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Vision and touch are automatically integrated for the perception of sequences of events.

The purpose of the present experiment was to investigate the integration of sequences of visual and tactile events. Subjects were presented with sequences of visual flashes and tactile taps simultaneously and instructed to count either the flashes (Session 1) or the taps (Session 2). The number of flashes could differ from the number of taps by +/-1. For both sessions, the perceived number of events was significantly influenced by the number of events presented in the task-irrelevant modality. Touch had a stronger influence on vision than vision on touch. Interestingly, touch was the more reliable of the two modalities-less variable estimates when presented alone. For both sessions, the perceptual estimates were less variable when stimuli were presented in both modalities than when the task-relevant modality was presented alone. These results indicate that even when one signal is explicitly task irrelevant, sensory information tends to be automatically integrated across modalities. They also suggest that the relative weight of each sensory channel in the integration process depends on its relative reliability. The results are described using a Bayesian probabilistic model for multimodal integration that accounts for the coupling between the sensory estimates.

Adult↗

Supplemental stimulation of premature infants: a treatment model.

Examined the human infant literature on supplemental stimulation to delineate a course of intervention based on the ontogeny of the nervous system and the impact that systematic stimulation may have on behavioral organization in the premature infant. Effects of vestibular, tactile/kinesthetic, auditory, and oral stimulation are discussed with respect to their similarity to the intra- or extra-uterine environment. Long-standing theoretical and methodological problems are discussed, and a "sequential multimodal treatment model" is introduced.

Child Development↗

Artificial Intelligence for Natural Products Discovery and Development.

Natural products (NPs) remain a cornerstone of modern drug discovery, offering stereochemical complexity and diverse bioactivities that precisely modulate therapeutic targets, refined through billions of years of evolution. However, their research has long been hindered by inefficient, empirical workflows, high resource consumption, structural complexity, and the "multicomponent, multi-target" nature of their mechanisms. The exponential growth of genomic, metabolomic, and spectral data has overwhelmed conventional analytical methods, exposing critical bottlenecks in handling high-dimensional, heterogeneous datasets that exceed human interpretive capacity. Artificial intelligence (AI) is emerging as a transformative paradigm to address these challenges, integrating multi-omics and chemical data to shift NP research from fragmented empiricism toward mechanism-driven, precision-oriented development. By leveraging deep learning architectures- including graph neural networks, Transformers, and diffusion-based generative models-AI enables systematic decoding of NP biosynthesis, automated structure elucidation, rational target identification, knowledge extraction from vast unstructured scientific literature, and de novo molecular design. This review comprehensively surveys recent advances in AI applications across the full NP discovery and development pipeline, encompassing genome mining, structure-based and ligand-based virtual screening, multimodal structural characterization, lead optimization, and biosynthetic pathway engineering. We further examine the emerging roles of protein-centric, molecule- centric, and multimodal foundation models, as well as large language models, in bridging genotype-to-chemotype gaps and unlocking unstructured scientific knowledge. Finally, we discuss critical challenges including data scarcity, representational limitations for complex stereochemistry, physical plausibility in generative models, and the urgent need for experimental validation, while outlining future directions toward autonomous experimentation, closed-loop optimization, and human-AI collaborative discovery.

Artificial intelligence↗

Multimodality cardiovascular image segmentation using a deformable contour model.

An automatic segmentation method has been developed for cardiovascular multimodality imaging. A "snake" model based on a curve shaping and an energy-minimizing process is used to detect blood-wall interfaces on Cine-CT, MRI and ultrasound images. Deformation of a reduced set of contour points was made according to a discretized global, regional and local minimum energy criterion. A continuous regional optimization process was also integrated into the deformation model, it takes into account a cubic spline interpolation and adaptive regularity constraints. The constraints provided rapid convergence toward a final contour position by successively stopping spline segments.

Algorithms↗

Dissociation between conditioned taste aversion and radial maze learning following seizure-induced multifocal brain damage: quantitative tests of serial vs. parallel circuit models of memory.

