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Results for “multimodal integration”

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PubMed2006

Assessing infants' cortical response to speech using near-infrared spectroscopy.

Sensitivity to spoken language is an integral part of infants' formative development, yet relatively little is known about the neural mechanisms that underlie the emerging ability to perceive and process speech. This is in large part because there are a limited number of non-invasive techniques available to measure brain functioning in human infants. Near-infrared spectroscopy (NIRS), an optical imaging technique that estimates changes in neuronal activity by measuring changes in total hemoglobin concentration and oxygenation, may be a viable procedure for assessing the relation between speech processing and brain function in human infants. While auditory processing data have been gathered from newborn and preterm infants using NIRS, such data have not been collected from older infants. Many behavioral measures used to establish linguistic sensitivity in this population are accompanied by visual stimuli; however, it is unclear how coupling of auditory and visual stimuli influences neural processing. Here we studied cortical activity in infants aged 6-9 months, as measured by NIRS, during exposure to linguistic stimuli paired with visual stimuli and compared this to the activity observed in the same regions during exposure to visual stimuli alone. Results dissociate infants' hemodynamic responses to multimodal and unimodal stimuli, demonstrating the utility of NIRS for studying perceptual development in infants. In particular, these findings support the use of NIRS to study the neurobiology of language development in older infants, a task that is difficult to accomplish without the use of attention-getting visual stimuli.

Female↗

PubMed1998

Interaction of vestibular, somatosensory and visual signals for postural control and motion perception under terrestrial and microgravity conditions--a conceptual model.

This article considers the intersensory interaction mechanisms and biomechanical aspects of human spatially oriented behavior and asks to what extent these are interrelated on earth by gravity and how they might be affected under microgravity. The interactions between vestibular, somatosensory and visual inputs for postural control are obscured by several complications (biomechanics, multi-body dynamics, multimodal feedback control, cognition etc.). However, they can be revealed in psychophysical studies on human self-motion perception. Based on such studies, we present a conceptual model, which we think is valid also for postural control. It accounts for the multi-segmental structure of the body, allowing local control of inter-segmental joints, but uses one global reference system for all segments, which is derived from the intersensory interactions. We hold that, at a sensory level, the system is tied together by linkages between vestibular, visual and somatosensory information which develop through experience of inertial and gravitational reaction forces. On earth these linkages are established even in the absence of active behavior by gravity, allowing the incorporation of one's body and its support into a notion (Gestalt) of ourselves in the environment. Under microgravity, in contrast, the linkages have to be actively established for postural and perceptual stability in the environment (e.g., by grasping a handle on the wall). From this work we recommend that future research under altered gravity conditions should be guided by models that include biomechanics, considerations of intersensory interaction and dynamic control mechanisms. Such an integrative conceptual framework will be helpful for reaching a general understanding of spatially oriented behavior.

Gravitation↗

PubMed2003

TNM: evolution and relation to other prognostic factors.

The TNM Classification describes the anatomic extent of cancer. TNM's ability to separately classify the individual tumor (T), node (N), and metastasis (M) elements and then group them into stages differs from other cancer staging classifications (e.g., Dukes), which are only concerned with summarized groups. The objectives of the TNM Classification are to aid the clinician in the planning of treatment, give some indication of prognosis, assist in the evaluation of the results of treatment, and facilitate the exchange of information. During the past 50 years, the TNM system has evolved under the influence of advances in diagnosis and treatment. Radiographic imaging (e.g., endoscopic ultrasound for the depth of invasion of esophageal and rectal tumors) has improved the accuracy of the clinical T, N, and M classifications. Advances in treatment have necessitated more detail in some T4 categories. Developments in multimodality therapy have increased the importance of the "y" symbol and the R (residual tumor) classification. New surgical techniques have resulted in the elaboration of the sentinel node (sn) symbol. The use of immunohistochemistry has resulted in the classification of isolated tumor cells and their distinction from micrometastasis. The most important challenge facing users of the TNM Classification is how it should interface with the large number of non-anatomic prognostic factors that are currently in use or under study. As non-anatomic prognostic factors become widely used, the TNM system provides an inviting foundation upon which to build a prognostic classification; however, this carries a risk that the system will be overwhelmed by a variety of prognostic data. An anatomic extent-of-disease classification is needed to aid practitioners in selecting the initial therapeutic approach, stratifying patients for therapeutic studies, evaluating non-anatomic prognostic factors at specific anatomic stages, comparing the weight of non-anatomic factors with extent of disease, and communicating the extent of disease data in a uniform manner. Methods are needed to express the overall prognosis without losing the vital anatomic content of TNM. These methods should be able to integrate multiple prognostic factors, including TNM, while permitting the TNM system to remain intact and distinct. This article discusses examples of such approaches.

