A comprehensive analysis of minimally differentially methylated regions common to pediatric and adult solid tumors.

Cancer is the second most common cause of death in children aged 1-14 years in the United States, with 11,000 new cases and 1200 deaths annually. Pediatric cancers typically have lower mutational burden compared to adult-onset cancers, however, the epigenomes in pediatric cancer are highly altered, with widespread DNA methylation changes. The rarity of pediatric cancers poses a significant challenge to developing cancer-type specific biomarkers for diagnosis, prognosis, or treatment monitoring. In the current study, we explored the potential of a DNA methylation profile common across various pediatric cancers. To do this, we conducted whole genome bisulfite sequencing (WGBS) on 31 recurrent pediatric tumor tissues, 13 normal tissues, and 20 plasma cell-free (cf)DNA samples, representing 11 different pediatric cancer types. We defined minimal focal regions that were differentially methylated across samples in the multiple cancer types which we termed minimally differentially methylated regions (mDMRs). These methylation changes were also observed in 506 pediatric and 5691 adult cancer samples accessed from publicly available databases, and in 44 pediatric cancer samples we analyzed using a targeted hybridization probe capture assay. Finally, we found that these methylation changes were detectable in cfDNA and could serve as potential cfDNA methylation biomarkers for early detection or minimal residual disease.

Characterization of Induced Current Density During Transcorneal Electrical Stimulation to Promote Neuroprotection in the Degenerating Retina.

OBJECTIVE: Transcorneal electrical stimulation (TES) is a promising approach to delay retinal degeneration by inducing extracellular electric field-driven neuroprotective effects within photoreceptors. Although achieving precise electric field control is feasible in vitro, characterizing these fields becomes intricate and largely unexplored in vivo due to uneven distribution in the heterogeneous body. In this paper, we investigate and characterize electric fields within the retina during TES to assess the potential for therapeutic approaches Methods: We developed a computational model of a rat's head, enabling us to generate predictive simulations of the voltage and current density induced in the retina. Subsequently, an in vivo experimental setup involving Royal College of Surgeon (RCS) rats was implemented to measure the voltage across the retina using identical electrode configurations as employed in the simulations. RESULTS: A stimulation amplitude of 0.2-0.3 mA may be necessary during TES in rats to induce a current density of at least 20 A/m2 in the retina, which is the lower limit for triggering neuroprotective effects according to culture studies on neural cells. Measurement taken from cadaveric pigs' eyes revealed that a stimulation amplitude of 1 mA is necessary for achieving the same current density. CONCLUSION: The computational modeling approach presented in this study was validated with experimental data and can be leveraged for predictive simulations to optimize the electrode design and stimulation parameters of TES. SIGNIFICANCE: Once validated, the flexibility and low research cost of computational models are valuable in optimization studies where testing on live subjects is not feasible.

Effect of negative pressure therapy on the treatment response to scar thickness and viscoelasticity.

Patients with scars face a grave threat to their mental and physical health. Negative pressure has been used for scar therapy in medical care and provides a microenvironment conducive to scar healing while stimulating cell regeneration. Negative pressure may disrupt scar tissue regeneration when the pressure is too high or too low, so finding a suitable negative pressure is important. We hypothesized that different negative pressure magnitudes would affect scar tissue properties differently. This research aimed to provide practical recommendations for scar therapy. This study used three negative pressures (-105 mmHg, -125 mmHg, and -145 mmHg) to compare scar material properties. We measured scar tissue thickness and viscoelasticity with a motor-driven ultrasound indentation system. According to the results of this study, scar thickness is most effectively reduced at a negative pressure of -105 mmHg. In comparison, scar viscoelasticity continuously increases at a negative pressure of -125 mmHg. Negative pressure therapy can be recommended to scar care clinics based on the results of this study.

Plantar pressure gradient and pressure gradient angle are affected by inner pressure of air insole.

