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Nevin Manimala Statistics

Clinical features and risk factors for secondary hemophagocytic lymphohistiocytosis in elderly patients with severe SARS-CoV-2 infection: a multicenter retrospective cohort study

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2023 Aug;35(8):793-799. doi: 10.3760/cma.j.cn121430-20230510-00158.

ABSTRACT

OBJECTIVE: To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.

METHODS: A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People’s Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.

RESULTS: Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio (OR) = 0.997, 95% confidence interval (95%CI) was 0.996-0.998], D-dimer (OR = 0.960, 95%CI was 0.944-0.977), LDH (OR = 0.998, 95%CI was 0.997-0.999) and TG (OR = 0.706, 95%CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer (OR = 1.001, 95%CI was 1.001-1.002), LDH (OR = 1.004, 95%CI was 1.002-1.005) and D-dimer (OR = 1.036, 95%CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients (OR = 7.692, 95%CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95%CI was 0.866-0.973, P = 0.000].

CONCLUSIONS: Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

PMID:37593855 | DOI:10.3760/cma.j.cn121430-20230510-00158

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Nevin Manimala Statistics

Affordable, accurate and unbiased RNA sequencing by manual library miniaturization: A case study in barley

Plant Biotechnol J. 2023 Aug 18. doi: 10.1111/pbi.14126. Online ahead of print.

ABSTRACT

We present an easy-to-reproduce manual miniaturized full-length RNA sequencing (RNAseq) library preparation workflow that does not require the upfront investment in expensive lab equipment or long setup times. With minimal adjustments to an established commercial protocol, we were able to manually miniaturize the RNAseq library preparation by a factor of up to 1:8. This led to cost savings for miniaturized library preparation of up to 86.1% compared to the gold standard. The resulting data were the basis of a rigorous quality control analysis that inspected: sequencing quality metrics, gene body coverage, raw read duplications, alignment statistics, read pair duplications, detected transcripts and sequence variants. We also included a deep dive data analysis identifying rRNA contamination and suggested ways to circumvent these. In the end, we could not find any indication of biases or inaccuracies caused by the RNAseq library miniaturization. The variance in detected transcripts was minimal and not influenced by the miniaturization level. Our results suggest that the workflow is highly reproducible and the sequence data suitable for downstream analyses such as differential gene expression analysis or variant calling.

PMID:37593840 | DOI:10.1111/pbi.14126

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Nevin Manimala Statistics

Promotore-Led Versus Registered Nurse-Led Diabetes Self-Management Education in Mexican Americans: A Randomized Clinical Trial

Sci Diabetes Self Manag Care. 2023 Aug 18:26350106231192353. doi: 10.1177/26350106231192353. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to compare the benefits of a diabetes self-management program led by registered nurses (RNs) versus community health workers (promotores) for Spanish-speaking Mexican Americans with type 2 diabetes (T2DM).

METHODS: Three hundred thirty Spanish-speaking Mexican American adults with T2DM were randomly assigned to “Tomando Control de Su Diabetes” delivered for six 2.5-hour sessions either by promotores or RNs. The primary outcome measure was the Summary of Diabetes Self-Care Activities (SDSCA). Evaluations were made at baseline, 6 weeks, and at 3, 6, and 12 months. Mixed-effects regression models were fit to test if participants had differential changes in the SDSCA total score by group over time, controlling for demographic and clinical factors.

RESULTS: SDSCA scores were significantly higher at all time points compared to baseline and not statistically different between the 2 groups. Only years of education correlated with improvement in diabetes self-management behaviors. No moderating variables predicted improvement between groups.

CONCLUSIONS: Spanish-speaking Mexican American adults with T2DM who participated in a diabetes educational program with promotores or RNs demonstrated similar improvements. Promotores may increase the accessibility of effective diabetes self-management training for this difficult-to-reach population.

PMID:37593833 | DOI:10.1177/26350106231192353

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Nevin Manimala Statistics

Quadriceps and gluteus medius activity during stable and unstable loading exercises in athletes. A Cross-sectional study

J Orthop Res. 2023 Aug 18. doi: 10.1002/jor.25680. Online ahead of print.

