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PubMedDate not supplied

Accuracy of positioning the cervical spine for radiation therapy and the relationship to GTV, CTV and PTV.

The purpose of the study was to evaluate the accuracy and precision of a rigid positioning device for repositioning the cervical spine accurately and precisely during conformal radiation therapy of dogs. Fifteen purpose bred research dogs in a radiation therapy study were included. The dogs were positioned using a head holder and a deflatable pillow attached to the treatment table. Port films were reviewed retrospectively, and repositioning precision was recorded by measurements in three orthogonal planes of the head, 2nd cervical vertebra and 1st thoracic spinous process. Mean treatment position was compared to the planning position for a measurement of systematic set-up error. Mean interfraction position variation of the 2nd cervical vertebra was 0.2, 0.1 and 0.2 cm for the ventrodorsal, caudocranial and laterolateral directions respectively, and the average systematic set up error was 0.2, 0.1 and 0.2 cm for the ventrodorsal, caudocranial and laterolateral directions respectively. Knowledge of the magnitude of reposition errors should be included when determining the margins around the tumor.

Animals↗
PubMed1980

Clinical efficacy of computed body tomography, II.

The contribution to diagnostic understanding and therapeutic decision making by computed body tomography (CT) was measured in 623 patients using prospective and retrospective inquiry of referring physicians. CT improved diagnostic understanding in 52% of patients, reassured the physician about previously planned therapy in 43%, improved precision of previously planned treatment in 23%, and contributed to a change in therapy in 14%. There was a significant increase over time in reports of improved diagnostic understanding which was probably related to increasing clinical experience with the technique. However, this improvement in diagnostic understanding did not correspondingly increase the frequency of beneficially altered therapy. CT contributed to a substantial decrease in preplanned invasive imaging tests and a decision not to perform surgery in 19% of patients in whom an operation had been previously planned. The value of a CT examination to patient care varied considerably with the clinical problem; the most consistent contributions were observed in patients with diseases suspected in the mediastinum and retroperitoneum.

Attitude of Health Personnel↗
PubMed2025

BOGO: A Proteome-Wide Gene Overexpression Platform for Discovering Rational Cancer Combination Therapies.

Cancer drug resistance remains a major barrier to durable treatment success, often leading to relapse despite advances in precision oncology. While combination therapies are being increasingly investigated, such as chemotherapy with small molecule inhibitors, predicting drug response and identifying rational drug combinations based on resistance mechanisms remain major challenges. Therefore, a proteome-wide, single-gene overexpression screening platform is essential for guiding rational therapy selection. Here, we present BOGO (Bxb1-landing pad human ORFeome-integrated system for a proteome-wide Gene Overexpression), a robust, scalable, and reproducible screening platform that enables single-copy, site-specific integration and overexpression of ~19,000 human open across cancer cell models. Using BOGO, we identified drug-specific response drivers for 16 chemotherapeutic agents and integrated clinical datasets to uncover proliferation and resistance-associated genes with prognostic potential. Drug response similarity networks revealed both shared and unique mechanisms, highlighting key pathways such as autophagy, apoptosis, and Wnt signaling, and notable resistance-associated genes including BCL2, POLD2, and TRADD. In particular, we proposed a synergistic combination of the BCL2 family inhibitor ABT-263 (Navitoclax®) and the DNA analog TAS-102 (Lonsurf®), which revealed that lysosomal modulation is a key mechanism driving DNA analog resistance. This combination therapy selectively enhanced cytotoxicity in colorectal and pancreatic cancer cells in vitro, and demonstrated therapeutic benefit in vivo in both cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Together, these findings establish BOGO as a powerful gene overexpression perturbation platform for systematically identifying chemoresistance and chemosensitization drivers, and for discovering rational combination therapies. Its scalability and reproducibility position BOGO as a broadly applicable tool for functional genomics and therapeutic discovery beyond cancer resistance.

Journal Article↗
PubMed2006

Minimally invasive diagnostics and treatment using micro/nano machining.