Multivariate analyses between conditioned taste aversion (CTA) and radial maze acquisition (RMA) scores and percentages of neuronal dropout within thalamic and telencephalic structures were completed for rats in which overt seizures had been evoked following a single systemic injection of lithium/pilocarpine. Despite multifocal damage, only the amount of damage within the hippocampus (CA1) and the basolateral amygdala was most strongly associated with attenuated CTA, whereas damage within the mediodorsal thalamus was primarily associated with RMA. There was no significant correlation between CTA or RMA. Multiple regression analyses for specific Paxinos and Watson structures and their traditional aggregates supported more precise delineation of neuronal substrates of learning/memory and a multimodal (parallel) model for these processes.

Animals↗

Multimodal rehabilitation for faecal incontinence: experience of an Italian centre devoted to faecal disorder rehabilitation.

BACKGROUND: Sphincter exercises and biofeedback therapy have been used to treat faecal incontinence but results have been unpredictable and standards of treatment have not yet been established. The aim of this study was to retrospectively evaluate the effects of a new multimodal rehabilitation model on faecal incontinence. METHODS: All of the rehabilitative procedures are guided by manometric data. Primary study outcome criteria were the determination of changes or deterioration in incontinence, failure to achieve full continence and/or presence of faecal urgency. The clinical outcome was designed according to the Jorge-Wexner incontinence score. RESULTS: Between 1997 and 2001, one hundred forty-nine incontinent patients (85 F and 64 M; age range, 41-73 years; mean age, 60.6 years) underwent multimodal rehabilitation at our outpatient unit. The overall mean incontinence score had significantly improved after treatment ( p<0.001), and 58 patients (38.9%) were symptom free. No patient reported any deterioration in incontinence. Faecal urgency persisted in 23 patients (15.4%). CONCLUSION: In conclusion, multimodal rehabilitation, using manometric study, can modify the incontinence score.

Adult↗

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Adolescent↗

Joint Effects of Long-Term Obesity and Genetic Susceptibility on Sex-Specific Brain Aging.

OBJECTIVE: This study aimed to examine the associations of longitudinal obesity trajectories and polygenic risk with sex-specific brain aging. METHODS: We analyzed 35,092 UK Biobank participants (16,484 males and 18,608 females). Sex-specific XGBoost models estimated multimodal brain age. We derived 16-year longitudinal obesity trajectories from repeatedly collected anthropometric measurements. Polygenic risk scores were constructed based on 55 independent genetic loci. Multivariable logistic regression examined associations of obesity trajectories and genetic risk with brain age acceleration. RESULTS: A total of 8198 (49.73%) males and 9089 (48.84%) females had accelerated brain aging. High genetic risk significantly increased brain age acceleration odds (males: OR&#x2009;=&#x2009;1.39; females: OR&#x2009;=&#x2009;1.34). Crucially, the high-stable obesity trajectory exerted a stronger effect in males (OR&#x2009;=&#x2009;1.90, 95% CI: 1.64-2.21) than in females (OR&#x2009;=&#x2009;1.25, 95% CI: 1.12-1.40), with the joint presence of high genetic risk and high-stable obesity amplifying risk to an OR of 2.78 in males and 1.57 in females. Conversely, shifting from obesity to non-obesity reduced risk by 30% in males and 18% in females. CONCLUSIONS: These findings underscore long-term obesity as a critical, sex-dimorphic driver of accelerated brain aging, and midlife weight management offers robust neuroprotection even in genetically susceptible individuals.

brain aging↗

Hyperacute imaging of ischemic stroke: role in therapeutic management.

