Nevin Manimala

Nat Med. 2022 Sep 5. doi: 10.1038/s41591-022-02000-0. Online ahead of print.

ABSTRACT

Cardiac symptoms are increasingly recognized as late complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in previously well individuals with mild initial illness, but the underlying pathophysiology leading to long-term cardiac symptoms remains unclear. In this study, we conducted serial cardiac assessments in a selected population of individuals with Coronavirus Disease 2019 (COVID-19) with no previous cardiac disease or notable comorbidities by measuring blood biomarkers of heart injury or dysfunction and by performing magnetic resonance imaging. Baseline measurements from 346 individuals with COVID-19 (52% females) were obtained at a median of 109 days (interquartile range (IQR), 77-177 days) after infection, when 73% of participants reported cardiac symptoms, such as exertional dyspnea (62%), palpitations (28%), atypical chest pain (27%) and syncope (3%). Symptomatic individuals had higher heart rates and higher imaging values or contrast agent accumulation, denoting inflammatory cardiac involvement, compared to asymptomatic individuals. Structural heart disease or high levels of biomarkers of cardiac injury or dysfunction were rare in symptomatic individuals. At follow-up (329 days (IQR, 274-383 days) after infection), 57% of participants had persistent cardiac symptoms. Diffuse myocardial edema was more pronounced in participants who remained symptomatic at follow-up as compared to those who improved. Female gender and diffuse myocardial involvement on baseline imaging independently predicted the presence of cardiac symptoms at follow-up. Ongoing inflammatory cardiac involvement may, at least in part, explain the lingering cardiac symptoms in previously well individuals with mild initial COVID-19 illness.

PMID:36064600 | DOI:10.1038/s41591-022-02000-0

Trials. 2022 Sep 5;23(1):745. doi: 10.1186/s13063-022-06695-x.

ABSTRACT

BACKGROUND: Overweight and obesity are typical risk factors for the increased prevalence and incidence of gout. The existing guidelines unequivocally indicated that exercise is highly advantageous for patients with gout. Nevertheless, there is still a lack of specific guidance and clinical evidence. The effects of exercise on improving gout, and the optimal frequency, timing, and types of exercise have not been fully clarified. The present trial aims to determine the effects of a specific aerobic exercise program on body composition in overweight and obese patients with gout.

METHODS: In this randomized, open-labeled, controlled trial, a total of 60 overweight and obese patients with gout [body mass index (BMI) ≥ 24 kg/m²; age,18-55 years old] are equally randomized (1:1) into two groups (n = 30): moderate-intensity aerobic exercise group (MIAEG), heart rate reserve (HRR) = [(HRmax-HRrest) × 60% intensity] + HRrest, and control group (CG). The moderate-intensity aerobic exercise training program will be conducted for 30-40 min/session and 3 days/week for 12 weeks. Participants in the CG will be asked to avoid making changes in their exercise habits. There will be no limitation in the type of exercise. The primary outcome is the number of patients whose body fat is reduced after 12 weeks. The secondary outcomes include the changes in BMI, waist-to-hip ratio (WHR), insulin resistance index (IRI), serum uric acid (sUA), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hepatic steatosis, and adverse effects after 12 weeks. One-way analysis of variance (ANOVA) will be used to compare the mean values of normally distributed variables between MIAEG and GC.

DISCUSSION: The effect and optimal frequency of exercise for improving the status of overweight and obese patients with gout have not yet been determined. We design a 12-week randomized controlled trial and evaluate the effects of individualized aerobic exercise program on patients with gout. The results may assist such patients with a personalized scientific exercise program based on the disease status and motor abilities, so that patients are prone to exercise under the condition of low risk and achieve the greatest benefits.

TRIAL REGISTRATION: ChiCTR2200062153. Registered on July 25, 2022, with ChiCTR. http://www.chictr.org.cn/.

PMID:36064594 | DOI:10.1186/s13063-022-06695-x

J Hematol Oncol. 2022 Sep 5;15(1):126. doi: 10.1186/s13045-022-01339-8.

ABSTRACT

BACKGROUND: The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K).

METHODS: Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal-Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate.

RESULTS: Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002).

CONCLUSION: In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.

PMID:36064577 | DOI:10.1186/s13045-022-01339-8

Int Breastfeed J. 2022 Sep 5;17(1):67. doi: 10.1186/s13006-022-00501-9.

ABSTRACT

BACKGROUND: Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two.

METHODS: This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228.

RESULTS: Thirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics.

