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PubMed1999

[Homeless and mentally ill. Review of recent research and results on a doubly disadvantaged minority].

There are about 200,000 homeless persons in Germany, 35,000 of them living on the streets. They suffer from unemployment, poverty, social isolation and physical impairments. More than two-thirds of them suffer from mental illness as well. Substance abuse predominates, but also schizophrenic and affective disorders and personality disorders show a higher prevalence than among the general population. Comorbidity is found frequently. However, mental disorders are just one of several factors contributing to the process of becoming homeless. Due to the complex combination of mental, physical, social and economic problems of the homeless mentally ill psychiatric care is not sufficient. Yet recent US studies show that a combination of multimodal clinical measures and a network of outpatient assistance can improve both physical and mental health and the social situation. Having established reliable epidemiological data, future research should concentrate on analysing the influence of homelessness on mental health, and on planning and evaluating specific programmes for the homeless mentally ill.

Ill-Housed Persons↗
PubMed1984

Prediction of outcome in non-traumatic coma in childhood.

The data in 104 comatose children were analysed, neonates and those with head injury being excluded. The median age was 30 months, with a range of one month to 17 years. 50% were normal, 32% died and the remainder had handicaps ranging from mild to severe. A number of individual clinical variables related with outcome. Stepwise multivariate discriminate analysis individually classified 75% of 102 cases correctly into one of 5 outcome groups, using clinical information obtained at the time of initial assessment within 12 hours of the onset of coma; 67% of 66 cases could be classified correctly on the basis of information available at 24 hours after the onset of coma. There were, respectively, 8% and 3% serious misclassification errors for the 2 time periods. Our data suggest that the stepwise procedure may be a useful method for the early prediction of outcome in comatose children. Classification errors may be minimized by enlarging the data base, by using alternate statistical methods and by taking into account information from investigative variables, the most promising of which seems to be multimodality evoked potentials.

Child↗
PubMed2001

Brain areas in abyssal demersal fishes.

Four areas of the brain which receive primary projections from chemical senses ([1] olfactory bulb, [2] gustatory area including facial and vagal lobes), the eye ([3] optic tectum), and mechanosensory, and-hair-cell based systems i.e. the lateral line, vestibular and auditory systems ([4] trigeminal and octavolateral regions) have been studied and relative size differences used to make deductions on the sensory preferences of 35 fish species living on or near the bottom of the deep sea. Furthermore the relative volumes of the telencephalon and the corpus cerebelli were determined. Two evaluation modes were applied: (1) the relative mean of each system was calculated and species with above-average areas identified; (2) a cluster analysis established multivariate correlations among the sensory systems. The diversity of sensory brain areas in this population of fish suggests that the benthic and epibenthic environment of the abyss presents a rich sensory environment. Vision seems to be the single most important sense suggesting the presence of relevant bioluminescent stimuli. However, in combination the chemical senses, smell and taste, surpass the visual system; most prominent among them is olfaction. The trigeminal/octavolateral area indicating the role of lateral line input and possibly audition is also well represented, but only in association with other sensory modalities. A large volume telencephalon was often observed in combination with a prominent olfactory system, whereas cerebella of unusually large sizes occurred in species with above-average visual, hair-cell based, but also olfactory systems, confirming their role as multimodal sensorimotor coordination centers. In several species the predictions derived from the volumetric brain analyses were confirmed by earlier observations of stomach content and data obtained by baited cameras.

Adaptation, Physiological↗
PubMed2002

Is the association of National Institutes of Health Stroke Scale scores and acute magnetic resonance imaging stroke volume equal for patients with right- and left-hemisphere ischemic stroke?