Biomarkers, Tumor↗

PubMed2006

ECoG factors underlying multimodal control of a brain-computer interface.

Most current brain-computer interface (BCI) systems for humans use electroencephalographic activity recorded from the scalp, and may be limited in many ways. Electrocorticography (ECoG) is believed to be a minimally-invasive alternative to electroencephalogram (EEG) for BCI systems, yielding superior signal characteristics that could allow rapid user training and faster communication rates. In addition, our preliminary results suggest that brain regions other than the sensorimotor cortex, such as auditory cortex, may be trained to control a BCI system using similar methods as those used to train motor regions of the brain. This could prove to be vital for users who have neurological disease, head trauma, or other conditions precluding the use of sensorimotor cortex for BCI control.

Adult↗

PubMed2003

[Complex regional pain syndrome type I (CRPS I). Pathophysiology, diagnostics, and therapy].

Complex regional pain syndrome type I (CRPS type I)--formerly termed Sudeck's atrophy or reflex sympathetic dystrophy (RSD)--causes chronic, poorly controllable pain, autonomic, sensorimotor disorders,and serious trophic alterations in the later stages. It develops in the distal extremities mostly after minimal trauma or surgical intervention and rarely spontaneously. The severity of symptoms is disproportionate to the causative event. The latest scientific findings show that the previously called reflex sympathetic dystrophy (RSD), which was supposed to be a result of a hyperreactive autonomic nervous system,is a very complex syndrome that occurs on different integration levels of the nervous system. Sympathetically maintained pain (SMP) may be facultatively characteristic, but is not to be misunderstood as an underlying mechanism. A neurogenic inflammation reaction has recently been discussed, just as had been postulated by Paul Sudeck long before. That was the reason why the International Association for the Study of Pain (ISAP) introduced the more descriptive term "complex regional pain syndrome" (CRPS) type I in 1994. Due to the complexity of the process necessitating qualified knowledge, it is important to immediately refer patients to a specialized pain OPD or clinic. The diagnosis of CRPS type I is based upon a carefully taken case history and a clinical examination by an experienced practitioner. Imaging diagnostic tools and laboratory findings are of no or only low predicative value. The question of whether SMP exists after diagnosing CRPS type I is eminent for therapy planning. Therefore, diagnostic regional anesthetics are still important in spite of their uncertain prognostic relevance. Physical therapy, occupational therapy, medical treatment, and psychotherapy play an important role in the primary treatment of CRPS type I as noninvasive procedures. Despite heavy criticism, invasive sympathetic block, subsequent to adequate diagnostics, is an important part of the therapeutic concept. A multimodal therapeutic concept, which includes all available possibilities, is absolutely necessary to avoid grave permanent disabilities caused by insufficient or failed therapy. Nevertheless, already established as well as new treatment modalities have to be critically observed by further randomized, prospective control trials.

Autonomic Nervous System↗

PubMed2026

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

PubMed1993

Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.

PURPOSE: To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer. PATIENTS AND METHODS: Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling. RESULTS: Significantly reduced (P < .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P < .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P < .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P < .001). CONCLUSION: Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.

Aged↗

PubMed1995

Failure to update the egocentric representation of the visual space through labyrinthine signal.

