Search

PacBio HiFi sequencing was employed in combination with metagenomic binning to produce a high-quality reference genome of Cosmopolites sordidus . We compared k-mer and alignment reference based pre-binning and post-binning approaches to remove contamination. We were also interested to know if the post-binning approach had interspersed bacterial contamination within intragenic regions of Arthropoda binned contigs. Our analyses identified 3,433 genes that were composed with reads identified as of putative bacterial origins. The pre-binning approach yielded a C. sordidus genome of 1.07 Gb genome composed of 3,089 contigs with 98.6% and 97.1% complete and single copy genome and protein BUSCO scores respectively. In this article we demonstrate that in this case the pre-binning approach does not sacrifice assembly quality for more stringent metagenomic filtering. We also determine post-binning allows for increased intragenic contamination increased with increasing coverage, but the frequency of gene contamination increased with lower coverage. Future work should focus on developing reference free pre-binning approaches for HiFi reads produced from eukaryotic based metagenomic samples., Competing Interests: The authors declare that they have no competing interests., (© 2023 Rodriguez Ruiz and Van Dam.)

Objectives: To assess the stand-alone and combined performance of artificial intelligence (AI) detection systems for digital mammography (DM) and automated 3D breast ultrasound (ABUS) in detecting breast cancer in women with dense breasts., Methods: 430 paired cases of DM and ABUS examinations from a Asian population with dense breasts were retrospectively collected. All cases were analyzed by two AI systems, one for DM exams and one for ABUS exams. A selected subset (n = 152) was read by four radiologists. The performance of AI systems was based on analysis of the area under the receiver operating characteristic curve (AUC). The maximum Youden's index and its associated sensitivity and specificity were also reported for each AI systems. Detection performance of human readers in the subcohort of the reader study was measured in terms of sensitivity and specificity., Results: The performance of the AI systems in a multi-modal setting was significantly better when the weights of AI-DM and AI-ABUS were 0.25 and 0.75, respectively, than each system individually in a single-modal setting (AUC-AI-Multimodal = 0.865; AUC-AI-DM = 0.832, p = 0.026; AUC-AI-ABUS = 0.841, p = 0.041). The maximum Youden's index for AI-Multimodal was 0.707 (sensitivity = 79.4%, specificity = 91.2%). In the subcohort that underwent human reading, the panel of four readers achieved a sensitivity of 93.2% and specificity of 32.7%. AI-multimodal achieves superior or equal sensitivity as single human readers at the same specificity operating points on the ROC curve., Conclusion: Multimodal (ABUS + DM) AI systems for detecting breast cancer in women with dense breasts are a potential solution for breast screening in radiologist-scarce regions., (© 2023. The Author(s).)

Objective: To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage., Method: Co-expression behavior of WWP2 with genes expressed in lesioned OA articular cartilage (N = 35 samples) was explored. By applying lentiviral particle mediated WWP2 upregulation in 3D in vitro pellet cultures of human primary chondrocytes (N = 8 donors) the effects of upregulation on cartilage matrix deposition was evaluated. Finally, we transfected primary chondrocytes with miR-140 mimics to evaluate whether miR-140 and WWP2 are involved in similar pathways., Results: Upon performing Spearman correlations in lesioned OA cartilage, 98 highly correlating genes (|ρ| > 0.7) were identified. Among these genes, we identified GJA1, GDF10, STC2, WDR1, and WNK4. Subsequent upregulation of WWP2 on 3D chondrocyte pellet cultures resulted in a decreased expression of COL2A1 and ACAN and an increase in EPAS1 expression. Additionally, we observed a decreased expression of GDF10, STC2, and GJA1. Proteomics analysis identified 42 proteins being differentially expressed with WWP2 upregulation, which were enriched for ubiquitin conjugating enzyme activity. Finally, upregulation of miR-140 in 2D chondrocytes resulted in significant upregulation of WWP2 and WDR1., Conclusions: Mimicking the effect of OA risk allele rs1052429-A on WWP2 expression initiates detrimental processes in the cartilage shown by a response in hypoxia associated genes EPAS1, GDF10, and GJA1 and a decrease in anabolic markers, COL2A1 and ACAN., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Studies examining seizures (Szs) and epileptiform abnormalities (EAs) using continuous EEG in acute ischemic stroke (AIS) are limited. Therefore, we aimed to describe the prevalence of Sz and EA in AIS, its impact on anti-Sz drug management, and association with discharge outcomes., Methods: The study included 132 patients with AIS who underwent continuous EEG monitoring >6 hours. Continuous EEG was reviewed for background, Sz and EA (lateralized periodic discharges [LPD], generalized periodic discharges, lateralized rhythmic delta activity, and sporadic epileptiform discharges). Relevant clinical, demographic, and imaging factors were abstracted to identify risk factors for Sz and EA. Outcomes included all-cause mortality, functional outcome at discharge (good outcome as modified Rankin scale of 0-2 and poor outcome as modified Rankin scale of 3-6) and changes to anti-Sz drugs (escalation or de-escalation)., Results: The frequency of Sz was 7.6%, and EA was 37.9%. Patients with Sz or EA were more likely to have cortical involvement (84.6% vs. 67.5% P = 0.028). Among the EAs, the presence of LPD was associated with an increased risk of Sz (25.9% in LPD vs. 2.9% without LPD, P = 0.001). Overall, 21.2% patients had anti-Sz drug changes because of continuous EEG findings, 16.7% escalation and 4.5% de-escalation. The presence of EA or Sz was not associated with in-hospital mortality or discharge functional outcomes., Conclusions: Despite the high incidence of EA, the rate of Sz in AIS is relatively lower and is associated with the presence of LPDs. These continuous EEG findings resulted in anti-Sz drug changes in one-fifth of the cohort. Epileptiform abnormality and Sz did not affect mortality or discharge functional outcomes., Competing Interests: M. B. Dhakar received research support for clinical trials from UCB Pharma and Marinus Pharmaceuticals; in the past, she received an honorarium for a consultancy from Adamas Pharmaceuticals; she also receives salary support from NIH. Z. Sheikh received travel reimbursements from Medtronic for attending meetings on deep brain stimulation in epilepsy. A. Rodriguez has participated in an education symposium sponsored by Neuropace, Inc. H. A. Haider receives consultant support from Ceribell, Inc, author royalties from UpToDate, Inc and Springer Publishing, and serves on the advisory board of Esai, Inc. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2020 by the American Clinical Neurophysiology Society.)