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) is an established measure of neurological impairment; however, it can award more points for tests of presumed left-hemisphere function, such as language, than for tests of right-hemisphere function, such as neglect. This difference may be important if a low NIHSS score is used to exclude patients with right-hemisphere stroke from clinical trials or established treatments. The aim of this study was to investigate whether the relationship between acute NIHSS score and acute stroke volume as determined by acute diffusion- and perfusion-weighted MRI (DWI and PWI) differs between right- and left-sided stroke. METHODS: This was a retrospective study of 153 patients with acute stroke seen at Beth Israel Deaconess Medical Center between January 1995 and March 2000 who underwent an MRI examination and NIHSS within 24 hours of stroke onset. NIHSS score was recorded prospectively by the admitting stroke fellow at the time of acute presentation, immediately preceding imaging. Computerized volumetric analysis of the MRI lesions was performed by investigators blinded to clinical data. RESULTS: There were significant correlations between the acute NIHSS scores and acute DWI lesion volumes (r=0.48 right, r=0.58 left) and between acute NIHSS scores and perfusion-weight imaging hypoperfusion volumes (r=0.62 right, r=0.60 left). For patients with NIHSS scores of 0 to 5, the DWI volume of right cerebral lesions was greater than that of left-sided lesions (mean volume, 8.8 versus 3.2 cm3; P=0.04). Among patients with DWI lesions larger than the median volume (9 cm3), 8 of 37 with right-sided stroke had an NIHSS score of 0 to 5 compared with 1 of 39 patients with left-sided stroke (P=0.01). Multiple linear regression analysis revealed a significantly lower acute NIHSS on the right compared with the left side when adjusted for stroke volume on chronic T2 imaging (P=0.03). CONCLUSIONS: Patients with right-sided stroke may have a low NIHSS score despite substantial DWI lesion volume. Acute imaging information, such as that available with multimodal MRI, may be useful to identify patients for inclusion in acute stroke protocols when there is clinical uncertainty about eligibility. Prospective evaluation of criteria incorporating acute imaging data is required.

Adult↗
PubMed2005

Multimodality therapy and significance of serum CYFRA21-1 for thymic carcinoma.

Thymic carcinoma is a rare mediastinal neoplasm with a poor prognosis due to delayed diagnosis and highly malignant behavior. To evaluate 7 serum tumor markers and the outcome of treatment, 11 stage III-IVb thymic carcinomas undergoing multimodality treatment were reviewed. High levels of serum CYFRA21-1 were detected in 5 patients (45%) and correlated with the progression of disease. Of the patients, 6 underwent surgery. The median survival time was 38.4 months, and the 5-year survival rate was 15.6%. The metastatic stage (IVb) and treatment without resection were significantly associated with poorer overall survival (p=0.0034 and p=0.0041, respectively). Our data demonstrated that serum CYFRA21-1 may represent a potential new biomarker in thymic carcinoma. Stage may provide a basis for prognosis in stage III-IVb thymic carcinoma, and resection is one of the most important parts of multimodality treatment for advanced thymic carcinoma. Effective neoadjuvant treatment is therefore essential.

Aged↗
PubMed1996

Recurrences of rectal cancers: results of a multimodal approach with intraoperative radiation therapy. French Group of IORT. Intraoperative Radiation Therapy.

PURPOSE: Prognosis of recurrent rectal cancer remains poor, mainly because of the difficulties of achieving a satisfactory local control. Intraoperative radiation therapy (IORT) allows for the delivery of a complementary single dose to the tumor residues or to the tumor bed and could be useful jn a multimodal treatment. In an attempt to evaluate this interest, a retrospective analysis of patients treated with IORT in six French hospitals has been performed. METHODS AND MATERIALS: Data have been collected in 73 patients (41 men), with a mean age of 62 years, treated with IORT. Initial rectal tumors were large (mean diameter: 45 mm), partially or totally fixed to the contiguous structures in 39%, and with nodal involvement in 50% of the cases. Initial surgery had been a sphincter-sparing surgery in 67%; external radiation therapy had been delivered in 52%, and a chemotherapy had been given in 10% of the patients. Recurrences were isolated (without metastases) in 86%, and were posterior or posterolateral in 55% of the cases. Surgery allowed for a complete macroscopical resection in 57%, a partial resection with gross residual disease in 29%, and no resection in 14% of the recurrences. Intraoperative radiation therapy was delivered in a dose of 10 to 25 Gy (mean 18.5) through localizators of a mean diameter of 75 mm (60 to 110). External radiation therapy, either preoperative or postoperatively was given to 30 patients without prior radiation therapy. Ten patients received additional chemotherapy with 5-fluorouracil. RESULTS: Four postoperative deaths occurred. Postoperative morbidity occurred in 16 patients and some complications were probably related to the IORT procedure. Four long-term complications were observed. Overall actuarial survival occurred in 72.4% of the patients at 1 year, in 44.6% at 2 years, and in 30.6% at 3 years. Twenty-one local failures have been observed. Actuarial local control occurred in 71.3% of the patients at 1 year, 47.7% at 2 years, and 31.3% at 3 years. CONCLUSION: Intraoperative radiation therapy is a complementary treatment for recurrences of rectal cancer. It provides encouraging results, particularly in some selected situations, when patients have not previously been treated with external radiation therapy. Further studies of multimodal treatments are necessary.