The present study evaluated the capacity to compare retinal and vestibular signals in a heterosensorial matching task. In the first experiment, subjects evaluated the magnitude of passive whole-body rotations in relation to the eccentricity of a visual target briefly presented before rotation. Such a task elicits multimodal sensory stimulations experienced by a subject during normal goal-oriented head movements, i.e., retinal and vestibular stimulations. A good capacity to evaluate vestibular signals in relation with retinal inputs might suggest that the labyrinthine output is part of a cognitive feedback-loop controlling active head movements oriented toward a visual target and/or that the labyrinthine signal might make a major contribution to judging the position of the target in space after goal-directed head movements. Results showed that body rotation magnitudes had to exceed the amplitude of the visual target by about 120 and 89% to be perceived as having a similar magnitude to a 10 degree and an 18 degree visual target, respectively. A second experiment was designed to test whether this major discrepancy originated either from (a) an overestimation of the peripheral visual target locations, (b) an underestimation of the labyrinthine signal, (c) a deficiency in matching sensory signals from different modalities, or (d) any combination of (a), (b), and (c). In the second experiment, the actual perception of retinal and labyrinthine signals, as indicated by verbal responses, was quantified. Results from this experiment showed that most of the large underestimation of the vestibular stimulation found in Experiment I ought to emerge from a poor capacity to integrate heterogeneous sensory signals by the perceptual system rather than from pure misperception of the retinal and/or labyrinthine signals. Overall, results from Experiments I and II argue for a deficiency of the CNS to integrate labyrinthine signals for updating the egocentric representation of the peripheral visual target during passive body (head) rotations.

Adult↗

PubMedDate not supplied

A 3D medical image database management system.

We describe the design and implementation of QBISM (Query By Interactive, Spatial Multimedia), a prototype for querying and visualizing 3D spatial data. Our medical image application is focused on the brain mapping requirements for multimodality relationships across multiple subjects. It incorporates data describing both structure and function. It includes data structures that describe anatomy, physiology, coordinates using rendered imagery and statistical output. The system is built on top of the Starburst DBMS extended to handle spatial data types, specially, scalar fields and arbitrary regions or space within such fields. In this paper we list the requirements of the application, discuss the logical and physical database design issues, and present timing results from our prototype. We observed that the DBMS' early spatial filtering results in significant performance savings because the system response time is dominated by the amount of data retrieved, transmitted, and rendered.

Brain Mapping↗

PubMedDate not supplied

The research logic of radiation oncology in combined modality therapy.

The integration of radiation, chemotherapy, and surgery depends on the delineation of failure patterns for each specific cancer. By identifying the failure pathways it is possible to design therapeutic strategies for each pattern. The main issues focus upon selecting the best therapeutic sequence and combination that can be employed first to reduce the tumor to subclinical stages, but ultimately to achieve a total cure. Although radiation therapy and chemotherapy can be given simultaneously or sequentially the variety of drugs now available and the many dose schedules for radiation therapy and chemotherapy make the possible permutations almost infinite. It is for this reason that the drug-radiation therapy interactions should be better understood, and that is why new terminology is being developed to describe the different types of interactions that may occur. With the innovations in radiation therapy (systemic half-body irradiation, radiosensitizers, and hyperthermia), there are now more potential combinations of standard modalities and new investigative techniques than can be explored clinically. For this reason, experimental models may be able to offer a better scientific basis for combining modes, but even in the laboratory too many probabilities exist. The need for a cooperative effort (both in laboratory and clinical investigations) for combined modality treatment approaches to cancer has become a mandate for oncology protocol design in this multimodal era.

Clinical Trials as Topic↗

PubMed2006

[Long-term efficiency of orthopedic rehabilitation in chronic back pain--the integrative orthopedic psychosomatic concept (IopKo)].

