Original Score Research Articles

Molecular Generation, QSAR, and Molecular Dynamic Simulation Studies for Virtual Screening of DNA Polymerase Theta Inhibitors.

The machine learning-based QSAR modeling procedure, molecular generations, and molecular dynamic simulations were applied to virtually screen the DNA polymerase theta inhibitors. The DNA polymerase theta (Polθ or POLQ) is an attractive target for treatments of homologous recombination deficient (such as BRCA deficient) cancers. There are no approved drugs for targeting POLQ, and only one inhibitor is in Phase Ⅱclinical trials; thus, it is necessary to develop novel POLQ inhibitors. To build machine learning models that predict the bioactivities of POLQ inhibitors. To build molecular generation models that generate diverse molecules. To virtually screen the generated molecules by the machine learning models. To analyze the binding modes of the screening results by molecular dynamic simulations. In the present work, 325 inhibitors with POLQ polymerase domain bioactivities were Collected. Two machine learning methods, random forest and deep neural network, were used for building the ligand- and structure-based quantitative structure-activity relationship (QSAR) models. The substructure replacement-based method and transfer learning-based deep recurrent neural network method were used for molecular generations. Molecular docking and consensus QSAR models were carried out for virtual screening. The molecular dynamic simulations and MM/GBSA binding free energy calculation and decomposition were used to further analyze the screening results. The MCC values of the best ligand- and structure-based consensus QSAR models reached 0.651 and 0.361 for the test set, respectively. The machine learning-based docking scores had better-predicted ability to distinguish the highly and weakly active poses than the original docking scores. The 96490 molecules were generated by both molecular generation methods, and 10 molecules were retained by virtual screening. Four favorable interactions were concluded by molecular dynamic simulations. We hope that the screening results and the binding modes are helpful for designing the highly active POLQ polymerase inhibitors and the models of the molecular design workflow can be used as reliable tools for drug design.

Creativity in a music composition community: an analysis of online comments

ABSTRACT Scholars have often highlighted the intrinsic features of technology to support the generation and sharing of ideas (Craft 2011). By studying user interactions within informal online communities, researcher can elucidate the ways technology impacts creativity and learning within these groups. This qualitative content analysis (Hsieh and Shannon 2005) used a systems-based approach to creativity (Csikszentmihalyi 1999) to examine the interactions within an online community (Noteflight) focused on Western standard music notation-based composition. One popular, publicly available, original musical score was selected. Online comments were collected and analysed. Findings highlight the diversity and abundance of feedback given to the composer as well as the many ways users engaged with domain knowledge. This online community allows individuals to share knowledge, learn about the social norms associated with giving feedback, and explore creative ideas regarding music composition. Implications from this study highlight the ways music educators and technology designers can develop web-based music learning environments that support creativity and life-long engagement.

Comparison of preoperative NT-proBNP and simple cardiac risk scores for predicting postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk

BackgroundChronic heart failure (HF) is frequent in elderly patients undergoing non-cardiac surgery. Preoperative risk stratification is vital and can be achieved using simple clinical risk scores or preoperative N-terminal prohormone of brain natriuretic peptide (NT-proBNP) measurement. This study aimed to compare the predictivity of the revised cardiac risk index (RCRI), the American University of Beirut cardiovascular risk index (AUB-HAS2), and a score proposed by Andersson et al. for postoperative 30-day morbidity to preoperative NT-proBNP.MethodsPreoperative NT-proBNP was measured in 199 consecutive patients aged ≥ 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk. The areas under the receiver operating characteristic curve (AUCROC) for the composite morbidity endpoint (CME) comprising the incidence of any rehospitalisation, acute decompensated HF, acute kidney injury, and any infection at postoperative day 30 were assessed. Multivariable logistic regression analysis derived new scores from the simple risk scores and the NT-proBNP cut-off of 450 pg/mL.ResultsAUB-HAS2, but not RCRI or Andersson score, significantly predicted the CME (AUB-HAS2: AUCROC 0.646, p < 0.001; RCRI: AUCROC 0.560, p = 0.126; Andersson: AUCROC 0.487, p = 0.760). The AUCROC was comparable between preoperative NT-proBNP (0.679, p < 0.001) and AUB-HAS2 (p = 0.334). Multivariable analyses revealed a preoperative NT-proBNP ≥ 450 pg/mL to be the strongest predictor of CME among the individual score components (p < 0.001). Adding preoperative NT-proBNP improved the predictive value of AUB-HAS2 and RCRI (modified AUB-HAS2: AUCROC 0.703, p < 0.001; modified RCRI: AUCROC 0.679, p < 0.001; both p < 0.001 vs original scores). The predictive value of the modified RCRI and AUB-HAS2 was comparable to preoperative NT-proBNP alone (p = 0.988 vs modified RCRI, p = 0.367 vs modified AUB-HAS2).ConclusionsThe predictive value of postoperative morbidity varies significantly between the available simple perioperative risk scores and can be enhanced by preoperative NT-proBNP. New scores, including preoperative NT-proBNP, should be evaluated in large multicentre cohorts.Trial registrationGerman Clinical Trials Register: DRKS00027871.