Several medical tools with various functions have been developed for minimally invasive diagnostics and treatment. Microfabrication techniques such as MEMS technology are useful for the realization of high-performance multifunctional minimally invasive medical tools with small sizes. An ultra-miniature pressure sensor and an intravascular ultrasonic forward-viewing imager have been developed as microsensors for use in the human body. Active bending catheters have been developed for steering catheter tips without using traction of wires from outside the body. An ultrasonic therapeutic tool for sonodynamic therapy and sonoporation, and a micro scanner for precise laser treatment have been developed as therapeutic tools for use in the human body. High-functionalized endoscopic tools and catheters will enable more precise and safe diagnostics and therapy, as well as novel diagnostics and treatment which have been impossible to date.

Alloys↗
PubMed2005

The effectiveness of extra corporeal shock wave therapy for plantar heel pain: a systematic review and meta-analysis.

BACKGROUND: There is considerable controversy regarding the effectiveness of extracorporeal shock wave therapy in the management of plantar heel pain. Our aim was to conduct a systematic review of randomised controlled trials to investigate the effectiveness of extracorporeal shock wave therapy and to produce a precise estimate of the likely benefits of this therapy. METHODS: We conducted a systematic review of all randomised controlled trials (RCTs) identified from the Cochrane Controlled trials register, MEDLINE, EMBASE and CINAHL from 1966 until September 2004. We included randomised trials which evaluated extracorporeal shock wave therapy used to treat plantar heel pain. Trials comparing extra corporeal shock wave therapy with placebo or different doses of extra corporeal shock wave therapy were considered for inclusion in the review. We independently applied the inclusion and exclusion criteria to each identified randomised controlled trial, extracted data and assessed the methodological quality of each trial. RESULTS: Six RCTs (n = 897) permitted a pooled estimate of effectiveness based on pain scores collected using 10 cm visual analogue scales for morning pain. The estimated weighted mean difference was 0.42 (95% confidence interval 0.02 to 0.83) representing less than 0.5 cm on a visual analogue scale. There was no evidence of heterogeneity and a fixed effects model was used. CONCLUSION: A meta-analysis of data from six randomised-controlled trials that included a total of 897 patients was statistically significant in favour of extracorporeal shock wave therapy for the treatment of plantar heel pain but the effect size was very small. A sensitivity analysis including only high quality trials did not detect a statistically significant effect.

Heel↗
PubMed2026

From scissors to editors: how the evolution of precision is redefining therapeutic genome editing.

Since its introduction as a genome-editing tool, CRISPR-based technology has undergone rapid refinement, with precision emerging as a central focus of development. Early CRISPR-Cas9 systems demonstrated unprecedented ease and efficiency in targeting specific DNA sequences, but concerns over off-target effects and variable editing outcomes limited their broader application. This review outlines the progression of CRISPR from its discovery in prokaryotes to its application as a versatile tool in precision medicine, where it supports targeted therapies for genetic disorders in various ways. Although technical challenges, including off-target editing and delivery inefficiencies, persist alongside ethical considerations of accessibility and long-term consequences, CRISPR's ongoing refinements and innovations reflect a clear trajectory toward greater specificity, safety, and predictability, positioning CRISPR as an increasingly precise platform for both fundamental research and therapeutic use.

Gene Editing↗
PubMed2005

Prostate cancer: precision of integrating functional MR imaging with radiation therapy treatment by using fiducial gold markers.

The use of intensity-modulated radiation therapy for treatment of dominant intraprostatic lesions may require integration of functional magnetic resonance (MR) imaging with treatment-planning computed tomography (CT). The purpose of this study was to compare prospectively the landmark and iterative closest point methods for registration of CT and MR images of the prostate gland after placement of fiducial markers. The study was approved by the institutional ethics review board, and informed consent was obtained. CT and MR images were registered by using fiducial gold markers that were inserted into the prostate. Two image registration methods--a commonly available landmark method and dedicated iterative closest point method--were compared. Precision was assessed for a data set of 21 patients by using five operators. Precision of the iterative closest point method (1.1 mm) was significantly better (P < .01) than that of the landmark method (2.0 mm). Furthermore, a method is described by which multimodal MR imaging data are reduced into a single interpreted volume that, after registration, can be incorporated into treatment planning.

