Signal Intensity Research Articles

A simple HPLC-UV method for monitoring therapeutic adherence in pulmonary arterial hypertension.

A considerable percentage of ineffective treatment in pulmonary arterial hypertension (PAH) may be related to subtherapeutic dosage or non-adherence. The aim of the study was to develop a simple analytical method suitable for plasma determination of selected drugs: riociguat (RIO), bosentan (BOS) and macitentan (MAC) administered to PAH patients. An isocratic HPLC-UV system (Spectra Physics - Shimadzu) with a manual injector (50μL loop) was applied. Chromatographic analysis was performed using a Suplecosil LC-CN column (150×4.6mm, 5μm) protected with a Supelguard precolumn at room temperature. The separation was carried out using the mobile phase: CH3CN:H2O:0.5M KH2PO4:85% H3PO4 (172:324.2:3.7:0.1, v/v) at a flow rate of 1.8mL/min. Ethyl acetate (4mL) was used for 10-min liquid-liquid extraction from 0.4mL alkalized plasma sample. Detection was performed at λ=245nm chosen as a compromise between signal intensity and matrix interference. The analytes were eluted at retention times of 4.4min (RIO), 5.4min (BOS), 8.9min (MAC) and 7.8min for gallopamil (internal standard, GAL). The method was found linear and calibrated in the ranges: 5-1000ng/mL for RIO, 10-2000ng/mL for BOS and 20-2000ng/mL for MAC, with r2 of 0.9991 for RIO, 0.9983 for BOS, and 0.9949 for MAC, respectively. Within the given ranges, the method ensured reliable results with the required precision and accuracy: ≤15% (≤20% for LLOQ). There was no significant carryover effect. The method has been successfully used in pilot study on adherence in patients treated for PAH, enabling monitoring of RIO, BOS and MAC. Drug concentrations were assessed in samples taken before (C0) and 3h after drug administration (C3). For RIO, BOS and MAC, the developed method was suitable for both C0 and C3 samples, allowing steady-state drug determination if used. The presented method can be recommended to laboratories equipped with basic HPLC apparatus as an attractive analytical tool for both TDM and adherence studies.

CT and MRI features of adrenal hemangioma: A study of 21 cases from two centers

PurposeTo retrospectively analyze the CT and MR imaging presentations of adrenal hemangioma (AH) and to strengthen the recognition for such tumors. Materials and methodsThis retrospective study enrolled 21 patients with 22 lesions histologically proven AH from two centers between October 2010 and November 2023. The clinical presentation and preoperative diagnosis were recorded. Two radiologists reviewed the CT and MR imaging features in consensus, including number, size, shape, boundary, attenuation, signal intensity, and dynamic enhancement pattern. ResultsThe study included nine men and twelve women (mean age 55.6 ± 12.5 years, range, 35–77 years) without hormone production. AH was unilateral in 19 cases, bilateral in 2 cases. The maximum diameter was more than 3 cm in 19/22(86 %). AHs had oval (10/22,45 %), round (5/22, 23 %), or (7/22, 32 %) multilocular shape, and well-defined boundary (18/22,82 %). On unenhanced CT, 11/20 (55 %) displayed peripheral iso-density and central hypo-intensity, 3/20 (15 %) heterogeneously hyper-density, 6/20 (30 %) hypodensity, and 14/20 (70 %) contained speckled calcification. On T2-weighted images, 7/12 (58 %) exhibited nodular hyper-intensity peripherally, markedly hyper-intensity centrally, and hypo-intense fibrotic scar in between, 5/12 (42 %) hyperintensity. On T1-weighted images, 6/12 (50 %) displayed center hyper-intensity surrounded by peripheral hypo-intensity,5/12 hypo-intensity, 1/11 (9 %) hyperintensity. On DWI, 7/12 (58 %) demonstrated peripheral hyper-intensity and central hypo-intensity, 5/12 (42 %) hyper-intensity. CT and MR imaging findings were suggestive of cystic change and necrosis (19/22,86 %, 4 cystic tumors), hemorrhage (15/22,68 %), fat (7/22, 33 %) within the tumors. CT and MR enhanced images showed peripheral nodular enhancement with (3/22,14 %) or without (13/22, 59 %) delayed central filling, nodular peripheral and center enhancement with progressive partial fill-in (2/22,9%), capsular and/or septal mild enhancement (4/22, 18 %), and capsule (16/22,73 %). The solid part was significantly enhanced, similar to the abdominal aorta (AA) with no statistical difference between the two (P > 0.05). ConclusionsSmall AHs (<3cm) have the typical imaging features of hemangioma. The imaging findings of large AHs were various, the combination of T2-hyperintense signal with inner hypo-intense fibrotic scar, speckled calcification, central extensive necrosis and hemorrhage, and nodular peripheral enhancement with persistently slight further contrast accumulation may contribute to suggest the possibility. Cystic AH should be considered as a differential diagnosis for cystic adrenal masses.

