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A multimode dynamometer for in vivo MRS studies of human skeletal muscle.

The implementation of muscle ergometry during magnetic resonance spectroscopy and imaging is complicated by the restrictive dimensions of the magnet bore and the presence of a strong static magnetic field. We have developed a dynamometer that is compatible with these constraints. This device can provide resistance to voluntary muscle contraction during isometric, isokinetic concentric, and isokinetic eccentric muscle contractions. While controlling muscle contraction speed, the dynamometer simultaneously records muscle torque production at a 10-Hz sampling frequency to allow assessment of compliance and retrospective normalization of power output for the mass of active muscle. All parameters relevant to muscle contraction are selectable, including percentage of maximal voluntary contraction, velocity of muscle contraction, duty cycle, and range of motion for the contraction. This paper provides examples of 31P-magnetic resonance spectroscopic measurements during isokinetic concentric contractions of the ankle dorsiflexors, isokinetic eccentric contractions of the soleus, and isometric contractions of the soleus. Operation of the dynamometer has no adverse effects on the integrity of the 31P-magnetic resonance spectra at 4 T, permitting temporal resolution of the phosphocreatine resynthesis rate of approximately 1 spectrum/s. The unique capabilities of this dynamometer will facilitate studies into the metabolic response of working muscle in healthy and diseased populations.

Adult↗

Multimodal fMRI tractography in normal subjects and in clinically recovered traumatic brain injury patients.

In this study, we defined an operator-independent protocol for reconstructing the anatomical connections originating from fMRI activations in order to demonstrate that results obtained with this protocol are affected by alterations of functional activations. Seven healthy volunteers and two patients who sustained traumatic brain injury underwent an fMRI with a finger tapping task and a DTI scan. Cortical fMRI activations were used directly as seed mask for tractography for the reconstruction of individual motor pathways. On patients we observed a different motor network if compared to healthy subjects. However, when the activations of healthy subjects were used as seed masks for the tractography in patients, we observed for the patients a pattern of connectivity more similar to what was observed for healthy subjects. At the same time, when the activations of patients were used for the tractography on healthy subjects, we obtained patterns of connectivity similar to those obtained for patients. These results show the potential of the integration of fMRI and tractography for clarifying the mechanisms of cortical plasticity in the recovery of motor functions.

Adult↗

Brainvox: an interactive, multimodal visualization and analysis system for neuroanatomical imaging.

A study of cognition emerging from a neurobiological perspective, as opposed to one emerging from a purely computational or psychological perspective, begins with observations of the human brain in normal and pathological states and is furthered by the investigation of hypotheses which are articulated using neuroanatomical nomenclature. Brainvox is an interactive three-dimensional brain imaging software package designed to permit such research through the support of the description and quantification of brain pathology in magnetic resonance images and of the experimental investigation of human cognition in lesion and functional imaging studies. Important general features of Brainvox, for these purposes, are: (1) adaptation of volume rendering for brain lesions and for corendered datasets; (2) shared memory architecture, which enables the user to identify and label anatomical structures, while inspecting the brain in multiple views simultaneously; (3) modular program design, including interlocking command-line utilities, which make Brainvox extensible and empower users without programming expertise to implement new analysis techniques through Unix shell scripting; and (4) full integration of three-dimensional tools for visualization with tools for analysis. Specific features include a new object templating technique (MAP-3) for studies of groups of brain-lesioned subjects, a complete and extensible suite of command-line processing utilities, a three-dimensional optimal graph-searching tool, and a method for planning PET slices and matching MR and PET slices (MP_FIT).

Artificial Intelligence↗

The forgotten indwelling ureteral stent: a urological dilemma.

Ureteral stents are an integral part of urological practice. However, stents that migrate, fragment or are forgotten pose a management and legal dilemma. Our series consists of 31 patients, 22 with forgotten stents that were left indwelling for more than 6 months (mean 22.7) and 9 migrated stents. Of the forgotten stents 15 (68%) were calcified, 10 (45%) were fragmented, and 3 (14%) were calcified and fragmented. Procedures to render the patient stent-free were ureteroscopy in 16 (52%), percutaneous nephroscopy in 8 (26%), cystoscopic electrohydraulic lithotripsy in 6 (19%), extracorporeal shock wave lithotripsy in 10 (32%), open cysto-litholapaxy in 1 (3%) and simple nephrectomy in 1 (3%). Multiple procedures were required in 6 patients (19%). Management of such complicated ureteral stents requires a multimodal therapeutic approach incorporating the latest in extracorporeal shock wave lithotripsy and endourological techniques. These patients are at increased risk for loss of renal function. A computerized tracking registry of ureteral stents may help prevent this urological travesty.

