Category: Nevin Manimala

Infect Dis (Lond). 2023 Mar 21:1-9. doi: 10.1080/23744235.2023.2190813. Online ahead of print.

ABSTRACT

BACKGROUND: Pyogenic liver abscess (PLA) is a rare but potentially life-threatening disease, and estimates suggest a gradual increase in the incidence during the last decades. The primary aim of this study was to report the incidence, trend and aetiology of PLA during a decade in Southern Sweden.

METHODS: This was a population-based observational cohort study between 2011 and 2020 in Skåne, Southern Sweden. Data were retrieved from the Swedish National Board of Health and Welfare for all individuals diagnosed with liver abscess (K750) according to ICD-10 (International Statistical Classification of Diseases, 10th revision).

RESULTS: A total of 456 episodes of PLA occurred in 364 patients during the study period. The median age of the first PLA episode was 71 years (range 3-97) and 57% (n = 206) were men. The mean incidence of all patients was 3.4/100,000 person-years (range 1.8-5.2). The incidence increased almost three times, from 1.8/100,000 person-years in 2011 to 5.2/100,000 person-years in 2020. Streptococcus species, Escherichia coli and Klebsiella species accounted for the vast majority of both mono- and polymicrobial findings in both blood and local abscess cultures. 16s rDNA added information about aetiology in 37% of episodes.

CONCLUSION: The incidence of PLA increased during the study period, and Streptococcus spp., Klebsiella spp. and E. coli dominated both blood and local cultures. Despite antimicrobial therapy, pathogens could be found in local abscess cultures several weeks into treatment. Increased use of 16s rDNA in the management of PLA could be beneficial.

PMID:36943906 | DOI:10.1080/23744235.2023.2190813

Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2214525120. doi: 10.1073/pnas.2214525120. Epub 2023 Mar 21.

ABSTRACT

Diagnosing dynamical changes in the climate system, such as those in atmospheric circulation patterns, remains challenging. Here, we study 1950 to 2021 trends in the frequency of occurrence of atmospheric circulation patterns over the North Atlantic. Roughly 7% of atmospheric circulation patterns display significant occurrence trends, yet they have major impacts on surface climate. Increasingly frequent patterns drive heatwaves across Europe and enhanced wintertime storminess in the northern part of the continent. Over 91% of recent heatwave-related deaths and 33% of high-impact windstorms in Europe were concurrent with increasingly frequent atmospheric circulation patterns. While the trends identified are statistically significant, they are not necessarily anthropogenic. Atmospheric patterns which are becoming rarer correspond instead to wet, cool summer conditions over northern Europe and wet winter conditions over continental Europe. The combined effect of these circulation changes is that of a strong, dynamically driven year-round warming over most of the continent and large regional and seasonal changes in precipitation and surface wind.

PMID:36943887 | DOI:10.1073/pnas.2214525120

J Cosmet Dermatol. 2023 Mar 21. doi: 10.1111/jocd.15730. Online ahead of print.

ABSTRACT

BACKGROUND: Oxidative damage is one of the major mechanisms of ultraviolet B (UVB)-induced damage to the skin. Maslinic acid (MA) is a natural compound of pentacyclic triterpene acids. It has been proved to have anti-inflammatory and antioxidant properties.

OBJECTIVE: This study aimed to explore the effects of MA on oxidative damage in human foreskin fibroblast cells (HFF-1) and the potential molecular mechanisms.

METHODS: A specific dose of UVB radiation was used to induce oxidative damage in HFF-1. Based on this, we performed measurements of cell proliferation, reactive oxygen species (ROS) levels, antioxidant enzyme activity, inflammation-related mediators, and NF-κB nuclear localization with or without the addition of MA.

RESULTS: MA significantly promoted cell proliferation viability at 10 and 20 μM. The addition of MA 24 h before UVB irradiation was more effective at enhancing cell proliferation and also produced lower ROS levels compared to co-cultured fibroblasts and MA for 24 h after irradiation. However, there was no statistically significant difference between groups at concentrations of 10 and 20 μM. The pretreatment group with MA had elevated superoxide dismutase and catalase activities, decreased IL-6 generation, and lowered mRNA levels of IL-6, TNF-α and MMP3 in comparison with the UVB-irradiated group without additional MA. Meanwhile, the nuclear translocation of NF-κB and the degradation of IκB were inhibited by MA pretreatment.

CONCLUSION: Taken together, these findings suggest that MA may alleviate UVB-induced oxidative damage in HFF-1 by inhibiting the nuclear translocation of NF-κB.

