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The integration of platinum and radiotherapy in the treatment of lung cancer.

Combined-modality therapy in lung cancer is a common practice throughout the world. The use of radiochemotherapy appears to be firmly established in the treatment of small cell lung cancer, but the role of prophylactic cranial irradiation remains undecided. Many recommend its use in the treatment of non-small cell lung cancer as well, but no facts exist to support this position. Because of poor long-term outcome and high frequency of systemic relapse, integration of chemotherapy for the treatment of non-small cell lung cancer is becoming more prevalent. This article discusses methods of integration, the problems of combined- modality toxicity, recent trials, and reports of multimodal therapy in lung cancer. The advantages of certain regimens of chemotherapy and new methods of radiotherapy are also discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Multivolumetric analysis of CT scans on patients with glioma.

Brain tumor volumes in patients having multimodal therapy for cerebral gliomas were calculated using graphic methods and Simpsonian integration. Volume assessment calculations differed from the clinical assessment of the patient significantly in some cases. These calculations may be useful in on-going tumor therapy and should be used as a true scientific end point in brain tumor treatment protocols.

Brain Neoplasms↗

Comprehensive oral X-ray diagnosis: Scanora multimodal radiography. A preliminary description.

Scanora (Soredex, Orion Corporation, Helsinki, Finland) is a multimodal radiography system which utilizes the principles of narrow beam radiography and spiral tomography. The system includes an integrated multifunction X-ray unit, a coordinate system for object localization and a wide selection of dental and maxillofacial imaging problems. All imaging procedures are computer controlled and executed automatically. Clinical experience and preliminary results show that the multimodal imaging system has great potential in the detection of pathological conditions of the maxillofacial region.

Humans↗

High sensitivity to multisensory conflicts in agoraphobia exhibited by virtual reality.

The primary aim of this study was to evaluate the effect of auditory feedback in a VR system planned for clinical use and to address the different factors that should be taken into account in building a bimodal virtual environment (VE). We conducted an experiment in which we assessed spatial performances in agoraphobic patients and normal subjects comparing two kinds of VEs, visual alone (Vis) and auditory-visual (AVis), during separate sessions. Subjects were equipped with a head-mounted display coupled with an electromagnetic sensor system and immersed in a virtual town. Their task was to locate different landmarks and become familiar with the town. In the AVis condition subjects were equipped with the head-mounted display and headphones, which delivered a soundscape updated in real-time according to their movement in the virtual town. While general performances remained comparable across the conditions, the reported feeling of immersion was more compelling in the AVis environment. However, patients exhibited more cybersickness symptoms in this condition. The result of this study points to the multisensory integration deficit of agoraphobic patients and underline the need for further research on multimodal VR systems for clinical use.

Adult↗

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans↗

Listening to talking faces: motor cortical activation during speech perception.

Neurophysiological research suggests that understanding the actions of others harnesses neural circuits that would be used to produce those actions directly. We used fMRI to examine brain areas active during language comprehension in which the speaker was seen and heard while talking (audiovisual) or heard but not seen (audio-alone) or when the speaker was seen talking with the audio track removed (video-alone). We found that audiovisual speech perception activated a network of brain regions that included cortical motor areas involved in planning and executing speech production and areas subserving proprioception related to speech production. These regions included the posterior part of the superior temporal gyrus and sulcus, the pars opercularis, premotor cortex, adjacent primary motor cortex, somatosensory cortex, and the cerebellum. Activity in premotor cortex and posterior superior temporal gyrus and sulcus was modulated by the amount of visually distinguishable phonemes in the stories. None of these regions was activated to the same extent in the audio- or video-alone conditions. These results suggest that integrating observed facial movements into the speech perception process involves a network of multimodal brain regions associated with speech production and that these areas contribute less to speech perception when only auditory signals are present. This distributed network could participate in recognition processing by interpreting visual information about mouth movements as phonetic information based on motor commands that could have generated those movements.

Adult↗

Novel approaches to imaging brain tumors.

Brain imaging techniques are assuming a greater range of roles in neuro-oncology. New techniques promise earlier recognition of the spread of tumors to the brain, which is useful in staging of disseminated disease, as well as better definition of small lesions associated with presentations of epilepsy. There is the promise that entirely noninvasive, specific diagnosis of brain tumors may become possible. Imaging methods are being used increasingly to direct and monitor therapy. Preoperative and intraoperative imaging are being used for guiding tumor surgery. An exciting potential goal for greater use of imaging is in the individualization of medical therapies either by analysis of in vitro responses or by visualization of drug responses on the tumor in situ. An important focus for technical development is in the robust integration of complementary information to allow optimization of the sensitivity and specificity of multimodal examinations.

Antineoplastic Agents↗

Bayesian inference of lineage trees by joint analysis of single-cell multimodal lineage-tracing data with BiLinT.

