Stereotactic central/core ablative radiation therapy: results of a phase I study of a novel strategy to treat bulky tumor.

Purpose: Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART. Methods and materials: We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents. Results: 21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 14-85) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009). Conclusion: SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.

Development and Validation of a 3D Resnet Model for Prediction of Lymph Node Metastasis in Head and Neck Cancer Patients.

The accurate diagnosis and staging of lymph node metastasis (LNM) are crucial for determining the optimal treatment strategy for head and neck cancer patients. We aimed to develop a 3D Resnet model and investigate its prediction value in detecting LNM. This study enrolled 156 head and neck cancer patients and analyzed 342 lymph nodes segmented from surgical pathologic reports. The patients' clinical and pathological data related to the primary tumor site and clinical and pathology T and N stages were collected. To predict LNM, we developed a dual-pathway 3D Resnet model incorporating two Resnet models with different depths to extract features from the input data. To assess the model's performance, we compared its predictions with those of radiologists in a test dataset comprising 38 patients. The study found that the dimensions and volume of LNM + were significantly larger than those of LNM-. Specifically, the Y and Z dimensions showed the highest sensitivity of 84.6% and specificity of 72.2%, respectively, in predicting LNM + . The analysis of various variations of the proposed 3D Resnet model demonstrated that Dual-3D-Resnet models with a depth of 34 achieved the highest AUC values of 0.9294. In the validation test of 38 patients and 86 lymph nodes dataset, the 3D Resnet model outperformed both physical examination and radiologists in terms of sensitivity (80.8% compared to 50.0% and 91.7%, respectively), specificity(90.0% compared to 88.5% and 65.4%, respectively), and positive predictive value (77.8% compared to 66.7% and 55.0%, respectively) in detecting individual LNM + . These results suggest that the 3D Resnet model can be valuable for accurately identifying LNM + in head and neck cancer patients. A prospective trial is needed to evaluate further the role of the 3D Resnet model in determining LNM + in head and neck cancer patients and its impact on treatment strategies and patient outcomes.

Deep Learning Detection and Segmentation of Brain Arteriovenous Malformation on Magnetic Resonance Angiography.

BACKGROUND: The delineation of brain arteriovenous malformations (bAVMs) is crucial for subsequent treatment planning. Manual segmentation is time-consuming and labor-intensive. Applying deep learning to automatically detect and segment bAVM might help to improve clinical practice efficiency. PURPOSE: To develop an approach for detecting bAVM and segmenting its nidus on Time-of-flight magnetic resonance angiography using deep learning methods. STUDY TYPE: Retrospective. SUBJECTS: 221 bAVM patients aged 7-79 underwent radiosurgery from 2003 to 2020. They were split into 177 training, 22 validation, and 22 test data. FIELD STRENGTH/SEQUENCE: 1.5 T, Time-of-flight magnetic resonance angiography based on 3D gradient echo. ASSESSMENT: The YOLOv5 and YOLOv8 algorithms were utilized to detect bAVM lesions and the U-Net and U-Net++ models to segment the nidus from the bounding boxes. The mean average precision, F1, precision, and recall were used to assess the model performance on the bAVM detection. To evaluate the model's performance on nidus segmentation, the Dice coefficient and balanced average Hausdorff distance (rbAHD) were employed. STATISTICAL TESTS: The Student's t-test was used to test the cross-validation results (P < 0.05). The Wilcoxon rank test was applied to compare the median for the reference values and the model inference results (P < 0.05). RESULTS: The detection results demonstrated that the model with pretraining and augmentation performed optimally. The U-Net++ with random dilation mechanism resulted in higher Dice and lower rbAHD, compared to that without that mechanism, across varying dilated bounding box conditions (P < 0.05). When combining detection and segmentation, the Dice and rbAHD were statistically different from the references calculated using the detected bounding boxes (P < 0.05). For the detected lesions in the test dataset, it showed the highest Dice of 0.82 and the lowest rbAHD of 5.3%. DATA CONCLUSION: This study showed that pretraining and data augmentation improved YOLO detection performance. Properly limiting lesion ranges allows for adequate bAVM segmentation. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Mechanistic study of the Aldo-keto reductase family 1 member A1 in regulating mesenchymal stem cell fate decision toward adipogenesis and osteogenesis.