Objective: Based on the promising results of randomized controlled trials, deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used increasingly in the treatment of patients with drug-resistant epilepsy. Drug-resistant temporal lobe epilepsy (TLE) is an indication for either DBS of the anterior nucleus of the thalamus (ANT) or temporal lobe (TL) RNS, but there are no studies that directly compare the seizure benefits and adverse effects associated with these therapies in this patient population. We, therefore, examined all patients who underwent ANT-DBS or TL-RNS for drug-resistant TLE at our center., Methods: We performed a retrospective review of patients who were treated with either ANT-DBS or TL-RNS for drug-resistant TLE with at least 12 months of follow-up. Along with the clinical characteristics of each patient's epilepsy, seizure frequency was recorded throughout each patient's postoperative clinical course., Results: Twenty-six patients underwent ANT-DBS implantation and 32 patients underwent TL-RNS for drug-resistant TLE. The epilepsy characteristics of both groups were similar. Patients who underwent ANT-DBS demonstrated a median seizure reduction of 58% at 12-15 months, compared to a median seizure reduction of 70% at 12-15 months in patients treated with TL-RNS (p > .05). The responder rate (percentage of patients with a 50% decrease or more in seizure frequency) was 54% for ANT-DBS and 56% for TL-RNS (p > .05). The incidence of complications and stimulation-related side effects did not significantly differ between therapies., Significance: We demonstrate in our single-center experience that patients with drug-resistant TLE benefit similarly from either ANT-DBS or TL-RNS. Selection of either ANT-DBS or TL-RNS may, therefore, depend more heavily on patient and provider preference, as each has unique capabilities and configurations. Future studies will consider subgroup analyses to determine if specific patients have greater seizure frequency reduction from one form of neuromodulation strategy over another., (© 2022 International League Against Epilepsy.)

The three isoenzymes of iodothyronine deiodinases (DIO1-3) are membrane-anchored homo-dimeric selenoproteins which share the thioredoxin-fold structure. Several questions regarding their catalytic mechanisms still remain open. Here, we addressed the roles of several cysteines which are conserved among deiodinase isoenzymes and asked whether they may contribute to dimerization and reduction of the oxidized enzyme with physiological reductants. We also asked whether amino acids previously identified in DIO3 play the same role in DIO1. Human DIO1 and 2 were recombinantly expressed in insect cells with selenocysteine replaced with cysteine (DIO1 U126C ) or in COS7 cells as selenoprotein. Enzyme activities were studied by radioactive deiodination assays with physiological reducing agents and recombinant proteins were characterized by mass spectrometry. Mutation of Cys124 in DIO1 prevented reduction by glutathione, while 20 mM dithiothreitol still regenerated the enzyme. Protein thiol reductants, thioredoxin and glutaredoxin, did not reduce DIO1 U126C . Mass spectrometry demonstrated the formation of an intracellular disulfide between the side-chains of Cys124 and Cys(Sec)126. We conclude that the proximal Cys124 forms a selenenyl-sulfide with the catalytic Sec126 during catalysis, which is the substrate of the physiological reductant glutathione. Mutagenesis studies support the idea of a proton-relay pathway from solvent to substrate that is shared between DIO1 and DIO3.

Objectives: To evaluate if artificial intelligence (AI) can discriminate recalled benign from recalled malignant mammographic screening abnormalities to improve screening performance., Methods: A total of 2257 full-field digital mammography screening examinations, obtained 2011-2013, of women aged 50-69 years which were recalled for further assessment of 295 malignant out of 305 truly malignant lesions and 2289 benign lesions after independent double-reading with arbitration, were included in this retrospective study. A deep learning AI system was used to obtain a score (0-95) for each recalled lesion, representing the likelihood of breast cancer. The sensitivity on the lesion level and the proportion of women without false-positive ratings (non-FPR) resulting under AI were estimated as a function of the classification cutoff and compared to that of human readers., Results: Using a cutoff of 1, AI decreased the proportion of women with false-positives from 89.9 to 62.0%, non-FPR 11.1% vs. 38.0% (difference 26.9%, 95% confidence interval 25.1-28.8%; p < .001), preventing 30.1% of reader-induced false-positive recalls, while reducing sensitivity from 96.7 to 91.1% (5.6%, 3.1-8.0%) as compared to human reading. The positive predictive value of recall (PPV-1) increased from 12.8 to 16.5% (3.7%, 3.5-4.0%). In women with mass-related lesions (n = 900), the non-FPR was 14.2% for humans vs. 36.7% for AI (22.4%, 19.8-25.3%) at a sensitivity of 98.5% vs. 97.1% (1.5%, 0-3.5%)., Conclusion: The application of AI during consensus conference might especially help readers to reduce false-positive recalls of masses at the expense of a small sensitivity reduction. Prospective studies are needed to further evaluate the screening benefit of AI in practice., Key Points: • Integrating the use of artificial intelligence in the arbitration process reduces benign recalls and increases the positive predictive value of recall at the expense of some sensitivity loss. • Application of the artificial intelligence system to aid the decision to recall a woman seems particularly beneficial for masses, where the system reaches comparable sensitivity to that of the readers, but with considerably reduced false-positives. • About one-fourth of all recalled malignant lesions are not automatically marked by the system such that their evaluation (AI score) must be retrieved manually by the reader. A thorough reading of screening mammograms by readers to identify suspicious lesions therefore remains mandatory., (© 2021. The Author(s).)