The advent of single-cell lineage-tracing technologies has enabled the simultaneous profiling of gene expression and lineage barcodes. However, accurate, high-resolution reconstruction of cell lineage trees remains challenging because most existing approaches treat these modalities separately and therefore fail to fully exploit their complementary information. Here we present BiLinT, a Bayesian framework that jointly models multimodal single-cell lineage-tracing data for lineage tree reconstruction. BiLinT integrates barcode evolution (a continuous-time Markov chain) with gene expression dynamics (an Ornstein-Uhlenbeck process) within a unified probabilistic model. Across synthetic and real data sets, BiLinT provides accurate lineage-tree reconstruction and reveals differentiation-associated clonal structure and developmental fate biases.

Journal Article↗

The effect of gestational age at birth on somatosensory-evoked potentials performed at term.

Multimodality-evoked potentials are widely used in newborns to assess the maturation and integrity of the sensory pathways. Reliable normative data are needed to maximize the utility of this technique as a diagnostic and research tool. Several electrophysiologic studies on the maturational changes of the auditory brain-stem response have demonstrated that latency measurements decrease as a function of increasing conceptional age. However, maturational studies of the somatosensory-evoked potential, particularly in low-risk premature infants, are limited. The existing evoked potential literature in healthy newborns proposes that maturation of the central nervous system occurs at a predictable rate, irrespective of a given gestational age at birth. Behavioral studies of premature infants suggest that neurologic development may be altered by early extrauterine exposure. The purpose of this study was to determine whether brain-stem auditory- or somatosensory-evoked potential conduction times were comparable in premature and full-term infants matched for conceptional age. The results of this study suggest that myelination is determined by conceptional age, independent of premature birth.

Brain Stem↗

Cockroach allergy and asthma in a 30-year-old man.

A growing body of evidence has implicated allergens derived from cockroaches as an important environmental factor that may aggravate asthma in sensitized persons. We present the case of a 30-year-old man with asthma and a cockroach allergy. Allergy skin testing confirmed hypersensitivity to cockroach extract, and a home visit revealed visual evidence of infestation and the presence of Bla g 1 German cockroach allergen in vacuumed dust. As is typical of patients with a cockroach allergy and asthma, multiple factors in addition to cockroach allergen appeared to aggravate the patient's asthma. A multimodality therapeutic regimen, which included medications as well as cleaning of the home, integrated pest management, and professional application of chemical controls, resulted in substantial clinical improvement. The pathophysiology, epidemiology, and clinical features of cockroach-allergic asthma are reviewed, and an approach to diagnosis and management is suggested.

Adult↗

Mirror neurons, procedural learning, and the positive new experience: a developmental systems self psychology approach.

In summary, we are impressed with the existence of a mirror neuron system in the prefrontal cortex that serves as part of a complex neural network, including afferent and efferent connections to the limbic system, in particular the amygdala, in addition to the premotor and motor cortex. We think it is possible to arrive at an integration that postulates the mirror neuron system and its many types of associated multimodal neurons as contributing significantly to implicit procedural learning, a process that underlies a range of complex nonconscious, unconscious, preconscious and conscious cognitive activities, from playing musical instruments to character formation and traumatic configurations. This type of brain circuitry may establish an external coherence with developmental systems self psychology which implies that positive new experience is meliorative and that the intentional revival of old-old traumatic relational configurations might enhance maladaptive procedural patterns that would lead to the opposite of the intended beneficial change. When analysts revive traumatic transference patterns for the purpose of clarification and interpretation, they may fail to appreciate that such traumatic transference patterns make interpretation ineffective because, as we have stated above, the patient lacks self-reflection under such traumatic conditions. The continued plasticity and immediacy of the mirror neuron system can contribute to positive new experiences that promote the formation of new, adaptive, implicit-procedural patterns. Perhaps this broadened repertoire in the patient of ways of understanding interrelational events through the psychoanalytic process allows the less adaptive patterns ultimately to become vestigial and the newer, more adaptive patterns to emerge as dominant. Finally, as we have stated, we believe that the intentional transferential revival of trauma (i.e., the old-old relational configuration) may not contribute to therapeutic benefit. In contrast, the revival of trauma in the old-new configuration (i.e., in the presence of a helpful other who can reduce anxiety and foster eventual positive new experience) can be beneficial, as trauma research has demonstrated. This is the process that promotes new implicit-procedural learning, new-new relational configurations, and a richer understanding of the self narrative.

Brain↗

Multimodal approach and its impact on survival for patients with hepatocellular carcinoma.