Trends and updates on the epidemiology of cancer-associated thrombosis: a systematic review

For cancer patients, cancer-associated thrombosis (CAT) is a serious complication. An updated epidemiology of CAT over the last ten years is summarized in this review. A comprehensive analysis of pertinent population cohort research released between 2011 and 2024 was carried out. In patients with unselected cancers, the 12-month incidence of CAT is roughly 3-5% (9-fold increase vs to the matched non-cancer population); however, in patients with advanced cancers requiring systemic therapy, the risk rises to 6-8% (20-fold increase vs. to the matched non-cancer population). Anticoagulation use and adherence have improved, but the risk of recurrence is still high, at 5-8% at 6 months and 7-15% at 12 months. The type, stage, and treatment of cancer, a history of venous thromboembolism (VTE), prolonged hospitalization or immobilization, and obesity are significant clinical predictors of the development of CAT. The modified Vienna-CATS and EHR-CAT have the best performance (area under the curve 0.68-0.71) among the clinical risk prediction scores for CAT using the original Khorana score backbone that has been externally validated. However, additional research is required to guarantee appropriate implementation and utilization of these models. Even with contemporary antineoplastic treatments, CAT is still a major complication for cancer patients. We encourage interdisciplinary partnerships among hematologists, data scientists, epidemiologists, and oncologists to guarantee the integration of customized VTE risk evaluation into standard oncologic treatment.

Performance and Perception of Creativity and Academic Achievement in Elementary School Students: A Normal Mixture Modeling Study

ABSTRACTCreativity can be assessed using various methods, including divergent thinking performance, self‐ratings, and teacher ratings. However, these measures may not always align, as they may not consistently identify creative potential in the same manner. The present study aimed to identify latent subgroups of students based on their observed originality, creative self‐efficacy, teacher‐rated originality, academic achievement in reading and mathematics, and demographic background characteristics. Data were collected from 243 elementary school students. We applied the normal mixture technique to classify participants into latent subgroups. Five latent subgroups of students were identified: Overconfident Low Performers, Creative High Achievers, Under‐Confident Below‐Average Achievers, Mathematically Oriented Students, and Calibrated Above‐Average Achievers. Female students tended to fall disproportionately into the subgroup of Creative High Achievers. Students receiving free/reduced lunch had a lower probability of being Creative High Achievers. Special education students had a higher probability of falling into the subgroup Overconfident Low Performers. Teacher ratings of students' originality were more in line with student academic performance rather than with their performance‐based originality scores. Students' self‐ratings of creativity bifurcated across subgroups, with Creative High Achievers and Overconfident Low Performers reporting the highest self‐ratings of originality, despite displaying very different levels of performance on the divergent thinking assessment.

Interrater Agreement of BT-RADS for Evaluation of Follow-up MRI in Patients with Treated Primary Brain Tumor.