AIMS: Akr1A1 is a glycolytic enzyme catalyzing the reduction of aldehyde to alcohol. This study aims to delineate the role of Akr1A1 in regulating the adipo-osteogenic lineage differentiation of mesenchymal stem cells (MSCs). MAIN METHODS: MSCs derived from human bone marrow and Wharton Jelly together with gain- and loss-of-function analysis as well as supplementation with the S-Nitrosoglutathione reductase (GSNOR) inhibitor N6022 were used to study the function of Akr1A1 in controlling MSC lineage differentiation into osteoblasts and adipocytes. KEY FINDINGS: Akr1A1 expression, PKM2 activity, and lactate production were found to be decreased in osteoblast-committed MSCs, but PGC-1α increased to induce mitochondrial oxidative phosphorylation. Increased Akr1A1 inhibited the SIRT1-dependent pathway for decreasing the expressions of PGC-1α and TAZ but increasing PPAR γ in adipocyte-committed MSCs, hence promoting glycolysis in adipogenesis. In contrast, Akr1A1 expression, PKM2 activity and lactate production were all increased in adipocyte-differentiated cells with decreased PGC-1α for switching energy utilization to glycolytic metabolism. Reduced Akr1A1 expression in osteoblast-committed cells relieves its inhibition of SIRT1-mediated activation of PGC-1α and TAZ for facilitating osteogenesis and mitochondrial metabolism. SIGNIFICANCE: Several metabolism-involved regulators including Akr1A1, SIRT1, PPARγ, PGC-1α and TAZ were differentially expressed in osteoblast- and adipocyte-committed MSCs. More importantly, Akr1A1 was identified as a new key regulator for controlling the MSC lineage commitment in favor of adipogenesis but detrimental to osteogenesis. Such information should be useful to develop perspective new therapeutic agents to reverse the adipo-osteogenic differentiation of BMSCs, in a way to increase in osteogenesis but decrease in adipogenesis.

Innovative analysis of diazepam, zolpidem and their main metabolites in human urine by micelle-to-solvent stacking in capillary electrophoresis.

Diazepam and zolpidem are the most widely used medications for managing insomnia. However, significant concerns regarding the potential risks of misuse and abuse problems arose in many literatures. While urine analysis is a valuable diagnostic tool, a challenge arises from the fact that some parent drugs may remain undetectable in urine. This necessitates concurrent monitoring of their metabolites. Here, we described an innovative on-line sample preconcentration technique known as micelle to solvent stacking (MSS) for the analysis of diazepam, zolpidem, and their main metabolites in urine. Several key parameters warrant further discussion to optimize the MSS model, enhancing its performance in terms of sensitivity and resolution. After optimizing the conditions, we conducted a validation test, achieving high correlation coefficients (greater than 0.9977) for intra-day and inter-day regression lines. Additionally, both the relative standard deviation (RSD) and relative error (RE) remained below 6.10% and 12.55%, respectively. The limits of detection (LODs, S/N = 3) for all five analytes ranged from 2.0 to 56 ng/mL. Compared to the conventional capillary zone electrophoresis method, this new approach exhibited remarkable sensitivity enhancements, ranging from 123 to 235-fold. Upon applying this method to actual urine samples from patients, we successfully detected nordiazepam, zolpidem, and its metabolites. This simple and sensitive approach has promising applications in supporting patient medication safety and bolstering forensic investigations.

The impact of blood pressure variability on the development of parenchymal hematoma in acute cerebral infarction with atrial fibrillation.

