Tag: nevin manimala

Redox Biol. 2023 Mar 24;62:102680. doi: 10.1016/j.redox.2023.102680. Online ahead of print.

ABSTRACT

DNA damage is a common cellular feature seen in cancer and neurodegenerative disease, but fast and accurate methods for quantifying DNA damage are lacking. Comet assays are a biochemical tool to measure DNA damage based on the migration of broken DNA strands towards a positive electrode, which creates a quantifiable ‘tail’ behind the cell. However, a major limitation of this approach is the time needed for analysis of comets in the images with available open-source algorithms. The requirement for manual curation and the laborious pre- and post-processing steps can take hours to days. To overcome these limitations, we developed AutoComet, a new open-source algorithm for comet analysis that utilizes automated comet segmentation and quantification of tail parameters. AutoComet first segments and filters comets based on size and intensity and then filters out comets without a well-connected head and tail, which significantly increases segmentation accuracy. Because AutoComet is fully automated, it minimizes curator bias and is scalable, decreasing analysis time over ten-fold, to less than 3 s per comet. AutoComet successfully detected statistically significant differences in tail parameters between cells with and without induced DNA damage, and was more comparable to the results of manual curation than other open-source software analysis programs. We conclude that the AutoComet algorithm provides a fast, unbiased and accurate method to quantify DNA damage that avoids the inherent limitations of manual curation and will significantly improve the ability to detect DNA damage.

PMID:37001328 | DOI:10.1016/j.redox.2023.102680

Drug Alcohol Depend. 2023 Mar 27;246:109856. doi: 10.1016/j.drugalcdep.2023.109856. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop and validate a machine-learning algorithm to predict fatal overdose using Pennsylvania Prescription Drug Monitoring Program (PDMP) data.

METHODS: The training/testing (n = 3020,748) and validation (n = 2237,701) cohorts included Pennsylvania residents with a prescription dispensing from February 2018-September 2021. Potential predictors (n = 222) were measured in the 6 months prior to a random index date. Using a gradient boosting machine, we developed a 20-variable model to predict risk of fatal drug overdose in the 6 months after the index date.

RESULTS: Beneficiaries in the training (n = 1,812,448), testing (n = 1,208,300), and validation (n = 2,237,701) samples had similar age, with low rates of fatal overdose during 6-month follow up (0.12%, 0.12%, 0.04%, respectively). The validation c-statistic was 0.86 for predicting fatal overdose using 20 PDMP variables. When ranking individuals based on risk score, the prediction model more accurately identified fatal overdose at 6 months compared to using opioid dosage or opioid/benzodiazepine overlap, although the percentage of individuals in the highest risk percentile who died at 6 months was less than 1%.

CONCLUSIONS AND POLICY IMPLICATIONS: A gradient boosting machine algorithm predicting fatal overdose derived from twenty variables performed well in discriminating risk across testing and validation samples, improving on single factor risk measures like opioid dosage.

PMID:37001323 | DOI:10.1016/j.drugalcdep.2023.109856

Drug Alcohol Depend. 2023 Mar 24;246:109854. doi: 10.1016/j.drugalcdep.2023.109854. Online ahead of print.

ABSTRACT

INTRODUCTION: Opioid use disorder (OUD) remains prevalent. Medications for OUD (MOUD) are standard care for pregnant and non-pregnant women. Previous research has identified barriers to MOUD for women with Medicaid but did not account for the type of MOUD (methadone vs. buprenorphine) or pregnancy status. We examined access to MOUD by treatment type for pregnant and non-pregnant women with Medicaid in Florida.

METHODS: A secondary analysis of Florida “secret-shopper” data was conducted. Calls were made to clinicians from the 2018 Substance Abuse and Mental Health Services Administration provider list by women posing as either a pregnant or non-pregnant woman with OUD and Medicaid. We examined 546 calls to buprenorphine-waivered providers (BWP) and 139 to opioid treatment programs (OTP). Counts and percentages were used to describe caller success by type of treatment and pregnancy status. Chi-square tests were used to identify statistical differences.