UNLABELLED: Chronic diseases of the musculoskeletal system rank first as causes of early retirement in Germany. Therefore orthopaedic rehabilitation has to identify patients with work-related problems and to promote return to work through differential treatment and vocational counselling. In the framework of the IopKo-Project such measures were developed and evaluated. These measures encompass: (1) an intensive and multiprofessional diagnostic pathway which allows early detection and treatment of mental disorders and job related problems; (2) homogeneous treatment groups based on multiprofessional diagnostics; (3) differential treatments, among these a multidisciplinary programme for patients with chronic low back pain or high risk of chronification (Rückenfit); (4) interactive training modules which mediate principles of performance and disability expertise, the legal bases of retirement pensioning, and measures to support occupational rehabilitation; and (5) a work hardening training programme. METHOD: To evaluate the effects of these measures in comparison to a control group with usual care, a prospective longitudinal study was conducted. A total of 307 patients were assigned to the multidisciplinary in-patient treatment programme, whereas 176 patients in the control group had a standard rehabilitation programme. RESULTS: The results show positive moderate and strong effects in the intervention group concerning function, pain, psychic strains as well as the number of sick days and return to work rates 10 months after discharge. The effects in the intervention group exceeded the effects achieved in the control group. PATIENTS WITH HIGH RISK OF CHRONIFICATION: Beside the full sample, a subgroup of patients with chronic pain or high risk of chronification was analyzed, who had received a multidisciplinary functional restoration treatment. Also for this subgroup we found moderate and strong effects of treatment for function, psychic strains and sick days superior to those in the control group. CONCLUSION: By this study we were able to show that orthopedic rehabilitation in a multimodal and multidisciplinary setting with a focus on activating and motivating therapy can have sustainable positive effects on pain, function and psychic well-being as well as on economic parameters. We interpret these persistent and superior effects in the treatment group (1) as a result of multiprofessional diagnosis and assignment which helps to subdivide the inhomogeneous group of patients with unspecific back pain into more homogeneous and thus more effective subgroups, (2) as a result of increased motivation by closed treatment groups, (3) as a result of intense and multilevel counselling of work related problems, (4) as a result of work hardening modules, and (5) as a result of direct and efficient treatment of psychic strains. The results also demonstrate the significance of inpatient rehabilitation, which will be efficient if differential treatment - adequate to the problems of the patient - is offered.

Adult↗

PubMed1992

Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival.

Radiation therapy combined with cisplatin as a chemoradiation sensitizer (CT/RT) has been reported to enhance tumor response in squamous cell carcinoma of the head and neck. In the present study, CT/RT was used preoperatively in advanced Stage III and IV head and neck cancer. Fifty-three patients were entered prospectively into a Phase II study. Treatment consisted of 4500 cGy of radiation therapy in 5 weeks combined with cisplatin 20 mg/m2 for 4 days during weeks 1 and 4 of radiation therapy. This was followed 4 to 8 weeks later by curative surgery. Pretherapy dental care; long-term nutritional support; individualized skin, mouth, and wound care; and continuous interdisciplinary communication were integral parts of this regimen. In four patients, CT/RT toxicity was seen (8%); three episodes of skin reaction or stomatitis and three episodes of leukopenia (less than 2500/microliters), causing a delay in CT/RT treatment in one patient. Three patients died of other causes during the preoperative interval, without clinical evidence of toxicity. Fifty patients (94%) had a complete (CR) or partial response (PR) to CT/RT. Clinical CR was seen in 38 of 51 (75%) primary tumors and 21 of 27 (78%) cervical nodes. Forty-one patients (77%) underwent curative surgery. In 27 of 32 (84%) resected CR primary tumors and 16 of 18 (89%) CR metastatic nodes, the surgical specimen was microscopically free of tumor. Postoperative morbidity was 32%. Five patients (12%) required additional surgery for their complications. Perioperative mortality was 5%. Five patients had tumor recurrence: three postoperatively after clinical PR to CT/RT and two in clinical CR patients who refused further treatment after CT/RT, then had a recurrence and were salvaged surgically. No patient with a CR in both the tumor and nodes who underwent surgery had a tumor recurrence. With a follow-up of 8 years (median, 40 months), the median survival for all patients was 45 months. The 5-year actuarial survival rate was 43% for all patients and 55% for patients who had CT/RT and surgery. This multimodality treatment of advanced head and neck cancer has low toxicity and impressive survival. It renders a significant number of patients tumor-free before surgery. These patients may be candidates for additional study triaging additional CT/RT for complete CR only and surgery for PR and biopsy-proved residual disease.

Adult↗

PubMed1994

Somatovisceral projections from spinal cord and dorsal column nuclei to the thalamus in hedgehog tenrecs.

