Immediate Effects of Two Different Methods of Trunk Elastic Taping on Pelvic Inclination, Trunk Impairment, Balance, and Gait in Stroke Patients.

Background and Objectives: Stroke patients often experience changes in their pelvic tilt, trunk impairments and decreased gait and balance. While various therapeutic interventions have been attempted to improve these symptoms, there is a need for interventions that are easy to apply and reduce the physical labor of physical and occupational therapists. We aimed to investigate the immediate effects of two different methods of trunk elastic taping on the pelvic inclination, trunk impairment, balance, and gait in chronic stroke patients. Materials and Methods: We performed a single-blind randomized controlled trial involving 45 patients with chronic stroke. Participants were randomly assigned to one of three groups: forward rotation with posterior pelvic tilt taping (FRPPT, n = 14), backward rotation with posterior pelvic tilt taping (BRPPT, n = 14), or placebo taping (PT = 14). This study was conducted from December 2023 to January 2024. All the measurements were performed twice: before the intervention and immediately after the intervention. The pelvic inclination was assessed using the anterior pelvic tilt angle. The trunk impairment scale (TIS) was used to measure the trunk impairment. The balance and gait were evaluated using a force plate and walkway system. Results: The pelvic inclination was significantly different in the FRPPT and BRPPT groups compared to the PT group (p < 0.05, p < 0.001). The TIS and gait were significantly increased in the FRPPT group compared to the PT group (p < 0.05). The balance significantly improved in the FRPPT and BRPPT within groups (p < 0.05). Conclusions: Two different methods of posterior pelvic tilt taping improved the anterior pelvic tilt in chronic hemiplegic stroke patients compared with PT, and the FRPPT method also improved the trunk impairment and gait. Therefore, posterior pelvic tilt taping can be used as an intervention with immediate effect.

Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression.

Tobacco smoking (TS) is implicated in lung cancer (LC) progression through the development of metabolic syndrome. However, direct evidence linking metabolic syndrome to TS-mediated LC progression remains to be established. Our findings demonstrate that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (NNK and BaP; NB), components of tobacco smoke, induce metabolic syndrome characteristics, particularly hyperglycemia, promoting lung cancer progression in male C57BL/6 J mice. NB enhances glucose uptake in tumor-associated macrophages by increasing the expression and surface localization of glucose transporter (GLUT) 1 and 3, thereby leading to transcriptional upregulation of insulin-like growth factor 2 (IGF2), which subsequently activates insulin receptor (IR) in LC cells in a paracrine manner, promoting its nuclear import. Nuclear IR binds to nucleophosmin (NPM1), resulting in IR/NPM1-mediated activation of the CD274 promoter and expression of programmed death ligand-1 (PD-L1). Restricting glycolysis, depleting macrophages, or blocking PD-L1 inhibits NB-mediated LC progression. Analysis of patient tissues and public databases reveals elevated levels of IGF2 and GLUT1 in tumor-associated macrophages, as well as tumoral PD-L1 and phosphorylated insulin-like growth factor 1 receptor/insulin receptor (pIGF-1R/IR) expression, suggesting potential poor prognostic biomarkers for LC patients. Our data indicate that paracrine IGF2/IR/NPM1/PD-L1 signaling, facilitated by NB-induced dysregulation of glucose levels and metabolic reprogramming of macrophages, contributes to TS-mediated LC progression.

Effects of Transcutaneous Electrical Nerve Stimulation with Taping on Wrist Spasticity, Strength, and Upper Extremity Function in Patients with Stroke: A Randomized Control Trial.