RESULTS: Only 42 % of calls reached a treatment provider in Florida. Pregnant and non-pregnant women were less likely to obtain an appointment with Medicaid coverage by a BWP than an OTP (p < 0.01). Nearly 40 % of OTPs offered appointments to callers with Medicaid compared to only 17 % of BWPs. Both types of providers denied appointments more often for pregnant women. Thirty-eight percent of BWP’s and 12 % of OTP’s denied appointments to pregnant women using cash or Medicaid payment.

CONCLUSIONS: Our study demonstrates logistical and financial barriers to treatment for OUD among pregnant and non-pregnant women with Medicaid in Florida and highlights the need for improved systems of care.

PMID:37001322 | DOI:10.1016/j.drugalcdep.2023.109854

Epilepsy Res. 2023 Mar 29;192:107133. doi: 10.1016/j.eplepsyres.2023.107133. Online ahead of print.

ABSTRACT

OBJECTIVE: In the presurgical evaluation of epilepsy, identifying the epileptogenic zone is challenging if magnetic resonance imaging (MRI) is negative. Several studies have shown the benefit of using a morphometric analysis program (MAP) on T1-weighted MRI scans to detect subtle lesions. MAP can guide a focused re-evaluation of MRI to ultimately identify structural lesions that were previously overlooked. Data on patients where this additional review after MAP analysis did not reveal any lesions is limited. Here we evaluate the diagnostic yield of MAP in a large group of truly MRI-negative patients.

METHODS: We identified 68 patients with MRI-negative focal epilepsy and clear localization of the epileptogenic zone by intracranial EEG or postoperative seizure freedom. High resolution 3D T1 data of patients and 73 healthy controls were acquired on a 3 T scanner. Morphometric analysis was performed with MAP software, creating five z-score maps, reflecting different structural properties of the brain and a patient’s deviation from the control population, and a neural network-based focal cortical dysplasia probability map. Ten brain regions were specified to quantify whether MAP findings were located in the correct region. Receiver operating characteristic (ROC) analyses were performed to identify the optimal thresholds for each map.

RESULTS: MAP-guided visual re-evaluation of the original MRI revealed overlooked lesions in three patients. The remaining 65 truly MRI-negative patients were included in the statistical analysis. At the optimal thresholds, maximum sensitivity was 84 %, with 35 % specificity. Balanced accuracy (arithmetic mean of sensitivity and specificity) of the respective maps ranged from 51 % to 60 %, creating three to six times more false positive than true positive findings.

CONCLUSION: This study confirms that MAP is useful in detecting previously overlooked subtle structural lesions. However, in truly MRI-negative patients, the additional diagnostic yield is very limited.

PMID:37001290 | DOI:10.1016/j.eplepsyres.2023.107133

Breast. 2023 Mar 28;69:323-329. doi: 10.1016/j.breast.2023.03.016. Online ahead of print.

ABSTRACT

INTRODUCTION: Residual tumor cellularity (RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy (NAC) are prognostic factors associated with improved outcomes in breast cancer (BC). However, the majority of patients achieve partial pathologic response (pPR) and no clear correlation between RTC patterns and outcomes was described. Our aims were to define predictive factors for pCR and compare different outcomes of patients with pCR or pPR and with different RTC patterns.

MATERIALS AND METHODS: Baseline and post-NAC demographics, clinicopathological characteristics, post-operative data, survival and recurrence status were recorded from our institutional database. A multivariable analysis was performed using a logistic regression model to identify independent predictors of pCR. Disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) analyses were performed using the Kaplan-Meier method.

RESULTS: Overall, of the 495 patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the median RTC was 40%. Multivariable analysis identified 3 independent factors predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4 15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative 29.8% versus luminal-like 15.5%), and vascular invasion (absence 98.0% versus presence 2.0%). We found statistically significant longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no difference was observed in terms of OS between RTC <40% and RTC ≥40% groups.