The Brain Tumor Reporting and Data System (BT-RADS) is a structured radiology reporting algorithm that was introduced to provide uniformity in posttreatment primary brain tumor follow-up and reporting, but its interrater reliability (IRR) assessment has not been widely studied. Our goal is to evaluate the IRR among neuroradiologists and radiology residents in the use of BT-RADS. This retrospective study reviewed 103 consecutive MR studies in 98 adult patients previously diagnosed with and treated for primary brain tumor (January 2019 to February 2019). Six readers with varied experience (4 neuroradiologists and 2 radiology residents) independently evaluated each case and assigned a BT-RADS score. Readers were blinded to the original score reports and the reports from other readers. Cases in which at least 1 neuroradiologist scored differently were subjected to consensus scoring. After the study, a post hoc reference score was also assigned by 2 readers by using future imaging and clinical information previously unavailable to readers. The interrater reliabilities were assessed by using the Gwet AC2 index with ordinal weights and percent agreement. Of the 98 patients evaluated (median age, 53 years; interquartile range, 41-66 years), 53% were men. The most common tumor type was astrocytoma (77%) of which 56% were grade 4 glioblastoma. Gwet index for interrater reliability among all 6 readers was 0.83 (95% CI: 0.78-0.87). The Gwet index for the neuroradiologists' group (0.84 [95% CI: 0.79-0.89]) was not statistically different from that for the residents' group (0.79 [95% CI: 0.72-0.86]) (χ2 = 0.85; P = .36). All 4 neuroradiologists agreed on the same BT-RADS score in 57 of the 103 studies, 3 neuroradiologists agreed in 21 of the 103 studies, and 2 neuroradiologists agreed in 21 of the 103 studies. Percent agreement between neuroradiologist blinded scores and post hoc reference scores ranged from 41%-52%. A very good interrater agreement was found when tumor reports were interpreted by independent blinded readers by using BT-RADS criteria. Further study is needed to determine if this high overall agreement can translate into greater consistency in clinical care.

Stability of Assessment Using Creativity‐Related Indices

AbstractThe aim of this study is to determine how many raters are required for the design products proposed in this study to obtain stable ratings of creativity over time using the Consensual Assessment Technique (CAT) and to examine the creativity subscales, namely, originality and practicality, and their composite scores in a similar manner. The results revealed that creativity assessment using the CAT was stable over time if the assessment was conducted by about 10 to 15 raters. On the contrary, originality and practicality assessment was found to be stable over time with about three raters. However, when the sum of the originality and practicality scores was used as a composite score, the assessment was found to be unstable. This could be attributed to the negative correlation between the originality and practicality assessments of the products. Further, when the product of the originality and practicality scores or the Euclidean distance within these dimensions was used, stable scores were obtained over time by using about 15 to 20 raters.

How much or how often? Examining the screening properties of the DSM cross-cutting symptom measure in a youth population-based sample.

The DSM Level 1 Cross-Cutting Symptom Measure (DSM-XC) allows for assessing multiple psychopathological domains. However, its capability to screen for mental disorders in a population-based sample and the impact of adverbial framings (intensity and frequency) on its performance are unknown. The study was based on cross-sectional data from the 1993 Pelotas birth cohort in Brazil. Participants with completed DSM-XC and structured diagnostic interviews (n = 3578, aged 22, 53.6% females) were included. Sensitivity, specificity, positive (LR+), and negative (LR-) likelihood ratios for each of the 13 DSM-XC domains were estimated for detecting five internalizing disorders (bipolar, generalized anxiety, major depressive, post-traumatic stress, and social anxiety disorders) and three externalizing disorders (antisocial personality, attention-deficit/hyperactivity, and alcohol use disorders). Sensitivities and specificities >0.75, LR+ > 2 and LR- < 0.5 were considered meaningful. Values were calculated for the DSM-XC's original scoring and for adverbial framings. Several DSM-XC domains demonstrated meaningful screening properties. The anxiety domain exhibited acceptable sensitivity and LR- values for all internalizing disorders. The suicidal ideation, psychosis, memory, repetitive thoughts and behaviors, and dissociation domains displayed acceptable specificity for all disorders. Domains also yielded small but meaningful LR+ values for internalizing disorders. However, LR+ and LR- values were not generally meaningful for externalizing disorders. Frequency-framed questions improved screening properties. The DSM-XC domains showed transdiagnostic screening properties, providing small but meaningful changes in the likelihood of internalizing disorders in the community, which can be improved by asking frequency of symptoms compared to intensity. The DSM-XC is currently lacking meaningful domains for externalizing disorders.

User tendency-based rating scaling in online trading networks.

