Comparison of Glomerular Filtration Rate Equations in a Rural New Mexico Cohort: Results from the COMPASS Study.

Rationale and Objective: The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Study design: Prospective community cohort study. Setting and Participants: rural New Mexico clinic with patients > 18 yo. Methods: Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Results: Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Limitations: Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. Conclusion: B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.

Feasibility and performance of spin-echo EPI MR elastography at 3 Tesla for staging hepatic fibrosis in the presence of hepatic iron overload.

PURPOSE: To assess the feasibility and performance of MR elastography (MRE) for quantifying liver fibrosis in patients with and without hepatic iron overload. METHODS: This retrospective single-center study analyzed 139 patients who underwent liver MRI at 3 Tesla including MRE (2D spin-echo EPI sequence) and R2* mapping for liver iron content (LIC) estimation. MRE feasibility and diagnostic performance between patients with normal and elevated LIC were compared. RESULTS: Patients with elevated LIC (21%) had significantly higher MRE failure rates (24.1% vs. 3.6%, p < 0.001) compared to patients with normal LIC (79%). For those with only insignificant to mild iron overload (LIC < 5.4 mg/g; 17%), MRE failure rate did not differ significantly from patients without iron overload (8.3% vs. 3.6%, p = 0.315). R2* predicted MRE failure with fair accuracy at a threshold of R2* ≥ 269 s-1 (LIC of approximately 4.6 mg/g). MRE showed good diagnostic performance for detecting significant (≥ F2) and severe fibrosis (≥ F3) in patients without (AUC 0.835 and 0.900) and with iron overload (AUC 0.818 and 0.889) without significant difference between the cohorts (p = 0.884 and p = 0.913). For detecting cirrhosis MRE showed an excellent diagnostic performance in both groups (AUC 0.944 and 1.000, p = 0.009). CONCLUSION: Spin-echo EPI MRE at 3 Tesla is feasible in patients with mild iron overload with good to excellent performance for detecting hepatic fibrosis with a failure rate comparable to patients without iron overload.

Improved gradient echo magnitude- and phase-based mapping of T 2 $$ {\mathrm{T}}_2 $$ using multiple RF spoiling increments at 3T and 7T.

PURPOSE: The transverse relaxation time T 2 $$ {}_2 $$ holds significant relevance in clinical applications and research studies. Conventional T 2 $$ {}_2 $$ mapping approaches rely on spin-echo sequences, which require lengthy acquisition times and involve high radiofrequency (RF) power deposition. An alternative gradient echo (GRE) phase-based T 2 $$ {}_2 $$ mapping method, utilizing steady-state acquisitions at one small RF spoil phase increment, was recently demonstrated. Here, a modified magnitude- and phase-based T 2 $$ {}_2 $$ mapping approach is proposed, which improves T 2 $$ {\mathrm{T}}_2 $$ estimations by simultaneous fitting of T 1 $$ {\mathrm{T}}_1 $$ and signal amplitude ( A ∝ P D $$ A\propto PD $$ ) at three or more RF spoiling phase increments, instead of assuming a fixed T 1 $$ {\mathrm{T}}_1 $$ value. METHODS: The feasibility of the magnitude-phase-based method was assessed by simulations, in phantom and in vivo experiments using skipped-CAIPI three-dimensional-echo-planar imaging (3D-EPI) for rapid GRE imaging. T 2 $$ {\mathrm{T}}_2 $$ , T 1 $$ {\mathrm{T}}_1 $$ and PD estimations obtained by our method were compared to T 2 $$ {\mathrm{T}}_2 $$ of the phase-based method and T 1 $$ {\mathrm{T}}_1 $$ and PD of spoiled GRE-based multi-parameter mapping using a multi-echo version of the same sequence. RESULTS: The agreement of the proposed T 2 $$ {\mathrm{T}}_2 $$ with ground truth and reference T 2 $$ {\mathrm{T}}_2 $$ values was higher than that of phase-based T 2 $$ {\mathrm{T}}_2 $$ in simulations and in phantom data. While phase-based T 2 $$ {\mathrm{T}}_2 $$ overestimation increases with actual T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ , the proposed method is accurate over a large range of physiologically meaningful T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ values. At the same time, precision is improved. In vivo results were in line with these observations. CONCLUSION: Accurate magnitude-phase-based T 2 $$ {}_2 $$ mapping is feasible in less than 5 min scan time for 1 mm nominal isotropic whole-head coverage at 3T and 7T.