ABSTRACT

The aim of this study was to evaluate the muscle activation of the vastus medialis, vastus lateralis, and gluteus medius during different strength and stability exercises with a water tank compared to a sandbag. A cross-sectional study was conducted in the Functional Anatomy Laboratory, and the sample consisted of 28 athletes. The main outcome measures were surface electromyography (dependent variable), water tank and sandbag, and exercise type (independent variables): Isometric Single Leg Stance (ISLS), One Leg Deadlift (OLDL), Front Rack Forward Lunge (FRFL), and Lateral Lunge (LL). Repeated measures ANOVA revealed a significant Group*Time interaction in gluteus medius Root Mean Square (RMS) (F=14.198, p<0.001, ŋ2=0.35), vastus lateralis RMS (F=24.374, p<0.001, ŋ2=0.47), and vastus medialis RMS (F=27.261, p<0.001, ŋ2=0.50). In the between-group analysis, statistically significant differences were observed in gluteus medius RMS in the ISLS: 28.5±15.8 water tank and 20.8±12.6 sandbag (p<0.001, ŋ2=0.08) and OLDL: 29.7±13.3 water tank and 26.5±13.1 sandbag (p<0.001, ŋ2=0.01). In vastus lateralis in ISLS: 30.4±37.6 water tank and 19.0±26.7 sandbag (p<0.001, ŋ2=0.03). In vastus medialis in ISLS: 14.2±13.0 water tank and 7.0±5.6 sandbag (p<0.001, ŋ2=0.12), OLDL: 21.5±16.9 water tank and 15.5±10.7 sandbag (p=0.002, ŋ2=0.04), and LL: 51.8±29.6 water tank and 54.3±29.3 sandbag (p=0.017, ŋ2=0.00). These results confirm significantly greater activation of the gluteus medius and vastus medialis in the ISLS and OLDL exercises, and of the vastus lateralis in the water tank ISLS exercise. However, the vastus medialis shows greater activation in the LL exercise. This article is protected by copyright. All rights reserved.

PMID:37593805 | DOI:10.1002/jor.25680

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Nevin Manimala Statistics

Multilevel joint frailty model for hierarchically clustered binary and survival data

Stat Med. 2023 Sep 20;42(21):3745-3763. doi: 10.1002/sim.9829. Epub 2023 Jun 13.

ABSTRACT

Hierarchical data arise when observations are clustered into groups. Multilevel models are practically useful in these settings, but these models are elusive in the context of hierarchical data with mixed multivariate outcomes. In this article, we consider binary and survival outcomes and assume the hierarchical structure is induced by clustering of both outcomes within patients and clustering of patients within hospitals which frequently occur in multicenter studies. We introduce a multilevel joint frailty model that analyzes the outcomes simultaneously to jointly estimate their regression parameters and explicitly model within-patient correlation between the outcomes and within-hospital correlation separately for each outcome. Estimation is facilitated by a computationally efficient residual maximum likelihood method that further predicts cluster-specific frailties for both outcomes and circumvents the formidable challenges induced by multidimensional integration that complicates the underlying likelihood. The performance of the model and estimation procedure is investigated via extensive simulation studies. The practical utility of the model is illustrated through simultaneous modeling of disease-free survival and binary endpoint of platelet recovery in a multicenter allogeneic bone marrow transplantation dataset that motivates this study.

PMID:37593802 | DOI:10.1002/sim.9829

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Nevin Manimala Statistics

Intrapartum time intervals and transfer of nulliparae from community births to maternity care units in Germany

Birth. 2023 Aug 18. doi: 10.1111/birt.12752. Online ahead of print.

ABSTRACT

BACKGROUND: Over one-third of nulliparae planning births either at home or in freestanding midwife-led birthing centers (community births) in high-income countries are transferred during labor. Perinatal data are reported each year in Germany for women planning community birth. So far, data sets have not been linked to describe time-related factors associated with nulliparous transfer to hospital.

OBJECTIVES: To describe the prevalence of referral for nulliparae and assess maternal and labor characteristics associated with intrapartum transfer.

METHODS: Perinatal data from 2010 to 2015 were linked (n = 26,115). Women were reviewed with respect to international eligibility criteria for community birth; 1997 women were excluded (7.6%). Descriptive statistics were reported; unadjusted and adjusted odds ratios with 95% confidence intervals (CI) tested the predictive effect of demographic and labor factors on rates of intrapartum transfer.

RESULTS: One in three nulliparous women (30.6%) were transferred to hospital. Compared with community births, transferred women were significantly more likely to experience longer time intervals during labor: from rupture of membranes (ROM) until birth lasting 5 to 18 h (OR 6.05, CI 5.53-6.61) and 19 to 24 h (OR 10.83, CI 9.45-12.41) compared to one to 4 h; and from onset of labor until birth 11 to 24 h (OR 6.72, CI 6.24-7.23) and 25 to 29 h (OR 26.62, CI 22.77-31.11) compared to one to 10 h. When entering all factors into the model, we found the strongest predictors of transfer to be fetal distress, longer time intervals between ROM until birth and onset of labor until birth.

CONCLUSIONS: Nulliparous transfer rates were similar to rates in other high-income countries; 94% of referrals were non-urgent. Time was found to be an independent risk factor for the transfer of nulliparae planning community birth.

PMID:37593788 | DOI:10.1111/birt.12752

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Nevin Manimala Statistics

Molecular characterization, gene expression and functional analysis of goldfish (Carassius auratus L.) macrophage colony stimulating factor 2

Front Immunol. 2023 Aug 1;14:1235370. doi: 10.3389/fimmu.2023.1235370. eCollection 2023.