Social networks often involve the users rating each other based on their beliefs, abilities, and other characteristics. This is particularly common in e-commerce platforms where buyers rate sellers based on their trustworthiness. However, the rating tends to vary between users due to differences in their individual scoring criteria. For example, in a transaction network, a positive user may give a high rating unless the transaction was unsatisfactory while a neutral user may give a mid-rating, consequently giving the same numeric score to different levels of satisfaction. In this paper, we propose a novel method called user tendency-based rating scaling, which adjusts the current rating (its score) based on the pattern of past ratings. We investigate whether this rating scaling method can classify between "good users" and "bad users" in online trade social networks better when compared with using the original rating scores without scaling. Classifying between good users and bad users is especially important for anonymous rating networks like Bitcoin transaction networks, where users' reputations must be recorded to preclude fraudulent and risky users. We evaluate the proposed rating scaling method by performing user classification, link prediction, and clustering tasks, using three real-world online rating network datasets. We use both the original ratings and the scaled ratings as weights of graphs and use a weighted graph embedding method to find node representations that reflect users' positive and negative information. The experimental results showed that using the proposed rating scaling method outperformed using the original (i.e., unscaled) ratings by up to 17% in classification accuracy, and by up to 2.5% in link prediction based on the AUC ROC measure, and by up to 21% in the clustering tasks based on the Dunn-index.

“Donasdogama Micma”

To this day, Dante Alighieri’s Divine Comedy, written in the early fourteenth century, remains one of the most significant literary works of Western culture. It has not only been adapted in music, film, and art, but also in the world of video games. Since the early 1980s, video games have chosen the poetry as a basis for their plots, and various approaches to musical interpretation have emerged. With the release of Dante’s Inferno (2010), for the first time an approach was demonstrably chosen that resulted from an intensive examination of the Divine Comedy. This article explores the thesis that using literary works as a basis for video games not only affects the plot, gameplay, and character design, but also significantly influences the musical concept. Thus, it is evident that the literary source and its interpretation should be incorporated into the analysis of video game music. Thanks to Garry Schyman, who made the original scores available for analysis, the resulting musical concept will be examined more closely and compared with the previous Dante games.

Circular Intuitionistic Fuzzy Median Ranking Model with a Novel Scoring Mechanism for Multiple Criteria Decision Analytics

ABSTRACT This study aims to pioneer an innovative circular intuitionistic fuzzy (C-IF) scoring-mediated median ranking model designed for multiple criteria decision analytics. The primary goal is to establish a comprehensive precedence ranking for competing alternatives, effectively addressing the inherent uncertainties present in decision-analytic challenges within the C-IF environment. The core content delves into the creation of an original scoring mechanism tailored to navigate the complexities of C-IF uncertainties. Moreover, the research introduces a specialized C-IF median ranking model for decision analytics, leveraging the foundational concept of the C-IF scoring mechanism. A significant contribution is made through the formulation of a robust implementation procedure, specifically tailored for the seamless operation of the C-IF scoring-mediated median ranking model within the framework of C-IF information. Drawing from the suggested C-IF scoring mechanism, this research introduces novel concepts related to comprehensive C-IF scoring functions and comprehensive disagreement metrics. Subsequently, a comprehensive disagreement matrix is formulated, with its entries quantifying the extent of disagreement in assigning specific ranks to each alternative across all criterion-wise precedence relationships. This paves the way for the development of a new C-IF scoring-mediated median ranking model, offering decision analysts a tool to navigate intricate C-IF information and derive dependable decision-analytic outcomes.

Comparative Predictive Accuracies of the Simplified Mortality Score for the Intensive Care Unit, Sepsis Severity Score, and Standard Severity Scores for 90-day Mortality in Sepsis Patients.