Objective: Six months after the onset of stroke, over 60% of patients experience upper limb dysfunction, with spasticity being a major contributor alongside muscle weakness. This study investigated the effect of transcutaneous electrical nerve stimulation (TENS) with taping on wrist spasticity, strength, and upper extremity function in patients with stroke. Methods: In total, 40 patients with stroke were included and randomly divided into two groups: the TENS + taping (n = 20, age 52.4 ± 9.3 (range: 39 to 70)) and TENS (n = 20, age 53.5 ± 10.8 (range: 39 to 74)) groups. All subjects performed 30 sessions of task-related training, which included 10 min of postural control training and 20 min of task performance. Additionally, all subjects received TENS on the spastic muscle belly for 30 min before task-related training. In the TENS + taping group, taping was additionally applied to the forearm and wrist but not in the TENS group. The Modified Ashworth Scale was used to measure spasticity, and a handheld dynamometer was used to measure muscle strength. The Fugl-Meyer Assessment of Upper Extremity was used to evaluate the functional ability of the upper extremity. Results: In the TENS + taping group, spasticity and upper extremity function were significantly improved as compared to those in the TENS group (p < 0.05). However, no significant difference in muscle strength was observed between the two groups (p > 0.05). Conclusions: This study demonstrated that the combination of TENS and taping for spasticity and function of the upper extremity was more effective in relieving the spasticity than TENS alone. Therefore, we suggest this combination as an additional treatment for spasticity and function of the upper extremity.

Direct and Indirect Chimeric Antigen Receptor T-Cell Imaging with PET/MRI in a Tumor Xenograft Model.

Background Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored. Purpose To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors. Materials and Methods CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells. After direct labeling with zirconium 89 (89Zr)-p-isothiocyanatobenzyl-desferrioxamine (DFO), CAR T cells were intravenously injected into immunodeficient mice with a CD19-positive and CD19-negative human tumor xenograft on the left and right flank, respectively. PET/MRI was used for direct in vivo imaging of 89Zr-DFO-labeled CAR T cells on days 0, 1, 3, and 7 and for indirect cell imaging with the radiolabeled somatostatin receptor-targeted ligand gallium 68 (68Ga)-DOTA-Tyr3-octreotide (DOTATOC) on days 6, 9, and 13. On day 13, mice were euthanized, and tissues and tumors were excised. Results The 89Zr-DFO-labeled CAR T cells were observed on PET/MRI scans in the liver and lungs of mice (n = 4) at all time points assessed. However, they were not visualized in CD19-positive or CD19-negative tumors, even on day 7. Serial 68Ga-DOTATOC PET/MRI showed CAR T cell accumulation in CD19-positive tumors but not in CD19-negative tumors from days 6 to 13. Notably, 68Ga-DOTATOC accumulation in CD19-positive tumors was highest on day 9 (mean percentage injected dose [%ID], 3.7% ± 1.0 [SD]) and decreased on day 13 (mean %ID, 2.6% ± 0.7) in parallel with a decrease in tumor volume (day 9: mean, 195 mm3 ± 27; day 13: mean, 127 mm3 ± 43) in the group with tumor growth inhibition. Enhanced immunohistochemistry staining of cluster of differentiation 3 (CD3) and hSSTr2 was also observed in excised CD19-positive tumor tissues. Conclusion Direct and indirect cell imaging with PET/MRI enabled in vivo tracking and monitoring of CAR T cells in an animal model. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Bulte in this issue.

18F-ASEM PET/MRI targeting alpha7-nicotinic acetylcholine receptor can reveal skeletal muscle denervation.

BACKGROUND: The increased expression of the nicotinic acetylcholine receptor (nAChR) in muscle denervation is thought to be associated with electrophysiological acetylcholine supersensitivity after nerve injury. Hence, we investigated the utility of the 18F-ASEM alpha7-nAChR targeting radiotracer as a new diagnostic method by visualizing skeletal muscle denervation in mouse models of sciatic nerve injury. METHODS: Ten-week-old C57BL/6 male mice were utilized. The mice were anesthetized, and the left sciatic nerve was resected after splitting the gluteal muscle. One week (n = 11) and three weeks (n = 6) after the denervation, 18F-ASEM positron emission tomography/magnetic resonance imaging (PET/MRI) was acquired. Maximum standardized uptake values (SUVmax) of the tibialis anterior muscle were measured for the denervated side and the control side. Autoradiographic evaluation was performed to measure the mean counts of the denervated and control tibialis anterior muscles at one week. In addition, immunohistochemistry was used to identify alpha7-nAChR-positive areas in denervated and control tibialis anterior muscles at one week (n = 6). Furthermore, a blocking study was conducted with methyllycaconitine (MLA, n = 5). RESULTS: 18F-ASEM PET/MRI showed significantly increased 18F-ASEM uptake in the denervated tibialis anterior muscle relative to the control side one week and three weeks post-denervation. SUVmax of the denervated muscles at one week and three weeks showed significantly higher uptake than the control (P = 0.0033 and 0.0277, respectively). The relative uptake by autoradiography for the denervated muscle was significantly higher than in the control, and immunohistochemistry revealed significantly greater alpha7-nAChR expression in the denervated muscle (P = 0.0277). In addition, the blocking study showed no significant 18F-ASEM uptake in the denervated side when compared to the control (P = 0.0796). CONCLUSIONS: Our results suggest that nAChR imaging with 18F-ASEM has potential as a noninvasive diagnostic method for peripheral nervous system disorders.