Imaging features and management of tuberculomas: a review of cases and literature.

To describe the imaging features of patients presenting with soft tissue masses and a provisional diagnosis of soft tissue tumours, for whom biopsy confirmed the presence of necrotising granulomata consistent with tuberculoma. A review of the histopathology database for patients who had a diagnosis of necrotising granulomata in nonspinal sites. Patients with bone and joint-based pathology were excluded. Patient age, sex, lesion location, and relevant history were recorded, as were the radiographic, magnetic resonance imaging (MRI), and US findings. Four males and three females were included, with a mean age of 45.7 years (range 20-71 years). Radiographs showed soft tissue calcification in two cases. On MRI, three lesions were mildly hyperintense on T1W TSE images, and a 'penumbra sign' was seen in six cases. T2W FSE and fat suppressed PDW FSE/STIR sequences demonstrated mixed fluid/solid signal intensity in all cases. All patients showed peri-lesional oedema, while postcontrast studies in two patients showed rim enhancement and heterogeneous enhancement, respectively. On US, one lesion appeared mainly solid, and six were predominantly fluid. US-guided needle biopsy established the diagnosis of necrotising granulomatous infection in all cases. Soft tissue tuberculomas can present as soft tissue masses mimicking sarcomas. However, the presence of a 'penumbra sign' on T1W TSE sequences and peri-lesional oedema should raise the possibility of infection. Biopsy specimens should therefore be sent for both histopathology and microbiology culture and sensitivity.

Reduced physiology-induced temporal instability achieved with variable-flip-angle fast low-angle excitation echo-planar technique with multishot echo planar time-resolved imaging.

Echo planar time-resolved imaging (EPTI) is a new imaging approach that addresses the limitations of EPI by providing high-resolution, distortion- and T2/ blurring-free imaging for functional MRI (fMRI). However, as in all multishot sequences, intershot phase variations induced by physiological processes can introduce temporal instabilities to the reconstructed time-series data. This study aims to reduce these instabilities in multishot EPTI. In conventional multishot EPTI, the time intervals between the shots comprising each slice can introduce intershot phase variations. Here, the fast low-angle excitation echo-planar technique (FLEET), in which all shots of each slice are acquired consecutively with minimal time delays, was combined with a variable flip angle (VFA) technique to improve intershot consistency and maximize signal. A recursive Shinnar-Le Roux RF pulse design algorithm was used to generate pulses for different shots to produce consistent slice profiles and signal intensities across shots. Blipped controlled aliasing in parallel imaging simultaneous multislice was also combined with the proposed VFA-FLEET EPTI to improve temporal resolution and increase spatial coverage. The temporal stability of VFA-FLEET EPTI was compared with conventional EPTI at 7 T. The results demonstrated that VFA-FLEET can provide spatial-specific increase of temporal stability. We performed high-resolution task-fMRI experiments at 7 T using VFA-FLEET EPTI, and reliable BOLD responses to a visual stimulus were detected. The intershot phase variations induced by physiological processes in multishot EPTI can manifest as specific spatial patterns of physiological noise enhancement and lead to reduced temporal stability. The VFA-FLEET technique can substantially reduce these physiology-induced instabilities in multishot EPTI acquisitions. The proposed method provides sufficient stability and sensitivity for high-resolution fMRI studies.