Ischemic stroke remains a significant cause of morbidity and mortality. Current therapeutic options for acute ischemic stroke include intravenous thrombolysis and endovascular approaches for recanalization of proximal arterial occlusion. The rapid identification of underlying stroke etiology or mechanism may facilitate selection criteria for emergent therapy. Hyperacute imaging plays an integral role in the delineation of stroke pathophysiology and the formulation of rational stroke therapy. Hyperacute imaging of ischemic stroke may demonstrate proximal vascular occlusion, compensatory collateral circulation, residual or collateral tissue perfusion, and the differentiation of ischemic core from penumbral regions. Characterization of the ischemic field, including core and penumbra, with various mismatch models on multimodal computed tomography or MRI may refine current therapeutic strategies for cerebral ischemia. The diagnostic and therapeutic role of hyperacute imaging has emerged as a pivotal component in the evaluation and management of ischemic stroke.

Brain↗

[Surgery and chemoradiation in stage IIIA non-small cell lung cancer].

Combination of surgery and radiotherapy has become a standard regimen in multiple cancers. Because of its toxicity and the higher metastatic potential of lung cancer, leading to underestimate the impact of loco-regional treatments, this strategy is currently used only in a clinical trial setting. Recent results from phase III studies comparing surgery and radiotherapy in stage IIIA-N2 locally advanced non-small cell lung cancer after induction treatment showed that surgery should only be performed in patients presenting with a major mediastinal downstaging and possible curative resection within a lobectomy. In all other cases, exclusive chemoradiation remains the therapeutic standard at the time. In this way, all patients with stage III non-small cell lung cancer may receive induction treatment, consisting either in chemotherapy or in sequential or concurrent chemoradiation, which has shown its feasibility and its efficacy regarding tumor response, resectability and local control rates. These two induction regimens are currently compared in randomized trials including stage III resectable and unresectable tumors at time of diagnosis. These developments make treatment of locally advanced non-small cell lung cancer a model for multimodal strategies in oncology, combining chemotherapy, radiotherapy and surgery.

Antineoplastic Combined Chemotherapy Protocols↗

[Neoadjuvant chemoradiation in non-small cell lung cancer].

In 2006 preoperative chemoradiation is a major part of the treatment of stage III locally advanced non-small cell lung cancer. Previous studies have clearly demonstrated the feasibility both regarding toxicities and resectability rates of the sequential and concurrent combination of radiation to chemotherapy in a neoadjuvant setting. However, induction chemoradiation has never been randomly compared to exclusive preoperative chemotherapy. Besides, the doses of radiation and the optimal drug combination remain undetermined at the time. Regarding the global therapeutic strategy of stage III non-small cell lung cancer, recently reported phase III trials evaluating the role of surgical resection after induction chemotherapy or chemoradiation, all showed the prognostic importance of the tumoral and mediastinal downstaging to select patients really benefiting from surgery. These developments make of the treatment of locally advanced non-small cell lung cancer a model for multimodal therapeutic strategies combining chemotherapy, radiotherapy and surgery.

Antineoplastic Agents↗

Primary mediastinal nonseminomatous germ cell tumors: the influence of postchemotherapy pathology on long-term survival after surgery.

OBJECTIVES: The treatment of nonseminomatous germ cell tumors with cisplatin-based chemotherapy followed by aggressive surgical resection of residual disease is one of the most successful models for multimodality cancer therapy. We reviewed the case histories of 91 patients treated at our institution from 1981 to 1998 with primary mediastinal nonseminomatous germ cell tumors to evaluate variables that may influence survival after surgery. METHODS: Twelve of the 91 patients did not undergo postchemotherapy resection because of progressive disease. Seventy-nine of them underwent 82 thoracic surgical procedures and are the basis of this review. The majority (71/75) had elevated serum tumor markers, 75% (n = 50) of which returned to normal levels after first- or second-line chemotherapy. RESULTS: There were 3 operative deaths and 1 late death, attributed to pulmonary complications. Twenty-four patients died of recurrent disease and 3 of leukemia, for an overall survival of 61% after an average follow-up of 48 months. The pathologic findings of complete tumor necrosis (n = 19) and benign teratoma (n = 28) in the surgical specimen predicted excellent and good long-term survival, respectively, which was statistically better than that of patients having persistent nonseminomatous germ cell tumors (n = 24) or carcinomatous/sarcomatous degeneration (n = 8). CONCLUSIONS: Primary nonseminomatous germ cell tumors of the mediastinum can be cured with a multimodality therapy, particularly in the subset of patients with postchemotherapy pathologic findings of tumor necrosis and teratoma. Survival is poor but possible in patients with unfavorable pathologic findings after chemotherapy, currently justifying an aggressive surgical approach in patients with otherwise operable disease.