PMID:36943873 | DOI:10.1111/jocd.15730

Oncologist. 2023 Mar 21:oyad024. doi: 10.1093/oncolo/oyad024. Online ahead of print.

ABSTRACT

BACKGROUND: Hyperglycemia is recognized as a common adverse event for patients receiving alpelisib but has been little studied outside of clinical trials. We report the frequency of alpelisib-associated hyperglycemia in a real-world setting and evaluate proposed risk factors.

PATIENTS AND METHODS: We retrospectively identified patients with PIK3CA-mutated, hormone receptor-positive, metastatic breast cancer who initiated treatment with alpelisib plus fulvestrant between August 2019 and December 2021. Ordinal logistic regression evaluated 5 characteristics (diabetes, prediabetes, body mass index [BMI], age, and Asian ancestry) as independent risk factors for ALP-associated hyperglycemia grades 2-4. Risk of error from multiple hypothesis testing was controlled using the false discovery rate method.

RESULTS: The study included n = 92 subjects, all but 1 female, mean age 59.9 (+11.9) years with 50% non-Hispanic White, 15% Hispanic/Latino, 13% Asian, 9% African/Black, and 13% other/unknown. In total 34% of patients had diabetes, 10% had pre-diabetes, and 56% had normoglycemia. Thirty-six percent were obese, 32% were overweight, 25% were normal weight, and 7% were lean. Frequency of grades 1-4 hyperglycemia in current subjects (64.1%) was similar to hyperglycemia reported in the SOLAR-1 trial (63.7%). Our subjects’ risk of grades 2-4 hyperglycemia was independently increased by pre-existing diabetes (Odds ratio 3.75, 95% CI, 1.40-10.01), pre-diabetes (6.22, 1.12-34.47), Asian ancestry (7.10, 1.75-28.84), and each unit of BMI above 20 (1.17, 1.07-1.28).

CONCLUSION: While receiving alpelisib, patients of Asian ancestry, as well as patients with pre-existing hyperglycemia and/or BMI above 20, should be closely monitored for hyperglycemia. The mechanism underlying the current association of alpelisib-associated hyperglycemia with Asian ancestry is independent of BMI and merits further study. The high incidence of hyperglycemia resulted in a change in practice to include consultation with a diabetes nurse educator or endocrinologist at the start of alpelisib.

PMID:36943382 | DOI:10.1093/oncolo/oyad024

Bioinformatics. 2023 Mar 21:btad138. doi: 10.1093/bioinformatics/btad138. Online ahead of print.

ABSTRACT

MOTIVATION: Deep learning attained excellent results in Digital Pathology recently. A challenge with its use is that high quality, representative training data sets are required to build robust models. Data annotation in the domain is labor intensive and demands substantial time commitment from expert pathologists. Active Learning (AL) is a strategy to minimize annotation. The goal is to select samples from the pool of unlabeled data for annotation that improves model accuracy. However, AL is a very compute demanding approach. The benefits for model learning may vary according to the strategy used, and it may be hard for a domain specialist to fine tune the solution without an integrated interface.

RESULTS: We developed a framework that includes a friendly user interface along with run-time optimizations to reduce annotation and execution time in AL in digital pathology. Our solution implements several AL strategies along with our Diversity-Aware Data Acquisition (DADA) acquisition function, which enforces data diversity to improve the prediction performance of a model. In this work, we employed a model simplification strategy (Network Auto-Reduction (NAR)) that significantly improves AL execution time when coupled with DADA. NAR produces less compute demanding models, which replace the target models during the AL process to reduce processing demands. An evaluation with a Tumor-Infiltrating Lymphocytes (TILs) classification application shows that: (i) DADA attains superior performance compared to state-of-the-art AL strategies for different Convolutional Neural Networks (CNNs), (ii) NAR improves the AL execution time by up to 4.3 ×, and (iii) target models trained with patches/data selected by the NAR reduced versions achieve similar or superior classification quality to using target CNNs for data selection.

AVAILABILITY: Source code: https://github.com/alsmeirelles/DADA.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36943380 | DOI:10.1093/bioinformatics/btad138

Rheumatology (Oxford). 2023 Mar 21:kead121. doi: 10.1093/rheumatology/kead121. Online ahead of print.

ABSTRACT

OBJECTIVES: To examine the effect of pre-course e-learning on residents’ practical performance in musculoskeletal ultrasound (MSUS).

METHODS: Multicentre, randomized controlled study following the CONSORT statement. Residents with no or little MSUS experience were randomized to either an e-learning group or a traditional group. One week before a 2-day face-to-face MSUS course, the e-learning group received access to an interactive platform consisting of online lectures, assignments, and practical instruction videos aligned with the content of the course. The traditional group only received standard pre-course information (program, venue, and time). All participants performed a pre- and post-course practical MSUS examination and were assessed by two individual raters, blinded to the group allocation, using the validated Objective Structured Assessment of Ultrasound skills (OSAUS) tool.