Background The high volume of data in digital breast tomosynthesis (DBT) and the lack of agreement on how to best implement it in screening programs makes its use challenging. Purpose To compare radiologist performance when reading single-view wide-angle DBT images with and without an artificial intelligence (AI) system for decision and navigation support. Materials and Methods A retrospective observer study was performed with bilateral mediolateral oblique examinations and corresponding synthetic two-dimensional images acquired between June 2016 and February 2018 with a wide-angle DBT system. Fourteen breast screening radiologists interpreted 190 DBT examinations (90 normal, 26 with benign findings, and 74 with malignant findings), with the reference standard being verified by using histopathologic analysis or at least 1 year of follow-up. Reading was performed in two sessions, separated by at least 4 weeks, with a random mix of examinations being read with and without AI decision and navigation support. Forced Breast Imaging Reporting and Data System (categories 1-5) and level of suspicion (1-100) scores were given per breast by each reader. The area under the receiver operating characteristic curve (AUC) and the sensitivity and specificity were compared between conditions by using the public-domain iMRMC software. The average reading times were compared by using the Wilcoxon signed rank test. Results The 190 women had a median age of 54 years (range, 48-63 years). The examination-based reader-averaged AUC was higher when interpreting results with AI support than when reading unaided (0.88 [95% CI: 0.84, 0.92] vs 0.85 [95% CI: 0.80, 0.89], respectively; P = .01). The average sensitivity increased with AI support (64 of 74, 86% [95% CI: 80%, 92%] vs 60 of 74, 81% [95% CI: 74%, 88%]; P = .006), whereas no differences in the specificity (85 of 116, 73.3% [95% CI: 65%, 81%] vs 83 of 116, 71.6% [95% CI: 65%, 78%]; P = .48) or reading time (48 seconds vs 45 seconds; P = .35) were detected. Conclusion Using a single-view digital breast tomosynthesis (DBT) and artificial intelligence setup could allow for a more effective screening program with higher performance, especially in terms of an increase in cancers detected, than using single-view DBT alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Chan and Helvie in this issue.

Objectives/hypothesis: To assess the evolution of laryngeal and extralaryngeal symptoms and findings of laryngopharyngeal reflux (LPR) throughout a 3-month to 9-month treatment., Study Design: Prospective Controlled Study., Methods: One hundred twenty-seven LPR patients and 123 healthy individuals were enrolled from four European hospitals. Patients were managed with a 3-month personalized treatment considering the LPR characteristics at the impedance-pH monitoring. Regarding the clinical therapeutic response, treatment was adapted for 3 to 6 additional months. Symptoms and findings were assessed throughout the therapeutic course with the Reflux Symptom Score (RSS) and the short version of the Reflux Sign Assessment (sRSA). The relationship between patient and reflux characteristics, symptoms, and findings was assessed., Results: One hundred twenty-one LPR patients completed the study. LPR patients exhibited more laryngeal and extralaryngeal symptoms and findings than healthy individuals. RSS significantly improved from baseline to 6 weeks posttreatment and continued to improve from 3 months to 6 months posttreatment. sRSA significantly improved from baseline to 3 months posttreatment. No further improvement was noted at 6 months posttreatment for pharyngeal and oral findings. Laryngeal findings continued to improve from 3 months to 6 months posttreatment. There was a significant association between patient stress level and RSS (P = .045). At 3 months posttreatment, 28.1% of patients had high or complete response, whereas 47.1% required 6 months or 9 months of treatment. Overall, 24.8% of patients had an LPR chronic course., Conclusions: Laryngeal and extralaryngeal symptoms and findings significantly improved throughout treatment in LPR patients. The improvement of laryngeal findings was slower. Regarding the low prevalence of some digestive or otolaryngological symptoms, a short version of the RSS could be developed., Level of Evidence: 3 Laryngoscope, 131:1332-1342, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To assess the evolution of symptoms and findings of laryngopharyngeal reflux (LPR) patients according to the type of reflux (acid, non-acid, mixed and gastro-oesophageal (GERD))., Design: Prospective uncontrolled multicentre study., Methods: One hundred and six patients with LPR have been recruited from 3 European Hospitals. According to the reflux characteristics at the impedance-pH monitoring (acid, non-acid, mixed, GERD), patients received a personalised treatment based on the association of diet, pantoprazole, alginate or magaldrate for 3 months. Reflux Symptom Score (RSS) was assessed at baseline, 6 and 12 weeks post-treatment. Reflux Sign Assessment (RSA) has been used to rate laryngeal and extra-laryngeal findings at baseline and 12 weeks post-treatment. Overall success rate and the evolution of symptoms and findings were evaluated according to the LPR types., Results: One hundred and two LPR patients (42 acid, 33 non-acid, 27 mixed, including 49 with LPR and GERD) completed the study. RSS and RSA total scores significantly improved from baseline to post-treatment time in acid, mixed and non-acid groups. The presence of GERD in addition to LPR did not impact the clinical improvement. The 3-month success rates of treatment ranged from 62% to 64%, and there were no significant differences between groups. The success rate of patients with non-acid LPR was similar to those of patients with mixed and acid LPR., Conclusion: MII-pH is useful to specify the type of LPR and the related most adequate therapeutic regimen. Non-acid or mixed LPR similarly respond to treatment than acid LPR but require a treatment based on alginate or magaldrate covering the non-acid proximal reflux events., (© 2021 John Wiley & Sons Ltd.)