CONCLUSIONS: Interventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021224228.

PMID:36064573 | DOI:10.1186/s13006-022-00501-9

Vet Med Sci. 2022 Sep 5. doi: 10.1002/vms3.925. Online ahead of print.

ABSTRACT

BACKGROUND: Respiratory disease is the most common presenting complaint at veterinary clinics and a priority concern for equid owners and veterinary practitioners in Ethiopia.

OBJECTIVES: This study aimed to report the molecular detection of EHV-2 and EHV-5 and to assess the risk factors associated with infection in working equids in central Ethiopia.

METHODS: Nasopharyngeal swabs were collected from 58 horses and donkeys to detect EHV-2 and EHV-5 using PCR targeting the conserved region of glycoprotein B (gB) genes.

RESULTS: From 58 equids, EHV-5 and EHV-2 were detected in 20 (34.5%) and 19 (32.8%) equids, respectively. Concurrent infection with EHV-2 and EHV-5 was found in 6 (10.3%) equids who exhibited respiratory clinical signs. EHV-2 was detected in a significantly higher (p = 0.002) proportion of horses (54.5%; n = 18) than donkeys (4%; n = 1). In contrast, EHV-5 was detected in a significantly higher (p = 0.004) proportion of donkeys (56%; n = 14) compared to horses (18.2% n = 6). EHV-2-positive equids were seven times more likely to display clinical signs of respiratory disease than EHV-2-negative equids (Odds ratio (OR) = 6.9; 95%CI: 1.72-27.60). However, statistically significant (p = 0.832) difference was not observed for EHV-5. EHV-2 was detected in a significantly higher (p = 0.004) proportion of female (50%; n = 16) compared to male equids (11.5%; n = 3).

CONCLUSIONS: This study revealed the molecular detection of EHV-2 and EHV-5 in horses and donkeys residing in central Ethiopia. The association between EHV-2-test-positive equids and displaying of clinical signs of respiratory disease was observed, which suggests EHV-2 involvement in the development of respiratory disease; however, it deserves further investigation.

PMID:36063540 | DOI:10.1002/vms3.925

Bioinformatics. 2022 Sep 5:btac599. doi: 10.1093/bioinformatics/btac599. Online ahead of print.

ABSTRACT

MOTIVATION: Cell-cell communications regulate internal cellular states, e.g., gene expression and cell functions, and play pivotal roles in normal development and disease states. Furthermore, single-cell RNA sequencing methods have revealed cell-to-cell expression variability of highly variable genes (HVGs), which is also crucial. Nevertheless, the regulation on cell-to-cell expression variability of HVGs via cell-cell communications is still largely unexplored. The recent advent of spatial transcriptome methods has linked gene expression profiles to the spatial context of single cells, which has provided opportunities to reveal those regulations. The existing computational methods extract genes with expression levels influenced by neighboring cell types. However, limitations remain in the quantitativeness and interpretability: they neither focus on HVGs nor consider the effects of multiple neighboring cell types.

RESULTS: Here, we propose CCPLS (Cell-Cell communications analysis by Partial Least Square regression modeling), which is a statistical framework for identifying cell-cell communications as the effects of multiple neighboring cell types on cell-to-cell expression variability of HVGs, based on the spatial transcriptome data. For each cell type, CCPLS performs PLS regression modeling and reports coefficients as the quantitative index of the cell-cell communications. Evaluation using simulated data showed our method accurately estimated the effects of multiple neighboring cell types on HVGs. Furthermore, applications to the two real datasets demonstrate that CCPLS can extract biologically interpretable insights from the inferred cell-cell communications.

AVAILABILITY: The R package is available at https://github.com/bioinfo-tsukuba/CCPLS. The data are available at https://github.com/bioinfo-tsukuba/CCPLS_paper.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:36063454 | DOI:10.1093/bioinformatics/btac599

Ann ICRP. 2022 Jul;51(3):9-103. doi: 10.1177/01466453221080101.