ABSTRACT

BACKGROUND: Macrophage colony-stimulating factor 2 (MCSF-2) is an important cytokine that controls how cells of the monocyte/macrophage lineage proliferate, differentiate, and survive in vertebrates. Two isoforms of MCSF have been identified in fish, each exhibiting distinct gene organization and expression patterns. In this study, we investigated a goldfish MCSF-2 gene in terms of its immunomodulatory and functional properties.

METHODS: In this study, goldfish were acclimated for 3 weeks and sedated with TMS prior to handling. Two groups of fish were used for infection experiments, and tissues from healthy goldfish were collected for RNA isolation. cDNA synthesis was performed, and primers were designed based on transcriptome database sequences. Analysis of gfMCSF-2 sequences, including nucleotide and amino acid analysis, molecular mass prediction, and signal peptide prediction, was conducted. Real-time quantitative PCR (qPCR) was used to analyze gene expression levels, while goldfish head kidney leukocytes (HKLs) were isolated using standard protocols. The expression of gfMCSF-2 in activated HKLs was investigated, and recombinant goldfish MCSF-2 was expressed and purified. Western blot analysis, cell proliferation assays, and flow cytometric analysis of HKLs were performed. Gene expression analysis of transcription factors and pro-inflammatory cytokines in goldfish head kidney leukocytes exposed to rgMCSF-2 was conducted. Statistical analysis using one-way ANOVA and Dunnett’s post hoc test was applied.

RESULTS: We performed a comparative analysis of MCSF-1 and MCSF-2 at the protein and nucleotide levels using the Needleman-Wunsch algorithm. The results revealed significant differences between the two sequences, supporting the notion that they represent distinct genes rather than isoforms of the same gene. Sequence alignment demonstrated high sequence identity with MCSF-2 homologs from fish species, particularly C. carpio, which was supported by phylogenetic analysis. Expression analysis in various goldfish tissues demonstrated differential expression levels, with the spleen exhibiting the highest expression. In goldfish head kidney leukocytes, gfMCSF-2 expression was modulated by chemical stimuli and bacterial infection, with upregulation observed in response to lipopolysaccharide (LPS) and live Aeromonas hydrophila. Recombinant gfMCSF-2 (rgMCSF-2) was successfully expressed and purified, showing the ability to stimulate cell proliferation in HKLs. Flow cytometric analysis revealed that rgMCSF-2 induced differentiation of sorted leukocytes at a specific concentration. Moreover, rgMCSF-2 treatment upregulated TNFα and IL-1β mRNA levels and influenced the expression of transcription factors, such as MafB, GATA2, and cMyb, in a time-dependent manner.

CONCLUSION: Collectively, by elucidating the effects of rgMCSF-2 on cell proliferation, differentiation, and the modulation of pro-inflammatory cytokines and transcription factors, our findings provided a comprehensive understanding of the potential mechanisms underlying gfMCSF-2-mediated immune regulation. These results contribute to the fundamental knowledge of MCSF-2 in teleosts and establish a foundation for further investigations on the role of gfMCSF-2 in fish immune responses.

PMID:37593738 | PMC:PMC10431942 | DOI:10.3389/fimmu.2023.1235370

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Nevin Manimala Statistics

Joint models quantify associations between immune cell kinetics and allo-immunological events after allogeneic stem cell transplantation and subsequent donor lymphocyte infusion

Front Immunol. 2023 Aug 1;14:1208814. doi: 10.3389/fimmu.2023.1208814. eCollection 2023.

ABSTRACT

Alloreactive donor-derived T-cells play a pivotal role in alloimmune responses after allogeneic hematopoietic stem cell transplantation (alloSCT); both in the relapse-preventing Graft-versus-Leukemia (GvL) effect and the potentially lethal complication Graft-versus-Host-Disease (GvHD). The balance between GvL and GvHD can be shifted by removing T-cells via T-cell depletion (TCD) to reduce the risk of GvHD, and by introducing additional donor T-cells (donor lymphocyte infusions [DLI]) to boost the GvL effect. However, the association between T-cell kinetics and the occurrence of allo-immunological events has not been clearly demonstrated yet. Therefore, we investigated the complex associations between the T-cell kinetics and alloimmune responses in a cohort of 166 acute leukemia patients receiving alemtuzumab-based TCD alloSCT. Of these patients, 62 with an anticipated high risk of relapse were scheduled to receive a prophylactic DLI at 3 months after transplant. In this setting, we applied joint modelling which allowed us to better capture the complex interplay between DLI, T-cell kinetics, GvHD and relapse than traditional statistical methods. We demonstrate that DLI can induce detectable T-cell expansion, leading to an increase in total, CD4+ and CD8+ T-cell counts starting at 3 months after alloSCT. CD4+ T-cells showed the strongest association with the development of alloimmune responses: higher CD4 counts increased the risk of GvHD (hazard ratio 2.44, 95% confidence interval 1.45-4.12) and decreased the risk of relapse (hazard ratio 0.65, 95% confidence interval 0.45-0.92). Similar models showed that natural killer cells recovered rapidly after alloSCT and were associated with a lower risk of relapse (HR 0.62, 95%-CI 0.41-0.93). The results of this study advocate the use of joint models to further study immune cell kinetics in different settings.

