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Toward large-scale mass spectrometry-based omics for clinical applications.

INTRODUCTION: As healthcare advances toward personalized medicine, mass spectrometry-based research is advancing our understanding of cellular biology and disease states, and translating these findings into clinical applications. This review highlights recent advances in methodology and technology that demonstrate the capabilities of mass spectrometry-based proteomics, lipidomics, and metabolomics in clinical practice. AREAS COVERED: The ability to directly analyze functional molecules with mass spectrometry uncovers crucial clinical information. Each data modality (proteins, lipids, and metabolites) provides essential insight into healthy and disease states. As technology advances, integrating data from different modalities unlocks new possibilities for clinical research. To gain the most from this multi-omic data, unsupervised integration methods can provide detailed insights into complex biological processes. As the field applies this knowledge, healthcare could experience significant leaps in the near future. This review examines recent advancements in mass spectrometry-based proteomics, lipidomics, and metabolomics, focusing on how improvements in sample preparation, automation, and multi-omics data integration are making large-scale clinical studies more accessible. EXPERT OPINION: Recent technical and methodological advancements in mass spectrometry analysis have propelled healthcare toward a tipping point, shifting from traditional RNA- and DNA-based research to downstream analysis of protein, lipid, and metabolite effectors.

Humans

Biofeedback and self-control of physiological functions: clinical applications.

The parameters amenable to biofeedback learning are mentioned, including brainwaves, muscle tension, temperature, the cardiovascular system, and others. A discussion follows of the clinical application of biofeedback in the treatment of such disorders as tension headaches, neuromuscular re-education, epilepsy, "dysponesis," cardiac arrhythmias, blood pressure and migraines. The usefulness of biofeedback has been demonstrated also in the field of psychotherapy for purposes of desensitization, treating anxious patients, encouraging specific personality changes, and indicating stress to patients.

Anxiety

Clinical applications of biofeedback: implications for psychiatry.

The authors briefly describe biofeedback techniques such as EMG feedback, temperature feedback, and heart rate feedback, along with reports from the literature about their application to specific problems such as subvocalization while reading, Raynaud's disease, cardiac arrhythmias, and epilepsy. Many clinical applications of biofeedback are aimed at inducing relaxation, a state that has important psychotherapeutic potential. The authors suggest that biofeedback could be used to reduce a patient's general level of arousal or as an adjunct to behavior therapy or insight therapy. While there have been no reports in the literature of any harmful effects secondary to feedback training, the authors caution that some patients may respond negatively to an objectively measured state of relaxation.

Anxiety

New developments in the clinical application of evoked potentials.

The introduction of the pattern-evoked response and of far field recording of the auditory and somatosensory short latency responses has provided to major advances in the clinical application of evoked potentials. The sensitivity of the pattern response in the detection of minimal lesions of the visual pathways is now well established, and makes the test of particular value in the diagnosis of demyelinating disease and in the early detection of compressive lesions. The short latency auditory and somatosensory responses also show a high incidence of abnormalities in demyelinating disease. The technique will not compete directly with such well established methods as audiometry and perimetry, but it can provide valuable additional information, not accessible to these methods, particularly where the lesions are clinically silent or inconspicuous.

Auditory Cortex

Clinical application of a single compartment model to urea and creatinine kinetics in dialysis therapy.

A single compartment mathematical model has been shown to accurately described changing serum concentrations of low molecular weight solutes (urea and creatinine) during dialysis. Clinical application of the model permits prediction of serum concentrations in response to changes in prescription of dialysis therapy. The programs presented here can be used to predict the effect of changes in treatment time and dialyzer clearance on serum concentrations. Sequential pre- and end-dialysis solute concentrations are displayed on a programmable pocket calculator. Dialyzer clearance during any individual dialysis can be calculated. These programs permit an evaluation of the efficacy of prescribed dialysis treatment schedules in advance of therapeutic trials.

Computers

Clinical application of evoked electroencephalographic responses in newborn infants. I: Perinatal asphyxia.

Evoked electroencephalographic responses are useful for the study of cerebral maturation in full-term and pre-term newborn infants. In an attempt to achieve wider clinical application, 57 newborn infants with differing degrees of perinatal asphyxia were examined. Altogether 154 examinations were performed. In all of them photostimulation was used, and in 72 investigations somatosensory evoked responses were also recorded. The following results were obtained: (1) Visual evoked responses were affected in 85 per cent of the cases. Somatosensory evoked responses were affected less often - in 65 per cent of the newborn babies examined. The incidence and degree of deviations were related to the degree of asphyxia. (2) The most characteristic features of the evoked responses in asphyxiated infants were abnormal response patterns, increase of latency and poor photic driving. (3) On the basis of all alterations observed, a scoring system was developed which enabled quantitative evaluation. The evoked response risk-score correlated well with the degree of asphyxia. (4) Repeated observations were important: a permanently high risk-score at repeated investigations was a serious prognostic sign.

Asphyxia Neonatorum

Pulse-Doppler ultrasound and its clinical application.