Adult↗
PubMed2003

[The problem of assessment of efficacy of antihypertensive therapy using 24-hour blood pressure monitoring].

Main advantages of the use of 24-hour blood pressure (BP) monitoring for assessment of effects of antihypertensive therapy consist in more precise selection of patients requiring drug treatment and more objective evaluation of results of therapy. However methodological limitations also exist. Among them are susceptibility of results to regression to the mean, insufficient understanding of many characteristics of 24-hour BP profile, interdependence (co-linearity) of various parameters. Lack of convincing data on prognosis of patients whose antihypertensive treatment has been guided by 24-hour BP monitoring also presents a serious problem. Promising direction of further research is investigation of reproducibility and reliability of different parameters of BP monitoring in relatively short-term studies including those with surrogate end points.

Antihypertensive Agents↗
PubMed2025

Gut microbiota: a hidden player in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects reproductive-aged women worldwide, causing hormonal imbalances and ovarian dysfunction. PCOS affects metabolic health and increases the risk of obesity, insulin resistance, and cardiovascular disease, in addition to infertility. This review delves deeper into the connections of gut microbiota with PCOS pathophysiology, particularly into its impact on hormone metabolism, obesity, inflammation, and insulin resistance by way of short-chain fatty acids, lipopolysaccharides, and gut-brain axis. Studies also show that changes in the metabolic processes and immune responses are seen in changes in the gut microbiota in PCOS subjects, such as changes in the Bacteroidetes and Firmicutes groups. Some bacteria, like Escherichia and Shigella, have been associated with dysbiosis in patients with PCOS, leading to systemic inflammation and changed hormone levels, which further worsen the clinical symptoms. Therapeutic interventions targeting the gut microbiota comprise probiotics, prebiotics, and fecal microbiota transplantation; these have potential to alleviate the symptoms of PCOS. Other precision microbiome-based therapies include postbiotics, and CRISPR-Cas9 genome editing, which are relatively new avenues toward precision treatment. This complex interlink of gut microbiota and PCOS pathophysiology will open the avenues for possible treatments for hormonal imbalances and metabolic problems that characterize these complex disorders. The review here focuses on the requirement of further studies to be able to elucidate the specific pathways relating gut microbiota dysregulation to PCOS and, thus, improve microbiome-based therapies for better clinical outcomes in affected individuals.

Humans↗
PubMed1987

Staging and therapy of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Some patients require no therapy and have prolonged survival. Others have brief survival despite intensive treatment. Several staging systems have been developed. These are useful in predicting outcome and need of therapy, but controversies exist. Additional prognostic factors have been identified such as cytogenetics, lymphocyte levels or doubling time, bone marrow morphology, and others. Patients with low-stage CLL have not been shown to benefit from treatment. In patients with intermediate disease, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) has not been shown to be superior to chlorambucil with or without prednisone. The therapy of high stage CLL is controversial; therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) may be superior to CVP. Future directions of therapeutic research include the treatment of patients with low stage disease, more precise identification of patients requiring therapy, and more precise definition of therapeutic response.

Antibodies, Monoclonal↗
PubMed2025

Integration of ALK gene mutations and targeted therapies in pediatric high-risk neuroblastoma: advancements in precision oncology.