The expand indication of HER2 targeted therapies by monitoring of circulating tumor cells.

482 Background: Despite success in the HER2 targeted therapies for metastatic gastric cancer patients, the conventional assessment of HER2 status in tumor tissue specimens is still under debate. Methods: On-chip sorting system was used for the isolation of circulating tumor cells (CTCs). The fluorescence signal intensity &gt; 50 is set to be a threshold value for distinguishing between positive and negative HER2 on CTCs. Epithelial mesenchymal transition (EMT) was assessed by the vimentin and cytokeratin. DNA was extracted from CTCs and applied to the cancer gene panel. Results: In 27 patients with metastatic gastric cancer, 13 patients showed HER2 positive in tumor tissues (Group A) who were treated with cytotoxic agents and HER2-targeted therapy while 14 patients exhibited negative and treated with cytotoxic agents. In these 14 patients, 8 patients showed HER2 positive (Group B) and 6 patients displayed HER2 negative (Group C) on CTCs. HER2 expression on CTCs was associated with EMT (p&lt;0.001). Increased expression of EMT was seen in Group A and B, indicating they are likely to have metastasis. Group B exhibited worse PFS than others (13.8 M in A, 7.0 M in B and not reached in C, p=0.012). In addition, genomic analysis identified cancer gene mutations, some of which were involved in mechanisms underlying EMT and were shared between Group A and B. Considering HER2 expression on CTCs in Group B, an additional HER2-targeted therapy may be beneficial. Conclusions: Our study suggests that monitoring of circulating tumor cells leads to the expand indication of the HER2 targeted therapies in patients with metastatic gastric cancer.

Transdural location as a predictor of recurrence in spinal cord meningiomas.

Spinal cord meningiomas are typically benign, rare tumors that pose clinical challenges owing to their location and potential for spinal cord compression. This study aimed to assess the radiological features of spinal cord meningiomas and the key factors associated with their recurrence. We conducted a retrospective, single-institution study on 67 patients with pathologically confirmed spinal cord meningiomas who were surgically treated between January 2016 and December 2023. Radiological features, such as tumor size, en plaque growth, tumor signal intensity, and anatomical location, were assessed using preoperative magnetic resonance imaging. Clinical outcomes were evaluated using univariate and multivariate logistic regression analyses to identify risk factors for recurrence. Of the 67 patients, six (9.0%) experienced a recurrence during a mean follow-up of 31.8months. Results of univariate analysis suggested that a younger age, high World Health Organization grade, en plaque growth, and transdural location were significantly associated with tumor recurrence (p<0.05). Multivariate analysis confirmed that a younger age (p=0.027) and transdural growth (p=0.006) were significant independent predictors of recurrence. Our study identified younger age and transdural tumor location as significant risk factors for spinal cord meningioma recurrence. A total resection is the primary surgical goal; however, tumors with complex anatomical presentations, especially those exhibiting transdural growth, pose significant challenges. The findings highlight the importance of developing tailored surgical approaches and intensifying postoperative surveillance in high-risk patients to reduce the recurrence likelihood.

Developing a method for the study of perfusion effects in topical product pharmacokinetics

Topical drug products are delivered to skin structures to treat numerous skin diseases. Due to the complexities of the skin environment and barrier, topical drug pharmacokinetics are difficult to determine, especially in vivo, as most pharmacokinetic assessment methods can only be performed ex vivo. Notably, in vivo conditions include perfusion via dermal capillaries, which influences topical drug uptake by acting as a clearance route and a “sink” driving permeation through the skin. In this study, we develop a method to examine the effects of perfusion on topical drug uptake in vivo using stimulated Raman scattering (SRS) microscopy, a chemically-specific imaging modality ideal for visualizing topical drug permeation over time. In this pilot study, we imaged the in vivo and ex vivo uptake of tazarotene in 70/30 v/v Transcutol:EtOH in paired mouse ear skin, comparing the effects of perfusion on tazarotene concentration (linearly proportional to SRS signal intensity) over time and pharmacokinetic parameters (Tmax, Cmax, AUC) in lipid-rich and lipid-poor regions in the stratum corneum and sebaceous glands. Obvious variations in SRS signal-time trends and statistically significant differences in stratum corneum pharmacokinetic parameters comparing uptake in lipid-rich and lipid-poor regions in vivo and ex vivo indicated slowed tazarotene flux through ex vivo skin in the absence of perfusion. The observed permeation differences in lipid-rich and lipid-poor regions in perfused and non-perfused skin reflects increased tazarotene permeation rate and removal in the presence of perfusion (in vivo) and decreased permeation rate and lack of elimination route in the absence of perfusion (ex vivo). Our method is demonstrated to be effective in assessing in vivo perfusion effects on topical drug uptake, promoting a better understanding of the influence of perfusion on topical drug delivery.