Doppler devices can provide clinically useful information about blood flow. This paper describes how a pulse-Doppler instrument has been linked to a B-scan machine so that flow patterns in any ultrasonically accessible vessel can be monitored from the skin surface. The same transducer is used for both modes of investigation to enable accurate and reliable positioning of the sample-volume. After briefly summarizing the principles of continuous-wave and pulse-Doppler operation, the concepts and relative advantages of coherent and non-coherent detection are explained. The potential clinical uses of the pulse-echo-Doppler hybrid and Doppler devices in general are then discussed.

Blood Flow Velocity

[Arterial thrombosis induced by direct electric current. Clinical applications (author's transl)].

Authors have demonstrated that it is possible to induce arterial thrombosis by applying direct electric current (10 mA -V). By the use of this method several thromboses were formed in the rabbit. This technique is now well established and the first clinical applications on human arteries give rise to considerable hopes, since it is simple, reliable, and much less dangerous than other types of embolisation. Experiments are being done to apply this technique to aneurysms.

Adult

Personalizing endometrial cancer care beyond histology: clinical applications and limits of molecular classification.

Endometrial cancer is a biologically heterogeneous disease whose management has been reshaped by molecular classification. This review summarizes the current evidence supporting the integration of molecular subgroups into prognostic assessment and treatment personalization across stages of disease. The Cancer Genome Atlas classification and its clinically applicable surrogates identify four major molecular categories: POLE-mutated, mismatch repair-deficient, p53-abnormal, and no specific molecular profile tumors. These groups differ substantially in biology, prognosis, treatment sensitivity, and areas of unmet need. POLE-mutated tumors have an excellent prognosis and represent the clearest candidates for adjuvant treatment de-escalation, particularly in early-stage disease. Mismatch repair-deficient tumors show intermediate prognosis but strong sensitivity to immune checkpoint inhibition, which has transformed the management of advanced and recurrent disease and is now being tested in earlier settings. p53-abnormal tumors represent the highest-risk subgroup, requiring multimodal treatment and offering opportunities for biomarker-driven strategies including HER2-directed therapy and DNA damage repair targeting. No specific molecular profile tumors remain the most heterogeneous category, increasingly refined by estrogen receptor status, grade, L1 cell adhesion molecule overexpression, and other biomarkers. Mismatch repair-proficient advanced/recurrent disease should be interpreted as a composite clinical trial population rather than a molecular class. Molecular classification should be integrated with traditional clinicopathologic factors, emerging biomarkers, and local implementation strategies to support equitable, biologically informed treatment selection in endometrial cancer.

Humans

[The clinical application of serum sialyl transferase determination as criterion of malignant transformation of cell surface structure (author's transl)].

The activity of a specific glycosyl transferase, namely, sialyl transferase was determined in a sera of patients with malignant disease. Increased serum sialyl transferase activity was observed in a high percentage of examined cases. The serum enzyme activity was also correlated to the clinical state of the patients and was found to depend on the tumor size. The enzyme activity decreased following surgical removal of the tumor mass and increased an appearance of metastases. These findings may be the basis for possible clinical application in the follow-up of patients with malignant disease, because the diagnostic value of serum sialyl transferase determination is greater than that of other serum analyses.

Bronchial Neoplasms

The Clinical Application of Refined Risk Estimates Study in BRCA1 and BRCA2 Pathogenic Variant Carriers: A Randomized Controlled Trial.

UNLABELLED: Individuals with germline BRCA1 or BRCA2 pathogenic variants (PV) may struggle with risk management decision-making. Advancements in technology could provide more specific risk information to patients, but the impact of this information is unknown. The Clinical Application of Refined Risk Estimates Study is a two-arm randomized controlled trial in women with a BRCA1/BRCA2 PV. The primary objective was to determine whether genotype-informed personalized cancer risk estimates (GRE) compared with standard lifetime cancer risk estimates (SRE) decreased decisional conflict related to cancer risk management decision-making. Women were recruited following the disclosure of their PV results. Participants completed a baseline survey and were randomized 1:1 to receive a GRE or SRE. After receiving their results, participants completed a follow-up survey. Likert and continuous data measures were analyzed using linear regression. There were no differences in decisional conflict between study arms at follow-up. However, individuals in the SRE arm showed an increased need for personal structure compared with those in the GRE arm (P = 0.02). Compared with baseline, individuals within the SRE arm showed decreased decisional conflict (P = 0.003) and increased perceived stress (P = 0.02) at follow-up. A more personalized cancer risk estimate did not decrease decisional conflict in women with BRCA1/BRCA2 PVs. Future studies will determine whether a GRE affects actual decision-making behaviors. PREVENTION RELEVANCE: Women with a germline PV in BRCA1 or BRCA2 have significantly elevated risks of developing breast and ovarian cancers. This randomized controlled trial evaluates the impact of polygenic risk scores on decisional conflict related to breast and ovarian cancer prevention and risk management in those with BRCA1/BRCA2 PVs.

Humans

Current Evidence for Circulating Tumor DNA in Sarcoma: Challenges and Opportunities for Clinical Application.

