation. DESIGN: The patient, "Mr. S," transcribed sinewave sentences of natural speech under audio-only (AO), visual-only (VO), and audio-visual (A+V) conditions. His performance was compared with the data collected from 25 normal-hearing adults. RESULTS: Although normal-hearing participants performed better than Mr. S for AO sentences (65% versus 53% syllables correct), Mr. S was superior for VO sentences (43% versus 18%). For A+V sentences, Mr. S's performance was comparable with the normal-hearing group (90% versus 86%). An estimate of the amount of visual enhancement, R, obtained from seeing the talker's face showed that Mr. S derived a larger gain from the additional visual information than the normal-hearing controls (78% versus 59%). CONCLUSIONS: The findings from this case study of an exceptionally good cochlear implant user suggest that he is perceiving the sinewave sentences on the basis of coherent variation from multimodal sensory inputs, and not on the basis of lipreading ability alone. Electrocochlear stimulation is evidently useful in multimodal contexts because it preserves dynamic speech-like variation, despite the absence of speech-like auditory qualities.

Adult↗

Prophylactic cranial irradiation as a component of intensified initial treatment of locally advanced non-small cell lung cancer.

Patients with locally advanced non-small cell lung cancer are threatened by the concurrent risks of local, regional and distant failure. By improving local and regional control with multimodality protocols, the brain becomes one of the major sites of relapse. PCI has a high potential to reduce the risk of brain metastases. Long-term toxicity is presently poorly defined and represents an important potential risk. The value of PCI as an adduct to present aggressive multimodality protocols and the optimal total dose with conventional fractionation will be investigated within clinical studies by two study groups in the future. As the best dose and fractionation still remains undefined, the integration of PCI into multimodality protocols.

Brain Neoplasms↗

Multimodal characterisation of cortical areas by multivariate analyses of receptor binding and connectivity data.

Cortical areas are regarded as fundamental structural and functional units within the information processing networks of the brain. Their properties have been described extensively by cyto-, myelo- and chemoarchitectonics, cortical and extracortical connectivity patterns, receptive field mapping, activation properties, lesion effects, and other structural and functional characteristics. Systematic integrative approaches aiming at multimodal characterisations of cortical areas or at the delineation of global features of the cortical network, however, are still scarce and usually limited to a single data modality, such as cytoarchitectonical or tract tracing data. Here we describe a methodological framework for the systematic evaluation, comparison and integration of different data modalities from the brain and demonstrate its practical application and significance in the analysis of receptor binding and connectivity data within the motor and visual cortices of macaque monkeys. The framework builds on algorithmic methods to convert data between different cortical parcellation schemes, as well as on statistical techniques for the exploration of multivariate data sets comprising data of different types and scales. Thereby, we establish a relationship between intrinsic area properties as expressed by quantitative receptor binding, and extrinsic inter-area communication, which relies on anatomical connectivity. Our analyses provide preliminary evidence for a good correspondence of these two data types in the motor cortex, and their partial discrepancy in the visual cortex, raising hypotheses about the different organisational aspects highlighted by receptors and connectivity. The methodological framework presented here is flexible enough to accommodate a wide range of further data modalities, and is specific enough to permit novel insights and predictions concerning brain organisation. Thus, this approach promises to be very useful in the endeavour to characterise multimodal structure-function relationships in the brain.

Animals↗

Medical management of unresectable, recurrent low-grade retroperitoneal liposarcoma: integration of cytotoxic and non-cytotoxic therapies into multimodality care.

Liposarcomas of the retroperitoneum are rare tumors, and best managed by an expert multidisciplinary team consisting of a surgical oncologist with appropriate medical oncology and radiation oncology collaboration. For large tumors, surgical excision with wide margins is difficult to achieve, and even wide margins cannot ensure that microscopic remnants of residual disease will not grow back in the future. For these reasons, even following expert resection, local recurrence is common. For patients with recurrent and unresectable liposarcoma, treating the sarcoma while maintaining quality of life becomes the major therapeutic goal. Importantly, patients with advanced recurrent disease demonstrate the need for multidisciplinary team involvement, with timely consideration of palliative surgical, radiation therapy, and chemotherapy options. Such patients also represent ideal candidates for investigational approaches aimed at identifying new agents with which to treat this disease. In addition to the development of new cytotoxic agents, patients may be candidates for novel strategies such as differentiation therapies or anti-angiogenic approaches. The recent explosion of knowledge regarding the cytogenetics, molecular, and cellular biology of liposarcomas allows us to remain positive that new translational therapies will be developed to improve the clinical outcomes of patients with these diseases. Current strategies, such as the use of PPARgamma ligands to differentiate liposarcomas, will soon be tested in major national collaborative trials, and the cooperation of surgeons and medical oncologists at all levels of community and academic practice will be crucial to obtain answers in this field. This review will summarize an illustrative case in the process of describing the natural history and potential interventions which should be considered for patients with this disease.