RESULTS: Twenty-eight participants completed the study. There were no statistically significant differences in the pre- or post-course practical MSUS performance between the e-learning group and the traditional group; the mean pre-course OSAUS score (±SD) in the e-learning group was 5.4 ± 3.7 compared with 5.2 ± 2.4 in the traditional group, p= 0.8, whereas the post-course OSAUS score in the e-learning group was 11.1 ± 2.8 compared with 10.9 ± 2.4 in the traditional group, p= 0.8. There was a significant difference between the mean pre- and post-course scores (5.74-point p< 0.001). The OSAUS assessment tool demonstrated good inter-rater reliability (ICC = 0.84).

CONCLUSION: We found no significant impact of pre-course e-learning on novices’ acquisition of practical MSUS skills. Hands-on training is of utmost importance and improves MSUS performance significantly. The OSAUS assessment tool is an applicable tool with high interrater reliability.

TRIAL REGISTRATION: https://clinicaltrials.gov/ NCT04959162.

PMID:36943374 | DOI:10.1093/rheumatology/kead121

Health Educ Res. 2023 Mar 21:cyad014. doi: 10.1093/her/cyad014. Online ahead of print.

ABSTRACT

In 2021, guidelines for early childhood education and care were released recommending children are provided access to outdoor areas during all free play sessions to reduce the risk of coronavirus disease of 2019 transmission, aligning with the existing recommendations to increase children’s physical activity. There is a need to understand how to disseminate guidelines in this setting as dissemination is a prerequisite of adoption and implementation. This randomized controlled trial explored the impact of a video-based strategy to disseminate guidelines on family day care educators’ intentions to adopt outdoor free play guidelines. Educators (N = 255) were randomized to receive a video (intervention) or text-based (usual care) resource via email describing recommendations. Educators were invited to participate in a post-intervention survey at 5-week follow-up assessing intentions to adopt guidelines. The secondary outcomes included knowledge, beliefs about capabilities, beliefs about consequences, social/professional role and identity, goals, implementation of guidelines, acceptability of resource and intervention reach. There was no statistically significant difference between groups in intentions to adopt guidelines [ß = 0.01 (95% confidence interval -0.50 to 0.52), P = 0.97], nor for any secondary outcomes. Further investigation is needed to identify effective dissemination strategies in the family day care setting to increase the adoption of public health guidelines.

PMID:36943373 | DOI:10.1093/her/cyad014

Bioinformatics. 2023 Mar 21:btad139. doi: 10.1093/bioinformatics/btad139. Online ahead of print.

ABSTRACT

MOTIVATION: Accurate power and sample size estimation is crucial to the design and analysis of genetic association studies. When analyzing a binary trait via logistic regression, important covariates such as age and sex are typically included in the model. However, their effects are rarely properly considered in power or sample size computation during study planning. Unlike when analyzing a continuous trait, the power of association testing between a binary trait and a genetic variant depends, explicitly, on covariate effects, even under the assumption of gene-environment independence. Earlier work recognizes this hidden factor but the implemented methods are not flexible.

METHOD: We thus propose and implement a generalized method for estimating power and sample size for (discovery or replication) association studies of binary traits that a) accommodates different types of non-genetic covariates E, b) deals with different types of G-E relationships, and c) is computationally efficient.

RESULTS: Extensive simulation studies show that the proposed method is accurate and computationally efficient for both prospective and retrospective sampling designs with various covariate structures. A proof-of-principle application focused on the understudied African sample in the UK Biobank data. Results show that, in contrast to studying the continuous blood pressure trait, when analyzing the binary hypertension trait ignoring covariate effects of age and sex leads to overestimated power and underestimated replication sample size.

AVAILABILITY: The simulated datasets can be found on the online web-page of this manuscript, and the UK Biobank application data can be accessed at https://www.ukbiobank.ac.uk. The R package SPCompute that implements the proposed method is available at CRAN. The genome-wide association studies are carried out using the software PLINK 2.0 (Purcell et al., 2007).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36943372 | DOI:10.1093/bioinformatics/btad139

Mil Med. 2023 Mar 21:usad081. doi: 10.1093/milmed/usad081. Online ahead of print.