Recent advances in lateral flow assays for MicroRNA detection.

Lateral flow assays (LFAs) have emerged as pivotal tools for the rapid and reliable detection of microRNAs (miRNAs). It is believed that these biomarkers are crucial for the diagnosis and prognosis of various diseases, particularly cancer. Traditional miRNA detection techniques, such as quantitative PCR, are highly sensitive but have limited efficacy due to their complexity, high cost, and technical requirements. LFAs are valuable due to their simplicity, affordability, and portability, making them ideal for point-of-care testing in low-resource environments. However, challenges remain in developing highly sensitive and accurate LFA devices for miRNA detection. This review explores recent advancements in LFAs to improve miRNA detection sensitivity and specificity. Key innovations include signal amplification using isothermal methods, the application of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas systems for direct targeting of miRNAs, and the incorporation of nanomaterials, such as gold nanoparticles and nanorods, to enhance signal intensity. Using artificial intelligence (AI) algorithms enables precise, automated, and rapid quantification of miRNAs. Moreover, this review examines the ability of LFA-based devices to detect multiple miRNAs simultaneously. One of the most significant advancements is the detection of miR-21 levels as low as 20 pM and let-7a levels as low as 40 pM within ten minutes. This highlights the potential of these devices for clinical diagnostics.

Post-marketing safety of pimavanserin: a real-world pharmacovigilance study based on the FDA adverse event reporting system (FAERS)

ABSTRACT Background Pimavanserin is a new non-dopamine neurotransmitter antipsychotic drug. This study aimed to conduct a post-marketing pharmacovigilance study of pimavanserin, through data mining technology using the FDA Adverse Event Reporting System (FAERS) database. Research design and methods We analyzed adverse event reports for patients using pimavanserin. Data were classified using systematic organ classification (SOC) and preferred term (PT) of the Medical Dictionary for Regular Activities (MedDRA). Four signal algorithms [reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma poisson shrinker (MGPS), and bayesian confidence propagation neural network (BCPNN)] were used to detect positive signals, and the median time-to-onset was determined. Results Adverse drug events (ADEs) related to pimavanserin (n = 31,852) were analyzed, exhibiting an annual linear upward trend (p = 0.027). The ADEs involved 27 SOCs, but only ‘Psychiatric disorders’ simultaneously satisfied four algorithms. Overall, 153 PTs simultaneously satisfied four algorithms. Subgroup analysis of differences in the top 30 signal intensity PTs according to sex yielded significant results for seven PTs (p < 0.05). The median time-to-onset was 97 days, the highest proportion occurred within the first 30 days (31.79%). Conclusions Some new PT signals not listed in the label were identified, and some PT signals showed differences according to sex.

A Biomimetic Passive Mechanotransduction Mechanism Based on Interfacial Regulation of Ionic p-n Junctions.

Natural skin receptors use ions as signal carriers, while most of the developed artificial tactile sensors utilize electrons as information carriers. To imitate the biological ionic sensing behavior, here, we present a kind of biomimetic, ionic, and fully passive mechanotransduction mechanism leveraging mechanical modulation of interfacial ionic p-n junction (IPNJ) through microchannels. Sensors based on this mechanism do not rely on an external power supply and can encode external tactile stimuli into highly analogous signal outputs to those of natural skin receptors, in terms of both signal type (i.e., ionic potential difference) and signal intensity (≈120 mV). More importantly, the instant interfacial IPNJ regulation characteristic endows the sensors with superior performance when compared to the state-of-the-art piezoionic sensors, including a low detection limit of 0.01 N, fast response/recovery speeds (16 ms/16 ms), ultralow power consumption (pW level), excellent reproducibility (over 100,000 cycles), and good capabilities to resolve both static and dynamic mechanical stimulations. As demonstrations, machine-learning-assisted high accuracy (over 99%) surface texture recognition and object classification are successfully demonstrated with the sensors integrated on robotic hands. This work enriches the family of mechanical sensing mechanisms and provides a path to mimicking natural tactile sensory systems for smart skins, artificial prostheses, and intelligent robots.

YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer.

Hyperactivation of the YAP/TEAD transcriptional complex in cancers facilitates the development of an immunosuppressive tumor microenvironment. Herein, we observed that the transcription factor SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer (CRC). In response to serum stimulation, PKCζ (protein kinase C ζ) was found to phosphorylate SP1 and enhance its interaction with TEAD4. As a result, SP1 enhanced the transcriptional activity of YAP/TEAD and coregulated the expression of a group of YAP/TEAD target genes. The immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) was identified as a direct target of the SP1-YAP/TEAD4 complex and found to be widely expressed in CRC cells. Importantly, YAP-induced VISTA upregulation in human CRC cells was found to strongly suppress the antitumor function of CD8+ T cells. Consistently, elevated VISTA expression was found to be correlated with hyperactivation of the SP1-YAP/TEAD axis and associated with poor prognosis of CRC patients. In addition, we found by serendipity that enzymatic deglycosylation significantly improved the anti-VISTA antibody signal intensity, resulting in more accurate detection of VISTA in clinical tumor samples. Overall, our study identified SP1 as a positive modulator of YAP/TEAD for the transcriptional regulation of VISTA and developed a protein deglycosylation strategy to better detect VISTA expression in clinical samples. These findings revealed a new tumor cell-intrinsic mechanism of YAP/TAZ-mediated cancer immune evasion.

Enhancing trace DNA profile recovery in forensic casework using the amplicon RX post-PCR clean-up kit

This study evaluated the effectiveness of the amplicon RX post-PCR clean-up kit in enhancing trace DNA profile recovery from forensic casework samples amplified using the GlobalFiler PCR amplification kit. The impact of post-PCR clean-up on allele recovery and signal intensity was assessed in both trace casework samples and control samples across a range of DNA concentrations. The results showed that the amplicon RX method significantly improved allele recovery compared to the 29-cycle protocol (p = 8.30 × 10−12) and achieved slightly better results than the 30-cycle protocol (p = 0.019). Additionally, the Amplicon RX method demonstrated a significant increase in signal intensity (p = 2.70 × 10−4), reflecting improved sensitivity in detecting trace DNA profiles compared to the 30-cycle protocol. In the evaluation of control samples, the amplicon RX method consistently outperformed both the 29- and 30-cycle protocols, especially at lower DNA concentrations (D3: 0.001 ng/µL). While the performance of all methods declined at the lowest concentration (D4: 0.0001 ng/µL), the Amplicon RX method still demonstrated superior allele recovery (p = 0.014 compared to 29 cycles; p = 0.011 compared to 30 cycles). Therefore, the Amplicon RX method should be widely adopted in forensic laboratories to enhance the analysis of extremely low-template and compromised samples. These findings highlight the potential of the amplicon RX post-PCR clean-up kit to improve trace DNA analysis in forensic casework. Further research is recommended to validate these results and explore its broader application in forensic DNA analysis, particularly in complex DNA mixtures and extremely low-template samples.