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBPmax (p = 0.0426), SBPSV (p = 0.0006), DBPmax-min (p = 0.0437), DBPSV (p = 0.0358), DBPSD (p = 0.0393), PPmax-min (p = 0.0478), PPSV (p < 0.0001), PPSD (p = 0.0034), and PPCV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF.

Evaluating the Potential of Delta Radiomics for Assessing Tyrosine Kinase Inhibitor Treatment Response in Non-Small Cell Lung Cancer Patients.

Our study aimed to harness the power of CT scans, observed over time, in predicting how lung adenocarcinoma patients might respond to a treatment known as EGFR-TKI. Analyzing scans from 322 advanced stage lung cancer patients, we identified distinct image-based patterns. By integrating these patterns with comprehensive clinical information, such as gene mutations and treatment regimens, our predictive capabilities were significantly enhanced. Interestingly, the precision of these predictions, particularly related to radiomics features, diminished when data from various centers were combined, suggesting that the approach requires standardization across facilities. This novel method offers a potential pathway to anticipate disease progression in lung adenocarcinoma patients treated with EGFR-TKI, laying the groundwork for more personalized treatments. To further validate this approach, extensive studies involving a larger cohort are pivotal.

Fluorescence detection of apolipoprotein E gene polymorphisms based on oligonucleotide ligation and magnetic separation.

Alzheimer's disease is a progressive neurodegenerative condition that causes brain cell death and is the leading cause of dementia. Most patients with Alzheimer's disease are diagnosed with late-onset Alzheimer's disease (LOAD), with apolipoprotein E (APOE) genotypes being highly associated with the frequency of LOAD risk. A fluorescence detection system coupled with oligonucleotide ligation and magnetic separation was developed to identify two single-nucleotide polymorphisms (SNPs) for the APOE gene and recognize APOE alleles for LOAD. The system utilized a fluorescence probe with one base-discriminating nucleoside for SNP (F probe) and a perfectly complementary biotin-modified sequence against the target DNA (P probe). When the F and P probes matched the target DNA sequences, DNA ligation occurred, and ligation products were produced. Streptavidin magnetic beads were subsequently employed to remove the ligation products, and a decrease in fluorescence intensity was observed in the supernatant compared to when there was no target DNA. This system detected two SNPs of APOE alleles, namely rs429358 and rs7412. The results indicated that the R-values ((F0 - F1)/F0) for rs429358 were 0.92 ± 0.002 for the T/T target, 0.47 ± 0.004 for the T/C target and 0.11 ± 0.004 for the C/C target, respectively. The R-values for rs7412 were 0.73 ± 0.009 for the C/C target, 0.42 ± 0.001 for the C/T target and 0.16 ± 0.007 for the T/T target, respectively. F0 and F1 represent the fluorescence intensity of the F probe without and with target DNA, respectively. Based on fluorescence intensity, the fluorescence detection system was able to identify the genotypes of the APOE gene accurately to evaluate the risk of Alzheimer's disease.

Method Development for Determination of Doripenem in Human Plasma via Capillary Electrophoresis Coupled with Field-Enhanced Sample Stacking and Sweeping.

In this study, we established a novel capillary electrophoresis method for monitoring the concentration of doripenem in human plasma. As a time-dependent antibiotic, doripenem maximizes its antibacterial effects and minimizes the potential for antibiotic resistance through careful therapeutic drug monitoring. Two online preconcentration techniques, field-enhanced sample stacking (FESS) and sweeping, were coupled to enhance the detection sensitivity. Briefly, an uncoated fused silica capillary (40 cm × 50 µm i.d) was rinsed with a high conductivity buffer (HCB) composed of 150 mM phosphate buffer (NaH2PO4, pH 2.5) and 20% methanol. A large sample plug prepared in a low-conductivity phosphate buffer (50 mM NaH2PO4, pH 2.5) was then hydrodynamically injected (5 psi, 80 s) into the capillary. Under an applied voltage of -30 kV, the analyte was accumulated at the FESS boundary and swept by the negatively charged micelles toward the UV detector. Plasma samples were pretreated by solid-phase extraction (SPE) to eliminate endogenous interferences. The validation results demonstrated a high coefficient of determination (r2 > 0.9995) for the regression curve with impressive precision and accuracy: relative standard deviation (RSD) <5.86% and relative error <4.63%. The limit of detection (LOD, S/N = 3) for doripenem was determined to be 0.4 µg/mL. Compared to the conventional micellar electrokinetic chromatography method, our developed method achieved a sensitivity enhancement of up to 488-fold for doripenem. Furthermore, the newly developed method successfully quantified doripenem concentrations in plasma samples obtained from patients accepting doripenem regimens, proving its application potential in the clinical realm.

