Nevin Manimala

J Cogn Neurosci. 2021 Mar 3:1-24. doi: 10.1162/jocn_a_01697. Online ahead of print.

ABSTRACT

Receiver operating characteristic (ROC) analysis is the standard tool for studying recognition memory. In particular, the curvilinearity and the y-offset of recognition ROC curves have been interpreted as indicative of either memory strength (single-process models) or different memory processes (dual-process model). The distinction between familiarity and recollection has been widely studied in cognitive neuroscience in a variety of conditions, including lesions of different brain regions. We develop a computational model that explicitly shows how performance in recognition memory is affected by a complex and, as yet, underappreciated interplay of various factors, such as stimulus statistics, memory processing, and decision-making. We demonstrate that (1) the factors in the model affect recognition ROC curves in unexpected ways, (2) fitting R and F parameters according to the dual-process model is not particularly useful for understanding the underlying processes, and (3) the variability of recognition ROC curves and the controversies they have caused might be due to the uncontrolled variability in the contributing factors. Although our model is abstract, its functional components can be mapped onto brain regions, which are involved in corresponding functions. This enables us to reproduce and interpret in a coherent framework the diverse effects on recognition memory that have been reported in patients with frontal and hippocampal lesions. To conclude, our work highlights the importance of the rich interplay of a variety of factors in driving recognition memory performance, which has to be taken into account when interpreting recognition ROC curves.

PMID:33656399 | DOI:10.1162/jocn_a_01697

Cancer Biother Radiopharm. 2021 Mar 2. doi: 10.1089/cbr.2020.4554. Online ahead of print.

ABSTRACT

Background: The purpose of this study was to develop a rapid, reliable, and efficient tool for three-dimensional (3D) dosimetry treatment planning and post-treatment evaluation of liver radioembolization with ⁹⁰Y microspheres, using tissue-specific dose voxel kernels (DVKs) that can be used in everyday clinical practice. Materials and Methods: Two tissue-specific DVKs for ⁹⁰Y were calculated through Monte Carlo (MC) simulations. DVKs for the liver and lungs were generated, and the dose distribution was compared with direct MC simulations. A method was developed to produce a 3D dose map by convolving the calculated DVKs with the activity biodistribution derived from clinical single-photon emission computed tomography (SPECT) or positron emission tomography (PET) images. Image registration for the SPECT or PET images with the corresponding computed tomography scans was performed before dosimetry calculation. The authors first compared the DVK convolution dosimetry with a direct full MC simulation on an XCAT anthropomorphic phantom. They then tested it in 25 individual clinical cases of patients who underwent ⁹⁰Y therapy. All MC simulations were carried out using the GATE MC toolkit. Results: Comparison of the measured absorbed dose using tissue-specific DVKs and direct MC simulation on 25 patients revealed a mean difference of 1.07% ± 1.43% for the liver and 1.03% ± 1.21% for the tumor tissue, respectively. The largest difference between DVK convolution and full MC dosimetry was observed for the lung tissue (10.16% ± 1.20%). The DVK statistical uncertainty was <0.75% for both media. Conclusions: This semiautomatic algorithm is capable of performing rapid, accurate, and efficient 3D dosimetry. The proposed method considers tissue and activity heterogeneity using tissue-specific DVKs. Furthermore, this method provides results in <1 min, making it suitable for everyday clinical practice.

PMID:33656372 | DOI:10.1089/cbr.2020.4554

J Cosmet Dermatol. 2021 Mar 2. doi: 10.1111/jocd.14034. Online ahead of print.

ABSTRACT

BACKGROUND: Acne vulgaris is a disease of pilosebaceous units and manifests with polymorphic lesions. Vitamin D acts at various stages in its pathogenesis. Recently, vitamin D and metabolic syndrome have shown to be associated with acne vulgaris and its severity.

AIMS: To see the effects of serum 25(OH)D3 levels and body mass index on acne vulgaris and their correlation with the severity of acne.

METHODS: Fifty patients of acne vulgaris and thirty age and sex-matched healthy volunteers were recruited. Global Acne Grading System was used to grade the acne severity. Body mass index of all patients and control group was calculated and serum levels of 25(OH)D3 were measured using chemiluminescence immunoassay.

RESULTS: Vitamin D deficiency was detected in 28% of patients with acne but only in 6.7% of the healthy controls (p value 0.022). However, there was no significant difference in mean serum 25(OH)D levels in acne patients and controls. Vitamin D deficiency was seen in 60% of the very severe and 33% of the severe acne cases. Eighty percent of patients with very severe acne and 73.33% of severe acne patients had high body mass index. The relationship between severity of acne and body mass index was statistically significant.

CONCLUSION: Vitamin D deficiency was more prevalent in acne and with the increase in severity of acne, an inverse relation between serum levels of vitamin D and body mass index was seen but, statistically significant relation was found only in the very severe cases of acne vulgaris.