Diagnostic performance of contrast-enhanced T2-FLAIR MRI in the detection of meningitis

Background: The contrast-enhanced T2-FLAIR (CE-T2-FLAIR) sequence on MRI, through the suppression of CSF and vascular signals, can detect subtle meningeal enhancement in meningitis that may not be appreciable on the routinely used contrast-enhanced T1W (CE-T1W) sequence.Objectives: To assess CE-T2-FLAIR compared to CE-T1W in the diagnosis of meningitis, using CSF analysis as the gold standard, using both qualitative and quantitative approaches for assessment.Method: A retrospective study was conducted on 53 patients with clinically suspected meningitis referred for brain MRI. Twenty-seven patients, positive for meningitis on CSF analysis, were classified as the case group; the remaining patients were designated as controls. The pre-contrast, CE-T1W and CE-T2-FLAIR images were assessed and analysed, qualitatively for the detection of abnormal meningeal enhancement, and quantitatively by measuring single pixel signal intensities (SPSI) over the meninges and vessels.Results: Contrast-enhanced T2-FLAIR demonstrated significantly higher sensitivity (92.59% vs. 57.69%), negative predictive value (92.59% vs. 70.27%) and diagnostic accuracy (94.34% vs. 78.85%) compared to CE-T1W. Additionally, CE-T2-FLAIR showed significantly greater meningeal SPSI and enhancement than CE-T1W.Conclusion: Contrast-enhanced T2-FLAIR is better at detecting abnormal meningeal enhancement in meningitis than CE-T1W, because of significantly greater signal intensity and enhancement of the meninges compared to vessels.Contribution: This study reiterates the usefulness of CE-T2-FLAIR as an additional sequence for the detection of abnormal meningeal enhancement in cases of meningitis as confirmed both qualitatively and quantitatively.

T1 signal intensity ratio variability based on sampling strategies in the pancreas of children and young adults.

T1-weighted signal intensity ratios (SIR) comparing pancreas to spleen (SIRps) or muscle (SIRpm) can semiquantitatively assess T1 signal change associated with pancreatitis. However, there is no standardized methodology for generating these ratios. We set out to determine the impact of MRI sequence as well as region of interest (ROI) location, shape, and size on T1 SIR. Retrospective analysis of T1-weighted MR images from 118 patients acquired 2018-2023. A single observer placed ovoid ROIs in the pancreas body/tail and head/uncinate, spleen, and left erector spinae muscle and large irregular ROIs in the pancreas tail and spleen. ROIs were placed on images from two sequences: 3D radial 2 point mDIXON RF spoiled gradient recalled echo sequence (radial) and breath-hold 3D 2-point mDIXON RF spoiled gradient echo (BH). T1 SIR were calculated from mean signal intensity, and agreement was calculated with intraclass correlations coefficients (ICC) and Bland-Altman difference analyses. 118 participants, 57 (48%) female, withmean age 13.7 ± 5.6years (48%) were included. Agreement was good for SIRps based on irregular versus round ROIs (radial: ICC = 0.90; BH: ICC = 0.91). Agreement was moderate for SIR based on sampling the pancreas body/tail versus head/uncinate (ICC = 0.67-0.76) and poor to moderate based on reference organ (muscle vs. spleen) (ICC = 0.41-0.61). Between sequences, agreement was moderate (ICC = 0.55-0.72, mean difference 0.04-0.09). The size and shape of the ROI used to sample the pancreas does not meaningfully change T1 SIR but the location sampled, the reference organ used, and the MRI sequence used meaningfully change T1 SIR, potentially impacting disease diagnosis and staging.

Involvement of nuclear receptor corepressor 2 (NCOR2) in estrogen-induced repression of arcuate Kiss1 expression in female rats.

Hypothalamic arcuate (ARC) kisspeptin neurons are considered the gonadotropin-releasing hormone pulse generator in rats. In virgin rats, the expression of the ARC kisspeptin gene (Kiss1) is repressed by proestrous levels of estradiol-17β (high E2) but not by diestrous levels of E2 (low E2). In lactating rats, ARC Kiss1 expression is repressed by low E2 during late lactation. This study aimed to investigate whether nuclear receptor corepressor 2 (NCOR2, encoded by Ncor2), an estrogen receptor α corepressor, is involved in the estrogen-induced repression of ARC Kiss1 expression in rats. Double in situ hybridization for Kiss1 and Ncor2 revealed that approximately 80% of ARC Kiss1-expressing cells co-expressed Ncor2 in ovariectomized (OVX) + low E2 virgin rats, while approximately 90% of ARC Kiss1-expressing cells co-expressed Ncor2 in OVX + low E2 lactating rats. To further examine the role of Ncor2, we studied the effects of Kiss1-dependent Ncor2 knockdown on ARC Kiss1 expression and luteinizing hormone (LH) pulses. An adeno-associated virus vector carrying Cre-activated short hairpin RNA (shRNA) for Ncor2 was administered to the ARC in two Kiss1-Cre rat models: OVX + high E2 Kiss1-Cre virgin rats and OVX + low E2 Kiss1-Cre lactating rats. Ncor2-shRNA treatment significantly increased the number of ARC Kiss1-expressing cells and the intensity of Kiss1 signals in OVX + high E2 virgin rats but failed to fully restore low E2-induced Kiss1 repression in lactating rats. The Ncor2-shRNA treatment failed to affect LH pulses in both models. These findings suggest that NCOR2 in ARC kisspeptin neurons mediates high E2-induced repression of ARC Kiss1 expression in virgin rats.