Federated Learning: A Cross-Institutional Feasibility Study of Deep Learning Based Intracranial Tumor Delineation Framework for Stereotactic Radiosurgery.

BACKGROUND: Deep learning-based segmentation algorithms usually required large or multi-institute data sets to improve the performance and ability of generalization. However, protecting patient privacy is a key concern in the multi-institutional studies when conventional centralized learning (CL) is used. PURPOSE: To explores the feasibility of a proposed lesion delineation for stereotactic radiosurgery (SRS) scheme for federated learning (FL), which can solve decentralization and privacy protection concerns. STUDY TYPE: Retrospective. SUBJECTS: 506 and 118 vestibular schwannoma patients aged 15-88 and 22-85 from two institutes, respectively; 1069 and 256 meningioma patients aged 12-91 and 23-85, respectively; 574 and 705 brain metastasis patients aged 26-92 and 28-89, respectively. FIELD STRENGTH/SEQUENCE: 1.5T, spin-echo, and gradient-echo [Correction added after first online publication on 21 August 2023. Field Strength has been changed to "1.5T" from "5T" in this sentence.]. ASSESSMENT: The proposed lesion delineation method was integrated into an FL framework, and CL models were established as the baseline. The effect of image standardization strategies was also explored. The dice coefficient was used to evaluate the segmentation between the predicted delineation and the ground truth, which was manual delineated by neurosurgeons and a neuroradiologist. STATISTICAL TESTS: The paired t-test was applied to compare the mean for the evaluated dice scores (p < 0.05). RESULTS: FL performed the comparable mean dice coefficient to CL for the testing set of Taipei Veterans General Hospital regardless of standardization and parameter; for the Taichung Veterans General Hospital data, CL significantly (p < 0.05) outperformed FL while using bi-parameter, but comparable results while using single-parameter. For the non-SRS data, FL achieved the comparable applicability to CL with mean dice 0.78 versus 0.78 (without standardization), and outperformed to the baseline models of two institutes. DATA CONCLUSION: The proposed lesion delineation successfully implemented into an FL framework. The FL models were applicable on SRS data of each participating institute, and the FL exhibited comparable mean dice coefficient to CL on non-SRS dataset. Standardization strategies would be recommended when FL is used. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Application of Radiomics in Prognosing Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis.

In the context of non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs), this research evaluated the prognostic value of CT-based radiomics. A comprehensive systematic review and meta-analysis of studies up to April 2023, which included 3111 patients, was conducted. We utilized the Quality in Prognosis Studies (QUIPS) tool and radiomics quality scoring (RQS) system to assess the quality of the included studies. Our analysis revealed a pooled hazard ratio for progression-free survival of 2.80 (95% confidence interval: 1.87-4.19), suggesting that patients with certain radiomics features had a significantly higher risk of disease progression. Additionally, we calculated the pooled Harrell's concordance index and area under the curve (AUC) values of 0.71 and 0.73, respectively, indicating good predictive performance of radiomics. Despite these promising results, further studies with consistent and robust protocols are needed to confirm the prognostic role of radiomics in NSCLC.