Adult↗
PubMed2006

[ADHD and multimodal intervention].

During the year 2003, the National Register of the Attention deficit hyperactivity disorder (ADHD) has been implemented in Italy. It was commissioned by the Ministry of Health to the Istituto Superiore di Sanità, which is its leading technical and scientific body, with the aim to set up a sound database gathering detailed information on the prescription of Ritalin at the national level. The latter represents the most diffused elective drug treatment for such an early-onset neuropsychiatric syndrome. To this aim, the more prevalent theories on the pathogenesis of ADHD and the debate on therapy are reviewed and discussed. This paper is aimed at emphasizing that this kind of systematic data gathering of such a Register has not to be meant an unconditional approval of a therapeutical approach based on drug therapy only. Pharmacological therapies may or may not be included within the frame of a multimodal complex treatment plan which should also rely on psychological intervention.

Attention Deficit Disorder with Hyperactivity↗
PubMed2025

CrossAttOmics: multiomics data integration with cross-attention.

MOTIVATION: Advances in high throughput technologies enabled large access to various types of omics. Each omics provides a partial view of the underlying biological process. Integrating multiple omics layers would help have a more accurate diagnosis. However, the complexity of omics data requires approaches that can capture complex relationships. One way to accomplish this is by exploiting the known regulatory links between the different omics, which could help in constructing a better multimodal representation. RESULTS: In this article, we propose CrossAttOmics, a new deep-learning architecture based on the cross-attention mechanism for multiomics integration. Each modality is projected in a lower dimensional space with its specific encoder. Interactions between modalities with known regulatory links are computed in the feature representation space with cross-attention. The results of different experiments carried out in this article show that our model can accurately predict the types of cancer by exploiting the interactions between multiple modalities. CrossAttOmics outperforms other methods when there are few paired training examples. Our approach can be combined with attribution methods like LRP to identify which interactions are the most important. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/Sanofi-Public/CrossAttOmics and https://doi.org/10.5281/zenodo.15065928. TCGA data can be downloaded from the Genomic Data Commons Data Portal. CCLE data can be downloaded from the depmap portal.

Humans↗
PubMed1993

Merkel cell tumor of the head and neck. Five new cases with literature review.

Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly aggressive neoplasm with a marked propensity for local and distant metastasis. Despite the fact that more than half of the 600 cases of MCC reported in the literature involved primary sites in the head and neck, MCC has rarely been discussed in otolaryngology publications. We present five new cases of MCC of the head and neck and summarize 89 additional cases from the literature in which detailed treatment and survival data were given. Our findings again emphasize the difficulty in making the initial histopathologic diagnosis of MCC and demonstrate the necessity of early diagnosis and multimodality treatment.

Adult↗
PubMed2026

Human Systems Immunology in the Omics Era: Challenges, Methods, and Emerging Directions.

The human immune system is a highly complex, dynamic, and heterogeneous network shaped by genetic, environmental, and temporal influences. Advances in high-throughput omics technologies have transformed our ability to study this complexity directly and comprehensively in human cohorts. These developments have positioned systems immunology as a powerful framework for investigating coordinated immune responses, identifying regulatory mechanisms, and linking molecular patterns to clinical phenotypes. However, the analytical challenges inherent to large-scale, multimodal datasets-including batch effects, small sample sizes, high dimensionality, and substantial interindividual heterogeneity-require rigorous study design, robust statistical modeling, and thoughtful data analysis strategies. In this review, we summarize key technological foundations enabling modern human systems immunology, outline common analytical pitfalls and effective mitigation approaches, discuss data integration concepts, and highlight emerging opportunities in the field. Together, these technological and analytical advances are redefining how immune function is measured and interpreted in real-world human biology and hold significant promise for enhancing mechanistic insight, biomarker discovery, and precision medicine across immunological diseases and interventions.

Humans↗
PubMed1998

Preoperative chemoradiation strategies for localized adenocarcinoma of the pancreas.