Preclinical Study on Biodistribution of Mesenchymal Stem Cells after Local Transplantation into the Brain.

Therapeutic efficacy of mesenchymal stem cells (MSCs) is determined by biodistribution and engraftment in vivo. Compared to intravenous infusion, biodistribution of locally transplanted MSCs are partially understood. Here, we performed a pharmacokinetics (PK) study of MSCs after local transplantation. We grafted human MSCs into the brains of immune-compromised nude mice. Then we extracted genomic DNA from brains, lungs, and livers after transplantation over a month. Using quantitative polymerase chain reaction with human Alu-specific primers, we analyzed biodistribution of the transplanted cells. To evaluate the role of residual immune response in the brain, MSCs expressing a cytosine deaminase (MSCs/CD) were used to ablate resident immune cells at the injection site. The majority of the Alu signals mostly remained at the injection site and decreased over a week, finally becoming undetectable after one month. Negligible signals were transiently detected in the lung and liver during the first week. Suppression of Iba1-positive microglia in the vicinity of the injection site using MSCs/CD prolonged the presence of the Alu signals. After local transplantation in xenograft animal models, human MSCs remain predominantly near the injection site for limited time without disseminating to other organs. Transplantation of human MSCs can locally elicit an immune response in immune compromised animals, and suppressing resident immune cells can prolong the presence of transplanted cells. Our study provides valuable insights into the in vivo fate of locally transplanted stem cells and a local delivery is effective to achieve desired dosages for neurological diseases.

Aquaporin-4 Deficiency is Associated with Cognitive Impairment and Alterations in astrocyte-neuron Lactate Shuttle.

Cognitive impairment refers to notable declines in cognitive abilities including memory, language, and emotional stability leading to the inability to accomplish essential activities of daily living. Astrocytes play an important role in cognitive function, and homeostasis of the astrocyte-neuron lactate shuttle (ANLS) system is essential for maintaining cognitive functions. Aquaporin-4 (AQP-4) is a water channel expressed in astrocytes and has been shown to be associated with various brain disorders, but the direct relationship between learning, memory, and AQP-4 is unclear. We examined the relationship between AQP-4 and cognitive functions related to learning and memory. Mice with genetic deletion of AQP-4 showed significant behavioral and emotional changes including hyperactivity and instability, and impaired cognitive functions such as spatial learning and memory retention. 18 F-FDG PET imaging showed significant metabolic changes in the brains of AQP-4 knockout mice such as reductions in glucose absorption. Such metabolic changes in the brain seemed to be the direct results of changes in the expression of metabolite transporters, as the mRNA levels of multiple glucose and lactate transporters in astrocytes and neurons were significantly decreased in the cortex and hippocampus of AQP-4 knockout mice. Indeed, AQP-4 knockout mice showed significantly higher accumulation of both glucose and lactate in their brains compared with wild-type mice. Our results show that the deficiency of AQP-4 can cause problems in the metabolic function of astrocytes and lead to cognitive impairment, and that the deficiency of AQP4 in astrocyte endfeet can cause abnormalities in the ANLS system.