Chromans↗

Cross-modal links in spatial attention.

A great deal is now known about the effects of spatial attention within individual sensory modalities, especially for vision and audition. However, there has been little previous study of possible cross-modal links in attention. Here, we review recent findings from our own experiments on this topic, which reveal extensive spatial links between the modalities. An irrelevant but salient event presented within touch, audition, or vision, can attract covert spatial attention in the other modalities (with the one exception that visual events do not attract auditory attention when saccades are prevented). By shifting receptors in one modality relative to another, the spatial coordinates of these cross-modal interactions can be examined. For instance, when a hand is placed in a new position, stimulation of it now draws visual attention to a correspondingly different location, although some aspects of attention do not spatially remap in this way. Cross-modal links are also evident in voluntary shifts of attention. When a person strongly expects a target in one modality (e.g. audition) to appear in a particular location, their judgements improve at that location not only for the expected modality but also for other modalities (e.g. vision), even if events in the latter modality are somewhat more likely elsewhere. Finally, some of our experiments suggest that information from different sensory modalities may be integrated preattentively, to produce the multimodal internal spatial representations in which attention can be directed. Such preattentive cross-modal integration can, in some cases, produce helpful illusions that increase the efficiency of selective attention in complex scenes.

Attention↗

A microfluidic device with an integrated waveguide beam splitter for velocity measurements of flowing particles by Fourier transformation.

A microfabricated capillary electrophoresis device for velocity measurements of flowing particles is presented. It consists of a 1 x 128 planar waveguide beam splitter monolithically integrated with an electrically insulated fluidic channel network for fluorescence excitation at multiple points. Stray light rejection structures are included in order to suppress unwanted light between the detection regions. The emission pattern of particles passing the detection region was collected by a photomultiplier tube that was placed in close proximity to the channel, thereby avoiding the use of transfer optics. The integrated planar waveguide beam splitter was, furthermore, permanently connected to the light source by a glued-on optical fiber, to achieve a robust and alignment-free operation of the system. The velocity was measured using a Fourier transformation with a Shah function, since the response of the light array was designed to approximate a square profile. Deviations from this response were observed as a result of the multimode nature of the integrated waveguides.

Journal Article↗

Nonmodularity of the central auditory nervous system: implications for (central) auditory processing disorder.

This response to A. T. Cacace and D. J. McFarland (2005) identifies points of agreement and disagreement regarding the concept of modularity in the diagnosis of (central) auditory processing disorder [(C)APD]. We concur that the evaluation of (C)APD must take into consideration the influence of higher order global or pansensory issues on performance on tests of central auditory function. To accomplish this goal, multidisciplinary (e.g., multimodal) testing is an integral part of differential diagnosis of (C)APD. We also agree that the efficiency of diagnostic tests of (C)APD should not be evaluated by imprecise criteria [e.g., "presumed" or "suspected" (C)APD], which do not provide accurate measures of the true sensitivity and specificity of these tests. Our conceptualization and recommendations for clinical practice in this area diverge, however, from that of Cacace and McFarland in a number of pivotal ways. Based on the current limitations of multimodal assessment relative to issues related to scope of practice and test efficiency, as well as the accumulated basic science and clinical literature that demonstrates the nonmodularity and interactive organization of the brain, we recommend use of the sensitized test battery of the central auditory nervous system (CANS) in combination with multidisciplinary testing to differentially diagnose (C)APD and to guide treatment of the disorder. We assert that sensitivity and specificity measures derived from individuals with well-circumscribed lesions of the CANS provide an important guide to establishing the validity of central auditory diagnostic tests. We note that researchers in the area of auditory science and (C)APD must acknowledge the challenges of the clinical arena, and we encourage their continued help to develop diagnostic tools that are both efficient and practical for the differential diagnosis of (C)APD. We conclude that our approach, which combines multidisciplinary evaluation and specific tests of central auditory function that have demonstrated sensitivity and specificity for disorders of the CANS, allows us to identify (and thus rehabilitate) the auditory deficits present in individuals with (C)APD in its "purest" form. It also permits the identification and rehabilitation of auditory deficits in individuals who exhibit auditory perceptual problems that coexist with other processing problems, while ruling out those who perform poorly on auditory tests because of a global, supramodal problem involving cognition, attention, language, memory, or related skills.