Identifying Primary Sites of Spinal Metastases: Expert-Derived Features vs. ResNet50 Model Using Nonenhanced MRI.

The spinal column is a frequent site for metastases, affecting over 30% of solid tumor patients. Identifying the primary tumor is essential for guiding clinical decisions but often requires resource-intensive diagnostics. To develop and validate artificial intelligence (AI) models using noncontrast MRI to identify primary sites of spinal metastases, aiming to enhance diagnostic efficiency. Retrospective. A total of 514 patients with pathologically confirmed spinal metastases (mean age, 59.3 ± 11.2 years; 294 males) were included, split into a development set (360) and a test set (154). Noncontrast sagittal MRI sequences (T1-weighted, T2-weighted, and fat-suppressed T2) were acquired using 1.5 T and 3 T scanners. Two models were evaluated for identifying primary sites of spinal metastases: the expert-derived features (EDF) model using radiologist-identified imaging features and a ResNet50-based deep learning (DL) model trained on noncontrast MRI. Performance was assessed using accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve (ROC-AUC) for top-1, top-2, and top-3 indicators. Statistical analyses included Shapiro-Wilk, t tests, Mann-Whitney U test, and chi-squared tests. ROC-AUCs were compared via DeLong tests, with 95% confidence intervals from 1000 bootstrap replications and significance at P < 0.05. The EDF model outperformed the DL model in top-3 accuracy (0.88 vs. 0.69) and AUC (0.80 vs. 0.71). Subgroup analysis showed superior EDF performance for common sites like lung and kidney (e.g., kidney F1: 0.94 vs. 0.76), while the DL model had higher recall for rare sites like thyroid (0.80 vs. 0.20). SHapley Additive exPlanations (SHAP) analysis identified sex (SHAP: -0.57 to 0.68), age (-0.48 to 0.98), T1WI signal intensity (-0.29 to 0.72), and pathological fractures (-0.76 to 0.25) as key features. AI techniques using noncontrast MRI improve diagnostic efficiency for spinal metastases. The EDF model outperformed the DL model, showing greater clinical potential. Spinal metastases, or cancer spreading to the spine, are common in patients with advanced cancer, often requiring extensive tests to determine the original tumor site. Our study explored whether artificial intelligence could make this process faster and more accurate using noncontrast MRI scans. We tested two methods: one based on radiologists' expertise in identifying imaging features and another using a deep learning model trained to analyze MRI images. The expert-based method was more reliable, correctly identifying the tumor site in 88% of cases when considering the top three likely diagnoses. This approach may help doctors reduce diagnostic time and improve patient care. 3 TECHNICAL EFFICACY: Stage 2.

Extracellular and intracellular digestion in the bivalves studied by magnetic resonance imaging with a contrast reagent.

We investigated the extracellular and intracellular digestion of bivalves employing magnetic resonance imaging (MRI). Ruditapes philippinarum clams and Mytilus galloprovincialis mussels were incubated in seawater containing a contrast reagent (GdDTPA) at 20°C. The digestive systems, from the esophagus to the rectum, were visualized at a high signal intensity by the T1-weighted MRI. The crystalline style of the clam was also identified, which turned counterclockwise when viewed from a ventral-posterior position at a rate of 16 rpm. Determined using the T1 relaxation rate, the uptake and excretion rates of the GdDTPA in the mussel's digestive glands were 2.9 and 0.25 d-1, respectively, indicating that the intracellular digestion in the gland acinar cells is slower than the extracellular digestion. These results demonstrate that MRI with contrast reagents is useful to study the activity of digestive system in the bivalves, and this technique can likely be applied to the study of other invertebrates.