THOC2 expression and its impact on 5-fluorouracil resistance in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor prognosis and limited treatment options. While 5-fluorouracil (5-FU) has not been widely employed in GBM therapy, emerging research indicates its potential for effectiveness when combined with advanced drug delivery systems to improve its transport to brain tumors. This study aims to investigate the role of THOC2 expression in 5-FU resistance in GBM cell lines. We evaluated diverse GBM cell lines and primary glioma cells for 5-FU sensitivity, cell doubling times, and gene expression. We observed a significant correlation between THOC2 expression and 5-FU resistance. To further investigate this correlation, we selected five GBM cell lines and developed 5-FU resistant GBM cells, including T98FR cells, through long-term 5-FU treatment. In 5-FU challenged cells, THOC2 expression was upregulated, with the highest increase in T98FR cells. THOC2 knockdown in T98FR cells reduced 5-FU IC50 values, confirming its role in 5-FU resistance. In a mouse xenograft model, THOC2 knockdown attenuated tumor growth and extended survival duration after 5-FU treatment. RNA sequencing identified differentially expressed genes and alternative splicing variants in T98FR/shTHOC2 cells. THOC2 knockdown altered Bcl-x splicing, increasing pro-apoptotic Bcl-xS expression, and impaired cell adhesion and migration by reducing L1CAM expression. These results suggest that THOC2 plays a crucial role in 5-FU resistance in GBM and that targeting THOC2 expression could be a potential therapeutic strategy for improving the efficacy of 5-FU-based combination therapies in GBM patients.

Enhanced antitumor efficacy of mesenchymal stem cells expressing cytosine deaminase and 5-fluorocytosine combined with α-galactosylceramide in a colon cancer model.

Cancer immunotherapy has emerged as a promising approach for treating various malignancies. In this study, we investigated the combined therapeutic effects of mesenchymal stem cells expressing cytosine deaminase (MSC/CD) and 5-fluorocytosine (5-FC) with α-galactosylceramide (α-GalCer) in a colon cancer model. Our findings demonstrated that the combination of MSC/CD, 5-FC, and α-GalCer resulted in enhanced antitumor activity compared to the individual treatments. This was evidenced by increased infiltration of immune cells, such as natural killer T (NKT) cells, antigen-presenting cells (APCs), T cells, and natural killer (NK) cells, in the tumor microenvironment, as well as elevated expression of proinflammatory cytokines and chemokines. Furthermore, we observed no significant hepatotoxicity following the combined treatment. Our study highlights the potential therapeutic benefits of combining MSC/CD, 5-FC, and α-GalCer for colon cancer treatment and contributes valuable insights to the field of cancer immunotherapy. Future research should focus on elucidating the underlying mechanisms and exploring the applicability of these findings to other cancer types and immunotherapy strategies.

Assessment of Risks and Benefits of Using Antibiotics Resistance Genes in Mesenchymal Stem Cell-Based Ex-Vivo Therapy.

Recently, ex-vivo gene therapy has emerged as a promising approach to enhance the therapeutic potential of mesenchymal stem cells (MSCs) by introducing functional genes in vitro. Here, we explored the need of using selection markers to increase the gene delivery efficiency and evaluated the potential risks associated with their use in the manufacturing process. We used MSCs/CD that carry the cytosine deaminase gene (CD) as a therapeutic gene and a puromycin resistance gene (PuroR) as a selection marker. We evaluated the correlation between the therapeutic efficacy and the purity of therapeutic MSCs/CD by examining their anti-cancer effect on co-cultured U87/GFP cells. To simulate in vivo horizontal transfer of the PuroR gene in vivo, we generated a puromycin-resistant E. coli (E. coli/PuroR) by introducing the PuroR gene and assessed its responsiveness to various antibiotics. We found that the anti-cancer effect of MSCs/CD was directly proportional to their purity, suggesting the crucial role of the PuroR gene in eliminating impure unmodified MSCs and enhancing the purity of MSCs/CD during the manufacturing process. Additionally, we found that clinically available antibiotics were effective in inhibiting the growth of hypothetical microorganism, E. coli/PuroR. In summary, our study highlights the potential benefits of using the PuroR gene as a selection marker to enhance the purity and efficacy of therapeutic cells in MSC-based gene therapy. Furthermore, our study suggests that the potential risk of horizontal transfer of antibiotics resistance genes in vivo can be effectively managed by clinically available antibiotics.