Patients who undergo pancreaticoduodenectomy alone for adenocarcinoma of the pancreatic head or uncinate process have a median survival of 12 months, and a high incidence of local tumor recurrence (50%-80%) due to the common finding of positive margins following pathologic evaluation of pancreaticoduodenectomy specimens. The available prospective and retrospective data suggest improved survival duration and local-regional tumor control when pancreaticoduodenectomy is combined with 5-FU-based chemoradiation. However, the morbidity and prolonged recovery associated with pancreaticoduodenectomy frequently prevent the timely delivery of postoperative chemoradiation. In contrast, chemoradiation delivered prior to pancreaticoduodenectomy is not associated with toxic effects which delay surgery and has not been shown to increase surgical morbidity or mortality. In fact, recent data suggest that pancreaticojejunal anastomotic leaks, the most common major complication following pancreaticoduodenectomy, are decreased in patients who receive preoperative radiation therapy. Current and future multimodality treatment strategies will capitalize on our expanding understanding of tumor growth and metastasis, allowing more effective radiation sensitizing agents to be combined with external-beam irradiation and surgery, followed by the systemic or regional delivery of novel agents that inhibit essential steps in tumor cell growth.

Adenocarcinoma↗
PubMed1982

The acute effects of capsaicin on rat primary afferents and spinal neurons.

Capsaicin applied to the soma of fast and slow conducting primary afferent fibers had a depolarizing action associated with an increase in membrane conductance. The depolarizing effect desensitized rapidly and was only partially reversible in slow conducting fibers. Capsaicin application to the entry zone of the appropriate dorsal rootlets led to strong excitation of dorsal horn neurons receiving multimodal input. After acute capsaicin treatment the response to noxious heat was attenuated or totally absent, while other noxious stimuli were still effective. The present data suggest that capsaicin exerts its specific degenerative action by a long-lasting depolarizing action on small-calibre fibers.

Afferent Pathways↗
PubMed1983

Severe tactual memory deficits in monkeys after combined removal of the amygdala and hippocampus.

Monkeys with bilateral removals of both the amygdaloid complex and hippocampal formation were far more severely impaired on a tactual memory task than were monkeys with removal of either structure alone. These data parallel earlier findings on visual memory in monkeys and suggest that: (i) the memory deficit following combined ablations of the amygdala and hippocampus is multimodal; and (ii) the global anterograde amnesia observed in patients with medial temporal-lobe damage is also due to combined damage to these two structures.

Amygdala↗
PubMed2004

Treatment of brain metastases from lung cancer: chemotherapy.

Brain metastases are a frequent complication in patients suffering from Lung cancer, and a significant cause of morbidity and mortality. Brain metastases are found in about 10% of patients at the time of diagnosis, and approximately 40% of all patients with lung cancer develop brain metastases during the course of their disease. The prognosis of these patients is rather poor. The standard treatment for brain metastases, so far, has been whole-brain radiation therapy and surgery focussing on symptom palliation. The use of chemotherapy for the treatment of brain metastases has been limited because of a presumed lack of effectiveness due to the blood-brain barrier. However, the importance of the blood-brain barrier is probably overrated in the case of macroscopic metastases or relapsed disease as the blood-brain barrier has already been disrupted at this stage resulting from the newly developed blood vessels not provided with the physiological properties of the common blood-brain barrier. Chemotherapeutic agents initially lipid-insoluble or liquor-impermeable can also penetrate into the brain and, therefore, trigger action against tumour cells. A number of clinical trials have demonstrated that brain metastases resulting from both small-cell lung cancer and non-small-cell lung cancer are susceptible to systemic chemotherapy. In small-cell lung cancer, cerebral response rates up to 50% were observed even in the second-line situation and were comparable to the response rates observed in the primary tumour. In non-small-cell lung cancer, similar results were achieved. Therefore, it seems justified to further evaluate the significance of chemotherapy compared to whole-brain radiation therapy. Whether chemotherapy alone is superior to whole-brain radiation therapy, or whether the combination of both therapeutic modalities should be preferred for the management of brain metastases, has not yet been proven, and further randomised phase-III studies are clearly needed. Based on the current available data, and the promising response rates in patients with lung cancer, chemotherapy should be considered for the management of brain metastases as part of a multimodality (or "interdisciplinary") treatment concept.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2026