ABSTRACT

INTRODUCTION: Cervical spine immobilization in a low-resource environment is difficult secondary to limited equipment, prolonged transportation, and secondary complications. A structural aluminum malleable (SAM) splint is commonly utilized because of its availability and multipurpose intention. A one-step spray-on foam immobilization technique (Fast Cast) has been shown to be effective in lower-extremity splinting. The aim of this study was to demonstrate the ability of the Fast Cast to effectively immobilize the cervical spine in a head-to-head comparison against the SAM splint. We hypothesized that there would be no difference in surgeon scoring between Fast Cast and SAM splints for the immobilization of the cervical spine.

METHODS: This was a cadaveric experimental comparative study that compared a SAM splint versus Fast Cast for the immobilization of an unstable cervical spine. Each of the three cadaveric specimens had a corpectomy without fixation performed. A board-certified emergency medicine physician specialized in disaster medicine performed all SAM immobilizations. An orthopedic surgeon performed Fast Cast immobilizations. Each method of immobilization was done on each cadaver. Lateral fluoroscopic imaging was taken before and after immobilization and after log roll/gravity stress. Five board-certified orthopedic surgeons served as graders to independently score each splint. A 5-point Likert scale based on 10 splinting criteria (50 total points possible) was utilized to evaluate cervical spine immobilization. The lead statistical analyst was blinded to the immobilization groups. The statistical significance was assessed via a Wilcoxon signed-rank test and chi-square Fisher’s exact test with significance between groups set at α < .05. Inter-rater reliability of the Likert scale results was assessed with the interclass correlation coefficient.

RESULTS: Inter-rater reliability for the current Likert scale in the evaluation of cervical spine stabilization was good (interclass correlation coefficient = 0.76). For the cumulative Likert scale score, Fast Cast (32 [28-34]) exhibited a higher total score than SAM (44 [42-47]; P < .01). Likewise, Fast Cast exhibited a greater likelihood of higher Likert scores within each individual question as compared to SAM (P ≤ 0.04). In 100% of cases, raters indicated that Fast Cast passed the gravity stress examination without intrinsic loss of reduction or splinting material, whereas 33% of SAM passed (P < .01). In 100% of cases, raters indicated that Fast Cast passed the initial radiographic alignment following immobilization, whereas 66% of SAM passed (P = .04). In 100% of cases, raters indicated that Fast Cast passed radiographic alignment after the gravity stress examination, whereas 47% of SAM passed (P < .01).

CONCLUSION: The Fast Cast exceeded our expectations and was shown to be rated not equivalent but superior to SAM splint immobilization for the cervical spine. This has significant clinical implications as the single-step spray-on foam is easy to transport and has multifaceted applications. It also eliminates pressure points and circumferential wrapping and obstruction to airway/vascular access while immobilizing the cervical spine and allowing for radiographic examination. Further studies are needed for human use and application.

PMID:36943370 | DOI:10.1093/milmed/usad081

JMIR Form Res. 2023 Mar 21;7:e44666. doi: 10.2196/44666.

ABSTRACT

BACKGROUND: Early triage of patients with mushroom poisoning is essential for administering precise treatment and reducing mortality. To our knowledge, there has been no established method to triage patients with mushroom poisoning based on clinical data.

OBJECTIVE: The purpose of this work was to construct a triage system to identify patients with mushroom poisoning based on clinical indicators using several machine learning approaches and to assess the prediction accuracy of these strategies.

METHODS: In all, 567 patients were collected from 5 primary care hospitals and facilities in Enshi, Hubei Province, China, and divided into 2 groups; 322 patients from 2 hospitals were used as the training cohort, and 245 patients from 3 hospitals were used as the test cohort. Four machine learning algorithms were used to construct the triage model for patients with mushroom poisoning. Performance was assessed using the area under the receiver operating characteristic curve (AUC), decision curve, sensitivity, specificity, and other representative statistics. Feature contributions were evaluated using Shapley additive explanations.

RESULTS: Among several machine learning algorithms, extreme gradient boosting (XGBoost) showed the best discriminative ability in 5-fold cross-validation (AUC=0.83, 95% CI 0.77-0.90) and the test set (AUC=0.90, 95% CI 0.83-0.96). In the test set, the XGBoost model had a sensitivity of 0.93 (95% CI 0.81-0.99) and a specificity of 0.79 (95% CI 0.73-0.85), whereas the physicians’ assessment had a sensitivity of 0.86 (95% CI 0.72-0.95) and a specificity of 0.66 (95% CI 0.59-0.73).

CONCLUSIONS: The 14-factor XGBoost model for the early triage of mushroom poisoning can rapidly and accurately identify critically ill patients and will possibly serve as an important basis for the selection of treatment options and referral of patients, potentially reducing patient mortality and improving clinical outcomes.

PMID:36943366 | DOI:10.2196/44666