Adult↗

Electrophysiology of taste-mediated functions in parabrachial nuclei of behaving rabbit.

A single-unit analysis of parabrachial (PBN) neuronal activity associated with orolingual response to auditory-cued intraoral injections of basic type tastants and water revealed 7 major functional types of neurons. Several types dealt with mechanoreceptive orosensory input from superficial and/or deep receptors and from proprioceptors (possibly joint receptors). Some were multimodal in sensitivity. In one type, thermal or gustatory input acted to inhibit movement-related excitation in activity. Three types of taste-sensitive elements were distinguished. "Movement-taste sensitive" elements showed relations to orolingual movement and hedonic properties of fluid input. These cells may contribute to motivational control of licking activity. A tentative distinction was drawn between "taste-hedonic" and "taste" elements. One type responded to water and showed a bias toward hedonic properties of tastants. The other type exhibited no response to water and smaller responses to tastants that had no hedonic relationship. Both, however, had common properties, including inhibitory modulation of activity in apparent anticipation of fluid delivery. In addition to serving as a gustatory relay, PBN act to integrate orolingual response to taste and other orosensory input, and may operate as an output mechanism in the ventral forebrain control of ingestive behavior.

Animals↗

Multimodality cisplatin treatment in nonresectable alpha-fetoprotein-positive hepatoma.

Twenty-eight patients with alpha-fetoprotein-positive (AFP+) nonresectable hepatoma have been enrolled in a new multimodality Phase I, II program. Induction therapy consisted of 50 mg/m2 intravenous cisplatin followed by 2100 cGy irradiation to the tumor volume in seven fractions over 10 days. Hepatic arterial infusion of 50 mg/m2 cisplatin (IA-CDDP) was then administered at monthly intervals. Twenty-one patients have completed induction and at least two cycles of IA-CDDP. Twelve-month cumulative survival was 52% for all 28 patients and 69% for the 21 patients completing induction and IA-CDDP. Median survival has not yet been reached. Response rate (complete and partial) was 36% overall and 48% among the 21 patients who completed treatment. The improved survival of the present series of patients as well as the minimal hematologic toxicity suggests possible further integration of new modalities for therapy.

Adult↗

Single unit activity during a Go/NoGo task in the "prefrontal cortex" of pigeons.

Single unit activity was recorded during a delayed auditory/visual Go/NoGo task from the neostriatum caudolaterale (NCL) of pigeons, a multimodal associative avian forebrain structure comparable to the prefrontal cortex (PFC). The animals were trained to mandibulate (to open their beak) during the Go period after which they received a drop of water as reward. Neuronal activity changes were observed during the delay period (DELAY) between auditory and visual stimulation, to the onset of the visual stimulus or to the delivery of the reward. In some neurons, responses were related to the behavioral significance of the stimulus such that the neuronal activity was statistically different between Go and NoGo trials. Moreover, some units anticipated the upcoming reward or changed their firing frequency in a correlated manner prior to beak movements. These neuronal activity patterns suggest that the NCL provides a neural network that participates in the integration and processing of external stimuli in order to generate goal directed behavior.

Acoustic Stimulation↗

Role of clinically determined depth of tumor invasion in the treatment of esophageal carcinoma.

OBJECTIVE: We sought to evaluate the effectiveness of clinical staging of depth of tumor invasion (cT), the relationship of cT to survival, the benefits of downstaging cT, and the role of cT in treatment decisions. METHODS: The accuracy of determining T by means of endoscopic ultrasonography and the relationship of cT to survival were assessed in 209 patients undergoing esophagectomy alone for esophageal carcinoma. The benefit of downstaging cT was assessed in 128 patients undergoing induction therapy and esophagectomy. The role of cT in treatment decisions was determined by integrating these results with the results of previous work. RESULTS: Compared with pathologic T (pT), cT was 87% accurate, 82% sensitive, 91% specific, 89% positively predictive, and 86% negatively predictive of tumors confined to (< or =T2) or invading beyond (>T2) the esophageal wall. In cN0, increasing cT was predictive of progressively poorer survival. For each category of pT N0, cT accurately predicted survival, except for pT3, which was underestimated (P <.0001). In cN0, downstaging by induction therapy was beneficial only if tumors invaded beyond the wall (> or =cT3, P =.0003). In cN1, it was beneficial only when downstaging was synchronous in cT3/T4 (P <.001). CONCLUSIONS: cT should be the principal determinant of treatment in cN0. In cN0, if endoscopic ultrasonography identifies tumors of greater than cT2, multimodality therapy should be considered. However, only when cT3/T4 tumors are downstaged to pT2 or less will patients benefit, but their survival will not equal that of patients with tumors of cT2 or less having esophagectomy alone. If endoscopic ultrasonography identifies tumors of cT2 or less, esophagectomy alone should be used because induction therapy might adversely affect survival.