Auditory Diseases, Central↗

Web architecture for the remote browsing and analysis of distributed medical images and data.

To provide easy retrieval, integration and evaluation of multimodal medical images and data in a web browser environment, distributed application technologies and Java programming were used to develop a client-server architecture based on software agents. The server side manages secure connections and queries to heterogeneous remote databases and file systems containing patient personal and clinical data. The client side is a Java applet running in a web browser and providing a friendly medical user interface to perform queries on patient and medical test data and integrate and visualize properly the various query results. A set of tools based on Java Advanced Imaging API enables to process and analyze the retrieved bioimages, and quantify their features in different regions of interest. The platform-independence Java technology makes the developed prototype easy to be managed in a centralized form and provided in each site where an intranet or internet connection can be located. Giving the healthcare providers effective tools for browsing, querying, visualizing and evaluating comprehensively medical images and records in all locations where they can need them - e.g. emergency, operating theaters, ward, or even outpatient clinics- the implemented prototype represents an important aid in providing more efficient diagnoses and medical treatments.

Ambulatory Care Facilities↗

Clinical and microdissection genotyping analyses of the effect of intra-arterial cytoreductive chemotherapy in the treatment of lacrimal gland adenoid cystic carcinoma.

PURPOSE: To determine the effect of intra-arterial cytoreductive chemotherapy (IACC) as an adjunct of a multimodality protocol for the treatment of lacrimal gland adenoid cystic carcinoma (ACC). METHODS: This was a retrospective, comparative, consecutive case series. Nine consecutive patients with lacrimal gland ACC were treated with IACC, followed by orbital exenteration and chemoradiotherapy. This case series was compared with a series of seven patients treated by conventional local therapies. Clinical records, imaging studies, histologic sections, and archival specimens from all 16 patients were reviewed. Information analyzed included site of disease, histologic characteristics, extent of disease, local-regional recurrence or distant metastases, and disease-free survival time. Gene analysis was performed on microdissected tissue samples. Mutational allelotyping targeting nine genomic loci using 15 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes serve as markers for the presence of gene deletion. The effect of IACC was assessed by the radiographic response and survival outcome in comparison to a historical cohort of patients managed by conventional local therapies. A fractional mutation index was used to compare the acquired mutational load between different tumors having nonidentical patterns of microsatellite informativeness. RESULTS: The carcinoma cause-specific death rates between the two treatment groups was significant (P = .029, log-rank test). The cumulative 5-year carcinoma cause-specific death rate was 16.7% in the IACC-treated group compared with 57.1% in the conventional treatment group. 1p36 was the single most common site affected by allelic loss for microsatellite markers in this series. CONCLUSIONS: The preliminary data suggest that IACC as an integral component of a multimodal treatment strategy is potentially effective in improving local disease control and overall disease-free survival in lacrimal gland ACC. Allelic loss for microsatellite markers at 1p36 may be a common and an early event in ACC formation and progression.

Adult↗

Inflammatory breast cancer: the evolution of multimodality treatment strategies.

Inflammatory breast cancer is an aggressive subtype of invasive breast cancer. Early attempts to control the disease with local treatment modalities alone had a minimal impact on survival. More recently, multimodality treatment approaches that integrate systemic chemotherapy, surgery, and radiotherapy have resulted in improved local disease control and prolonged survival. Better systemic therapies need to be developed since metastatic disease develops in the majority of patients.

Adenocarcinoma↗

Advances in radiation therapy for head and neck cancer.

Radiation therapy either as a single modality or as part of multimodality plans remains an integral part of curative treatment for cancers of the head and neck. This paper traces the modernization of radiation therapy regarding tumors of the head and neck using examples of sites of malignancy where radiation therapy is the sole modality or where radiation therapy can be combined with surgery and chemotherapy for optimal results. As local-regional control rates have improved with the use of combined radiation therapy and surgery and aggressive hyperfractionation schemes for advanced primary tumors, distant metastases and second primary neoplasms are now accounting for a larger proportion of treatment failures. Until such time as more effective systemic therapy and cancer control mechanisms are developed to address these problems, radiation therapy will continue to play a major role in the overall management of patients with cancers of the head and neck.

Combined Modality Therapy↗