Rapid submillimeter QSM and R2* mapping using interleaved multishot 3D-EPI at 7 and 3 Tesla.

PURPOSE: To explore the high signal-to-noise ratio (SNR) efficiency of interleaved multishot 3D-EPI with standard image reconstruction for fast and robust high-resolution whole-brain quantitative susceptibility (QSM) and R 2 ∗ $$ {R}_2^{\ast } $$ mapping at 7 and 3T. METHODS: Single- and multi-TE segmented 3D-EPI is combined with conventional CAIPIRINHA undersampling for up to 72-fold effective gradient echo (GRE) imaging acceleration. Across multiple averages, scan parameters are varied (e.g., dual-polarity frequency-encoding) to additionally correct for B 0 $$ {\mathrm{B}}_0 $$ -induced artifacts, geometric distortions and motion retrospectively. A comparison to established GRE protocols is made. Resolutions range from 1.4 mm isotropic (1 multi-TE average in 36 s) up to 0.4 mm isotropic (2 single-TE averages in approximately 6 min) with whole-head coverage. RESULTS: Only 1-4 averages are needed for sufficient SNR with 3D-EPI, depending on resolution and field strength. Fast scanning and small voxels together with retrospective corrections result in substantially reduced image artifacts, which improves susceptibility and R 2 ∗ $$ {R}_2^{\ast } $$ mapping. Additionally, much finer details are obtained in susceptibility-weighted image projections through significantly reduced partial voluming. CONCLUSION: Using interleaved multishot 3D-EPI, single-TE and multi-TE data can readily be acquired 10 times faster than with conventional, accelerated GRE imaging. Even 0.4 mm isotropic whole-head QSM within 6 min becomes feasible at 7T. At 3T, motion-robust 0.8 mm isotropic whole-brain QSM and R 2 ∗ $$ {R}_2^{\ast } $$ mapping with no apparent distortion in less than 7 min becomes clinically feasible. Stronger gradient systems may allow for even higher effective acceleration rates through larger EPI factors while maintaining optimal contrast.

Vitamin D Metabolites in Mother-Infant Dyads and Associated Clinical Outcomes in a Population of Nigerian Women.

Low levels of vitamin D in maternal and cord blood have been associated with neonatal sepsis. This study assessed the association of vitamin D metabolites (25(OH)D, 3-epi-25(OH)D3, and 24,25(OH)2D3) levels in maternal and cord blood with newborn sepsis evaluation in Nigerian mother-infant dyads. Maternal and cord blood from 534 mothers and 536 newborns were processed using liquid chromatography-tandem mass spectrometry. Spearman correlation was used to compare continuous variables, Mann-Whitney for dichotomous variables, and Kruskal-Wallis for two or more groups. High cord percent 3-epi-25(OH)D3 levels were positively associated with newborn evaluation for sepsis (p = 0.036), while maternal and cord 25(OH)D and 24,25(OH)2D3 levels were not. Being employed was positively associated with maternal and newborn 3-epi-25(OH)D3 concentrations (p = 0.007 and p = 0.005, respectively). The maternal 3-epi-25(OH)D3 and percent 3-epi-25(OH)D3 were positively associated with vaginal delivery (p = 0.013 and p = 0.012, respectively). Having a weight-for-age Z-score ≤ -2 was positively associated with newborn percent 3-epi-25(OH)D3 levels (p = 0.004), while a weight-for-length Z-score ≤ -3 was positively associated with maternal and newborn percent 3-epi-25(OH)D3 levels (p = 0.044 and p = 0.022, respectively). Our study highlights the need to further investigate the biological role of 3-epi-25(OH)D3 and its clinical significance in fetal growth and newborn outcome.

Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease.