In order first to overcome the difficulties in understanding the increasing amount of information available regarding the mammalian somatosensory thalamus, and then to correlate the findings among different species and integrate them into a general concept of thalamic organization, the present study investigated the spinothalamic and medial lemniscal projections in Madagascan hedgehog tenrecs (Echinops telfairi and Setifer setosus). Tracer substances were injected into the dorsal column nuclei and into spinal segments at various levels; additional injections were made into the inferior colliculus. The ascending somesthetic projections were to predominantly contralateral posterolateral target areas, and were almost mirror-like on both sides to intralaminar and medial thalamic nuclei. The densest and most extensive projections, originating mainly from the high cervical spinal cord and the dorsal column nuclei, reached the posterolateral thalamus caudal to the lateral geniculate nucleus. This region was difficult to subdivide cytoarchitecturally; nevertheless, on the basis of its labeling pattern, several subdivisions could be described and preliminary named. Some of them compared tentatively with the internal portion of the medial geniculate nucleus (GM) and the ventral posterior nuclear complex (VPC) in more differentiated mammals. The most prominent subdivision, however, located subjacent to the lateral surface of the brainstem, was shown to receive additional fibers from the inferior colliculus. This region might be considered a further subdivision of GM, VPC, a perigeniculate area, and/or a region of its own not comparable at present, with thalamic regions in other mammals. On the other hand, it may also be a remnant of the hypothetical, diffuse multimodal region from which GM and VPC have possibly evolved.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed2026

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses↗

PubMed2004

[Apoptosis, tumor phenotype and pathogenesis of malignant tumors].

Integrity of multicellular organisms is maintained by balance between cell proliferation and programmed cell death (apoptosis). Apoptosis is programmed cell death by regulated active process characterized by specific morphological and biochemical changes, whereas necrosis is a passive and genetically uncontrolled process followed by an inflammatory reaction of surrounding tissue. Suppression of apoptosis may contribute to the development of malignant tumours by means of accumulation of continuously proliferating cells and disruption of elimination of genetically altered cells with increasing malignant potential. Cell proliferation, differentiation and apoptosis are regulated by p16-cyclin D1-CDK4-Rb and p19ARF-p53-p21WAF1 pathways, which interact through multifunctional genes Rb and p53. Malignant tumours result from an accumulation of mutations of oncogenes, tumour-suppressor genes, pro-apoptotic and anti-apoptotic genes or from functional alterations of protein products of these genes as well. That results in dysregulation of the cell cycle and apoptosis and in the development of other signs of tumour phenotype (chromosomal instability, disruption of DNA repair, disruption of cell-cell communications and interactions between cells and extracellular matrix, suppression of the cell differentiation and replicative senescence, angiogenesis and changes in cell motile activity). Alteration of apoptosis, and/or genes involved in its regulation, is expressed in most manifestations of tumour phenotype. Thus, alteration of apoptosis strongly affects biological properties of malignant tumours and efficacy of their multimodal therapy. Present-day multimodal therapy of malignant tumours is specifically aimed at promoting the rate of apoptosis within tumours.

Animals↗

PubMed2026

Cancer of unknown primary: the evolution of tissue of origin identification in the artificial intelligence era.

Cancer of Unknown Primary (CUP) presents substantial diagnostic and therapeutic challenges owing to its heterogeneous nature and the absence of an identifiable primary tumor site. This review provides a structured search of the pathogenesis, epidemiological characteristics, and limitations of traditional diagnostic and therapeutic approaches for CUP, with an emphasis on the evolution of Tissue of Origin (TOO) identification techniques. Recent advances in precision medicine have accelerated the development of machine learning-based TOO identification tools, representing a paradigm shift in CUP diagnostics. Deep learning (DL) algorithms that integrate multi-omics data (such as genomics and transcriptomics) with clinical features have markedly enhanced the accuracy of tracing tumor origin, and artificial intelligence (AI) driven TOO models are increasingly being incorporated into clinical practice, offering new insights for pathological diagnosis, treatment selection, and prognostic evaluation. Nevertheless, several challenges remain, including issues of data standardization, model generalizability, and interpretability. Ethical considerations related to data privacy, algorithmic fairness, and clinical implementation also warrant careful attention. Future research should focus on establishing standardized multi-center databases, developing more interpretable AI models, and fostering multidisciplinary collaborative strategies for CUP management. Through continued refinement of technical solutions and regulatory guidelines, TOO identification is anticipated to progress from research to routine clinical application, ultimately supporting precise and personalized care for patients with CUP.