INTRODUCTION: Neuroblastoma (NB) is the most common extracranial solid tumor in children. High-risk neuroblastoma remains a therapeutic challenge, with a 5-year survival rate of 60%. The anaplastic lymphoma kinase (ALK) oncogene plays a critical role in the pathogenesis of neuroblastoma, with mutations frequently observed in high-risk cases. In this review we explored the genomic landscape of high-risk neuroblastoma, focusing on ALK mutations and their role in disease progression. We have also discussed the efficacy of ALK-targeted therapies and potential combination strategies to overcome resistance. METHODS: A comprehensive literature search was conducted to collect peer-reviewed publications related to neuroblastoma's biology, classification, and treatment. Articles published between 1980 and 2025 were identified using databases such as PubMed, Scopus, Web of Science, and ClinicalTrials.gov. RESULTS: Neuroblastoma tumorigenesis implicates ALK mutations, particularly at ALK p.R1275Q, ALK p.F1174L, and ALK p.F1245C, with an enrichment in stage 4 tumors and younger patients. Several ALK inhibitors, like crizotinib, ceritinib, lorlatinib, repotrectinib, and alectinib, have shown different levels of success, but resistance to these treatments is still a big challenge. New treatment methods that combine farnesyltransferase inhibitors (FTIs) with ALK tyrosine kinase inhibitors (TKIs) are showing potential in improving how well the treatment works and in stopping the cancer from coming back. CONCLUSION: Precision oncology offers a novel and potentially more effective approach for treating high-risk neuroblastoma. While ALK inhibitors have shown promise, resistance mechanisms necessitate the development of combination therapies and next-generation inhibitors. Future research should focus on optimizing targeted treatment strategies to improve survival outcomes in pediatric patients with ALK-positive neuroblastoma.

ALK inhibitors↗
PubMed2003

Future and current surgical therapies in Parkinson's disease.

PURPOSE OF REVIEW: The mainstay of treatment for Parkinson's disease remains medical therapy. With improved surgical precision and decreased morbidity, stereotactic lesioning and deep brain stimulation have become more popular. New therapies currently in clinical trials include gene therapy and direct drug delivery to the brain. The present review discusses surgical therapies for the treatment of Parkinson's disease and the status of experimental strategies currently in preclinical and clinical testing. RECENT FINDINGS: Both stereotactic ablation and deep brain stimulation of the thalamus, globus pallidus interna, and subthalamic nucleus are discussed and compared in the current literature. New therapies such as drug infusions into the brain, gene therapy, and neural transplantation are in clinical trials and have been tested extensively in animals. Safety and efficacy of such therapies are discussed in recent literature. SUMMARY: Although medication remains the first and main line of treatment and the mainstay for Parkinson's disease, advances in techniques and safety of operations have made surgical interventions more popular. Thalamic surgery remains helpful only in a limited subset of patients with predominent tremor that is unresponsive to medication. Bilateral subthalamic nucleus DBS holds the most promising results for patients with tremor, severe motor fluctuations and dyskinesias from L-dopa, with the best improvements seen in daily activities and quality of life. Newer therapies currently in clinical trial include gene therapy to replace lost gamma-aminobutyric acid inputs to the subthalamic nucleus and globus pallidus interna/substantia nigra pars reticulata, and infusion of recombinant glial derived neurotrophic factor to support at-risk nigrostriatal neurons. Further developments in these areas, along with evolution in stem cell science that hopefully will permit replacement of lost neurons, may alter the nature of surgical practice in Parkinson's disease patients in the not too distant future.

Corpus Striatum↗
PubMedDate not supplied

Examining interaction in language therapy.

Discussions around a 'theory of therapy' have prompted attempts to delineate the components of therapy for language impairment in aphasia. Here it is suggested that the therapy components associated with how language therapy is enacted need more precise specification, especially in relation to what is entailed by interaction between therapist and person with aphasia. Presented too is a system used for the analysis of interaction in language impairment therapy for aphasia and its possible applications are discussed. Components of the system are described and a sample analysis presented. The methodological difficulties entailed in making comparisons of therapy enactment are discussed. It is suggested furthermore that unless more is known about precisely defined interactions in therapy, it will be difficult to answer basic questions not only about how language therapy is being carried out, but also, subsequently, whether the ways in which therapy tasks are enacted have a significant impact on the outcome.