ABSTRACT

Radiation detriment is a concept developed by the International Commission on Radiological Protection to quantify the burden of stochastic effects from low-dose and/or low-dose-rate exposures to the human population. It is determined from the lifetime risks of cancer for a set of organs and tissues and the risk of heritable effects, taking into account the severity of the consequences. This publication provides a historical review of detriment calculation methodology since ICRP Publication 26, with details of the procedure developed in ICRP Publication 103, which clarifies data sources, risk models, computational methods, and rationale for the choice of parameter values. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty in the calculation of radiation detriment. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the calculation of lifetime risk, and lethality fraction have a substantial impact on radiation detriment values. Although the current scheme of radiation detriment calculation is well established, it needs to evolve to better reflect changes in population health statistics and progress in scientific understanding of radiation health effects. In this regard, some key parameters require updating, such as the reference population data and cancer severity. There is also room for improvement in cancer risk models based on the accumulation of recent epidemiological findings. Finally, the importance of improving the comprehensibility of the detriment concept and the transparency of its calculation process is emphasised.© 2022 ICRP. Published by SAGE.

PMID:36063447 | DOI:10.1177/01466453221080101

Small. 2022 Sep 5:e2104318. doi: 10.1002/smll.202104318. Online ahead of print.

ABSTRACT

Analysis of the temperature- and stimulus-dependent imaging data toward elucidation of the physical transformations is an ubiquitous problem in multiple fields. Here, temperature-induced phase transition in BaTiO₃ is explored using the machine learning analysis of domain morphologies visualized via variable-temperature scanning transmission electron microscopy (STEM) imaging data. This approach is based on the multivariate statistical analysis of the time or temperature dependence of the statistical descriptors of the system, derived in turn from the categorical classification of observed domain structures or projection on the continuous parameter space of the feature extraction-dimensionality reduction transform. The proposed workflow offers a powerful tool for the exploration of the dynamic data based on the statistics of image representation as a function of the external control variable to visualize the transformation pathways during phase transitions and chemical reactions. This can include the mesoscopic STEM data as demonstrated here, but also optical, chemical imaging, etc., data. It can further be extended to the higher dimensional spaces, for example, analysis of the combinatorial libraries of materials compositions.

PMID:36063435 | DOI:10.1002/smll.202104318

J Am Med Inform Assoc. 2022 Sep 5:ocac152. doi: 10.1093/jamia/ocac152. Online ahead of print.

ABSTRACT

While many case studies have described the implementation of self-scheduling tools, which allow patients to schedule visits and imaging studies asynchronously online, none have explored the impact of self-scheduling on equitable access to care.1 Using an electronic health record patient portal, University of California San Francisco deployed a self-scheduling tool that allowed patients to self-schedule diagnostic imaging studies. We analyzed electronic health record data for the imaging modalities with the option to be self-scheduled from January 1, 2021 to September 1, 2021. We used descriptive statistics to compare demographic characteristics and created a multivariable logistic regression model to identify predictors of patient self-scheduling utilization. Among all active patient portal users, Latinx, Black/African American, and non-English speaking patients were less likely to self-schedule studies. Patients with Medi-Cal, California’s Medicaid program, and Medicare insurance were also less likely to self-schedule when compared with commercially insured patients. Efforts to facilitate use of patient portal-based applications are necessary to increase equitability and decrease disparities in access.

PMID:36063414 | DOI:10.1093/jamia/ocac152

Horm Mol Biol Clin Investig. 2022 Sep 6. doi: 10.1515/hmbci-2022-0049. Online ahead of print.

ABSTRACT

BACKGROUND: There has been several discussion and debates regarding the possible setremental influence of elevated serum progesterone (SP) on the day of human chorionic gonadotropin (hCG) administration. Our study aims to assess progestron to oocyte rates for assessing CPR and live birth rate (LBR) in IVF cycles and review previous articles.

METHODS: In this prospective cohort study, women under ovulation induction through IVF-ICSI using the GnRH-antagonist protocol were studied. Five specific indicators were considered to assess pregnancy outcome. The statistical analysis was done using SPSS software.

RESULTS: In the present research, 78 patients underwent IVF. The cut-off points for each of the three parameters were 1.2 (with a sensitivity of 65.4% and a specificity of 54%), 6.5 (with a sensitivity of 73.1% and a specificity of 56%), and 0.16 (with a sensitivity of 65.4% and a specificity of 60%, respectively). Only the number of oocytes (area below the curve of 0.64) was able to predict clinical pregnancy. The cut-off point for this parameter was 6.5 (with a sensitivity of 74.1% and a specificity of 66%). On the other hand, none of the parameters were able to predict live birth.

CONCLUSIONS: The findings of this study should assist in the clinical management of patients with high SP on the day of HCG administration. We recommend, that the ratio of SP to oocyte is a useful parameter for refining the criteria of patients who have had embryo freezing of all embryos (by selective freezing) and subsequent transfer of frozen embryos.

PMID:36063359 | DOI:10.1515/hmbci-2022-0049