The standard severity scores were used for predicting hospital mortality of intensive care unit (ICU) patients. Recently, the new predictive score, Simplified Mortality Score for the ICU (SMS-ICU), was developed for predicting 90-day mortality. To validate the ability of the SMS-ICU and compare with sepsis severity score (SSS) and original severity scores for predicting 90-day mortality in sepsis patients. An analysis of retrospective data was conducted in the ICU of a university teaching hospital. Also, 90-day mortality was used for the primary outcome. A total of 1,161 patients with sepsis were included. The 90-day mortality was 42.4%. The SMS-ICU presented the area under the receiver operating characteristic curve (AUROC) of 0.71, whereas the SSS had significantly higher AUROC than that of the SMS-ICU (AUROC 0.876, p < 0.001). The acute physiology and chronic health evaluation (APACHE) II and IV, and the simplified acute physiology scores (SAPS) II demonstrated good discrimination, with an AUROC above 0.90. The SMS-ICU provides poor calibration for 90-day mortality prediction, similar to the SSS and other standard severity scores. Furthermore, 90-day mortality was underestimated by the SMS-ICU, which had a standardized mortality ratio (SMR) of 1.36. The overall performance by Brier score demonstrated that the SMS-ICU was inferior to the SSS (0.222 and 0.169, respectively). Also, SAPS II presented the best overall performance with a Brier score of 0.092. The SMS-ICU indicated lower performance compared to the SSS, standard severity scores. Consequently, modifications are required to enhance the performance of the SMS-ICU. Sathaporn N, Khwannimit B. Comparative Predictive Accuracies of the Simplified Mortality Score for the Intensive Care Unit, Sepsis Severity Score, and Standard Severity Scores for 90-day Mortality in Sepsis Patients. Indian J Crit Care Med 2024;28(4):343-348.

The Rhinoplasty Rosetta Stone: using Rasch analysis to create and validate crosswalks between the NOSE and SCHNOS functional subscale.

The NOSE and SCHNOS functional subscale are widely used PROMs to measure functional outcomes of rhinoplasty. However, as different instruments produce scores on different metrics, results of these instruments cannot be linked directly. This hinders comparing and aggregating rhinoplasty outcome data from practices using either instrument. The aim of this study was to develop and validate crosswalks between the NOSE and SCHNOS-O. In a sample of 552 rhinoplasty patients who completed both instruments, the NOSE and SCHNOS-O scales were co-calibrated onto a common interval-scaled metric using Rasch analysis. Separate Rasch models were run per instrument and the latent constructs were estimated using the calibrated item parameters. By anchoring original PROM scores of both instruments to this Rasch computed measurement scale, the scores of both instruments were linked. A second independent sample was used to validate the created crosswalks. Total scores on the NOSE and SCHNOS-O were strongly correlated. The Rasch-based co-calibration of the NOSE and SCHNOS-O items resulted in a model that adequately fitted the data. Back-and-forth crosswalk tables were created from the NOSE to the SCHNOS-O. For patients with moderate nasal obstruction, predicted SCHNOS-O scores were slightly higher for a given level of the NOSE. Intraclass correlation coefficients between predicted and actual scores were 0.93 for both directions, indicating adequate agreement for group-level comparisons. This study developed and validated Rasch-based crosswalks from the NOSE to the SCHNOS-O and vice-versa. The provided crosswalks enhance comparison and harmonization of functional rhinoplasty outcomes.

Severe genu varus deformity does not affect enhanced recovery after surgery total knee arthroplasty outcomes.

Enhanced recovery after surgery (ERAS) has been increasingly adopted in orthopaedic surgery. Although not an exclusion criterion, patients undergoing total knee arthroplasty (TKA) with preoperative severe varus deformity may be less likely to be enrolled for ERAS. This study aimed to compare the success of ERAS TKA between patients with severe preoperative varus deformities (≥ 15° varus) and the control group (< 15° varus to 14° valgus). Our secondary aim was to compare postoperative complications and functional outcomes between the two groups. 310 TKAs performed from August 2019 to February 2021 were analyzed with a follow-up of 6 months postoperatively. The primary outcome, ERAS TKA success, was defined as length of hospital stay of < 24h. Other parameters included 30-day postoperative complications and clinical outcomes such as the original Oxford Knee Score (OKS), the Knee Society Knee (KSKS) and Function Score (KSFS), Visual Analog Scale for Pain (VAS-P), 36-Item Short-Form Health Survey (SF-36) Physical Component Summary (PCS) and SF-36 Mental Component Summary (MCS). There were 119 patients in the severe deformity group and 191 patients in the control group. There were no significant differences in ERAS success between the severe deformity group and control group, with both groups achieving similarly high rates (> 90%) of ERAS success. There were also no differences in 30-day postoperative complications and 6-month postoperative clinical outcomes. Patients with severe preoperative varus deformity undergoing ERAS TKA achieved high ERAS success rates (> 90%). Genu varum is not a contraindication for ERAS TKA.