Adenocarcinoma↗

The strategic and operational characteristics of a distributed phased archive for a multivendor incremental implementation of picture archiving and communications systems.

The long-term (10 years) multimodality distributed phased archive for the Medical Information, Communication and Archive System (MICAS) is being implemented in three phases. The selection process took approximately 10 months. Based on the mandatory archive attributes and desirable features, Cemax-Icon (Fremont, CA) was selected as the vendor. The archive provides for an open-solution allowing incorporation of leading edge, "best of breed" hardware and software and provides maximum flexibility and automation of workflow both within and outside of radiology. The solution selected is media-independent, provides expandable storage capacity, and will provide redundancy and fault tolerance in phase II at minimum cost. Other attributes of the archive include scalable archive strategy, virtual image database with global query, and an object-oriented database. The archive is seamlessly integrated with the radiology information system (RIS) and provides automated fetching and routing, automated study reconciliation using modality worklist manager, clinical reports available at any Digital Imaging and Communications in Medicine (DICOM) workstation, and studies available for interpretation whether validated or not. Within 24 hours after a new study is acquired, four copies will reside within different components of the archive including a copy that can be stored off-site. Phase II of the archive will be installed during 1999 and will include a second Cemax-Icon archive and database using archive manager (AM) Version 4.0 in a second computer room.

Computer Communication Networks↗

Psychosocial issues in oncologic practice.

Impressive gains in the survival of some patients with malignant diseases have primarily reflected the availability of multimodality programs for selected pediatric neoplasms and germ cell tumors and for subsets of patients with regional breast cancer, colorectal cancer, and small-cell lung cancer. Most patients with advanced solid tumors, however, will die of their disease. Sophisticated psychosocial investigations of patients with advanced cancer have targeted several areas in which clinicians can positively influence quality of life. Families often "cascade through an avalanche" of emotional upheavals as patients struggle with the sequelae of their illness. After a patient dies, clinicians should be familiar with some generally recognized patterns of behavior that are indicative of a normal mourning process. This knowledge may help clinicians be aware of situations that might necessitate intervention of other professionals, either medical or pastoral. Attention to psychosocial events is an integral part of a comprehensive oncologic program to facilitate patients and families to live in an atmosphere of peace and dignity.

Adaptation, Psychological↗

Integral equation for calculation of distribution function of activation energy of shear viscosity.

A new technique of calculation of a distribution function of activation energy (f(E)) of shear viscosity based on a regularization procedure applied to the Fredholm integral equation of the first kind has been developed using the Baxter-Drayton and Brady model for concentrated and flocculated suspensions. This technique has been applied to the rheological data obtained at different shear rates for aqueous suspensions with fumed silica A-300 and low-molecular (3,4,5-trihydroxybenzoic acid and 1,5-dioxynaphthalene) or high-molecular (poly(vinyl pyrrolidone) of 12.7 kDa and ossein of 20-29 kDa) compounds over a wide concentration range (up to 25 wt% of both components) and at different temperatures. Monomodal f(E) distributions are observed for the suspensions with individual A-300 or A-300 with a low amount of adsorbed organics. In the case of larger amounts of nanosilica and organics the f(E) distributions are multimodal because of stronger structurization and coagulation of the systems that require a high energy to break the coagulation structures resisting to the shear flow.

Journal Article↗

Compact fluorescence detection using in-fiber microchannels-its potential for lab-on-a-chip applications.

This paper reports a compact and practical fluorescence sensor using an in-fiber microchannel. A blue LED, a multimode PMMA or silica fiber and a mini-PMT were used as an excitation source, a light guide and a fluorescence detector, respectively. Microfluidic channels of 100 microm width and 210 microm depth were fabricated in the optical fibers using a direct-write CO(2) laser system. The experimental results show that the sensor has high sensitivity, able to detect 0.005 microg L(-1) of fluorescein in the PBS solution, and the results are reproducible. The results also show that the silica fiber sensor has better sensitivity than that of the PMMA fiber sensor. This could be due to the fouling effect of the frosty layer formed at the microchannel made within the PMMA fiber. It is believed that this fiber sensor has the potential to be integrated into microfluidic chips for lab-on-a-chip applications.