Adolescent↗

Temperature dependence of the Qy resonance Raman spectra of bacteriochlorophylls, the primary electron donor, and bacteriopheophytins in the bacterial photosynthetic reaction center.

Qy-excited resonance Raman spectra of the accessory bacteriochlorophylls (B), the bacteriopheophytins (H), and the primary electron donor (P) in the bacterial photosynthetic reaction center (RC) of Rhodobacter sphaeroides have been obtained at 95 and 278 K. Frequency and intensity differences are observed in the low-frequency region of the P vibrational spectrum when the sample is cooled from 278 to 95 K. The B and H spectra exhibit minimal changes of frequencies and relative intensities as a function of temperature. The mode patterns in the Raman spectra of B and H differ very little from Raman spectra of the chromophores in vitro. The Raman scattering cross sections of B and H are 6-7 times larger than those for analogous modes of P at 278 K. The cross sections of B and of H are 3-4 times larger at 95 K than at 278 K, while the cross sections of P are approximately constant with temperature. The temperature dependence of the Raman cross sections for B and H suggests that pure dephasing arising from coupling to low-frequency solvent/protein modes is important in the damping of their excited states. The weak Raman cross sections of the special pair suggest that the excited state of P is damped by very rapid (<<30 fs) electronic relaxation processes. These resonance Raman spectra provide information for developing multimode vibronic models of the excited-state structure and dynamics of the chromophores in the RC.

Bacteriochlorophylls↗

Fast track vaginal surgery.

OBJECTIVE: Our aim was to describe the need for postoperative hospitalization after vaginal surgery for utero-vaginal prolapse with well-defined charts for postoperative care. DESIGN: A prospective, descriptive study. Consecutive women admitted for first-time vaginal surgery for utero-vaginal prolapse at a public university hospital in Copenhagen, Denmark, underwent surgery and postoperative care in a fast track setting from September 15, 1999 to June 15 2000. METHODS: A multimodal rehabilitation model with emphasis on information, standardized general anesthesia, reduced surgical distress, optimized pain-relief, early oral nutrition and ambulation, minimal use of indwelling catheter and vaginal packing. OUTCOME MEASURES: Postoperative hospital stay, complications, re-admission, success rate, patients' satisfaction and acceptability. RESULTS: Forty-one women with a median age of 69 years (range, 44-88 years) were included. All underwent anterior and/or posterior vaginal repair. Nineteen (46.3%) underwent vaginal hysterectomy, and eight (19.5%) underwent the Manchester procedure. Postoperative hospital stay was median 24 hr. Only three (7.3%) were discharged later than 48 hr. No re-admissions occurred. The most frequent complications were urinary retention exceeding 450 ml, and urinary tract infection (12.2%, and 9.8%, respectively). Short-term success rate was 97.6%. Patients' satisfaction rates were 85.4-95.1%. The median score of acceptability was 10 on a 0-10 points scale. CONCLUSION: The need for postoperative hospitalization was median 24 hr after vaginal surgery in a fast track setting, independently of the complexity of the procedure performed. Short-term success rate, satisfaction rates, and acceptability were all excellent. Follow up has been established to evaluate long-term success rates and recurrence.

Adult↗

Pain management for joint arthroplasty: preemptive analgesia.