Remineralization and inactivation of carious lesions treated with silver fluoride in Brazilian children with special healthcare needs.

Providing conventional, restorative dental care to children with special healthcare needs (CSHCN) often requires sedation using general anesthesia. Saliva consistency, diet, and oral hygiene practice are different for CSHCN, and limited evidence is available on the efficacy of silver fluoride (SF) for the management of carious lesions for this vulnerable population. Parents of CSHCN were educated about silver fluoride as a treatment option for caries. In total, 550 carious lesions from 100 participants were identified and scored according to the Nyvad Caries criteria. A total of 100 lesions with Nyvad scores 1, 2, and 3 were treated with a single application of silver fluoride and observed postoperatively at 1, 3, and 6 weeks. The results indicate statistically significant (p < 0.05) differences in lesion remineralization over the 6-week follow-up period. At the 6-week follow-up, more than 85% of all lesions were remineralized across all children, regardless of condition or original Nyvad score of 1, 2, or 3. A single application of silver fluoride has demonstrated effectiveness in remineralization and inactivation of carious lesions over 6 weeks among Brazilian CSHCN. Silver fluoride should be considered an option for the management of carious lesions among CSHCN. Further studies are recommended, including larger sample sizes, longer follow-up times, a second application of SF, and different special needs conditions.

A Score-Based Deterministic Diffusion Algorithm with Smooth Scores for General Distributions

Score matching based diffusion has shown to achieve the state of art results in generation modeling. In the original score matching based diffusion algorithm, the forward equation is a differential equation for which the probability density equation evolves according to a linear partial differential equation, the Fokker-Planck equation. A drawback of this approach is that one needs the data distribution to have a Lipschitz logarithmic gradient. This excludes a large class of data distributions that have a compact support. We present a deterministic diffusion process for which the vector fields are always Lipschitz and hence the score does not explode for probability measures with compact support. This deterministic diffusion process can be seen as a regularization of the porous media equation equation, which enables one to guarantee long term convergence of the forward process to the noise distribution. Though the porous media equation is itself not always guaranteed to have a Lipschitz vector field, it can be used to understand the closeness of the output of the algorithm to the data distribution as a function of the the time horizon and score matching error. This analysis enables us to show that the algorithm has better dependence on the score matching error than approaches based on stochastic diffusions. Using numerical experiments we verify our theoretical results on example one and two dimensional data distributions which are compactly supported. Additionally, we validate the approach on a modified MNIST data set for which the distribution is concentrated on a compact set. In each of the experiments, the approach using deterministic diffusion performs better that the diffusion algorithm with stochastic forward process, when considering the FID scores of the generated samples.

Derivation and validation of a risk-stratification model for patients with probable or proven COVID-19 in EDs: the revised HOME-CoV score

BackgroundThe HOME-CoV (Hospitalisation or Outpatient ManagEment of patients with SARS-CoV-2 infection) score is a validated list of uniquely clinical criteria indicating which patients with probable or proven COVID-19 can be...

Measurement invariance of the Personality Inventory for DSM-5 across sex.

There has been an international movement towards dimensional models of personality disorders (PDs) in the last decades, which culminated in the publication of the Alternative Model of Personality Disorders (AMPD) in the Emerging Measures and Models section of the DSM-5. This model was accompanied by a APA-sanctioned Personality Inventory for DSM-5 (PID-5) for the assessment of the AMPD pathological personality traits. One major issue with the assessment of personality disorders pertains to sex differences, and measurement invariance across sex in assessment instruments for PDs is necessary in order to ensure non-biased evaluations and to make valid comparisons between men and women. This study aimed to provide more information on measurement invariance across sex for the PID-5, using both the original scoring approach provided by the authors of the instrument and the scoring approach suggested by the APA in the published version of the PID-5. This study was conducted with a sample of 2273 participants from the general Québec (Canada) adult population aged 18 to 90 years (M = 46.59; SD = 16.32; 51.8% women). The original scoring approach model showed good fit to data after freeing paths between certain traits and reached strict invariance. The APA scoring approach also showed good fit to data and reached strict invariance, but needed an adjustment (path freed between Emotional lability and Impulsivity in men) to reach scalar invariance. In line with previous research, the PID-5 is invariant across sex and the five-factor structure adjusts well to data. The APA scoring approach appears to attenuate the cross-loading problem observed with the original scoring approach. In light of these results, we recommend using the APA scoring approach to derive domain scores.