Fluorescein↗

Machine learning for population-level risk prediction of future cholangiocarcinoma.

BACKGROUND: The poor prognosis of cholangiocarcinoma (CCA) is largely driven by rapid, asymptomatic disease progression, which usually results in a late diagnosis in the absence of established screening strategies. An early, cost-effective, and universally applicable risk assessment strategy would therefore be valuable. METHODS: We developed machine learning (ML) models on prospective, multimodal data from 487,495 UK Biobank (UKB) participants, of whom 649 developed CCA during follow-up. Data from England (80%) were utilised for ML development via five-fold cross-validation, and then all models were tested on withheld data from Scotland, Wales, and Newcastle (20%). Iterative ablation studies reduced inputs from >150 features across demographic data, lifestyle, health records, blood parameters, genomics, and metabolomics to models built on five and ten routinely available clinical parameters. These were externally validated in the Penn Medicine Biobank (PMBB; n = 2638; 28 CCA), All of Us Research Program (AOU; n = 330,433; 362 CCA), Japan Medical Data Centre Claims Database (JMDC; n = 8,425,522; 723 CCA) and TriNetX (n = 728,886; 1592 CCA). FINDINGS: We show that ML models integrating biliary-disease associated health records and Gamma glutamyltransferase can stratify risk of future CCA. Evaluation on the UKB test set as well as three independent cohorts revealed robust performance and generalisability across ethnicities. We achieved AUROCs of 0.71 [95% CI: 0.703-0.711], 0.77 [95% CI: 0.764-0.778 ], 0.796 [95% CI: 0.795-0.798] and 0.8 [95% CI: 0.794-0.805] for UKB, PMBB, AOU, and JMDC respectively, with respective AUPRCs of 0.014 [95% CI: 0.009-0.018], 0.042 [95% CI: 0.037-0.048], 0.038 [95% CI: 0.033-0.042] and 0.001 [95% CI: 0.001-0.001]. In AOU, application of the Youden J-optimised threshold yielded a number needed to screen of 79. Separate models for intra- and extrahepatic CCA did not improve performance. In line with the pathophysiology, performance declined for longer intervals between assessment and event. A group-level analysis in the TriNetX cohort revealed hazard ratios of up to 82.5 [95% CI: 26.4-257.96]. We provide extensive interpretability results and release all source codes used to develop the presented models. INTERPRETATION: We provide a comprehensive framework for early CCA risk stratification in the general population, identifying key predictors, and demonstrating the potential of data-driven models in personalised screening for hepatobiliary cancer. FUNDING: German Cancer Aid (grant #70115730), Junior Principal Investigator Fellowship programme of RWTH Aachen Excellence strategy.

Humans↗

Comparison of dynamic and integrated light-scattering techniques in the study of the interaction of Candida rugosa lipase with DPPC liposomes.

Dynamic light-scattering (DLS) and wide angle integrated light-scattering (WAILS) spectroscopies were evaluated in the study of binding of Candida rugosa lipase (CRL) with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes. The use of cumulants analysis on DLS data allowed for the determination of general lipase-liposome-binding trends. Particle intensity distributions obtained from DLS data by a discrete inversion method revealed the different populations created upon lipase-liposome interactions. Using a discrete inversion technique on WAILS data, not only these populations could be differentiated but also accurate number distributions were obtained in short periods of time. Both DLS and WAILS are excellent tools for the study of lipase binding to lipid vesicles; however, care must be exercised in the analysis of the experimental data whenever particle size distributions are multimodal. The selection of the light scattering technique will depend on the information required.

1,2-Dipalmitoylphosphatidylcholine↗

Visual-vestibular interactive responses in the macaque ventral intraparietal area (VIP).

Self-motion detection requires the interaction of a number of sensory systems for correct perceptual interpretation of a given movement and an eventual motor response. Parietal cortical areas are thought to play an important role in this function, and we have thus studied the encoding of multimodal signals and their spatiotemporal interactions in the ventral intraparietal area of macaque monkeys. Thereby, we have identified for the first time the presence of vestibular sensory input to this area and described its interaction with somatosensory and visual signals, via extracellular single-cell recordings in awake head-fixed animals. Visual responses were driven by large field stimuli that simulated either backward or forward self-motion (contraction or expansion stimuli, respectively), or movement in the frontoparallel plane (visual increments moving simultaneously in the same direction). While the dominant sensory modality in most neurons was visual, about one third of all recorded neurons responded to horizontal rotation. These vestibular responses were typically in phase with head velocity, but in some cases they could signal acceleration or even showed integration to position. The associated visual responses were always codirectional with the vestibular on-direction, i.e. noncomplementary. Somatosensory responses were in register with the visual preferred direction, either in the same or in the opposite direction, thus signalling translation or rotation in the horizontal plane. These results, taken together with data on responses to optic flow stimuli obtained in a parallel study, strongly suggest an involvement of area VIP in the analysis and the encoding of self-motion.