Scheduled preoperative and postoperative analgesia should be offered in a multimodal management model. By a combined drug synergy effect, the central nervous system, afferent pathways, and peripheral wound site are modified collectively. In an ongoing effort to improve perioperative pain management, we retrospectively compared the results of a previously reported pain management protocol with 2 more recent groups of patients managed with modified pain protocols. In the earlier control protocol, epidural anesthesia was discontinued on arrival to the postanesthesia care unit, and regularly scheduled oral opioids and intravenous hydromorphone for breakthrough pain were initiated. The first more recent group used epidural anesthesia, and the second group used spinal anesthesia. Both protocols featured the use of cyclooxygenase-2-inhibiting anti-inflammatory medication administered for 2 weeks preoperatively and continued for 10 days postoperatively and patient-controlled analgesia for 24 hours followed by scheduled oral opioids.

Aged↗

More accurate identification of reversible ischemic injury in human stroke by cerebrospinal fluid suppressed diffusion-weighted imaging.

BACKGROUND AND PURPOSE: The apparent diffusion coefficient (ADC) derived from diffusion-weighted (DWI) MRI has been used to differentiate reversible from irreversible ischemic injury. However, the ADC can be falsely elevated by partial volume averaging of cerebrospinal fluid (CSF) with parenchyma, limiting the accuracy of this approach. This study tested the hypothesis that the accuracy of differentiating reversible from irreversible ischemic injury could be improved by CSF suppression at image acquisition. METHODS: Sixteen patients presenting within 6 hours from symptoms, and having partial reversal of the acute lesion on DWI were studied using conventional CSF-suppressed DWI. Lesions were segmented from coregistered acute DWI and follow-up fluid-attenuated inversion recovery (FLAIR) series. The segmented volumes were applied to conventional (ADC(C)) and CSF-suppressed ADC (ADC(FLIPD)) maps to classify each voxel as progressed to infarct or reversed. Individual voxel ADC values were pooled across all patients. Sensitivity to predict reversal, specificity, and accuracy were calculated for both methods. RESULTS: A total of 25 313 voxels were classified as progressed and 31 952 voxels reversed. Across all lesion voxels, ADC(FLIPD) values more accurately depicted tissue fate compared with ADC(C) values (P<0.0001). The largest difference in the two methods was in voxels with <75% parenchyma, where the accuracy of ADC(C) was only 50% compared with 62% for ADC(FLIPD.) CONCLUSIONS: CSF-suppressed ADC measurements gave a more accurate identification of reversible ischemic injury in this sample. We predict that multimodal MRI models of tissue viability in ischemic stroke will be more accurate if CSF-suppressed ADC measurements are used.

Adult↗

Enhancing community participation in intervention research: farmworkers and agricultural chemicals in North Carolina.

The participation of affected communities in the development of public health intervention research improves project sustainability and effectiveness by making projects more relevant and acceptable to the communities. This article presents a multimode, multidomain model approach for community participation in different project components, which ensures the benefits of participation without requiring the same level of participation in every activity or by every community sector. A case study is used to illustrate the model, describing procedures for establishing and maintaining farmworker participation in developing an intervention to reduce exposure to chemicals. Farmworkers are a poor and underserved population for which the empowering and culturally appropriate benefits of community participation are especially needed. However, this population presents challenges for participatory health projects: geographic dispersion, ethnic diversity, lack of organization, sense of powerlessness, and communication and transportation difficulties. The lessons learned in this case extend the method and theory of community participation.

Adult↗

Learning dialogue with and without movement.

In two experiments, we investigated the contribution of physical movement to the processing and eventual retrieval of dramatic dialogue by untrained nonactors after they had received only brief procedural coaching. It was found that participants who processed a script by reading the text aloud while simultaneously moving in accordance with a director's instructions retained more material than did those who used verbal communication only or controls who deliberately memorized the same material. Furthermore, when the recall of the participants in the moving condition was analyzed on a speech-by-speech basis, the results showed significantly greater memory for speeches that had been accompanied by movement than for speeches during which the same participant had remained in one place. These findings are discussed in the contexts of embodied cognition and multimodal memory models.

Adult↗