Concordance between pathologists and between specimen types in detection of HER2-low breast carcinoma by immunohistochemistry

ContextRecent clinical trials indicate that HER2-targeted therapy may benefit HER2-low breast cancer patients including HER2 score 1+ or 2+ and no gene amplification.Concordance between pathologists and between core biopsy and surgical excision in establishing HER2-low status was evaluated. Design57 patients with HER2 negative breast cancer (IHC 0, 1+, or 2+, no gene amplification) by core biopsy were included. Core biopsy and representative tumor from corresponding surgical excision was immunostained for HER2. Original HER2 IHC scores were interpreted using 2018 guidelines. Three pathologists independently interpreted again under 2023 guidelines. Kappa statistic evaluated agreement of HER2 IHC scores. ResultsApplying 2023 guidelines, HER2 IHC scores were concordant among study pathologists in 46 of 57 (81 %) core biopsy and 50 of 57 (88 %) surgical resections. Kappa statistics were 0.78 and 0.85 (substantial agreement), for inter-pathologist agreement of core biopsy and surgical resections under 2023 guidelines; 0.55 (moderate agreement) for agreement between first interpretation by 2018 guidelines and second interpretation by 2023 guidelines; and 0.13 (slight agreement) for agreement in HER2 consensus scores between outside core and surgical resection and 0.49 (moderate agreement) for inside core and surgical resection. Low HER2 expression was found in 28 of 57 (49 %) core biopsy and in 25 of 57 (44 %) surgical excisions. ConclusionsInterobserver agreement among study pathologists was good in core biopsy and surgical excisions, applying updated 2023 guidelines. Intratumoral heterogeneity in protein expression and preanalytical factors may result in variable identification of HER2-low status in core biopsy and surgical excision specimens.

Long-Term Satisfaction of Oral Sedation versus Standard-of-Care Intravenous Sedation for Ocular Surgery.

Long-term patient satisfaction may influence patients' perspectives of the quality of care and their relationship with their providers. This is a follow up to a comparative effectiveness study investigating oral to intravenous sedation (OIV study). The OIV study found that oral sedation was noninferior in patient satisfaction to standard intravenous (IV) sedation for anterior segment and vitreoretinal surgeries. This study aims to determine if patient satisfaction with oral sedation remained noninferior long term. Patients were re-interviewed using the same satisfaction survey given during the OIV study. Statistical analysis involved t-tests for noninferiority of the long-term mean satisfaction score of oral and IV sedation. We also compared the original mean satisfaction score and the follow-up mean satisfaction score for each type of sedation and for both groups combined. Participants were interviewed at a median of 1225.5 days (range 754-1675 days) from their surgery. The original mean satisfaction score was 5.26 ± 0.79 for the oral treatment group (n = 52) and 5.27 ± 0.64 for the intravenous treatment group (n = 46), demonstrating noninferiority with a difference in mean satisfaction score of 0.015 (p < 0.0001). The follow-up mean satisfaction score was 5.23 ± 0.90 for oral sedation and 5.60 ± 0.61 for IV sedation, with a difference in the mean satisfaction score of 0.371 (p = 0.2071). Satisfaction scores did not differ between the original mean satisfaction score and the follow-up mean satisfaction score for the oral treatment group alone (p = 0.8367), but scores in the intravenous treatment group increased longitudinally (p = 0.0004). In this study, long-term patient satisfaction with oral sedation was not noninferior to satisfaction with IV sedation, unlike our findings with short-term patient satisfaction in our original study. Patient satisfaction also remained unchanged over time for the oral treatment group, but patients in the intravenous treatment group reported higher long-term satisfaction with their anesthesia experience compared to the immediate post-operative period.