Sarcomas represent a diverse group of mesenchymal tumors with high rates of recurrence after resection. While recent technical advances have enabled the detection of rare circulating tumor DNA (ctDNA) in other malignancies, the complexity and heterogeneity of sarcoma genomics have historically limited ctDNA in these cancers. This narrative review highlights the rapidly evolving evidence supporting potential clinical applications of ctDNA in common sarcoma subtypes including gastrointestinal stromal tumor, leiomyosarcoma, rhabdomyosarcoma, osteosarcoma, and Ewing sarcoma.

Humans

Sensory conduction in medial plantar nerve: normal values, clinical applications, and a comparison with the sural and upper limb sensory nerve action potentials in peripheral neuropathy.

A method for recording the medial plantar sensory nerve action potential at the ankle with surface electrodes is described. Normal values in 69 control subjects are given and compared with the sural sensory nerve action potential in the same limb in the same subjects. Clinical applications were studied in 33 patients. The procedure may be applied in the diagnosis of L4-5 nerve plexus or root lesions, lesions of the sciatic, posterior tibial, and medial plantar nerves, and is a more sensitive test than other sensory nerve action potentials in the diagnosis of peripheral neuropathy.

Action Potentials

In-vitro effect of doxycycline on levels of adenosine triphosphate in bacterial cultures. Possible clinical applications.

Short-term effects of doxycycline on viability and levels of intracellular ATP in bacteria were studied. Inhibition of growth by doxycycline was reflected in a corresponding inhibition of the accumulation of intracellular ATP which was clearly demonstrable within 1-2 hours. The effects of doxycycline on intracellular ATP were dose-dependent and the use of ATP assays for quantitation of antibiotics in serum is discussed. In 45 clinical isolates exposed to doxycycline a positive correlation was found between antibiotic-induced inhibition of intracellular ATP levels and inhibitory zone diameters with the disc diffusion method, indicating possible clinical applications in rapid susceptibility testing.

Adenosine Triphosphate

Vascular thrombosis induced by direct electric current. A new technique for therapeutic embolisation; animal experimentation; first clinical applications.

A first series of experiments showed that the passage of a direct current along a positive electrode immersed in heparinised blood caused the formation of an adhering clot whose diameter increased with time and current intensity. A second series of experiments was done on 10 rabbits as follows: under general anaesthesia, a catheter used as a guide to the positive electrode was surgically inserted in the abdominal aorta. The negative electrode was placed on the thigh. A direct current (10 mA, 10V) was applied for 10-20 min. The first two clinical applications in man of this new method of treatment by electric current thrombosis were carried out using catheterisation of branches of the external carotid and cervical arteries.

Adolescent

Non-invasive electromagnetic measurement of the peripheral pulsatile blood flow: experimental study and clinical applications.

The non-invasive electromagnetic blood flowmeter described in this paper allows us to measure pulsatile flow through a limb. The limb is placed in a magnetic field and the blood flow rate induces electromagnetic forces which are detected at the skin surface with ECG electrodes (Faraday's law). A special computer technique is necessary to isolate the signal from artefacts (local ECG, BCG, EMG). In vitro calibration is performed using a circulatory model and in vivo using mongrel dogs. Its validity is assessed by comparing the results with the responses obtained from the invasive electromagnetic flowmeter. Sources of error in the measurement such as blood composition (Na+, K+), haematocrit (45% to 29%), and venous flow are reported here. The results indicate that the method is reliable, easy to utilise and offers a unique non-invasive way of measuring true pulsatile blood flow rate in humans. Various clinical applications are discussed for possible use of the device.

Animals

diffMONT: predicting methylation-specific PCR biomarkers based on nanopore sequencing data for clinical application.

MOTIVATION: DNA methylation serves as a key biomarker in clinical diagnostics, especially in cancer detection. With methylation-specific PCR (MSP), a widely used approach, patient samples can be screened fast and efficiently for differential methylation. During MSP, methylated regions are selectively amplified with specific primers. With nanopore sequencing, knowledge about DNA methylation is generated during direct DNA sequencing without needing pretreatment of the DNA. Multiple methods, mainly developed for whole-genome bisulfite sequencing (WGBS) data, exist to predict differentially methylated regions (DMRs) in the genome. However, the predicted DMRs are often very large and not sufficiently discriminating to generate meaningful results in MSP, creating a gap between theoretical cancer marker research and practical application, as no tool currently provides methylation difference predictions tailored for PCR-based diagnostics. RESULTS: Here, we present diffMONT, a tool that predicts differentially methylated regions specifically suited for MSP primer design, enabling rapid translation into practical applications. diffMONT takes into account (i) the specific length of primer and amplicon regions, (ii) the fact that one condition should be unmethylated, and (iii) a minimal required amount of differentially methylated cytosines within the primer regions. We compared the results of diffMONT to metilene and DSS based on a publicly available nanopore sequencing dataset and show that the regions predicted by diffMONT are more specific toward hypermethylated regions. diffMONT accelerates the design of methylation-specific diagnostic assays, bridging the gap between theoretical research and clinical application. AVAILABILITY AND IMPLEMENTATION: The source code for diffMONT, an open-source Python-based tool, is available at https://github.com/rnajena/diffMONT/, with an archived release under https://zenodo.org/records/17641031.

DNA Methylation