A novel tool to evaluate and quantify radiation pneumonitis: A retrospective analysis of correlation of dosimetric parameters with volume of pneumonia patch.

Introduction: In lung cancer, radiation-induced lung injury (RILI) or radiation pneumonitis (RP) are major concerns after radiotherapy. We investigated the correlation between volumes of RP lesions and their RP grades after radiotherapy. Methods and materials: We retrospectively collected data from patients with non-small lung cancer that received curative doses to the thorax without undergoing chest radiotherapy before this treatment course. The post-treatment computed tomography (CT) image was used to register to the planning CT to evaluate the correlation between dosimetric parameters and volume of pneumonia patch by using deformable image registration. Results: From January 1, 2019, to December 30, 2020, 71 patients with non-small cell lung cancer with 169 sets of CT images met our criteria for evaluation. In all patient groups, we found the RPv max and RP grade max to be significant (p<0.001). Some parameters that were related to the dose-volume histogram (DVH) and RP were lung Vx (x=1-66 Gy, percentage of lung volume received ≥x Gy), and mean lung dose. Comparing these parameters of the DVH with RP grade max showed that the mean lung dose and lung V1-V31 were significantly correlated. The cut-off point for the occurrence of symptoms in all patient groups, the RPv max value, was 4.79%, while the area under the curve was 0.779. In the groups with grades 1 and 2 RP, the dose curve of 26 Gy covered ≥80% of RP lesions in >80% of patients. Patients who had radiotherapy in combination with chemotherapy had significantly shorter locoregional progression-free survival (p=0.049) than patients who received radiation therapy in combination with target therapy. Patients with RPv max >4.79% demonstrated better OS (p=0.082). Conclusion: The percentage of RP lesion volume to total lung volume is a good indicator for quantifying RP. RP lesions can be projected onto the original radiation therapy plan using coverage of the 26 Gy isodose line to determine whether the lesion is RILI.

ZIF-8-derived Cu, N co-doped carbon as a bifunctional cathode catalyst for enhanced performance of microbial fuel cell.

The development of bifunctional catalysts is an effective way to simultaneously address the slow kinetics of oxygen reduction reaction (ORR) on the cathode and biofilm contamination in the microbial fuel cells (MFC). Cu-N/C@Cu composites were synthesized as bifunctional cathode catalysts for MFC by doping, adsorption, and two calcinations by using Cu-ZIF-8 as the precursor. The higher Cu-Nx content confers excellent ORR catalytic activity to the optimized Cu-N/C@Cu-2 catalyst. The half-wave potential for Cu-N/C@Cu-2 in a neutral solution is 0.67 V vs. RHE, which is close to that of commercial 20% Pt/C (0.70 V vs. RHE). The maximum power density of the MFCs assembled with Cu-N/C@Cu-2 reached 581 ± 13 mW m-2, which is even better than that using Pt/C (499 ± 13 mW m-2). Moreover, the results of antimicrobial activity and biomass test show that the higher Cu content made Cu-N/C@Cu-2 effective against the contamination of cathode biofilm. And the 16S rDNA results find that the community structure of the biofilm is favorable for the power production and purification of MFC. This work shows that copper-based materials can be used as potential bifunctional catalysts to promote MFC applications in wastewater treatment.

miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis.

We tried to unveil the clinical significance of miR-146a as a biomarker in M2 macrophage polarization in diabetic wound healing. Initially, we found reduced miR-146a in macrophages of diabetic patients. Next, dual-luciferase assay verified that toll-like receptor 4 (TLR4) was a target gene of miR-146 and was negatively regulated by miR-146. Moreover, after ectopic expression and depletion experiments of miR-146 and/or TLR4, lipopolysaccharide-induced inflammatory response of macrophages was detected. The results revealed that overexpression of miR-146a promoted the M2 macrophage polarization by suppressing the TLR4/nuclear factor-kappaB (NF-κB) axis, so as to enhance wound healing in diabetic ulcers. Further, mouse models with diabetic ulcers were established to investigate the effects of miR-146a on diabetic wound healing in vivo, which revealed that miR-146a promoted wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis. In conclusion, we demonstrate that miR-146a can induce M2 macrophage polarization to enhance wound healing in diabetic ulcers by inhibiting the TLR4/NF-κB axis.