Clinically, air insoles may be applied to shoes to decrease plantar pressure gradient (PPG) and increase plantar gradient angle (PGA) to reduce foot ulcers. PPG and PGA may cause skin breakdown. The effects of different inner pressures of inflatable air insoles on dynamic PPG and PGA distributions are largely unknown in non-diabetics and people with diabetes. This study aimed to explore the impact of varying inner air insole pressures on PPG and PGA to establish early mitigation strategies for people at risk of foot ulcers. A repeated measures study design, including three air insoles (80 mmHg, 160 mmHg, and 240 mmHg) and two walking durations (10 and 20 min) for a total of six walking protocols, was tested on 13 healthy participants (height, 165.8 ± 8.4 cm; age, 27.0 ± 7.3 years; and weight, 56.0 ± 7.9 kg, BMI: 20.3 ± 1.7 kg/m^2) over three consecutive weeks. PPG, a measurement of the spatial variation in plantar pressure around the peak plantar pressure (PPP) and PGA, a variation in the gradient direction values at the three plantar regions, big toe (T1), first metatarsal head (M1), and second metatarsal head (M2), were calculated. This study indicated that PPG was lower at 80 mmHg air insoles after 20 min of walking in the M1 region (p = 0.010). The PGA in the M2 increased at an air insole of 80 mmHg compared to 240 mmHg (p = 0.015). Compared to 20 min, the 10 min walking duration at 240 mmHg of air insole had the lowest PPG in the M1 (p = 0.015) and M2 (p = 0.034) regions. The 80 mmHg air insole significantly lowered the PPG compared to a 160 mmHg and 240 mmHg air insole. Moreover, the 80 mmHg air insole significantly decreased PPP and increased PGA compared to the 160 mmHg and 240 mmHg air insole. A shorter walking period (10 min) significantly lowered PPG. The findings of this study suggest that people with a higher risk of foot ulcers should wear softer air insoles to have a lower PPG, as well as an increased PGA.

Using cross-correlation analysis of multi-channel near infrared spectroscopy to assess the hemodynamic response to cupping therapy.

Cupping therapy is a common intervention for the management of musculoskeletal impairment. Previous studies have demonstrated that cupping therapy can improve muscle hemodynamic responses using single-channel near-infrared spectroscopy (NIRS). However, the effects of cupping therapy on spatial hemodynamic responses as well as the correlation between oxyhemoglobin and deoxy-hemoglobin are largely unknown. The cross-correlation function (CCF) algorithm was used to determine the correlation between time-series NIRS signals from inside and outside the cup as well as time-series oxyhemoglobin and deoxy-hemoglobin under 4 cupping intensities, including -225 and -300 mmHg for 5 and 10 min. The main finding was that the maximum CCF values of oxyhemoglobin was significantly higher than those in deoxy-hemoglobin (p < 0.05). Furthermore, it was found that there was a correlation between deoxy-hemoglobin with a longer duration and a larger magnitude of negative pressure. This is the first study investigating time-series hemodynamic responses after cupping therapy using cross-correlation function analysis of multi-channel NIRS signals.

The effects of different inner pressures of air insoles and walking durations on peak plantar pressure.

BACKGROUND: Exercise reduces chronic complications in individuals with diabetes and peripheral vascular diseases. In clinical practice, the use of air insole may reduce peak plantar pressure (PPP), and risk for diabetic foot ulcers (DFUs). However, there is no guideline on selecting air insole pressure for effectively reducing PPP. Therefore, this study aimed to investigate the effects of different air insole pressure on PPP at different walking durations. METHODS: We tested 13 participants using repeated measures study design, including 3 air insole pressures (80, 160, and 240 mm Hg) and 2 walking durations (10 and 20 minutes) for 6 walking conditions. PPP values at the first toe, first metatarsal head, and second metatarsal head were calculated. RESULTS: The one-way ANOVA showed significant pairwise differences of PPP at 20 minutes duration in the first metatarsal head between 80 and 240 mm Hg (P = .007) and between 160 and 240 mm Hg (P = .038); in the second metatarsal head between 80 and 240 mm Hg (P = .043). The paired t test confirmed that walking duration significantly has lower PPP at 10 minutes than 20 minutes with 240 mm Hg air insole in the first metatarsal head (P = .012) and the second metatarsal head (P = .027). CONCLUSION: People at risk of foot ulcers are suggested to wear shoes with 80 mm Hg of air insole for reducing PPP in the first metatarsal head and the second metatarsal head. Moreover, people may avoid wearing the stiffer insole (240 mm Hg) for more than 20 minutes.