Artificial intelligence↗

PubMed2003

Angiographic embolization for liver injuries: low mortality, high morbidity.

OBJECTIVE: Angiographic embolization (AE) is a safe and effective method for controlling hemorrhage in both blunt and penetrating liver injuries. Improved survival after hepatic injuries has been documented using a multimodality approach; however, patients still have significant long-term morbidity. This study examines further the role of AE in both blunt and penetrating liver injuries and the outcomes of its use. METHODS: The medical records of 37 consecutive patients admitted from 1995 to 2002 to a Level I trauma center who underwent hepatic angiography with the intent to embolize were reviewed. Demographic and clinical information including Injury Severity Score, length of stay, mortality, intra-abdominal complications, admission physiologic variables, and the number and type of abdominal operations performed were collected. RESULTS: Thirty-seven patients underwent hepatic angiography and 26 patients had hepatic embolization performed. Eleven patients underwent early-AE, immediately after computed tomographic scanning, and 15 underwent late-AE, after liver-related operations or later in their hospital course. There was a 27% mortality rate overall. There were 11 liver-related complications in the 26 embolizations. Excluding the early deaths, the associated morbidity was 58%, which included hepatic necrosis, hepatic abscesses, and bile leaks. CONCLUSION: There is increasing adjunctive use of AE in patients managed both operatively and nonoperatively. Intra-abdominal complications are common in these salvaged patients with severe liver injuries. Those patients that underwent early-AE received significantly fewer blood transfusions and more commonly had sterile hepatic collections. Only 26% of patients required liver-related surgery after AE. Therefore, the integration of AE as an adjunctive modality for patients with high-grade liver injuries is a safe and effective therapeutic option.

Adolescent↗

PubMed2026

High-Sensitivity ctDNA Analysis Uncovers Relevant Signals Missed by NGS in Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) carries high mortality despite multimodal therapy, and improved biomarkers are needed to guide perioperative care. This study evaluated the prognostic significance of Kirsten rat sarcoma virus (KRAS)-mutant circulating tumor DNA (ctDNA) detected by next-generation sequencing (NGS) and digital droplet PCR (ddPCR) in localized PDAC. EXPERIMENTAL DESIGN: In this prospective cohort study (2020-2024), patients with localized PDAC undergoing neoadjuvant chemotherapy (NAC) were enrolled across multiple sites within Northwestern Medicine. Blood samples for ctDNA were assessed at diagnosis, after NAC, and after resection using tumor-agnostic NGS and ddPCR targeting KRAS G12D/V/R mutations. Overall survival (OS) was assessed using Kaplan-Meier analysis. RESULTS: The cohort included 106 patients. At diagnosis, KRAS ctDNA was detected in 17.2% (17/99) by NGS and 64.9% (63/97) by ddPCR. Detection by both platforms was associated with shorter OS, with the higher-sensitivity ddPCR assay providing greater prognostic discrimination by identifying additional patients with poor outcomes not captured by NGS (NGS median OS 11.2 vs. 30.5 months, P < 0.001; ddPCR median OS 24.7 vs. 70.9 months, P = 0.004). Stratified by detection method, median OS was shortest in patients with ctDNA detected by both NGS and ddPCR (10.9 months), longest in those not detected by either platform (40.7 months), and intermediate in patients detected only by ddPCR (26.9 months; P < 0.001). CONCLUSIONS: In localized PDAC, KRAS-mutant ctDNA detected by NGS or ddPCR was associated with worse survival. ddPCR identified additional patients missed by NGS. Integrating ddPCR with NGS ctDNA measures may improve perioperative risk stratification, although validation is needed before clinical implementation.

Humans↗