PMID:33655695 | DOI:10.1111/jocd.14034

Oncologist. 2021 Mar 3. doi: 10.1002/onco.13740. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to characterize severe irAEs seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, ICI discontinuation, readmission, and death.

METHODS: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011 and October 24, 2018 were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death were collected.

RESULTS: In total, 450 admissions were classified as irAE admissions and represent the study’s cohort. Alongside the increasing use of ICIs at our institution the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (GI; 30.7%; N=138), pulmonary (15.8%; N=71), hepatic (14.2%; N=64), endocrine (12.2%; N=55), neurologic (8.4%; N=38), cardiac (6.7%; N=30), and dermatologic (4.4%; N=20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; P<0.001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; P<0.001), relative to PD-1/PD-L1 monotherapy recipients.

CONCLUSION: This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions that occur earlier after drug initiation.

PMID:33655682 | DOI:10.1002/onco.13740

Clin Exp Ophthalmol. 2021 Mar 2. doi: 10.1111/ceo.13913. Online ahead of print.

ABSTRACT

BACKGROUND: Optical coherence tomography angiography (OCTA) is available in varying size and resolution. We sought to characterize associations of cardiometabolic factors with retinal microvascular changes using 3×3-mm, 6×6-mm and 8×8-mm OCTA scans to determine differences in detection with varying scan size.

METHODS: Cross-sectional study of 247 cardiovascular patients from a single-centre tertiary-care hospital. Demographic, comorbidity, and medication data were obtained. Patients underwent 3×3-mm, 6×6-mm and 8×8-mm macula OCTA scanning using Carl Zeiss CIRRUS HD-OCT Model 5000. Angioplex and AngioTool software was used to quantify vascular parameters in the superficial capillary plexus.

RESULTS: Increasing age, hypertension, dyslipidemia, diabetes, chronic kidney disease, coronary artery disease, and peripheral vascular disease were associated with reductions in vessel density, vessel perfusion, average vessel length and/or junction density in 3×3-mm OCTA (p<0.05 for all). Conversely, smoking was associated with increased vessel density, vessel length, and junction density in 3×3-mm OCTA (p<0.05 for all). Associations of vessel abnormalities with cardiometabolic factors were progressively weakened and statistically attenuated in 6×6-mm and 8×8-mm OCTA scans. In multivariate analyses, dyslipidemia remained an independent predictor of reduced vessel density, average vessel length, and junction density (p<0.05).

CONCLUSIONS: Cardiometabolic factors are associated with multiple retinal microvascular changes in 3×3-mm OCTA scans. These associations were weakened and progressively attenuated in OCTA scans of larger 6×6-mm and 8×8-mm size. These findings advance our understanding of microcirculatory dysfunction and may have future implications for the screening and management of patients with cardiometabolic risk factors. Additional studies are required to further investigate these important associations.

PMID:33655679 | DOI:10.1111/ceo.13913

Colorectal Dis. 2021 Mar 2. doi: 10.1111/codi.15608. Online ahead of print.

ABSTRACT

BACKGROUND: Complex perianal fistulas pose a challenge to the surgeon since the fistulous tract must be eliminated without impairing continence. Although without strong scientific evidence, some bibliography has demonstrated the efficacy of some sealants in the treatment of anal fistulas. We aimed to assess the feasibility and safety of calcium alginate hydrogel injections into the fistulous tract as treatment for trans-sphincteric cryptoglandular fistulas.

METHODS: A prospective, single-center, case series of this novel technique was conducted in a level 3 Spanish hospital, including patients diagnosed with trans-sphincteric perianal fistulas and treated with a calcium alginate hydrogel sealant. A strict follow-up was performed by an independent surgeon at 1, 3, 6, and 12 months. The main outcome measures were feasibility, safety (number of adverse events) and efficacy of the treatment.

RESULTS: Twenty patients were treated. The treatment was performed in all patients. Seven adverse events related to the injection product or the surgical procedure were identified. After a 12-month follow-up, 12 patients were completely cured and 8 were not cured, with a greater response in the first 6 months. These findings were confirmed by endoanal ultrasound, with a Cohen’s kappa concordance rate of 0.89. No statistically significant differences were observed in pain measured using the Visual Analogue Scale, faecal incontinence measured using the Wexner scoring system, and quality of life analysed by the SF-36 Health Survey.

CONCLUSION: The treatment was feasible, safe, and with discrete satisfactory healing results. It also demonstrated an acceptable safety profile, without worsening of faecal incontinence, quality of life, and pain following treatment.

PMID:33655675 | DOI:10.1111/codi.15608

J Paediatr Child Health. 2021 Mar 3. doi: 10.1111/jpc.15370. Online ahead of print.

ABSTRACT

AIM: To evaluate nasopharyngeal aspirate cultures for screening otopathogen carriage in the adenoid in children 2-7 years of age.