OvaPrint-A Cell-free DNA Methylation Liquid Biopsy for the Risk Assessment of High-grade Serous Ovarian Cancer.

PURPOSE: High-grade serous ovarian carcinoma (HGSOC) is the most lethal epithelial ovarian cancer (EOC) and is often diagnosed at late stage. In women with a known pelvic mass, surgery followed by pathologic assessment is the most reliable way to diagnose EOC and there are still no effective screening tools in asymptomatic women. In the current study, we developed a cell-free DNA (cfDNA) methylation liquid biopsy for the risk assessment of early-stage HGSOC. EXPERIMENTAL DESIGN: We performed reduced representation bisulfite sequencing to identify differentially methylated regions (DMR) between HGSOC and normal ovarian and fallopian tube tissue. Next, we performed hybridization probe capture for 1,677 DMRs and constructed a classifier (OvaPrint) on an independent set of cfDNA samples to discriminate HGSOC from benign masses. We also analyzed a series of non-HGSOC EOC, including low-grade and borderline samples to assess the generalizability of OvaPrint. A total of 372 samples (tissue n = 59, plasma n = 313) were analyzed in this study. RESULTS: OvaPrint achieved a positive predictive value of 95% and a negative predictive value of 88% for discriminating HGSOC from benign masses, surpassing other commercial tests. OvaPrint was less sensitive for non-HGSOC EOC, albeit it may have potential utility for identifying low-grade and borderline tumors with higher malignant potential. CONCLUSIONS: OvaPrint is a highly sensitive and specific test that can be used for the risk assessment of HGSOC in symptomatic women. Prospective studies are warranted to validate OvaPrint for HGSOC and further develop it for non-HGSOC EOC histotypes in both symptomatic and asymptomatic women with adnexal masses.

An extraocular electrical stimulation approach to slow down the progression of retinal degeneration in an animal model.

Retinal diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are characterized by unrelenting neuronal death. However, electrical stimulation has been shown to induce neuroprotective changes in the retina capable of slowing down the progression of retinal blindness. In this work, a multi-scale computational model and modeling platform were used to design electrical stimulation strategies to better target the bipolar cells (BCs), that along with photoreceptors are affected at the early stage of retinal degenerative diseases. Our computational findings revealed that biphasic stimulus pulses of long pulse duration could decrease the activation threshold of BCs, and the differential stimulus threshold between ganglion cells (RGCs) and BCs, offering the potential of targeting the BCs during the early phase of degeneration. In vivo experiments were performed to evaluate the electrode placement and parameters found to target bipolar cells and evaluate the safety and efficacy of the treatment. Results indicate that the proposed transcorneal Electrical Stimulation (TES) strategy can attenuate retinal degeneration in a Royal College of Surgeon (RCS) rodent model, offering the potential to translate this work to clinical practice.

An approach to the diagnosis of lumbar disc herniation using deep learning models.