CONCLUSIONS: Tumor stage before NAC, BC sub-type, and vascular invasion are significant and independent factors associated with pCR. Patients with pCR and with RTC <40% have longer DFS, DDFS, and OS compared with patients with pPR.

PMID:37001289 | DOI:10.1016/j.breast.2023.03.016

Health Policy. 2023 Mar 21;132:104799. doi: 10.1016/j.healthpol.2023.104799. Online ahead of print.

ABSTRACT

Although patient choice of abortion method is a key component of quality care, medical abortion (MA) has become the most common method (87%) in England and Wales, as in many countries worldwide. This research aimed to critically examine factors influencing the growth in MA use in England and Wales. Mixed methods were used, combining multi-level regression analysis of national abortion statistics (2011-2020) and key informant interviews with abortion service managers, commissioners, and providers (n=27). Overall trends have been driven by growth in MA use for abortions under 10 weeks in the private non-profit sector. Variation in MA use between patient sub-groups and regions has narrowed over time. Qualitative findings highlight health system constraints that have influenced the shift towards MA, including workforce constraints, infrastructure requirements, provider policies, cost, and commissioning practices involving under-funding and competition, which have caused the private non-profit sector to limit method choice across their services to remain financially viable. While removal of legal restrictions on MA has expanded choice, similar policy progress has not been seen for surgical methods. The study concludes that abortion method choice has been constrained by structural health system factors, with potential negative consequences for service acceptability, inequalities, and patient-centredness.

PMID:37001286 | DOI:10.1016/j.healthpol.2023.104799

Eur J Radiol. 2023 Mar 26;162:110802. doi: 10.1016/j.ejrad.2023.110802. Online ahead of print.

ABSTRACT

PURPOSE: To compare the qualitative and quantitative features of peripheral lesions on localized (L) and whole-body (WB) magnetic resonance imaging (MRI) in people with neurofibromatosis type 1 (NF1) and schwannomatosis.

MATERIALS AND METHODS: This is a retrospective, HIPAA compliant study with twenty-seven patients (14 women, 13 men; mean age (years): 38 (3-67)) who underwent both L-MRI and WB-MRI without interval treatment. WB-MRI and L-MRI were comprised of T1-weighted, fat suppressed (FS) T2-weighted or short tau inversion recovery (STIR), diffusion-weighted imaging (DWI) using b-values of 50, 400, and 800 s/mm2, apparent diffusion coefficient (ADC) mapping and pre- and post-contrast FST1 sequences. Two readers recorded qualitative (T1 and T2/STIR signal intensity and heterogeneity, contrast enhancement and heterogeneity, perilesional enhancement, presence of a target sign and perilesional edema) and quantitative (size, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), ADC) features of peripheral lesions on L-MRI and WB-MRI.Descriptive statistics, Wilcoxon signed-rank test and McNemar’s test were used.

RESULTS: There were 31 peripheral lesions identified in 27 subjects, (mean size: 3.1 cm (range: 1-8.1 cm) on both L-MRI and WB-MRI).There were no differences in T1 signal and heterogeneity and T2/STIR signal and heterogeneity between WB-MRI and L-MRI ((p = 0.180, 0.083, 0.317 and 0.157 respectively). There were also no differences in contrast enhancement, heterogeneity and perilesional enhancement between WB-MRI and L-MRI (p = 1.000, 0.380 and 1.000 respectively). Presence of a target sign and perilesional edema did not differ between WB-MRI and L-MRI (p = 1.000 and 0.500 respectively). Craniocaudal (CC), mediolateral (ML) and anteroposterior (AP) size measurements on WB-MRI did not differ from CC, ML and AP size measurements on L-MRI (p = 0.597, 0.128 and 0.783 respectively). SNR on WB-DWI did not differ from SNR on L-DWI for b50, b400 and b800 images (p = 0.285, 0.166, and 0.974 respectively), and CNR on WB-DWI did not differ from CNR on L-DWI for b50, b400 and b800 images (p = 0.600, 0.124, and 0.787 respectively). There was no significant difference in minimum, mean and maximum ADC values between WB-DWI and L-DWI (p = 0.234, 0.481, and 0.441 respectively). Median minimum, mean and maximum ADC (×10(-3)mm(2)/s) differences between WB-DWI and L-DWI were 0.0 (range -1 to 0.7), 0.0 (range -0.5 to 0.6), and 0.1 (range -1.2 to 0.8) respectively. Relative ADC difference averages were 29.1% for minimum values, 10.1% for mean values, and 14.8% for maximum values.