In the past two decades, relevant advances have been made in the generation of engineered cardiac constructs to be used as functional in vitro models for cardiac research or drug testing, and with the ultimate but still challenging goal of repairing the damaged myocardium. To support cardiac tissue generation and maturation in vitro , the application of biomimetic physical stimuli within dedicated bioreactors is crucial. In particular, cardiac-like mechanical stimulation has been demonstrated to promote development and maturation of cardiac tissue models. Here, we developed an automated bioreactor platform for tunable cyclic stretch and in situ monitoring of the mechanical response of in vitro engineered cardiac tissues. To demonstrate the bioreactor platform performance and to investigate the effects of cyclic stretch on construct maturation and contractility, we developed 3D annular cardiac tissue models based on neonatal rat cardiac cells embedded in fibrin hydrogel. The constructs were statically pre-cultured for 5 days and then exposed to 4 days of uniaxial cyclic stretch (sinusoidal waveform, 10% strain, 1 Hz) within the bioreactor. Explanatory biological tests showed that cyclic stretch promoted cardiomyocyte alignment, maintenance, and maturation, with enhanced expression of typical mature cardiac markers compared to static controls. Moreover, in situ monitoring showed increasing passive force of the constructs along the dynamic culture. Finally, only the stretched constructs were responsive to external electrical pacing with synchronous and regular contractile activity, further confirming that cyclic stretching was instrumental for their functional maturation. This study shows that the proposed bioreactor platform is a reliable device for cyclic stretch culture and in situ monitoring of the passive mechanical response of the cultured constructs. The innovative feature of acquiring passive force measurements in situ and along the culture allows monitoring the construct maturation trend without interrupting the culture, making the proposed device a powerful tool for in vitro investigation and ultimately production of functional engineered cardiac constructs., (Copyright © 2020 Massai, Pisani, Isu, Rodriguez Ruiz, Cerino, Galluzzi, Pisanu, Tonoli, Bignardi, Audenino, Marsano and Morbiducci.)

Objective: To develop and validate the Reflux Sign Assessment (RSA), a clinical instrument evaluating the physical findings of laryngopharyngeal reflux (LPR)., Methods: A total of 106 patients completed a 3-month treatment based on the association of diet, pantoprazole, alginate, or magaldrate with the LPR characteristics (acid, nonacid, mixed). Forty-two asymptomatic individuals completed the study (control group). The RSA results and reflux finding score (RFS) were documented for the LPR patients at baseline and after treatment. Intrarater reliability was assessed through a test-retest blinded evaluation of signs (7-day intervals). Interrater reliability was assessed by comparing the RSA evaluations of three blinded otolaryngologists through Kendall's W. Responsiveness to change was evaluated through a comparison of the baseline and 3-month posttreatment findings. The RSA cutoffs for determining the presence and absence of LPR were examined by receiver operating characteristic (ROC) analysis., Results: A total of 102 LPR patients completed the study (68 females). The mean age was 53 years. The mean RSA at baseline was 25.95 ± 9.58; it significantly improved to 18.96 ± 7.58 after 3 months of therapy ( P  < .001). RSA exhibited good intra- ( r  = 0.813) and interrater (Kendall's W = 0.663) reliabilities (N = 56). There was no significant association between the RSA, gastrointestinal endoscopy findings, and the types of reflux (acid, nonacid, or mixed) according to impedance-pH monitoring. An RSA >14 may be suggestive of LPR., Conclusion: The RSA is a complete clinical instrument evaluating both laryngeal and extralaryngeal findings associated with LPR. The RSA demonstrated high intra- and interrater reliabilities and responsiveness to change.