Background: Genetic mitochondrial diseases are a major challenge in modern medicine, impacting around 1:4,000 individuals. Leigh syndrome is the most common pediatric presentation of mitochondrial disease. There are currently no effective clinical treatments for mitochondrial disease. In humans, patients are often treated with antioxidants, vitamins, and strategies targeting energetics. The vitamin-E related compound vatiquinone (EPI-743, α-tocotrienol quinone) has been the subject of at least 19 clinical trials in the US since 2012, but the effects of vatiquinone on an animal model of mitochondrial disease have not yet been reported. Here, assessed the impact of vatiquinone on disease progression and in two animal models of mitochondrial disease. Methods: The efficacy of vatiquinone in vitro was assessed using human fibroblasts treated with the general mitochondrial oxidative stress inducer paraquat, the GPX4 inhibitor RSL3, or the glutathione synthase inhibitor BSO in combination with excess iron. The therapeutic potential of vatiquinone in vivo was assessed using tamoxifen-induced mouse model for GPX4 deficiency and the Ndufs4 knockout mouse model of Leigh syndrome. In both models, animals were treated daily with vatiquinone or vehicle and relevant disease endpoints were assessed. Results: Vatiquinone robustly prevented death in cultured cells induced by RSL3 or BSO/iron, but had no effect on paraquat induced cell death. Vatiquinone had no impact on disease onset, progression, or survival in either the tamoxifen-inducible GPX4 deficient model or the Ndufs4(-/-) mouse model, though the drug may have reduced seizure risk. Conclusions: Vatiquinone provided no benefit to survival in two mouse models of disease, but may prevent seizures in the Ndufs4(-/-) model. Our findings are consistent with recent press statements regarding clinical trial results and have implications for drug trial design and reporting in patients with rare diseases.

Interferon regulatory factor 4 modulates epigenetic silencing and cancer-critical pathways in melanoma cells.

Interferon regulatory factor 4 (IRF4) was initially identified as a key controller in lymphocyte differentiation and function, and subsequently as a dependency factor and therapy target in lymphocyte-derived cancers. In melanocytes, IRF4 takes part in pigmentation. Although genetic studies have implicated IRF4 in melanoma, how IRF4 functions in melanoma cells has remained largely elusive. Here, we confirmed prevalent IRF4 expression in melanoma and showed that high expression is linked to dependency in cells and mortality in patients. Analysis of genes activated by IRF4 uncovered, as a novel target category, epigenetic silencing factors involved in DNA methylation (DNMT1, DNMT3B, UHRF1) and histone H3K27 methylation (EZH2). Consequently, we show that IRF4 controls the expression of tumour suppressor genes known to be silenced by these epigenetic modifications, for instance cyclin-dependent kinase inhibitors CDKN1A and CDKN1B, the PI3-AKT pathway regulator PTEN, and primary cilium components. Furthermore, IRF4 modulates activity of key downstream oncogenic pathways, such as WNT/ß-catenin and AKT, impacting cell proliferation and survival. Accordingly, IRF4 modifies the effectiveness of pertinent epigenetic drugs on melanoma cells, a finding that encourages further studies towards therapeutic targeting of IRF4 in melanoma.

Fast 3D fMRI acquisition with high spatial resolutions over a reduced FOV.

PURPOSE: To develop and demonstrate a fast 3D fMRI acquisition technique with high spatial resolution over a reduced FOV, named k-t 3D reduced FOV imaging (3D-rFOVI). METHODS: Based on 3D gradient-echo EPI, k-t 3D-rFOVI used a 2D RF pulse to reduce the FOV in the in-plane phase-encoding direction, boosting spatial resolution without increasing echo train length. For image acceleration, full sampling was applied in the central k-space region along the through-slab direction (kz) for all time frames, while randomized undersampling was used in outer kz regions at different time frames. Images were acquired at 3T and reconstructed using a method based on partial separability. fMRI detection sensitivity of k-t 3D-rFOVI was quantitively analyzed with simulation data. Human visual fMRI experiments were performed to evaluate k-t 3D-rFOVI and compare it with a commercial multiband EPI sequence. RESULTS: The simulation data showed that k-t 3D-rFOVI can detect 100% of fMRI activations with an acceleration factor (R) of 2 and ˜80% with R = 6. In the human fMRI data acquired with 1.5-mm spatial resolution and 800-ms volume TR (TRvol), k-t 3D-rFOVI with R = 4 detected 46% more activated voxels in the visual cortex than the multiband EPI. Additional fMRI experiments showed that k-t 3D-rFOVI can achieve TRvol of 480 ms with R = 6, while reliably detecting visual activation. CONCLUSIONS: k-t 3D-rFOVI can simultaneously achieve a high spatial resolution (1.5-mm isotropically) and short TRvol (480-ms) at 3T. It offers a robust acquisition technique for fast fMRI studies over a focused brain volume.

Determination of nine bisphenol analogues in human urine by high-throughput solid-phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis.