METHODS: Thirty-seven children, 2-7 years of age, scheduled for adenoidectomy were enrolled into this prospective study at Rockhampton, Australia. Adenoid biopsy and nasopharyngeal aspirate bacteriology were assessed by conventional culture. Demographic and environmental data were collected by questionnaire. Statistical analyses for descriptive, comparison and logistic regression tests between microbial, demographic, environmental and clinical groups were applied.

RESULTS: Streptococcus pneumoniae, Staphylococcus aureus, non-typeable Haemophilus influenzae and Moraxella catarrhalis were detected in 38, 38, 35 and 24% of cases, respectively. Streptococcus pneumoniae was an independent determinant for non-typeable H. influenzae and S. aureus colonisation, and S. aureus was an independent determinant for S. pneumoniae colonisation. The nasopharyngeal aspirate otopathogen cultures were strong predictors for otopathogens in the adenoid, with moderate-high test accuracy for all otopathogens (receiver operator characteristics area under the curve ranging from 71 to 97% for the otopathogens tested). Children with positive non-typeable H. influenzae, M. catarrhalis, S. pneumoniae and S. aureus nasopharyngeal aspirate cultures were more likely to have the equivalent species in adenoid cultures (positive likelihood ratios = undefined, 15.0, 9.09 and 5.85, respectively).

CONCLUSIONS: This study provides evidence that nasopharyngeal aspirate cultures are an indicator of otopathogens in the adenoid. Nasopharyngeal aspirate cultures may provide clinicians with information that informs clinical management. Strategies for improved management to reduce otopathogen carriage could reduce the prevalence of chronic upper respiratory infections that contribute to adenoidectomy.

PMID:33655670 | DOI:10.1111/jpc.15370

Asia Pac J Clin Oncol. 2021 Mar 2. doi: 10.1111/ajco.13528. Online ahead of print.

ABSTRACT

AIM: We aimed to clarify tumor features and prognosis of pregnancy-associated breast cancer (PABC) among Chinese women.

METHODS: PABC was defined as breast cancer diagnosed during pregnancy or within a year after delivery. Patients with PABC were selected from breast cancer cases of women ≤45 years treated at our institution between December 2012 and December 2017, and one non-PABC control was matched for stage, age, and year of diagnosis for each case.

RESULTS: Forty-one women with PABC were identified (22 diagnosed during pregnancy and 19 within 1 year of delivery). There were significantly more progesterone receptor (PR)- and triple-negative tumors in the PABC (56.1% and 24.4%, respectively) than in the non-PABC group (31.7% and 4.9%, respectively) (P = .045 and .026, respectively). Human epidermal growth factor receptor 2 positivity was the same in both groups (31.7%). Median disease-free survival (DFS) was 29.0 months (95% confidence interval [CI], 6.5-51.5 months) in the PABC and 40.9 months (95% CI, 22.8-58.8 months) in the non-PABC group (P = .167). Median overall survival (OS) was 82.8 months in the PABC (95% CI, 39.3-126.5 months) versus 80.1 months (95% CI, 56.7-103.6 months) in the non-PABC group (P = .131).

CONCLUSION: Histological features were similar in both groups, except that PR- and triple-negative tumors were more frequent in the PABC group. Survival analyses show similar OS for patients with PABC and non-PABC. DFS tended to be shorter in the PABC group; however, this difference was not statistically significant.

PMID:33655647 | DOI:10.1111/ajco.13528

Acta Ophthalmol. 2021 Mar 2. doi: 10.1111/aos.14808. Online ahead of print.

ABSTRACT

PURPOSE: High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far.

METHODS: We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models.

RESULTS: We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia.

CONCLUSION: Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large-scale real-world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia.

PMID:33655633 | DOI:10.1111/aos.14808

Mol Reprod Dev. 2021 Mar 3. doi: 10.1002/mrd.23459. Online ahead of print.

ABSTRACT

MicroRNA (miRNA) is a posttranscriptional downregulator that plays a vital role in a wide variety of biological processes. In this study, we constructed five ovarian and testicular small RNA libraries using two somatic libraries as reference controls for the identification of sex-biased miRNAs and gonadal differentially expressed miRNAs (DEMs) of the Chinese mitten crab, Eriocheir sinensis. A total of 535 known and 243 novel miRNAs were identified, including 312 sex-biased miRNAs and 402 gonadal DEMs. KEGG pathway analysis showed that DEM target genes were statistically enriched in MAPK, Wnt, and GnRH signaling pathway, and so on. A number of the sex-biased miRNAs target genes associated with sex determination/differentiation, such as IAG, Dsx, Dmrt1, and Fem1, while others target the genes related to gonadal development, such as P450s, Wnt, Ef1, and Tra-2c. Dual-luciferase reporter assay in vitro further confirmed that miR-34 and let-7b can downregulate IAG expression, miR-9-5p, let-7d, let-7b, and miR-8915 can downregulate Dsx. Taken together, these data strongly suggest a potential role for the sex-biased miRNAs in sex determination/differentiation and gonadal development in the crab.

PMID:33655621 | DOI:10.1002/mrd.23459