Objectives/hypothesis: To develop and validate the Reflux Symptom Score (RSS), a self-administered patient-reported outcome questionnaire for patients with laryngopharyngeal reflux (LPR)., Study Design: Prospective controlled study., Methods: A total of 113 patients with LPR were enrolled and treated with diet and 3 months of pantoprazole, alginate, and/or magaldrate depending on the LPR characteristics (acid, nonacid, or mixed). Eighty asymptomatic individuals completed the study. Patients and controls completed the RSS twice within a 7-day period to assess test-retest reliability. Internal consistency was measured using Cronbach's α for the RSS items in patients and controls. Validity was assessed by comparing the baseline RSS with the Reflux Symptom Index (RSI) and Voice Handicap Index (VHI). Seventy-seven patients completed the RSS at baseline and after 6 and 12 weeks of treatment to assess responsiveness to change. The RSS cutoff for determining the presence and absence of LPR was examined by receiver operating characteristic analysis., Results: Test-retest reliability (r s = 0.921) and internal consistency reliability (α = 0.969) were high. RSS exhibited high external validity indicated by a significant correlation with the RSI (r s = 0.831). Internal validity was excellent based on the higher RSS in patients compared with controls (P = .001). RSS, RSI, and VHI scores significantly improved from pre- to posttreatment, indicating a high responsiveness to change. RSS >13 can be considered suggestive of LPR-related symptoms. RSS was not influenced by the occurrence of gastroesophageal reflux disease, LPR subtypes, or patient characteristics., Conclusions: RSS is a self-administered patient-reported outcome questionnaire that demonstrates high reliability and excellent criterion-based validity. RSS can be used in diagnosing and monitoring LPR disease., Level of Evidence: 3b Laryngoscope, 130:E98-E107, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Artificial intelligence (AI) systems performing at radiologist-like levels in the evaluation of digital mammography (DM) would improve breast cancer screening accuracy and efficiency. We aimed to compare the stand-alone performance of an AI system to that of radiologists in detecting breast cancer in DM., Methods: Nine multi-reader, multi-case study datasets previously used for different research purposes in seven countries were collected. Each dataset consisted of DM exams acquired with systems from four different vendors, multiple radiologists' assessments per exam, and ground truth verified by histopathological analysis or follow-up, yielding a total of 2652 exams (653 malignant) and interpretations by 101 radiologists (28 296 independent interpretations). An AI system analyzed these exams yielding a level of suspicion of cancer present between 1 and 10. The detection performance between the radiologists and the AI system was compared using a noninferiority null hypothesis at a margin of 0.05., Results: The performance of the AI system was statistically noninferior to that of the average of the 101 radiologists. The AI system had a 0.840 (95% confidence interval [CI] = 0.820 to 0.860) area under the ROC curve and the average of the radiologists was 0.814 (95% CI = 0.787 to 0.841) (difference 95% CI = -0.003 to 0.055). The AI system had an AUC higher than 61.4% of the radiologists., Conclusions: The evaluated AI system achieved a cancer detection accuracy comparable to an average breast radiologist in this retrospective setting. Although promising, the performance and impact of such a system in a screening setting needs further investigation., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To study the feasibility of automatically identifying normal digital mammography (DM) exams with artificial intelligence (AI) to reduce the breast cancer screening reading workload., Methods and Materials: A total of 2652 DM exams (653 cancer) and interpretations by 101 radiologists were gathered from nine previously performed multi-reader multi-case receiver operating characteristic (MRMC ROC) studies. An AI system was used to obtain a score between 1 and 10 for each exam, representing the likelihood of cancer present. Using all AI scores between 1 and 9 as possible thresholds, the exams were divided into groups of low- and high likelihood of cancer present. It was assumed that, under the pre-selection scenario, only the high-likelihood group would be read by radiologists, while all low-likelihood exams would be reported as normal. The area under the reader-averaged ROC curve (AUC) was calculated for the original evaluations and for the pre-selection scenarios and compared using a non-inferiority hypothesis., Results: Setting the low/high-likelihood threshold at an AI score of 5 (high likelihood > 5) results in a trade-off of approximately halving (- 47%) the workload to be read by radiologists while excluding 7% of true-positive exams. Using an AI score of 2 as threshold yields a workload reduction of 17% while only excluding 1% of true-positive exams. Pre-selection did not change the average AUC of radiologists (inferior 95% CI > - 0.05) for any threshold except at the extreme AI score of 9., Conclusion: It is possible to automatically pre-select exams using AI to significantly reduce the breast cancer screening reading workload., Key Points: • There is potential to use artificial intelligence to automatically reduce the breast cancer screening reading workload by excluding exams with a low likelihood of cancer. • The exclusion of exams with the lowest likelihood of cancer in screening might not change radiologists' breast cancer detection performance. • When excluding exams with the lowest likelihood of cancer, the decrease in true-positive recalls would be balanced by a simultaneous reduction in false-positive recalls.

Importance: Laryngopharyngeal reflux (LPR) is a prevalent disease that is usually treated with diet, lifestyle modifications, and proton pump inhibitor therapy. However, nearly 10% to 30% of patients do not achieve adequate acid suppression even with high doses of proton pump inhibitors. For these patients with resistant disease, fundoplication may be recommended but the success rate of fundoplication surgery on laryngopharyngeal symptoms and findings remains uncertain., Objective: To determine whether fundoplication is associated with control of signs and symptoms in patients with LPR., Evidence Review: A literature search was conducted on PubMed, Cochrane Library, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline to identify studies published between 1990 and 2018 about the efficacy of fundoplication on clinical outcomes of LPR. Three investigators screened publications for eligibility and exclusion based on predetermined criteria. Study design, patient characteristics, diagnostic method, exclusion criteria, treatment characteristics, follow-up, and quality of the outcome assessment were evaluated., Findings: Of the 266 studies identified, 34 met the inclusion criteria, accounting for 2190 patients with LPR (1270 women and 920 men; mean [SD] age at the time of surgery, 49.3 [6.3] years). A weighted mean of 83.0% of patients (95% CI, 79.7%-86.3%) experienced improvement and a weighted mean of 67.0% of patients (95% CI, 64.1%-69.9%) experienced a disappearance of symptoms, but there is a high level of methodological heterogeneity among studies according to diagnostic method, exclusion criteria, and outcomes used to assess the efficacy of fundoplication. A pH study without impedance study was used in most studies but with various inclusion criteria. According to results of an a priori assessment, the clinical outcomes used were overall poor, excluding many symptoms and findings associated with LPR., Conclusion and Relevance: The reported studies of fundoplication in LPR disease have important heterogeneity in method of diagnosis, exclusion criteria, symptoms, and signs assessed as therapeutic outcomes; therefore, this systematic review was nonconclusive regarding whether surgery for LPR disease is associated with effective control of sight and symptoms. Otolaryngologists, gastroenterologists, and surgeons must establish a diagnostic criterion standard, clear indications for surgery, and future clinical outcomes to precisely assess the effectiveness of treatment.