Action Potentials↗

Therapeutic Potential of Terpenes in Lung Cancer: Modulation of 4-Oxo- Retinoic Acid, TNF-&#x3b1;, NF-&#x3ba;B, and HDAC2 Pathways.

Non-small cell lung cancer (NSCLC) includes various epithelial malignancies, such as squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Despite advancements in surgical resection, chemoradiotherapy, and multimodal therapies, NSCLC prognosis remains challenging due to its complex molecular landscape, drug resistance, and high treatment costs. Recent research highlights the potential of natural compounds, particularly terpenes and terpenoids, derived from essential oils (EOs), to enhance NSCLC treatment. These compounds exhibit anticancer properties and modulate key pathways like the 4-oxo-retinoic acid pathway, TNF-&#x3b1; signaling, NF-&#x3ba;B activation, and histone deacetylases (HDACs). Retinoids, a subclass of terpenes, show both chemopreventive and therapeutic benefits, especially when combined with other agents, though challenges in dosing and delivery methods limit their clinical application. Terpenes may also synergize with emerging therapies, such as antiangiogenic treatments and immunotherapy, to improve outcomes. Biomarkers, including genomic, epigenomic, and proteomic markers, play a critical role in predicting responses to terpene-based treatments, supporting personalized medicine. The integration of terpenes into existing regimens, in combination with conventional therapies, holds promise in overcoming clinical challenges, improving patient outcomes, and advancing natural compound use in modern oncology. Future research should focus on optimizing terpene therapies and addressing clinical hurdles.

Humans↗

Multimodal responses of the nonspiking giant interneurons in the brain of the crayfish Procambarus clarkii.

Three pairs of nonspiking giant interneurons (NGIs; G1, G2, and G3) of the crayfish brain responded with depolarizing and hyperpolarizing graded potentials to body tilt in roll to the ipsi- and contralateral sides in the dark. The higher and the larger the angle of body tilt, the larger was the amplitude of the geotactic responses. In ipsilaterally statocystectomized animals, all the NGIs responded with hyperpolarizing potentials only to the contralateral side-down tilt, whereas in contralaterally statocystectomized animals, they responded with depolarizing potentials only to the ipsilateral side-down tilt. In bilaterally statocystectomized animals, none of the NGIs responded to body tilt in the dark, but in the presence of an overhead light, they exhibited depolarizing and hyperpolarizing potentials in response to body tilt to the ipsi- and contralateral sides, respectively. All the NGIs responded with depolarizing and hyperpolarizing graded potentials to illumination of the contra- and ipsilateral eyes, respectively. The amplitude of these visual responses, however, varied in association with the amplitude of the geotactic response produced by body tilt. These results indicate that the NGIs integrate the sensory inputs from eyes and statocysts and that the interaction between sensory inputs from the left and right sensory organs with either the same modality or with different modalities enhance the directional sensitivity of NGIs as premotoneurons in the compensatory oculomotor system.

Afferent Pathways↗

Multimodal detection of perioperative myocardial ischemia.

Cardiac anesthesiologists have the responsibility to detect myocardial ischemia in a timely manner, which can be a challenging task in the perioperative environment. Transesophageal echocardiography pulmonary artery catheterization, and electrocardiography are the 3 major methods available for monitoring perioperative ischemia. Echocardiography, the newest and most sophisticated method, has been shown to be highly sensitive for detecting ischemia associated with systolic dysfunction. Echocardiography can detect wall-motion abnormalities before electrocardiographic changes develop in patients who are likely to experience supply-mediated ischemia. Perioperative ischemia that occurs after bypass and is detected using transesophageal echocardiography has been found to be related to an adverse outcome. However, the use of echocardiography has some limitations, including the detection of abnormalities not induced by ischemia and the presence of ischemia in areas not visible in the view selected. Pulmonary artery catheterization can provide information about systolic dysfunction, diastolic dysfunction, and mitral regurgitation, but the sensitivity and safety of catheterization have been questioned. Electrocardiography can be a superb monitoring device as long as clinicians pay adequate attention to lead selection and placement, filter selection, and gain adjustment. The optimal monitoring approach should integrate all 3 available monitoring systems in order to increase the likelihood of detecting both supply- and demand-mediated ischemia.

Anesthesiology↗