Polarimetric imaging of peripheral nerves: an intraoperative aid

In this work, we present a real-time method to aid intraoperative peripheral nerve identification. Using LEDs as the light sources, the device contains a driving motor that rotates a pair of orthogonally oriented linear polarizers. By performing lock-in processing to frames taken under the rotating crossed polarization imaging (RXPI) system, the AC components of the periodic intensity signal of chicken tissues are acquired and compared. With an area under the curve (AUC) of 93%, the chicken sciatic nerve is distinct for automatic identification. In both chicken thigh and cadaver arm models, the contrasts of nerve tissues are successfully enhanced in the lock-in processed output image. Real-time automatic nerve masking is successfully demonstrated in the chicken model using a portable prototype weighing 525 g. In conclusion, the RXPI system with lock-in processing methods can potentially serve as an intraoperative nerve identification aid.

Exploration of CCL11 and sTNFR2 as potential biomarkers for the efficacy of lymphocyte immunotherapy in women with unexplained recurrent spontaneous abortion

Objective: To explore biomarkers for the efficacy of lymphocyte immunotherapy (LIT) treating women with unexplained recurrent spontaneous abortion (URSA). Methods: Serum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015. Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT. Multifactor quantitative microsphere flow cytometry detection validated the levels of target cytokines. Based on the final pregnancy outcome after LIT, 24 URSA patients were divided into the full-term delivery group (15 cases) and the abortion group (9 cases). Furthermore, linear regression analysis were applied to evaluate the relationship between target cytokines and pregnancy outcomes. Results: Semiquantitative sandwich-based antibody arrays suggested that, among all 24 URSA patients included in this study, the intensities of the fluorescence signal were significantly lower post-LIT versus pre-LIT for the following cytokines: interleukin-15 (IL-15), monokine induced by γ-interferon (MIG), C-C motif chemokine ligand (CCL) 1 (all P<0.05). In the full-term delivery group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: IL-15, CCL1, macrophage inflammatory protein (MIP) 1α (all P<0.05). In the abortion group, the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines: MIG, MIP-1δ (all P<0.05). Linear regression analysis showed that the intensity of the fluorescence signal of CCL11 was increased and the intensity of the fluorescence signal of soluble tumor necrosis factor receptor 2 (sTNFR2) was decreased in the full-term delivery group after LIT, the differences were statistically significant (P=0.012, 0.029). Validation results of multifactor quantitative microsphere flow cytometry detection showed that the level of CCL11 was significantly increased (P=0.001) and the level of sTNFR2 was significantly decreased (P=0.001) in the full-term delivery group after LIT. Conclusion: CCL11 and sTNFR2 maybe serve as potential biomarkers that could predict pregnancy outcomes after LIT in women with URSA.

A sensitive determination of lead by hydride generation integrated with micro-sampling gas–liquid separator-FAAS after preconcentration by NiFe2O4 nanoparticles

In the present study, dispersive solid phase extraction – hydride generation integrated with micro–sampling gas–liquid separator – flame atomic absorption spectrometry was proposed to determine lead in lake water samples taken in the Horseshoe Island, Antarctica. In scope of this study, microwave assisted NiFe2O4 nanoparticles were synthesized, and the characterization of nanoparticles were carried out by FT-IR, XRD and SEM. All influential parameters of dispersive solid phase extraction and hydride generation were optimized to enhance signal intensity belonging to the analyte. System analytical performance studies were performed, and limit of detection and limit of quantitation were calculated as 2.16 µg kg–1 and 7.19 µg kg–1, respectively. Recovery studies were conducted to the spiked lake water samples and two different calibration strategies were applied. Percent recovery results were calculated between 102.0 and 169.5% by external calibration strategy while matrix matching calibration strategy provided recovery results in the range of 78.8–142.9%.