Bisphenol analogues (BPs) are a class of typical environmental endocrine-disrupting chemicals (EDCs). This study aimed to establish a highly sensitive and high-throughput method utilizing 96-well solid-phase extraction (96-well SPE) in conjunction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) employing multiple reaction monitoring (MRM), information-dependent acquisition (IDA), and enhanced product ion (EPI) scan modes for the identification and quantitative analysis of nine BPs in human urine. Urine samples were initially thawed to room temperature, followed by digestion using ß-glucuronidase in an ammonium acetate buffer solution at 37 °C overnight. Subsequently, they were purified using 96-well SPE and finally analyzed by UHPLC-MS/MS. The limits of detection (LOD) for the nine BPs ranged from 0.05 µg∙kg-1 to 0.3 µg kg-1. Average recoveries fell within the range of 92.8 % to 111.7 %. Moreover, both the intra-day and inter-day precisions were satisfactory, with relative standard deviations (RSDs) ranging from 2.2 % to 6.7 % and 3.5 % to 6.3 %, respectively. The targets in the samples exhibited a perfect match, with a purity fit value exceeding 70 % from the self-built library. The analytical method developed in this study demonstrates high accuracy and sensitivity. In addition, the MRM-IDA-EPI mode can effectively identifies the target BPs and prevents false positive detection of analytes in the urine.

Breast cancer epigenetics: current and evolving treatment.

BACKGROUND: Breast cancer (BC) presents persistent challenges due to subtype-specific limited efficacy and potential resistance to standard therapy, influenced by the dynamic reversible nature of epigenetic plasticity. This study aims to comprehensively explore the evolving BC epigenetic landscape, analyzing trends and evaluating the therapeutic potential of epigenetic drugs (epi-drugs) for BC treatment. METHODS: We conducted a cross-sectional study of BC epigenetic trials using ClinicalTrials.gov until July 18, 2023. Additionally, results from randomized controlled trials were retrieved from the registry or PubMed using trial registration numbers. RESULTS: In total, 22 epi-drugs were investigated in 100 trials, with 11 currently being studied in 38 ongoing trials for BC. Over the years, epigenetic clinical trials for BC have notably increased, with histone deacetylase inhibitors constituting 45.45% of the candidate agents in the development pipeline. All ongoing trials are enrolling human epidermal growth factor receptor2 (HER2)-negative BC patients. Epi-drugs are commonly explored in combination with multiple anti-cancer therapies, such as aromatase or microtubule inhibitors, using an intermittent sequential administration approach. Emerging strategies include new-generation epi-drugs and combination involving immunotherapy or targeted therapy. Among candidate drugs, tucidinostat and entinostat, in combination with exemestane, demonstrated significant improvements in progression-free survival in phase III trials for hormone receptor-positive, HER2-negative BC patients. CONCLUSION: This study highlights the growing interest in BC epigenetics, suggesting a potential shift from a one-size-fits-all approach to precision medicine, and emphasizes the necessity for robust evidence on their efficacy and safety to support continuous development and approval, addressing the unmet needs in BC treatment.

Biclustering for Epi-Transcriptomic Co-functional Analysis.

Dynamic and reversible N6-methyladenosine (m6A) modifications are associated with many essential cellular functions as well as physiological and pathological phenomena. In-depth study of m6A co-functional patterns in epi-transcriptomic data may help to understand its complex regulatory mechanisms. In this chapter, we describe several biclustering mining algorithms for epi-transcriptomic data to discover potential co-functional patterns. The concepts and computational methods discussed in this chapter will be particularly useful for researchers working in related fields. We also aim to introduce new deep learning techniques into the field of co-functional analysis of epi-transcriptomic data.

EPI-Trans: an effective transformer-based deep learning model for enhancer promoter interaction prediction.

BACKGROUND: Recognition of enhancer-promoter Interactions (EPIs) is crucial for human development. EPIs in the genome play a key role in regulating transcription. However, experimental approaches for classifying EPIs are too expensive in terms of effort, time, and resources. Therefore, more and more studies are being done on developing computational techniques, particularly using deep learning and other machine learning techniques, to address such problems. Unfortunately, the majority of current computational methods are based on convolutional neural networks, recurrent neural networks, or a combination of them, which don't take into consideration contextual details and the long-range interactions between the enhancer and promoter sequences. A new transformer-based model called EPI-Trans is presented in this study to overcome the aforementioned limitations. The multi-head attention mechanism in the transformer model automatically learns features that represent the long interrelationships between enhancer and promoter sequences. Furthermore, a generic model is created with transferability that can be utilized as a pre-trained model for various cell lines. Moreover, the parameters of the generic model are fine-tuned using a particular cell line dataset to improve performance. RESULTS: Based on the results obtained from six benchmark cell lines, the average AUROC for the specific, generic, and best models is 94.2%, 95%, and 95.7%, while the average AUPR is 80.5%, 66.1%, and 79.6% respectively. CONCLUSIONS: This study proposed a transformer-based deep learning model for EPI prediction. The comparative results on certain cell lines show that EPI-Trans outperforms other cutting-edge techniques and can provide superior performance on the challenge of recognizing EPI.

Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Acceptability and Feasibility of Human Papillomavirus Vaccine Introduction in Cameroon: A Mixed-Methods Study.

INTRODUCTION: Human papillomaviruses (HPV) are responsible for sexually transmitted infections, and some of these viruses have oncogenic potential. The HPV vaccine is due to be introduced in Cameroon in September 2019. Our study looked at the knowledge, perceptions, and attitudes of the population and healthcare professionals regarding cervical cancer and its vaccine prevention. This approach provides a solid basis for, among other things, developing a clear communication strategy for the introduction of the vaccine. OBJECTIVE: This study aimed to assess the feasibility and acceptability of introducing the HPV vaccine in Cameroon among key stakeholders including health workers and parents. METHODS: From March to May 2019, we conducted a qualitative and quantitative descriptive study in six health districts in the Centre Region. A total of 257 study participants were recruited, including 168 parents and 89 health professionals; 60 interviews were also conducted, 30 with parents and 30 with health professionals. The quantitative data collected were analyzed using IBM SPSS Statistics for Windows, Version 20.0 (Released 2011; IBM Corp., Armonk, New York, United States); for the qualitative analysis, we carried out repeated readings of the transcribed interviews. This work enabled us to identify the significant themes emerging from the interviewees' discourse. RESULTS: The vast majority of healthcare professionals claim to be aware of cervical cancer (93.3%), but only 15.7% of female healthcare professionals claim to have ever carried out a screening test. A significant proportion of these professionals have actual experience of cervical cancer. Among parents, knowledge of this cancer also appears to be relatively high for a lay audience (54.2%), with a low screening rate (7.1%). Awareness of the HPV vaccine as a cervical cancer prevention tool was very low: 14.9% among parents and 44.9% among healthcare professionals. In addition, we found that information about the existence of an HPV vaccine was still very low among parents (83.9% had never heard of it); 43.8% of healthcare professionals had been informed about the vaccine at their training school. As regards acceptance of the HPV vaccine, the quantitative and qualitative results point in the same direction. The majority of parents are in favor of a campaign and access to this new vaccine via the Expanded Program on Immunization (EPI). However, many of them (94.6%) explained that they wanted more information before making a decision. CONCLUSION: Informing and raising public awareness of cervical cancer, the HPV vaccine, and vaccine safety are essential measures to encourage public support for the HPV vaccination campaign.

Discovery of 2-phenylquinazolines as potent Mycobacterium avium efflux pump inhibitors able to synergize with clarithromycin against clinical isolate.

Nontuberculous mycobacteria (NTM), which include the Mycobacterium avium complex, are classified as difficult-to-treat pathogens due to their ability to quickly develop drug resistance against the most common antibiotics used to treat NTM infections. The overexpression of efflux pumps (EPs) was demonstrated to be a key mechanism of clarithromycin (CLA) resistance in NTM. Therefore, in this work, 24 compounds from an in-house library, characterized by chemical diversity, were tested as potential NTM EP inhibitors (EPIs) against Mycobacterium smegmatis mc2 155 and M. avium clinical isolates. Based on the acquired results, 12 novel analogs of the best derivatives 1b and 7b were designed and synthesized to improve the NTM EP inhibition activity. Among the second set of compounds, 13b emerged as the most potent NTM EPI. At a concentration of 4 µg/mL, it reduced the CLA minimum inhibitory concentration by 16-fold against the clinical isolate M. avium 2373 overexpressing EPs as primary mechanism of CLA resistance.

Independent isomeric yield ratios of fission products in the epi-cadmium neutron induced fission of 239Pu.

Measurement of independent isomeric yield ratios (IR) of 128,130,132Sb, 131,133Te, 132.134,136I, 135Xe and 138Cs have been carried out for the first time in the epi-cadmium neutron induced fission of 239Pu by using an off-line gamma-ray spectrometric technique. The average neutron energy () of the epi-cadmium reactor neutron spectrum is 1.9 MeV. From the IR values, root mean square fragment angular momenta (JRMS) were deduced by using spin dependent statistical model analysis. Effect of nuclear structure on JRMS values was examined. The present data in the epi-cadmium neutron induced fission of 239Pu were compared with the similar data in the thermal neutron induced fission of 239Pu to examine the role of excitation energy on JRMS values.