BACKGROUND: There are few studies evaluating the prognostic impact on survival of treatment strategy in patients with hepatocellular carcinoma (HCC). The aim of this study was to analyse whether a multimodal approach, that represents a synergic association of different therapeutic procedures, may improve survival of patients with HCC. PATIENTS AND METHODS: Two hundred and fourteen patients with HCC were enrolled in the study. The multimodal approach was chosen for 27 out of 106 (25%) non surgical patients, 42 out of 81 (52%) patients who underwent liver resection and 19 out of 27 (70%) patients who underwent liver transplantation. RESULTS: The long-term survival of patients who underwent the multimodal approach improved significantly with respect to patients treated by both resection and other therapies alone. The 5-year survival rates were 52% vs. 11% (p < 0.05) in the non surgical group and 40% vs. 24% (p < 0.05) in the resection group when a multimodal approach was used for the treatment of recurrences. In patients with advanced HCC undergoing liver transplantation, multimodal treatment resulted in long-term survival comparable to that of patients with early HCC. CONCLUSION: A multimodal approach should be suggested in all patients with HCC, since a careful integration of surgical and non surgical treatments may improve long-term survival in such patients.

Adolescent↗

Differences in the volume distributions of human lung mast cell granules and lipid bodies: evidence that the size of these organelles is regulated by distinct mechanisms.

We analyzed transmission electron micrographs of human lung mast cells by digitized planimetry and point counting to determine the cross-sectional areas of two distinct cytoplasmic organelles: specific granules and lipid bodies. Specific granules have a limiting membrane and often contain one or more cylindrical scroll-like inclusions. By contrast, lipid bodies are on average much larger than granules and lack both limiting membranes and inclusions. The measured cross-sectional areas of lipid bodies and scroll-containing granules were converted to equivalent volumes, and the noise in the frequency distribution of these volumes was smoothed using a moving bin technique. This analysis revealed (a) a periodic, multimodal distribution of granule equivalent volumes in which the modes fell at volumes that were integral multiples of the volume defined by the first mode (the "unit volume"), and (b) a modal granule equivalent volume frequency that occurred at a magnitude equal to four "unit volumes." Thus, specific granules appear to be composed of units of a narrowly fixed volume. Furthermore, the mean volume of intragranule inclusions was 0.0061 mu3, a value very similar to that calculated for the "unit volume" (0.0071 mu3). This result suggests that each "unit volume" comprising the individual scroll-type granules contains (or is capable of generating or accommodating) a single scroll-like inclusion. In contrast to the specific granules, mast cell lipid bodies lack a periodic, multimodal volume distribution. Taken together, these findings suggest that the volumes of human lung mast cell granules and lipid bodies are regulated by distinct mechanisms.

Cytoplasmic Granules↗

Global spectral-kinetic analysis of room temperature chlorophyll a fluorescence from light-harvesting antenna mutants of barley.

This study presents a novel measurement, and simulation, of the time-resolved room temperature chlorophyll a fluorescence emission spectra from leaves of the barley wild-type and chlorophyll-b-deficient chlorina (clo) f2 and f104 mutants. The primary data were collected with a streak-camera-based picosecond-pulsed fluorometer that simultaneously records the spectral distribution and time dependence of the fluorescence decay. A new global spectral-kinetic analysis programme method, termed the double convolution integral (DCI) method, was developed to convolve the exciting laser pulse shape with a multimodal-distributed decay profile function that is again convolved with the spectral emission band amplitude functions. We report several key results obtained by the simultaneous spectral-kinetic acquisition and DCI methods. First, under conditions of dark-level fluorescence, when photosystem II (PS II) photochemistry is at a maximum at room temperature, both the clo f2 and clo f104 mutants exhibit very similar PS II spectral-decay contours as the wild-type (wt), with the main band centred around 685 nm. Second, dark-level fluorescence is strongly influenced beyond 700 nm by broad emission bands from PS I, and its associated antennae proteins, which exhibit much more rapid decay kinetics and strong integrated amplitudes. In particular a 705-720 nm band is present in all three samples, with a 710 nm band predominating in the clo f2 leaves. When the PS II photochemistry becomes inhibited, maximizing the fluorescence yield, both the clo f104 mutant and the wt exhibit lifetime increases for their major distribution modes from the minimal 205-500 ps range to the maximal 1500-2500 ps range for both the 685 nm and 740 nm bands. The clo f2 mutant, however, exhibits several unique spectral-kinetic properties, attributed to its unique PS I antennae and thylakoid structure, indicating changes in both PS II fluorescence reabsorption and PS II to PS I energy transfer pathways compared to the wt and clo f104. Photoprotective energy dissipation mediated by the xanthophyll cycle pigments and the PsbS protein was uninhibited in the clo f104 mutant but, as commonly reported in the literature, significantly inhibited in the clo f2; the inhibited energy dissipation is partly attributed to its thylakoid structure and PS II to PS I energy transfer properties. It is concluded that it is imperative with steady-state fluorometers, especially for in vivo studies of PS II efficiency or photoprotective energy dissipation, to quantify the influence of the PS I spectral emission.