CONCLUSION: WB-MRI yields qualitative and quantitative features for peripheral lesions, including DWI and ADC measurements, that are comparable to L-MRI scans. WB-DWI can be reliably used for the assessment of peripheral nerve sheath tumors, obviating the need for a repeat follow-up L-DWI acquisition.

PMID:37001256 | DOI:10.1016/j.ejrad.2023.110802

J Mech Behav Biomed Mater. 2023 Mar 28;141:105806. doi: 10.1016/j.jmbbm.2023.105806. Online ahead of print.

ABSTRACT

PURPOSE: To compare the in-vitro performance and wear behavior of additively or subtractively fabricated resin-based composite molar crowns for temporary and permanent application.

MATERIALS AND METHODS: Identical molar crowns (n = 8 per group) were manufactured from materials for temporary or permanent application (3x temporary additive fabrication, 3x additive permanent fabrication, 1x temporary subtractive fabrication, 1x permanent subtractive fabrication). All crowns were adhesively bonded (Calibra Universal, Dentsply Sirona, USA) on standardized resin-based composite molars (FDI 46, P Pro temporary Crown & Bridge). Thermal cycling and mechanical loading (2 × 3000 × 5°C/55 °C, 2min, H₂0 dist., 1.2 × 10⁶ force 50N) were performed and fracture force was determined (v = 1 mm/min, Z010, Zwick, Germany). Mean wear, maximum wear, and roughness were investigated on polished (P1200) specimens (n = 8 per group, d = 8 mm) in a pin-on-block test (50N; 120000 cycles; 1.6Hz; H₂O). Statistics were performed by using one-way ANOVA, Bonferroni post-hoc-tests, and Pearson-correlation (α = 0.05).

RESULTS: All crowns survived TCML without failures. Fracture forces ranged from 1362.4 ± 182.4N to 2354.1 ± 373.3N for the additive temporary crowns, from 1680.4.4 ± 525.1N to 2601.6 ± 403.7N for the additive permanent crowns, and reached values of 2988.5 ± 604.7N for subtractive temporary crowns and 3092.0 ± 307.6 N for subtractive permanent crowns. Significant (p < 0.001) differences were identified between the various additively manufactured systems, but not for the subtractively fabricated systems (p = 0.673). Mean wear of the additive temporary crowns ranged between 114.5 ± 25.8 μm and 163.8 ± 21.4 μm without significant differences (p = 0.061). Mean wear of the additive permanent crowns ranged between 120.0 ± 27.5 μm and 171.3 ± 31.8 μm with significant differences (p = 0.004). No statistically significant differences were identified between temporary and permanent subtractively manufactured specimens, with mean wear ranging between 140.5 ± 51.1 μm and 176.6 ± 26.8 μm (p = 0.673). Maximum wear of additive temporary specimens ranged between 221.4.5 ± 53.3 μm and 322.1 ± 50.6 μm; significant differences were identified between the groups (p = 0.016). Maximum wear of additive permanent specimens ranged between 246.3 ± 47.3 μm and 337.4 ± 61.4 μm, and significant differences were identified between the groups (p = 0.006). Mean wear of the subtractive group (permanent and temporary) showed no differences in maximum wear from 277.9 ± 79.7.1 μm to 316.4 ± 58.1 μm (p = 0.288). Ra roughness ranged from 0.7 ± 0.2 μm to 3.6 ± 1.3 μm with significant differences (p < 0.001) and Rz reference between 65.9 ± 26.2 μm and 16.8 ± 6.3 μm.