Photoluminescent carbon nanomaterials for sensing of illicit drugs: focus.

The growth of illicit drugs is a serious social problem, putting great pressure on law enforcement officers to screen numerous suspicious samples at crime scenes. Although commercial colorimetric kits are available, they are limited to common illicit drugs. With increasing numbers of new psychoactive substances in the market, accurate and rapid screening assays are highly demanded. Carbon dots (C-dots) are photoluminescent (PL) carbon nanomaterials with unique properties of excellent stability against salt and photo-irradiation, low blinking, and biocompatibility. They can be prepared easily through various routes from numerous precursors. This Focus provides examples of C-dots based PL assays for screening illicit drugs. The drugs induce PL changes of C-dots mostly through electron transfer and energy transfer. Liquid- and solid-phase PL assays of C-dots can be applied for in-field screening, with advantages of rapidity, low cost, selectivity, and minimum color interference, showing their great commercial potential.

Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic trisomy 20 at amniocentesis in a pregnancy with a favorable outcome.

OBJECTIVE: We present our observation of cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes in mosaic trisomy 20 at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 35-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XX,+20[10]/46,XX[15]. Among 25 colonies of cultured amniocytes, 10 colonies had a karyotype of 47,XX,+20, while the rest were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1-22,X) × 2. The parental karyotypes were normal. Following genetic counseling, the woman underwent repeat amniocentesis at 20 weeks of gestation. Repeat amniocentesis revealed a karyotype of 47,XX,+20[3]/46,XX[35]. Among 38 colonies of cultured amniocytes, three colonies had a karyotype of 47,XX,+20, while the rest were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance, or arr (1-22,X) × 2. Interphase fluorescence in situ hybridization analysis on 101 uncultured amniocytes detected only one cell with three chromosome 20 signals with a mosaic trisomy 20 level of 1% (1/101 cells), compared with 0% in normal control. Polymorphic DNA marker analysis on the DNA extracted from uncultured amniocytes and parental bloods excluded uniparental disomy 20. At 38 weeks of gestation, a phenotypically normal 3120-g female baby was delivered. Cytogenetic analysis of cord blood, placental tissue and umbilical cord revealed a karyotype of 46,XX. The neonate was normal at postnatal follow-ups. Postnatal interphase fluorescence in situ hybridization analysis on 100 buccal mucosal cells revealed no trisomy 20 signals. CONCLUSION: Mosaic trisomy 20 at amniocentesis can be a cultured artifact. Complete cytogenetic discrepancy may occur between cultured amniocytes and uncultured amniocytes in mosaic trisomy 20 at amniocentesis, and molecular cytogenetic analysis on uncultured amniocytes is useful for rapid distinguishing true mosaicism from pseudomosaicism under such as circumstance.

Chronic low back pain is associated with impaired bed turning ability: Evaluation by a mobility detection system.

BACKGROUND: We aimed to assess and compare kinetics and kinematic variables of bed turning ability using a mobility detection system in patients with and without chronic low back pain and to observe the impacts of the disease on bed turning kinetics and kinematics. METHODS: Thirty-five patients with chronic low back pain were enrolled and compared to healthy controls (n = 34). Pain scores and disability level were assessed by Numeric Pain Rating Scale and the function questionnaires including Oswestry Disability Index and Roland Morris Disability Questionnaire. Bed turning ability was tested using the Mobile Detection System. Univariate and multivariate regression analysis were applied to compare the differences between groups. FINDINGS: Patients with chronic low back pain had significantly lower turning over and back force/weight ratio (p < 0.001) than those healthy controls. Turning over time was significantly longer in patients with Numeric Rating Scale score 3 than in those with Numeric Rating Scale score 2 (p = 0.015). Turning over and back force were significantly higher in male patients and patients with higher BMI after adjusting BMI and sex, respectively (all p < 0.001). When turning back, chronic low back pain patients with Numeric Rating Scale scores of 3 had lower turning back force/weight ratio than those with Numeric Rating Scale scores of 2 (p = 0.014). Male patients had higher turning back force/weight ratio after adjusting pain score (p = 0.001). INTERPRETATION: The novel Mobility Detection System can provide more objective assessments of bed turning kinetics and kinematics in patients with chronic low back pain.