Background: In magnetic resonance imaging (MRI), lumbar disc herniation (LDH) detection is challenging due to the various shapes, sizes, angles, and regions associated with bulges, protrusions, extrusions, and sequestrations. Lumbar abnormalities in MRI can be detected automatically by using deep learning methods. As deep learning models gain recognition, they may assist in diagnosing LDH with MRI images and provide initial interpretation in clinical settings. YOU ONLY LOOK ONCE (YOLO) model series are often used to train deep learning algorithms for real-time biomedical image detection and prediction. This study aims to confirm which YOLO models (YOLOv5, YOLOv6, and YOLOv7) perform well in detecting LDH in different regions of the lumbar intervertebral disc. Materials and methods: The methodology involves several steps, including converting DICOM images to JPEG, reviewing and selecting MRI slices for labeling and augmentation using ROBOFLOW, and constructing YOLOv5x, YOLOv6, and YOLOv7 models based on the dataset. The training dataset was combined with the radiologist's labeling and annotation, and then the deep learning models were trained using the training/validation dataset. Results: Our result showed that the 550-dataset with augmentation (AUG) or without augmentation (non-AUG) in YOLOv5x generates satisfactory training performance in LDH detection. The AUG dataset overall performance provides slightly higher accuracy than the non-AUG. YOLOv5x showed the highest performance with 89.30% mAP compared to YOLOv6, and YOLOv7. Also, YOLOv5x in non-AUG dataset showed the balance LDH region detections in L2-L3, L3-L4, L4-L5, and L5-S1 with above 90%. And this illustrates the competitiveness of using non-AUG dataset to detect LDH. Conclusion: Using YOLOv5x and the 550 augmented dataset, LDH can be detected with promising both in non-AUG and AUG dataset. By utilizing the most appropriate YOLO model, clinicians have a greater chance of diagnosing LDH early and preventing adverse effects for their patients.

ATM-Inhibitor AZD1390 Is a Radiosensitizer for Breast Cancer CNS Metastasis.

PURPOSE: Limited effective treatments are currently available for central nervous system (CNS) metastasis (CM). This is largely driven by the inability of current therapeutics to penetrate the blood brain barrier (BBB) and the lack of preclinical models for testing new therapies. Here we study the efficacy of AZD1390, a BBB penetrating ataxia-telangiectasia mutated inhibitor, as a radiosensitizer for breast cancer CM treatment. EXPERIMENTAL DESIGN: Three patient-derived xenograft (PDX) tumors including 2 HER2+ and 1 triple-negative breast cancer harboring DNA damage response (DDR) gene mutations, were implanted subcutaneously in the flank of mice to assess tumor growth inhibition by AZD1390 combined with radiation. Animal survival was further assessed by implanting the best responding PDX model orthotopically in the brain. RESULTS: Pretreatment with AZD1390 followed by radiation therapy inhibited growth of PDX tumors implanted in the flank, and improved survival in orthotopic models with average survival of 222 days compared with 123 days in controls. Administration of AZD1390 posttreatment for 21 days had no further benefits. While the combination therapy resulted in sustained tumor inhibition, sporadic regrowth was observed in some mice 50 to 100 days posttreatment in all models. Gene expression comparing these tumors with complete responders demonstrated changes in upregulation of oncogenic proteins, which are potential drivers of tumor growth after treatment. CONCLUSIONS: Our results demonstrate that AZD1390 effectively sensitizes breast cancer CM to radiation therapy in DDR mutant tumors. This study demonstrates the potential of using AZD1390 as a novel therapeutic agent for patients with breast cancer CM.

Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity.

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

A quantitative characterization of the spatial distribution of brain metastases from breast cancer and respective molecular subtypes.

PURPOSE: Brain metastases (BM) remain a significant cause of morbidity and mortality in breast cancer (BC) patients. Specific factors promoting the process of BM and predilection for selected neuro-anatomical regions remain unknown, yet may have major implications for prevention or treatment. Anatomical spatial distributions of BM from BC suggest a predominance of metastases in the hindbrain and cerebellum. Systematic approaches to quantifying BM location or location-based analyses based on molecular subtypes, however, remain largely unavailable. METHODS: We analyzed stereotactic Cartesian coordinates derived from 134 patients undergoing gamma- knife radiosurgery (GKRS) for treatment of 407 breast cancer BMs to quantitatively study BM spatial distribution along principal component axes and by intrinsic molecular subtype (ER, PR, Herceptin). We used kernel density estimators (KDE) to highlight clustering and distribution regions in the brain, and we used the metric of mutual information (MI) to tease out subtle differences in the BM distributions associated with different molecular subtypes of BC. BM location maps according to vascular and anatomical distributions using Cartesian coordinates to aid in systematic classification of tumor locations were additionally developed. RESULTS: We corroborated that BC BMs show a consistent propensity to arise posteriorly and caudally, and that Her2+ tumors are relatively more likely to arise medially rather than laterally. To compare the distributions among varying BC molecular subtypes, the mutual information metric reveal that the ER-PR-Her2+ and ER-PR-Her2- subtypes show the smallest amount of mutual information and are most molecularly distinct. The kernel density contour plots show a propensity for triple negative BC to arise in more superiorly or cranially situated BMs. CONCLUSIONS: We present a novel and shareable workflow for characterizing and comparing spatial distributions of BM which may aid in identifying therapeutic or diagnostic targets and interactions with the tumor microenvironment. Further characterization of these patterns with larger multi-institutional data-sets may have major impacts on treatment or management of cancer patients.