CONCLUSION: Temporary and permanent molar crowns provided at least acceptable in-vitro performance and fracture force for clinical mid-term application. Laboratory wear stability of the resin-based materials appeared sufficient, but should be verified under clinical conditions.

PMID:37001248 | DOI:10.1016/j.jmbbm.2023.105806

Am J Cardiol. 2023 Mar 3;195:23-26. doi: 10.1016/j.amjcard.2023.02.016. Online ahead of print.

ABSTRACT

Utilization of radio-opaque coronary artery bypass graft markers is known to decrease the amount of contrast dye required to complete the procedure. The practice of marking bypass grafts varies significantly among surgeons. Limited data exist comparing the outcomes of percutaneous coronary intervention with and without coronary artery bypass graft (CABG) markers. We sought to explore the impact of proximal radio-opaque markers placed during CABG in subsequent percutaneous coronary intervention procedural risks. In our understanding of the current literature, this is the first meta-analysis conducted to evaluate the association between procedural angiographic metrics and CABG radio-opaque markers. We performed a query of MEDLINE and Scopus databases through August 2022 to identify relevant studies evaluating procedural metrics among patients with previous CABG with and without radio-opaque markers who underwent angiography. The primary outcomes of interest were fluoroscopy time, amount of contrast, and duration of angiography. We identified a total of 4 studies with 2,046 patients with CABG (CABG with markers n = 688, CABG without markers n = 1,518).^2-5 Total fluoroscopy time was significantly reduced among patients with CABG markers compared with those with no markers (odds ratio [OR] -3.63, p <0.0001). The duration of angiography (OR -36.39, p >0.10) was reduced, although the result was not statistically significant. However, the amount of contrast utilization was significantly reduced (OR -33.41, p <0.0001). In patients who underwent CABG with radio-opaque markers, angiographic procedural metrics were improved, including reduced fluoroscopic time and the amount of contrast agent required compared with no markers.

PMID:37001240 | DOI:10.1016/j.amjcard.2023.02.016

Aquat Toxicol. 2023 Mar 21;258:106503. doi: 10.1016/j.aquatox.2023.106503. Online ahead of print.

ABSTRACT

We developed a model that quantifies aquatic cationic toxicity by a combination of the intrinsic toxicities of metals and protons and the intrinsic sensitivities of the test species. It is based on the WHAM-F_TOX model, which combines the calculated binding of cations by the organism with toxicity coefficients (α_H, α_M) to estimate the variable F_TOX, a measure of toxic effect; the key parameter α_M,max (applying at infinite time) depends upon both the metal and the test species. In our new model, WHAM-F_TOXβ, values of α_M,max are given by the product α_M* × β, where α_M* has a single value for each metal, and β a single value for each species. To parameterise WHAM-F_TOXβ, we assembled a set of 2182 estimates of α_M,max obtained by applying the basic model to laboratory toxicity data for 76 different test species, covering 15 different metals, and including results for metal mixtures. Then we fitted the log₁₀α_M,max values with α_M* and β values (a total of 91 parameters). The resulting model accounted for 72% of the variance in log₁₀α_M,max. The values of α_M* increased markedly as the chemical character of the metal changed from hard (average α_M* = 4.4) to intermediate (average α_M* = 25) to soft (average α_M* = 560). The values of log₁₀β were normally distributed, with a 5-95 percentile range of -0.73 to +0.56, corresponding to β values of 0.18 to 3.62. The WHAM-F_TOXβ model entails the assumption that test species exhibit common relative sensitivity, i.e. the ratio α_M,max / α_M* is constant across all metals. This was tested with data from studies in which the toxic responses of a single organism towards two or more metals had been measured (179 examples for the most-tested metals Ni, Cu, Zn, Ag, Cd, Pb), and statistically-significant (p < 0.003) results were obtained.

PMID:37001198 | DOI:10.1016/j.aquatox.2023.106503