Aphasia↗
PubMed2003

[Examination of HCV infection in hemodialysis patients with HCV-RNA assay using a magnetic extraction method (AmpliCap GT HCV MONITOR Test Kit v2.0 and AmpliCap GT HCV Specimen Preparation Kit v2.0)].

Hemodialysis(HD) patients are a high-risk group for hepatitis C virus(HCV) infection. Detection of HCV-RNA is important for safety and environmental protection in HD units. PCR-based methods are unsuitable for analyzing large samples of HD patients, because conventional centrifugal extraction method fails to eliminate heparin, a potent inhibitor of PCR. We have reported the usefulness of a new HCV-RNA extraction method using specific capture probes and magnetic particles in comparison with conventional centrifugal extraction method in hemodialysis patients. In this study, we evaluated the rate of HCV infection and HCV-RNA positivity by using a magnetic extraction method. As a result, the rate of HCV infection in dialysis patients was significantly higher than that of healthy people, and positivity for HCV infection was found to be related to the duration of hemodialysis. It has been assumed that the rate of new HCV infection is decreased as the result of improvement in dialysis equipment, a decrease in the need for blood transfusion due to the availability of erythropoietin for renal anemia, and the introduction of anti-HCV screening for blood donors. Hospital infection was strongly suggested from the evidence that the correlation with the rate of HCV infection and duration of dialysis was not significantly changed. HCV-RNA positivity was observed in two among 435 HCV antibody-negative patients. Since HCV-RNA positivity has been observed in HCV antibody-negative patients in HD units, combination with HCV-RNA by the magnetic extraction method and anti-HCV antibodies should be useful for the treatment of HCV infection. In this study, the effectiveness of IFN therapy was expected in 56.7%(38/67) that were genotype2 and/or had a low viral load. A precise diagnosis using HCV-RNA assay by the magnetic extraction method and precise medication including IFN therapy is desired for improving the long-term prognosis of dialysis patients.

Aged↗
PubMed1984

[Malignant lymphomas--review, classification and staging].

Malignant lymphomas are lympho-proliferative diseases in which the well-defined clinical pattern of Hodgkin's diseases is contrasted by the heterogeneous group of lymphomas of the non-Hodgkin type. A simplified form of the sub-classification of Hodgkin's disease suggested in 1966 by Lukes and Butler, has found world-wide recognition. However, no generally accepted classification scheme has been evolved so far for the histological classification of other lymphomas, and this leads to considerable difficulties when comparing the therapy results from different centres. Precise histological classification and accurate staging before onset of therapy enable well-defined prognoses and therapy planning in line with case requirements. Radiological methods (x-ray chest, sonography, computed tomography, lymphography, scintigraphy etc.) are important in diagnosis required for accurate staging.

Adolescent↗
PubMed1995

Clinical investigations of the arrest and reversal of coronary artery disease.

Trials of lipid-lowering therapy with angiographically monitored endpoints have demonstrated that regression of atherosclerosis can be achieved. Additionally, the unexpected clinical benefit seen in some trials has suggested that stabilization of lesions may be even more important clinically than regression, and more readily achievable. However, much additional research is needed to clarify the effects of therapy on the heterogeneous population of lesions and the precise mechanisms by which such therapy influences event rates. It is nonetheless clear that aggressive lowering of LDL cholesterol is indicated in patients with established coronary disease, who are at high risk for future events. Accordingly, the new guidelines of the USA National Cholesterol Education Program (NCEP) have adopted an LDL cholesterol goal of less than 100 mg/dl (2.6 mmol/l) in patients with confirmed atherosclerotic disease. Ongoing and future strategies for investigating lipid-lowering therapy and the progression of atherosclerosis include new imaging modalities, such as ultrasonography of the carotid arteries and PET scanning, and use of more potent lipid-lowering interventions.

Cholesterol, LDL↗