Effects of walking speeds and durations on the plantar pressure gradient and pressure gradient angle.

BACKGROUND: Walking exercise has been demonstrated to improve health in people with diabetes. However, it is largely unknown the influences of various walking intensities such as walking speeds and durations on dynamic plantar pressure distributions in non-diabetics and diabetics. Traditional methods ignoring time-series changes of plantar pressure patterns may not fully capture the effect of walking intensities on plantar tissues. The purpose of this study was to investigate the effect of various walking intensities on the dynamic plantar pressure distributions. In this study, we introduced the peak pressure gradient (PPG) and its dynamic patterns defined as the pressure gradient angle (PGA) to quantify dynamic changes of plantar pressure distributions during walking at various intensities. METHODS: Twelve healthy participants (5 males and 7 females) were recruited in this study. The demographic data were: age, 27.1 ± 5.8 years; height, 1.7 ± 0.1 m; and weight, 63.5 ± 13.5 kg (mean ± standard deviation). An insole plantar pressure measurement system was used to measure plantar pressures during walking at three walking speeds (slow walking 1.8 mph, brisk walking 3.6 mph, and slow running 5.4 mph) for two durations (10 and 20 min). The gradient at a location is defined as the unique vector field in the two-dimensional Cartesian coordinate system with a Euclidean metric. PGA was calculated by quantifying the directional variation of the instantaneous peak gradient vector during stance phase of walking. PPG and PGA were calculated in the plantar regions of the first toe, first metatarsal head, second metatarsal head, and heel at higher risk for foot ulcers. Two-way ANOVA with Fisher's post-hoc analysis was used to examine the speed and duration factors on PPG and PGA. RESULTS: The results showed that the walking speeds significantly affect PPG (P < 0.05) and PGA (P < 0.05), and the walking durations does not. No interaction between the walking duration and speed was observed. PPG in the first toe region after 5.4 mph for either 10 or 20 min was significantly higher than 1.8 mph. Meanwhile, after 3.6 mph for 20 min, PPG in the heel region was significantly higher than 1.8 mph. Results also indicate that PGA in the forefoot region after 3.6 mph for 20 min was significantly narrower than 1.8 mph. CONCLUSIONS: Our findings indicate that people may walk at a slow speed at 1.8 mph for reducing PPG and preventing PGA concentrated over a small area compared to brisk walking at 3.6 mph and slow running at 5.4 mph.

Advanced Cross-Correlation Function Application to Identify Arterial Baroreflex Sensitivity Variations From Healthy to Diabetes Mellitus.