Effects of Plantar Flexor Stretching on Static and Dynamic Balance in Healthy Adults.

Stretching can affect balance ability by generating biomechanical and physiological changes in the postural muscles. Stretching of the lower extremity muscles can greatly affect posture maintenance strategies and balance ability. However, the relationship between stretching and balance ability has not been clarified. Therefore, this study aimed to investigate the effect of plantar flexor stretching on balance ability. Forty-four healthy young adults were randomly assigned to four groups (static stretching, dynamic stretching, ballistic stretching, and control). Ankle joint range of motion, static balance ability, and dynamic balance ability were evaluated before, immediately after, and 20 min after stretching. Stretching did not affect balance ability in the open-eye condition. After stretching, the sway area was significantly reduced in the closed-eye condition (p < 0.05). After stretching, the reach distance of dynamic balance ability increased significantly (p < 0.05). The results show that plantar flexor stretching can positively affect balance ability. Therefore, plantar flexor stretching should be considered a rehabilitation method to improve balance.

Molecular characteristics of incidental lower-grade glioma for treatment decision-making.

OBJECTIVE: Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the "wait-and-see" strategy or immediate treatment. Therefore, in this study the authors explored iLGG's clinical and molecular landscape to improve its management. METHODS: The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed. RESULTS: There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation-related, cell migration-related, epithelial-to-mesenchymal transition-related, and negative regulation of cell death-related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide. CONCLUSIONS: The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.

The Immediate Effects of Muscle Energy Technique in Chronic Low Back Pain Patients with Functional Leg Length Discrepancy: A Randomized and Placebo-Controlled Trial.

This study was conducted to determine the effect of muscle energy technique (MET) on pelvic alignment, leg length, pain, and fatigue in chronic low back pain (CLBP) patients with leg length discrepancy (LLD). Forty-two CLBP patients with LLD volunteered to participate and were randomly assigned to the MET group (n = 21) and placebo group (n = 21). The intervention group performed three METs with 5 s of isometric contraction and 30 s of rest once, and the placebo group performed three times the placebo-MET, maintaining the same posture as the MET group without muscle isometric contraction. X-ray equipment, tape measure, and visual analog scale were used to evaluate pelvic alignment, leg length, pain, and fatigue before and after each intervention. In comparison pre- and postintervention, only the MET group showed significant changes in pelvic alignment, leg length, pain, and fatigue (p < 0.05). In comparison between groups, there were significant differences in all variables (pelvic alignment, leg length, pain, fatigue) (p < 0.05). The results of this study confirmed the therapeutic effect of MET for improving pelvic alignment, functional LLD, pain, and fatigue in CLBP patients with functional LLD. Future research is needed to evaluate the long-term effect on more chronic low back pain patients.

Corrigendum to "Effectiveness of Transcutaneous Electrical Nerve Stimulation with Taping for Stroke Rehabilitation".

[This corrects the article DOI: 10.1155/2021/9912094.].

Effects of Forest Healing Anti-Aging Program on Psychological, Physiological, and Physical Health of Older People with Mild Cognitive Impairment.

This study aimed to determine the effect of a forest healing anti-aging program on psychological, physiological, and physical health in older people with mild cognitive impairment (MCI). Twenty-two older people with MCI living in the city participated in a forest healing anti-aging program. Psychological indicators included the mini-mental state examination (MMSE), Beck depression inventory (BDI), profile of mood states (POMS), World Health Organization Quality of Life instrument (WHOQOL), and the Pittsburgh sleep quality index (PSQI). Physiological indicators included vital signs, body composition, and blood analysis. Physical indicators included the senior fitness test (SFT), muscle strength, spatiotemporal parameter of gait, static balance, and dynamic balance. Psychological, physiological, and physical indicators were evaluated at first and second pre-measurement, post-measurement, and one-month follow-up. MMSE, BDI, POMS, WHOQOL, body composition, blood analysis, SFT, muscle strength, spatiotemporal parameter of gait, and dynamic balance were significantly different between pre- and post-measurement. Beck depression inventory, POMS, WHOQOL, PSQI, SFT, muscle strength (elbow flexor muscle, knee extensor muscle), spatiotemporal parameter of gait significantly improved continually until the one-month follow-up. In conclusion, the forest healing program had a positive effect on the psychological, physiological, and physical health of older people with MCI.