Purpose: To compare breast cancer detection and depiction between planar synthetic mammography (SM) and rotating synthetic mammography (RM) generated from digital breast tomosynthesis (DBT)., Materials and Methods: In a fully-crossed multi-reader multi-case (MRMC) study, three radiologists retrospectively reviewed 190 cases (27 malignant, 31 benign, 132 normal), once with SM alone and once with RM alone, the DBT stack of slices was not reviewed. Lesions were scored using BI-RADS® and level of suspiciousness (1-10). Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were computed using MRMC Analysis of Variance using the open-access software iMRMC. Additionally, readers were asked to make a visual grading analysis (VGA) on visibility of calcifications and soft tissue lesions (1-5 scale with 5 = Excellent visualization). The VGA scores were analyzed using the visual grading characteristics (VGC) method., Results: On average, the AUC was similar between SM and RM (0.66 versus 0.67, P = 0.818). The sensitivity was equivalent (0.62 versus 0.60, P = 0.794), while specificity was significantly lower in SM than in RM (0.66 versus 0.72, P = 0.028). Radiologists significantly (P < 0.05) preferred the display of all types of lesions in RM over SM. The average reading time per case was higher for RM than for SM (30 s versus 23 s, P < 0.05)., Conclusion: Radiologists achieve similar cancer detection with RM as with SM. They prefer the 3D-like rotating representation of soft tissue lesions and calcifications in comparison to the 2D visualization, which might improve their specificity, but at the expense of longer reading time., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background The image quality of digital breast tomosynthesis (DBT) volumes depends greatly on the reconstruction algorithm. Purpose To compare two DBT reconstruction algorithms used by the Siemens Mammomat Inspiration system, filtered back projection (FBP), and FBP with iterative optimizations (EMPIRE), using qualitative analysis by human readers and detection performance of machine learning algorithms. Material and Methods Visual grading analysis was performed by four readers specialized in breast imaging who scored 100 cases reconstructed with both algorithms (70 lesions). Scoring (5-point scale: 1 = poor to 5 = excellent quality) was performed on presence of noise and artifacts, visualization of skin-line and Cooper's ligaments, contrast, and image quality, and, when present, lesion visibility. In parallel, a three-dimensional deep-learning convolutional neural network (3D-CNN) was trained (n = 259 patients, 51 positives with BI-RADS 3, 4, or 5 calcifications) and tested (n = 46 patients, nine positives), separately with FBP and EMPIRE volumes, to discriminate between samples with and without calcifications. The partial area under the receiver operating characteristic curve (pAUC) of each 3D-CNN was used for comparison. Results EMPIRE reconstructions showed better contrast (3.23 vs. 3.10, P = 0.010), image quality (3.22 vs. 3.03, P < 0.001), visibility of calcifications (3.53 vs. 3.37, P = 0.053, significant for one reader), and fewer artifacts (3.26 vs. 2.97, P < 0.001). The 3D-CNN-EMPIRE had better performance than 3D-CNN-FBP (pAUC-EMPIRE = 0.880 vs. pAUC-FBP = 0.857; P < 0.001). Conclusion The new algorithm provides DBT volumes with better contrast and image quality, fewer artifacts, and improved visibility of calcifications for human observers, as well as improved detection performance with deep-learning algorithms.

Purpose: To compare the performance of one-view digital breast tomosynthesis (1v-DBT) to that of three other protocols combining DBT and mammography (DM) for breast cancer detection., Materials and Methods: Six radiologists, three experienced with 1v-DBT in screening, retrospectively reviewed 181 cases (76 malignant, 50 benign, 55 normal) in two sessions. First, they scored sequentially: 1v-DBT (medio-lateral oblique, MLO), 1v-DBT (MLO) + 1v-DM (cranio-caudal, CC) and two-view DM + DBT (2v-DM+2v-DBT). The second session involved only 2v-DM. Lesions were scored using BI-RADS® and level of suspiciousness (1-10). Sensitivity, specificity, receiver operating characteristic (ROC) and jack-knife alternative free-response ROC (JAFROC) were computed., Results: On average, 1v-DBT was non-inferior to any of the other protocols in terms of JAFROC figure-of-merit, area under ROC curve, sensitivity or specificity (p>0.391). While readers inexperienced with 1v-DBT screening improved their sensitivity when adding more images (69-79 %, p=0.019), experienced readers showed similar sensitivity (76 %) and specificity (70 %) between 1v-DBT and 2v-DM+2v-DBT (p=0.482). Subanalysis by lesion type and breast density showed no difference among modalities., Conclusion: Detection performance with 1v-DBT is not statistically inferior to 2v-DM or to 2v-DM+2v-DBT; its use as a stand-alone modality might be sufficient for readers experienced with this protocol., Key Points: • One-view breast tomosynthesis is not inferior to two-view digital mammography. • One-view DBT is not inferior to 2-view DM plus 2-view DBT. • Training may lead to 1v-DBT being sufficient for screening.