Diabetes mellitus (DM) is a chronic disease characterized by elevated blood glucose levels, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys, and nerves. DM is of two types-types 1 or 2. In type 1, there is a problem with insulin secretion, and in type 2-insulin resistance. About 463 million people worldwide have diabetes, and 80% of the majority live in low- and middle-income countries, and 1.5 million deaths are directly attributed to diabetes each year. Autonomic neuropathy (AN) is one of the common diabetic complications, leading to failure in blood pressure (BP) control and causing cardiovascular disease. Therefore, early detection of AN becomes crucial to optimize treatment. We propose an advanced cross-correlation function (ACCF) between BP and heart rate with suitable threshold parameters to analyze and detect early changes in baroreflex sensitivity (BRS) in DM with AN (DM+). We studied heart rate (HR) and systolic BP responses during tilt in 16 patients with diabetes mellitus only (DM-), 19 diabetes mellitus with autonomic dysfunction (DM+), and 10 healthy subjects. The ACCF analysis revealed that the healthy and DM groups had different filtered percentages of significant maximum cross-correlation function (CCF) value (p < 0.05), and the maximum CCF value after thresholds was significantly reduced during tilt in the DM+ group (p < 0.05). The maximum CCF index, a parameter for the phase between HR and BP, separated the healthy group from the DM groups (p < 0.05). Due to the maximum CCF index in DM groups being located in the positive range and significantly different from healthy ones, it could be speculated that BRS dysfunction in DM and AN could cause a phase change from lead to lag. ACCF could detect and separate DM+ from DM groups. This fact could represent an advantage of the ACCF algorithm. A common cross-correlation analysis was not easy to distinguish between DM- and DM+. This pilot study demonstrates that ACCF analysis with suitable threshold parameters could explore hidden changes in baroreflex control in DM+ and DM-. Furthermore, the superiority of this ACCF algorithm is useful in distinguishing whether AN is present or not in DM.

A Deep Learning Method for Foot Progression Angle Detection in Plantar Pressure Images.

Foot progression angle (FPA) analysis is one of the core methods to detect gait pathologies as basic information to prevent foot injury from excessive in-toeing and out-toeing. Deep learning-based object detection can assist in measuring the FPA through plantar pressure images. This study aims to establish a precision model for determining the FPA. The precision detection of FPA can provide information with in-toeing, out-toeing, and rearfoot kinematics to evaluate the effect of physical therapy programs on knee pain and knee osteoarthritis. We analyzed a total of 1424 plantar images with three different You Only Look Once (YOLO) networks: YOLO v3, v4, and v5x, to obtain a suitable model for FPA detection. YOLOv4 showed higher performance of the profile-box, with average precision in the left foot of 100.00% and the right foot of 99.78%, respectively. Besides, in detecting the foot angle-box, the ground-truth has similar results with YOLOv4 (5.58 ± 0.10° vs. 5.86 ± 0.09°, p = 0.013). In contrast, there was a significant difference in FPA between ground-truth vs. YOLOv3 (5.58 ± 0.10° vs. 6.07 ± 0.06°, p < 0.001), and ground-truth vs. YOLOv5x (5.58 ± 0.10° vs. 6.75 ± 0.06°, p < 0.001). This result implies that deep learning with YOLOv4 can enhance the detection of FPA.

Anatomical and topographical variations in the distribution of brain metastases based on primary cancer origin and molecular subtypes: a systematic review.

BACKGROUND: While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuroimaging and spatial modeling analytics have facilitated further exploration into this field. METHODS: A systematic electronic database search for studies analyzing the distribution of brain metastases (BMs) from any primary systematic cancer published between January 1990 and July 2020 was conducted using PRISMA guidelines. RESULTS: Two authors independently reviewed 1957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8227 BMs from 2599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal cancers tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2-positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes. CONCLUSION: The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.

Stanniocalcin1 knockdown induces ferroptosis and suppresses glycolysis in prostate cancer via the Nrf2 pathway.

Stanniocalcin1 (STC1) is a secreted glycoprotein, which is highly expressed in prostate cancer cells. However, the biological functions of STC1 in modulating ferroptosis and glycolysis in prostate cancer are still not clear. The viability of PC-3 and DU145 cells was detected by CCK-8 assay. The relative Fe2+ level was detected by an Iron Assay Kit. MDA level was detected by Lipid Peroxidation MDA Assay Kit. Glucose uptake and lactate product were measured by Glycolysis Assay Kit and Lactate Assay Kit. In this study, STC1 was highly expressed in prostate cancer tissue specimens and cells. STC1 knockdown suppressed prostate cancer cell proliferation, and upregulated Fe2+ level, reduced glutathione (GSH) level, downregulated GPX4 and SLC7A11 protein expressions in PC-3 cells and DU145 cells. Besides, STC1 knockdown decreased glucose uptake, lactate product, and ATP level, as well as downregulated glycolysis-related protein HK2 and LDHA protein expressions. In addition, STC1 knockdown repressed the Nrf2/HO-1/NQO1 pathway. Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells. Moreover, Nrf2 pathway activator Oltipraz reversed the effect of STC1 knockdown on Fe2+ level and GPX4, SLC7A11, HK2, LDHA protein expressions in PC-3 cells and DU145 cells. Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.