Chlorophyll↗

Digital photography and 3D MRI-based multimodal imaging for individualized planning of resective neocortical epilepsy surgery.

PURPOSE: Invasive presurgical work up of pharmacoresistant epilepsies presumes integration of multiple diagnostic modalities into a comprehensive picture of seizure onset and eloquent brain areas. During resection, reliable transfer of evaluation results to the patient's individual anatomy must be made. We investigated the value of digital photography-based grid localization in combination with preoperative three-dimensional (3D) magnetic resonance imaging (MRI) for clinical routine. METHODS: Digital photographs of the exposed cortex were taken before and after grid placement. Location of electrode contacts on the cortex was identified and schematically indicated on native cortex prints. Accordingly, transfer of contact positions to a 3D MRI brain-surface rendering was carried out manually by using the rendering software. Results of the electrophysiologic evaluation were transferred to either electrode contact reproduction and co-registered with imaging-based techniques such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI). RESULTS: Digital photography allows precise and highly realistic documentation of electrode contact positions on the individual neocortical surface. Lesions underneath grids can be highlighted by semitransparent MRI surface rendering, and lobar boundaries can be identified. Because of integrating electrode contact positions into the postprocessed 3D MRI data set, imaging-based techniques can be codisplayed with the results of the electrophysiologic evaluation. Comparison with CT/MRI co-registration showed good accuracy of the method. However, grids not sewn to the dura at implantation can become subject to significant displacement. CONCLUSIONS: Digital photography in combination with preimplantation 3D MRI allows the generation of reliable tailored resection plans in neocortical epilepsy surgery. The method enhances surgical safety and confidence.

Adolescent↗

Integrating Radiogenomics and CSF-Based Liquid Biopsy Sequencing for Precision Neuro-Oncology.

Glioblastoma and diffuse gliomas pose major therapeutic challenges due to marked intratumoral heterogeneity, limited tissue accessibility, and the blood-brain barrier. Tissue-based next-generation sequencing (NGS) remains essential for WHO CNS5 molecular classification, yet it is invasive and poorly suited to serial monitoring. Two complementary non- or minimally invasive approaches have advanced rapidly: radiogenomics, which correlates multiparametric MRI features with genomic alterations, and cerebrospinal fluid (CSF) liquid biopsy sequencing, which detects circulating tumor DNA with high tissue concordance. This review examines the independent progress and synergistic integration of radiogenomics and CSF-NGS. Imaging signatures can non-invasively predict key drivers (IDH1/2, EGFR, TERT, PTEN, TP53) and molecular subtypes, while CSF-ctDNA sequencing enables real-time assessment of clonal evolution, therapy resistance (including post-temozolomide hypermutation), and residual disease. We discuss technical considerations, performance metrics, multimodal artificial-intelligence fusion, and emerging clinical applications for diagnosis, prognosis, treatment selection, and longitudinal surveillance. Critical challenges, standardization, prospective validation, and workflow integration are highlighted. By combining the spatial phenotypic information of radiogenomics with the temporal genomic resolution of CSF sequencing, this multimodal strategy offers a promising path toward precision neuro-oncology and reduced reliance on repeated invasive sampling.

Humans↗

Multimodal signals: enhancement and constraint of song motor patterns by visual display.

Many birds perform visual signals during their learned songs, but little is known about the interrelationship between visual and vocal displays. We show here that male brown-headed cowbirds (Molothrus ater) synchronize the most elaborate wing movements of their display with atypically long silent periods in their song, potentially avoiding adverse biomechanical effects on sound production. Furthermore, expiratory effort for song is significantly reduced when cowbirds perform their wing display. These results show a close integration between vocal and visual displays and suggest that constraints and synergistic interactions between the motor patterns of multimodal signals influence the evolution of birdsong.

Abdominal Muscles↗

The assessment of child sexual abuse allegations: using research to guide clinical decision making.

As reports of child sexual abuse (CSA) have risen, greater attention has been focused on how clinicians evaluate allegations of abuse. A common theme in the CSA assessment literature is to encourage comprehensive, multimodal assessments. This recommendation, however, is rarely accompanied by suggestions regarding how clinicians might integrate and differentially weight the information gathered. The present article is designed to address the issue of which sources of information clinicians should rely upon when conducting CSA assessments. Specifically, the commonly used indicators and procedures for assessing allegations of abuse are identified and then examined in light of their respective empirical literatures. It is concluded that medical examinations and the child's report are among the best sources of information, and should therefore be most heavily relied upon to arrive at accurate decisions. Clinicians are encouraged to adopt the mind set of a scientist conducting an a priori, hypothesis-driven research investigation. This approach should help clinicians avoid the temptation of post hoc analyses that reflect personal biases more than the actual data.

Art↗