Implications of Implementing the 2021 CKD-EPI Equation Without Race on Managing Patients With Kidney Disease in British Columbia, Canada.

Introduction: We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada. Methods: This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years. Results: A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94). Conclusion: CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD.

Partial Fourier in the presence of respiratory motion in prostate diffusion-weighted echo planar imaging.

PURPOSE: To investigate the effect of respiratory motion in terms of signal loss in prostate diffusion-weighted imaging (DWI), and to evaluate the usage of partial Fourier in a free-breathing protocol in a clinically relevant b-value range using both single-shot and multi-shot acquisitions. METHODS: A controlled breathing DWI acquisition was first employed at 3 T to measure signal loss from deep breathing patterns. Single-shot and multi-shot (2-shot) acquisitions without partial Fourier (no pF) and with partial Fourier (pF) factors of 0.75 and 0.65 were employed in a free-breathing protocol. The apparent SNR and ADC values were evaluated in 10 healthy subjects to measure if low pF factors caused low apparent SNR or overestimated ADC. RESULTS: Controlled breathing experiments showed a difference in signal coefficient of variation between shallow and deep breathing. In free-breathing single-shot acquisitions, the pF 0.65 scan showed a significantly (p < 0.05) higher apparent SNR than pF 0.75 and no pF in the peripheral zone (PZ) of the prostate. In the multi-shot acquisitions in the PZ, pF 0.75 had a significantly higher apparent SNR than 0.65 pF and no pF. The single-shot pF 0.65 scan had a significantly lower ADC than single-shot no pF. CONCLUSION: Deep breathing patterns can cause intravoxel dephasing in prostate DWI. For single-shot acquisitions at a b-value of 800 s/mm2, any potential risks of motion-related artefacts at low pF factors (pF 0.65) were outweighed by the increase in signal from a lower TE, as shown by the increase in apparent SNR. In multi-shot acquisitions however, the minimum pF factor should be larger, as shown by the lower apparent SNR at low pF factors.

Tiny Organs, Big Impact: How Microfluidic Organ-on-Chip Technology Is Revolutionizing Mucosal Tissues and Vasculature.

Organ-on-chip (OOC) technology has gained importance for biomedical studies and drug development. This technology involves microfluidic devices that mimic the structure and function of specific human organs or tissues. OOCs are a promising alternative to traditional cell-based models and animals, as they provide a more representative experimental model of human physiology. By creating a microenvironment that closely resembles in vivo conditions, OOC platforms enable the study of intricate interactions between different cells as well as a better understanding of the underlying mechanisms pertaining to diseases. OOCs can be integrated with other technologies, such as sensors and imaging systems to monitor real-time responses and gather extensive data on tissue behavior. Despite these advances, OOCs for many organs are in their initial stages of development, with several challenges yet to be overcome. These include improving the complexity and maturity of these cellular models, enhancing their reproducibility, standardization, and scaling them up for high-throughput uses. Nonetheless, OOCs hold great promise in advancing biomedical research, drug discovery, and personalized medicine, benefiting human health and well-being. Here, we review several recent OOCs that attempt to overcome some of these challenges. These OOCs with unique applications can be engineered to model organ systems such as the stomach, cornea, blood vessels, and mouth, allowing for analyses and investigations under more realistic conditions. With this, these models can lead to the discovery of potential therapeutic interventions. In this review, we express the significance of the relationship between mucosal tissues and vasculature in organ-on-chip (OOC) systems. This interconnection mirrors the intricate physiological interactions observed in the human body, making it crucial for achieving accurate and meaningful representations of biological processes within OOC models. Vasculature delivers essential nutrients and oxygen to mucosal tissues, ensuring their proper function and survival. This exchange is critical for maintaining the health and integrity of mucosal barriers. This review will discuss the OOCs used to represent the mucosal architecture and vasculature, and it can encourage us to think of ways in which the integration of both can better mimic the complexities of biological systems and gain deeper insights into various physiological and pathological processes. This will help to facilitate the development of more accurate predictive models, which are invaluable for advancing our understanding of disease mechanisms and developing novel therapeutic interventions.