Thyroid hormones and their metabolites constitute a vast class of related iodothyronine compounds that contribute to the regulation of metabolic activity and cell differentiation. They are in turn transported, transformed and recognized as signaling molecules through binding to a variety of proteins from a wide range of evolutionary unrelated protein families, which renders these proteins and their iodothyronine binding sites an example for extensive convergent evolution. In this review, we will briefly summarize what is known about iodothyronine binding sites in proteins, the modes of protein/iodothyronine interaction, and the ligand conformations. We will then discuss physiological and synthetic compounds, including popular drugs and food components, that can interfere with iodothyronine binding and recognition by these proteins. The discussion also includes compounds persisting in the environment and acting as endocrine disrupting chemicals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Ultrafast dynamic contrast-enhanced magnetic resonance imaging of the breast enables assessment of the contrast inflow dynamics while providing images with diagnostic spatial resolution. However, the slice thickness of common ultrafast techniques still prevents multiplanar reconstruction. In addition, some temporal blurring of the enhancement characteristics occurs in case view-sharing is used. We evaluate a prototype compressed-sensing volume-interpolated breath-hold examination (CS-VIBE) sequence for ultrafast breast MRI that improves through plane spatial resolution and avoids temporal blurring while maintaining an ultrafast temporal resolution (less than 5 seconds per volume). Image quality (IQ) of the new sequence is compared with an ultrafast view-sharing sequence (time-resolved angiography with interleaved stochastic trajectories [TWIST]), and assessment of lesion morphology is compared with a regular T1-weighted 3D Dixon sequence (VIBE-DIXON) with an acquisition time of 91 seconds., Materials and Methods: From April 2016 to October 2016, 30 women were scanned with the CS-VIBE sequence, replacing the routine ultrafast TWIST sequence in a hybrid breast MRI protocol. The need for informed consent was waived. All MRI scans were performed on a 3T MAGNETOM Skyra system (Siemens Healthcare, Erlangen, Germany) using a 16-channel bilateral breast coil. Two reader studies were conducted involving 5 readers. In the first study, overall IQ of CS-VIBE and TWIST in the axial plane was independently rated for 23 women for whom prior MRI examinations with TWIST were available. In addition, the presence of several types of artifacts was rated on a 5-point scale. The second study was conducted in women (n = 16) with lesions. In total, characteristics of 31 lesions (5 malignant and 26 benign) were described independently for CS-VIBE and VIBE-DIXON, according to the BI-RADS MRI-lexicon. In addition, a lesion conspicuity score was given., Results: Using CS-VIBE, a much higher through-plane spatial resolution was achieved in the same acquisition time as with TWIST, without affecting in-plane IQ (P = 0.260). Time-resolved angiography with interleaved stochastic trajectories showed slightly more motion artifacts and infolding and ghosting artifacts compared with CS-VIBE, whereas CS-VIBE showed more breathing and pulsation artifacts. For morphologic assessment, intrareader agreement between CS-VIBE and the more time-consuming VIBE-DIXON was slight to almost perfect, and generally higher than interreader agreement. Mean sensitivity (84.0% and 92.0% for CS-VIBE and VIBE-DIXON, P = 0.500) and specificity (60.0% and 55.4% for CS-VIBE and VIBE-DIXON, P = 0.327) were comparable for both sequences., Conclusions: Compressed-sensing volume-interpolated breath-hold examination allows an increase of the through-plane spatial resolution of ultrafast dynamic contrast-enhanced magnetic resonance imaging compared with TWIST at a comparable in-plane IQ. Morphological assessment of lesions using CS-VIBE is comparable to VIBE-DIXON, which takes 18 times longer. Consequently, CS-VIBE enables 3D evaluation of breast lesions in ultrafast breast MRI.

Rationale and Objectives: The study aimed to compare the breast density estimates from two algorithms on full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) and to analyze the clinical implications., Materials and Methods: We selected 561 FFDM and DBT examinations from patients without breast pathologies. Two versions of a commercial software (Quantra 2D and Quantra 3D) calculated the volumetric breast density automatically in FFDM and DBT, respectively. Other parameters such as area breast density and total breast volume were evaluated. We compared the results from both algorithms using the Mann-Whitney U non-parametric test and the Spearman's rank coefficient for data correlation analysis. Mean glandular dose (MGD) was calculated following the methodology proposed by Dance et al., Results: Measurements with both algorithms are well correlated (r ≥ 0.77). However, there are statistically significant differences between the medians (P < 0.05) of most parameters. The volumetric and area breast density median values from FFDM are, respectively, 8% and 77% higher than DBT estimations. Both algorithms classify 35% and 55% of breasts into BIRADS (Breast Imaging-Reporting and Data System) b and c categories, respectively. There are no significant differences between the MGD calculated using the breast density from each algorithm. DBT delivers higher MGD than FFDM, with a lower difference (5%) for breasts in the BIRADS d category. MGD is, on average, 6% higher than values obtained with the breast glandularity proposed by Dance et al., Conclusions: Breast density measurements from both algorithms lead to equivalent BIRADS classification and MGD values, hence showing no difference in clinical outcomes. The median MGD values of FFDM and DBT examinations are similar for dense breasts (BIRADS d category)., (Published by Elsevier Inc.)

Importance: Periodic and rhythmic electroencephalographic patterns have been associated with risk of seizures in critically ill patients. However, specific features that confer higher seizure risk remain unclear., Objective: To analyze the association of distinct characteristics of periodic and rhythmic patterns with seizures., Design, Setting, and Participants: We reviewed electroencephalographic recordings from 4772 critically ill adults in 3 academic medical centers from February 2013 to September 2015 and performed a multivariate analysis to determine features associated with seizures., Interventions: Continuous electroencephalography., Main Outcomes and Measures: Association of periodic and rhythmic patterns and specific characteristics, such as pattern frequency (hertz), Plus modifier, prevalence, and stimulation-induced patterns, and the risk for seizures., Results: Of the 4772 patients included in our study, 2868 were men and 1904 were women. Lateralized periodic discharges (LPDs) had the highest association with seizures regardless of frequency and the association was greater when the Plus modifier was present (58%; odds ratio [OR], 2.00, P < .001). Generalized periodic discharges (GPDs) and lateralized rhythmic delta activity (LRDA) were associated with seizures in a frequency-dependent manner (1.5-2 Hz: GPDs, 24%,OR, 2.31, P = .02; LRDA, 24%, OR, 1.79, P = .05; ≥ 2 Hz: GPDs, 32%, OR, 3.30, P < .001; LRDA, 40%, OR, 3.98, P < .001) as was the association with Plus (GPDs, 28%, OR, 3.57, P < .001; LRDA, 40%, P < .001). There was no difference in seizure incidence in patients with generalized rhythmic delta activity compared with no periodic or rhythmic pattern (13%, OR, 1.18, P = .26). Higher prevalence of LPDs and GPDs also conferred increased seizure risk (37% frequent vs 45% abundant/continuous, OR, 1.64, P = .03 for difference; 8% rare/occasional vs 15% frequent, OR, 2.71, P = .03, vs 23% abundant/continuous, OR, 1.95, P = .04). Patterns associated with stimulation did not show an additional risk for seizures from the underlying pattern risk (P > .10)., Conclusions and Relevance: In this study, LPDs, LRDA, and GPDs were associated with seizures while generalized rhythmic delta activity was not. Lateralized periodic discharges were associated with seizures at all frequencies with and without Plus modifier, but LRDA and GPDs were associated with seizures when the frequency was 1.5 Hz or faster or when associated with a Plus modifier. Increased pattern prevalence was associated with increased risk for seizures in LPDs and GPDs. Stimulus-induced patterns were not associated with such risk. These findings highlight the importance of detailed electroencephalographic interpretation using standardized nomenclature for seizure risk stratification and clinical decision making.