Perceptions of community dementia friendliness: A cross-sectional study of people with dementia, family caregivers, service providers, and the general public in Taiwan.

Promoting dementia-friendly communities is an important strategy for improving quality of life for people with dementia and dementia-family caregivers. The process of building dementia-friendly communities should include all people living in the community. The objective of this study was to compare perceived dementia friendliness in the community among people with dementia, family caregivers, service providers, and the general public. In Taiwan, we surveyed 60 people with dementia, 140 family caregivers, and 200 members of the general public face to face, with 200 service providers surveyed by mail. Participants completed the Perceived Community Dementia Friendliness measure, consisting of seven subscales: care services, community members, community environment, community interactions, transportation, hospitals, and stores and organisations. This measure has acceptable convergent validity, construct validity, and internal consistency reliability for use in Taiwan. Differences in perceived dementia friendliness were examined by chi-square tests/analysis of variance. Among the seven subscales, hospitals were rated with good dementia friendliness by 70% of people with dementia (n = 42); however, care services were rated poor by 23.3% of people with dementia (n = 14). Hospitals were also rated with good dementia friendliness by 39.2% of family caregivers (n = 54). Care services were rated as having good dementia friendliness by 43.5% of service providers (n = 87) and 47% of the general public (n = 86). Furthermore, community interactions were rated as good by small percentages of family caregivers (11.4%, n = 16), service providers (22.2%, n = 44), and the general public (30.9%, n = 58). Family caregivers, service providers, and the general public rated hospitals with the highest mean dementia-friendliness score and community interactions with the lowest. Perceived community-dementia friendliness among participants with dementia differed from that of participants without. People with dementia prioritised improving care services, while people without dementia rated facilitating community interactions as more vital. These differences provide vital insights into understanding the policies and administration of dementia-friendly communities.

Determination of 13-cis-Retinoic Acid and Its Metabolites in Plasma by Micellar Electrokinetic Chromatography Using Cyclodextrin-Assisted Sweeping for Sample Preconcentration.

The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl ß-CD (HP-ß-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224-257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.

m6 A transferase METTL3-induced lncRNA ABHD11-AS1 promotes the Warburg effect of non-small-cell lung cancer.

N6 -methyladenosine (m6 A) and long noncoding RNAs (lncRNAs) are both crucial regulators in non-small-cell lung cancer (NSCLC) tumorigenesis. However, the pathological roles of m6 A and lncRNAs in NSCLC progression are still limited and undefined. Here, lncRNA ABHD11-AS1 was upregulated in NSCLC tissue specimens and cells and the ectopic overexpression was closely correlated with unfavorable prognosis of NSCLC patients. Functionally, ABHD11-AS1 promoted the proliferation and Warburg effect of NSCLC. Mechanistically, m6 A profile was analyzed by methylated RNA immunoprecipitation sequencing (MeRIP-Seq). MeRIP-Seq presented that there was m6 A modification site in ABHD11-AS1. m6 A methyltransferase-like 3 (METTL3) installed the m6 A modification and enhanced ABHD11-AS1 transcript stability to increase its expression. In conclusion, our findings highlight the function and mechanism of METTL3-induced ABHD11-AS1 in NSCLC and inspire the understanding of m6 A and lncRNA in cancer biology.