Effectiveness of self-management of dry and wet cupping therapy for low back pain: A systematic review and meta-analysis.

BACKGROUND: Low back pain (LBP) can significantly affect a person's quality of life. Cupping has been used to treat LBP. However, various cupping methods are typically included in evaluating the efficacy of cupping therapy. Therefore, the objectives of this study were to evaluate the evidence from the literature regarding the effects of dry and wet cupping therapy on LBP in adults. Dry and wet cupping therapy are analyzed categorically in this study. METHODS: We searched for randomized clinical trials with cupping in LBP published between 2008 and 2022. In dry or wet cupping clinical studies, pain intensity was assessed using the Visual Analogue Scale and present pain intensity, and the quality of life intensity was measured using the Oswestry disability index. RESULTS: The 656 studies were identified, of which 10 studies for 690 patients with LBP were included in the meta-analysis. There was a significant reduction in the pain intensity score with present pain intensity using wet cupping therapy (P < .01). In addition, both cupping therapy groups displayed significant Oswestry disability index score reduction compared to the control group (both P < .01). The patients with LBP have a substantial reduction by using wet cupping but have not shown a considerable decrease by using dry cupping (P = .19). In addition, only wet cupping therapy groups displayed a significantly improved quality of life compared to the control group. The study had a very high heterogeneity (I2 > 50%). It means there is no standardization in the treatment protocol in randomized clinical trials. In the meta-regression, there was statistically significant evidence that the number of treatment times and intercepts were related (P < .01). CONCLUSION: The present meta-analysis shows that wet cupping therapy effectively reduces the pain intensity of LBP. Furthermore, both dry wet cupping therapy improved patients with LBP quality of life.

Hypertension and Stroke Cardiovascular Control Evaluation by Analyzing Blood Pressure, Cerebral Blood Flow, Blood Vessel Resistance and Baroreflex.

Cardiovascular diseases have been the leading causes of mortality in Taiwan and the world at large for decades. The composition of cardiovascular and cerebrovascular systems is quite complicated. Therefore, it is difficult to detect or trace the related signs of cardiovascular and cerebrovascular diseases. The characteristics and changes in cardiopulmonary system disease can be used to track cardiovascular and cerebrovascular disease prevention and diagnosis. This can effectively reduce the occurrence of cardiovascular and cerebrovascular diseases. This study analyzes the variability in blood pressure, cerebral blood flow velocity and the interaction characteristics using linear and nonlinear approaches in stroke, hypertension and healthy groups to identify the differences in cardiovascular control in these groups. The results showed that the blood pressure and cerebral blood flow of stroke patients and hypertensive patients were significantly higher than those of healthy people (statistical differences (p < 0.05). The cerebrovascular resistance (CVR) shows that the CVR of hypertensive patients is higher than that of healthy people and stroke patients (p < 0.1), indicating that the cerebral vascular resistance of hypertensive patients is slightly higher. From the patient's blood flow and vascular characteristics, it can be observed that the cardiovascular system is different from those in healthy people. Baroreflex sensitivity (BRS) decreased in stroke patients (p < 0.05). Chaotic analysis revealed that the blood pressure disturbance in hypertensive patients has a higher chaotic behavior change and the difference in initial state sensitivity. Cross-correlation (CCF) analysis shows that as the course of healthy→hypertension→stroke progresses, the maximum CCF value decreases significantly (p < 0.05). That means that blood pressure and cerebral blood flow are gradually not well controlled by the self-regulation mechanism. In conclusion, cardiovascular control performance in hypertensive and stroke patients displays greater variation. This can be observed by the bio-signal analysis. This analysis could identify a measure for detecting and preventing the risk for hypertension and stroke in clinical practice. This is a pilot study to analyze cardiovascular control variation in healthy, hypertensive and stroke groups.