Large cell neuroendocrine carcinoma of the lung: Current standards, emerging targets, and translational foundations.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is one of the most complex and heterogenous clinical entities in thoracic oncology, sharing features with both non-small cell lung cancer (NSLC) and neuroendocrine lung cancers. LCNEC diagnosis and classification relies on evolving histopathological and molecular criteria that define its diagnostic boundaries. Recent advances have confirmed the dual nature of LCNEC, with distinct small cell-like and non-small cell-like molecular characteristics, which guide treatment decisions. In this review, we synthesize current evidence on the diagnosis, molecular characterization, and multimodality management of LCNEC to provide a comprehensive framework for clinical and translational decision-making. A comprehensive literature search was conducted using the PubMed database with no date restrictions, last updated on 12th of April 2026. Articles were selected based on relevance to the diagnosis, molecular characterization, and management of pulmonary LCNEC. Emphasis was placed on studies providing clinical, pathological, and molecular insights into the field. In this review, we summarize contemporary diagnostic approaches, including the expanding role of immunohistochemistry, next‑generation sequencing, and integrated morpho‑molecular assessment. This review represents a consolidated update on LCNEC genomic and transcriptional landscapes, and actionable molecular alterations that are anticipated to impact treatment decisions. Additionally, it provides a state-of-the-art overview of multimodality management, covering surgical approaches, radiotherapy, perioperative therapy, systemic treatment, and the emerging role of immunotherapy. Despite incremental progress, LCNEC remains constrained by limited prospective data and lack of consensus on optimal treatment pathways. By conducting literature review, we identified persistent gaps in LCNEC published data and hereby highlight key priorities for future research.

Humans↗
PubMed2005

Investigating the post-stimulus undershoot of the BOLD signal--a simultaneous fMRI and fNIRS study.

Measuring the hemodynamic response with functional magnetic resonance imaging (fMRI) together with functional near-infrared spectroscopy (fNIRS) may overcome limitations of single-method approaches. Accordingly, we measured the event-related hemodynamic response with both imaging methods simultaneously in young subjects during visual stimulation. An intertrial interval of 60 s was chosen to include the prolonged post-stimulus undershoot of the blood oxygenation level dependent (BOLD) signal. During visual stimulation, the BOLD signal, oxy-, and total hemoglobin (Hb) increased, whereas deoxy-Hb decreased. The post-stimulus period was characterized by an undershoot of the BOLD signal, oxy-Hb, and an overshoot of deoxy-Hb. Total Hb as measured by fNIRS returned to baseline immediately after the end of stimulation. Results suggest that the post-stimulus events as measured by fNIRS are dominated by a prolonged high-level oxygen consumption in the microvasculature. The contribution of a delayed return of blood volume to the BOLD post-stimulus undershoot in post-capillary veins as suggested by the Balloon and Windkessel models remains ambiguous. Temporal changes in the BOLD signal were highly correlated with deoxy-Hb, with lower correlation values for oxy- and total Hb. Furthermore, data show that fNIRS covers the outer 1 cm of the brain cortex. These results were confirmed by simultaneous fMRI/fNIRS measurements during rest. In conclusion, multimodal imaging approaches may contribute to the understanding of neurovascular coupling.

Adult↗
PubMed2003

Expanding the biological basis of tinnitus: crossmodal origins and the role of neuroplasticity.

Tinnitus is most often initiated by modality specific otopathologic disturbances affecting peripheral and central auditory pathways. However, there is growing evidence indicating that the anatomical location generating tinnitus occurs at sites different from the initial pathology. Support for this notion is found in individuals where tinnitus can be triggered or modulated by inputs from other sensory modalities or sensorimotor systems (somatosensory, somatomotor, visual-motor). The use of functional imaging methods combined with psychophysics, detailed physical examinations and questionnaire-based assessments has reinforced and validated these observations. Available data suggest that tinnitus-related crossmodal interactions are more common than previously anticipated. This communication reviews these advancements and suggests that a relatively broad multimodal network of neurons is involved in generating and sustaining the tinnitus perception in some forms of the disorder. Also implicated as part of the tinnitus experience are interactions within large-scale neural networks subserving attention, cognition, and emotion. Incorporating this knowledge into contemporary psychophysiological models will help facilitate the conceptualization of this phantom perception in a more comprehensive manner.

Animals↗
PubMed2006

Neural correlates of epigenesis.

The effect of life stress on depression is moderated by a repeat length variation in the transcriptional control region of the serotonin transporter gene, which renders carriers of the short variant vulnerable for depression. We investigated the underlying neural mechanisms of these epigenetic processes in individuals with no history of psychopathology by using multimodal magnetic resonance-based imaging (functional, perfusion, and structural), genotyping, and self-reported life stress and rumination. Based on functional MRI and perfusion data, we found support for a model by which life stress interacts with the effect of serotonin transporter genotype on amygdala and hippocampal resting activation, two regions involved in depression and stress. Life stress also differentially affected, as a function of serotonin transporter genotype, functional connectivity of the amygdala and hippocampus with a wide network of other regions, as well as gray matter structural features, and affected individuals' level of rumination. These interactions may constitute a neural mechanism for epigenetic vulnerability toward, or protection against, depression.

Adult↗