Objective: Electrographic seizures in critically ill patients are often equivocal. In this study, we sought to determine the diagnostic accuracy of electrographic seizure annotation in adult intensive care units (ICUs) and to identify affecting factors., Methods: To investigate diagnostic accuracy, interreader agreement (IRA) measures were derived from 5,769 unequivocal and 6,263 equivocal seizure annotations by five experienced electroencephalogram (EEG) readers after reviewing 74 days of EEGs from 50 adult ICU patients. Factors including seizure equivocality (unequivocal vs. equivocal) and laterality (generalized, partial, or bilaterally independent), cyclicity (cyclic vs. noncyclic), persistency (occurrence of status epilepticus), and patient consciousness level (coma vs. noncoma) were further investigated for their influence on IRA measures., Results: On average, 70% of seizures marked by a reference reader overlapped, at least in part, with those marked by a test reader (any-overlap sensitivity, AO-Sn). Agreed seizure duration between reader pairs (overlap-integral sensitivity, OI-Sn) was 62%, while agreed nonseizure duration (overlap-integral specificity, OI-Sp) was 99%. A test reader would annotate one additional seizure not overlapping with a reference reader's annotation in every 11.7 h of EEG, that is, the false-positive rate (FPR) was 0.0854/h. Classifying seizure patterns into unequivocal and equivocal improved specificity and FPR (unequivocal patterns) but compromised sensitivity only for equivocal patterns. Sensitivity of all and unequivocal annotations was higher for patients with status epilepticus. Specificity was higher for partial than for bilaterally independent unequivocal seizure patterns, and lower for cyclic all seizure patterns., Significance: Diagnosing electrographic seizures in critically ill adults is highly specific and moderately sensitive. Improved criteria for diagnosing electrographic seizures in the ICU are needed.

Lanestosa is a chronically polluted site (derelict mine) where the soil (Lanestosa (LA) soil) exceeds screening values (SVs) of regulatory policies in force (Basque Country; Europe) for Zn, Pb and Cd. A scenario-targeted toxicity assessment was carried out on the basis of a multi-endpoint bioassay approach. Acute and chronic toxicity bioassays were conducted with selected test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates and with bioaccumulation studies in earthworms. Besides, the toxicity profile was compared with that of the mine runoff (RO) soil and of a fresh artificially polluted soil (LAAPS) resembling LA soil pollutant profile. Extractability studies in LA soil revealed that Pb, Zn and Cd were highly available for exchange and/or release into the environment. Indeed, Pb and Zn were accumulated in earthworms and LA soil resulted to be toxic. Soil respiration, V. fischeri, vegetative and developmental cycles of D. discoideum and survival and juvenile production of E. fetida were severely affected. These results confirmed that LA soil had unacceptable environmental risk and demanded intervention. In contrast, although Pb and Zn concentrations in RO soil revealed also unacceptable risk, both metal extractability and toxicity were much lower than in LA soil. Thus, within the polluted site, the need for intervention varied between areas that posed dissimilar risk. Besides, since LAAPS, with a high exchangeable metal fraction, was the most toxic, ageing under in situ natural conditions seemingly contributed to attenuate LA soil risk. As a whole, combining multi-endpoint bioassays with scenario-targeted analysis (including leaching and ageing) provides reliable risk assessment in soils posing unacceptable environmental risk according to SVs, which is useful to optimise the required intervention measures.

Toxicity profiles of two soils (a brownfield in Legazpi and an abandoned iron mine in Zugaztieta; Basque Country) contaminated with several metals (As, Zn, Pb and Cu in Legazpi; Zn, Pb, Cd and Cu in Zugaztieta) and petroleum hydrocarbons (in Legazpi) were determined using a multi-endpoint bioassay approach. Investigated soils exceeded screening values (SVs) of regulatory policies in force (Basque Country; Europe). Acute and chronic toxicity bioassays were conducted with a selected set of test species (Vibrio fischeri, Dictyostelium discoideum, Lactuca sativa, Raphanus sativus and Eisenia fetida) in combination with chemical analysis of soils and elutriates, as well as with bioaccumulation studies in earthworms. The sensitivity of the test species and the toxicity endpoints varied depending on the soil. It was concluded that whilst Zugaztieta soil showed very little or no toxicity, Legazpi soil was toxic according to almost all the toxicity tests (solid phase Microtox, D. discoideum inhibition of fruiting body formation and developmental cycle solid phase assays, lettuce seed germination and root elongation test, earthworm acute toxicity and reproduction tests, D. discoideum cell viability and replication elutriate assays). Thus, albeit both soils had similar SVs, their ecotoxicological risk, and therefore the need for intervening, was different for each soil as unveiled after toxicity profiling based on multiple endpoint bioassays. Such a toxicity profiling approach is suitable to be applied for scenario-targeted soil risk assessment in those cases where applicable national/regional soil legislation based on SVs demands further toxicity assessment.