Improving the Safety of Mesenchymal Stem Cell-Based Ex Vivo Therapy Using Herpes Simplex Virus Thymidine Kinase.

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC50) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma.

PURPOSE: This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate. EXPERIMENTAL DESIGN: We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG-non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo. RESULTS: High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models. CONCLUSIONS: Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC.

PET Imaging of System xC - in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease.

We aimed to explore whether the imaging of antiporter system xC - of immune cells with (4S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG) PET can assess inflammatory bowel disease (IBD) activity in murine models and patients (NCT03546868). Methods: 18F-FSPG PET imaging was performed to assess IBD activity in mice with dextran sulfate sodium-induced and adoptive T-cell transfer-induced IBD and a cohort of 20 patients at a tertiary care center in South Korea. Immunohistochemical analysis of system xC - and cell surface markers was also studied. Results: Mice with experimental IBD showed increased intestinal 18F-FSPG uptake and xCT expression in cells positive (+) for CD11c, F4/80, and CD3 in the lamina propria, increases positively associated with clinical and pathologic disease activity. 18F-FSPG PET studies in patients, most of whom were clinically in remission or had mildly active IBD, showed that PET imaging was sufficiently accurate in diagnosing endoscopically active IBD and remission in patients and bowel segments. 18F-FSPG PET correctly identified all 9 patients with superficial or deep ulcers. Quantitative intestinal 18F-FSPG uptake was strongly associated with endoscopic indices of IBD activity. The number of CD68+xCT+ and CD3+xCT+ cells in 22 bowel segments from patients with ulcerative colitis and the number of CD68+xCT+ cells in 7 bowel segments from patients with Crohn disease showed a significant positive association with endoscopic indices of IBD activity. Conclusion: The assessment of system xC - in immune cells may provide diagnostic information on the immune responses responsible for chronic active inflammation in IBD. 18F-FSPG PET imaging of system xC - activity may noninvasively assess the IBD activity.

Effects of Pelvic Stabilization Training with Lateral and Posterior Tilt Taping on Pelvic Inclination, Muscle Strength, and Gait Function in Patients with Stroke: A Randomized Controlled Study.

Background: This study was aimed at investigating the effect of pelvic tilt taping on muscle strength, pelvic inclination, and gait function in patients with stroke. Methods: A total of 60 patients with stroke were included in our study and randomly divided into three groups: the posterior pelvic tilt taping (PPTT, n = 20), the lateral pelvic tilt taping (LPPP) with PPTT (LPPP+PPTT, n = 20), and the control (n = 20) groups. All participants performed pelvic stabilization exercises consisting of 6 movements: supine, side lying, quadruped, sitting, squatting, and standing (30 min/day, five days/week, for six weeks). PPTT to correct anterior pelvic tilt was applied to the LPTT+PPTT and PPTT groups, and lateral pelvic tilt taping was additionally applied to the LPTT+PPTT group. LPTT was performed to correct the pelvis tilted to the affected side, and PPTT was performed to correct the anterior pelvic tilt. The control group did not undergo taping. A hand-held dynamometer was used to measure the hip abductor muscle strength. In addition, a palpation meter and 10-meter walk test were used to assess pelvic inclination and gait function. Results: Muscle strength was significantly stronger in the LPTT+PPTT group than in the other two groups (p = 0.01). The anterior pelvic tilt was significantly improved in the taping group compared to the control group (p < 0.001), and the lateral pelvic tilt was significantly improved in the LPTT+PPTT group compared to the other two groups (p < 0.001). Significantly greater improvements in gait speed were observed in the LPTT+PPTT group than in the other two groups (p = 0.02). Conclusions: PPPT can significantly affect pelvic alignment and walking speed in patients with stroke, and the additional application of LPTT can further strengthen these effects. Therefore, we suggest using taping as an auxiliary therapeutic-intervention method in postural control training.