PMID:37593737 | PMC:PMC10427852 | DOI:10.3389/fimmu.2023.1208814

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Nevin Manimala Statistics

Homologous versus Heterologous prime-boost COVID-19 Vaccination in autologous hematopoietic stem cell transplantation recipients: a blinded randomized controlled trial

Front Immunol. 2023 Aug 1;14:1237916. doi: 10.3389/fimmu.2023.1237916. eCollection 2023.

ABSTRACT

BACKGROUND/PURPOSE: Optimizing vaccine efficacy is of particular concern in patients undergoing hematopoietic stem cell transplantation (HSCT), which mainly have an inadequate immune response to primary SARS-CoV-2 vaccination. This investigation aimed to explore the potential prime-boost COVID-19 vaccination strategies following autologous (auto-) HSCT.

METHODS: In a randomized clinical trial, patients who had already received two primary doses of receptor-binding domain (RBD) tetanus toxoid (TT) conjugated SARS-CoV-2 vaccine during three to nine months after auto-HSCT were randomized to receive either a homologous RBD-TT conjugated or heterologous inactivated booster dose four weeks after the primary vaccination course. The primary outcome was comparing the anti-S IgG Immune status ratio (ISR) four weeks after the heterologous versus homologous booster dose. The assessment of safety and reactogenicity adverse events was considered as the secondary outcome.

RESULTS: Sixty-one auto-HSCT recipients were recruited and randomly assigned to receive either homologous or heterologous booster doses four weeks after the primary vaccination course. The mean ISR was 3.40 (95% CI: 2.63- 4.16) before the booster dose with a 90.0% seropositive rate. The ISR raised to 5.12 (95% CI: 4.15- 6.08) with a 100% seropositive rate after heterologous (P= 0.0064) and to 3.42 (95% CI: 2.67- 4.17) with a 93.0% seropositivity after the homologous booster doses (P= 0.96). In addition, the heterologous group suffered more AEs following the booster dosage than the homologous group, but this difference was not statistically significant (p = 0.955). In multivariable analysis, the prime-boost vaccination strategy (heterologous versus homologous), the level of ISR before the booster dose, and the length of time between auto-HSCT and booster dose were the positive predictors of serologic response to a booster dose. No serious adverse event is attributed to booster vaccination.

CONCLUSION: In patients who were primed with two SARS-CoV-2 vaccine doses during the first year after auto-HSCT, heterologous prime-boost COVID-19 vaccination with inactivated platform resulted in considerably enhanced serologic response and non-significantly higher reactogenicity adverse events than homologous RBD-TT conjugated prime-boost COVID-19 vaccination strategy.

PMID:37593732 | PMC:PMC10427916 | DOI:10.3389/fimmu.2023.1237916

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Nevin Manimala Statistics

The effect of educational intervention based on the PEN-3 model on breast cancer screening behaviors

Front Public Health. 2023 Aug 1;11:1123888. doi: 10.3389/fpubh.2023.1123888. eCollection 2023.

ABSTRACT

BACKGROUND: Breast cancer is the most important malignancy and the main cause of cancer deaths among women worldwide. Breast cancer screening is an effective way to reduce breast cancer deaths.

OBJECTIVES: The present study aimed to provide breast cancer screening behavior training for female teachers in Isfahan, Iran.

MATERIALS AND METHODS: This randomized controlled trial included 120 teachers who have randomly divided into two groups (60 in the control group and 60 in the intervention group). The data collection tool was a PEN-3 model-based questionnaire. Four 90 min training sessions were held for the intervention group to modify perception and enablers. Breast self-examination (BSE), Clinical breast exam (CBE), and mammography (MMG) were investigated in both groups before and after 6 months after the last training using SPSS20 and appropriate statistical tests.

RESULTS: The frequency of BSE (p = 0.02), CBE (p = 0.04), and MMG (p = 0.01) in the intervention group was significantly higher than in the control group 6 months after training. The mean scores of perception and enablers were significantly higher in the intervention group than in the control group 3 and 6 months after training (p < 0.001). The logistic regression analysis indicated that perception factors were the strongest predictors of breast cancer screening behavior in teachers.

CONCLUSION: Results of the present study indicated that using the PEN-3 model in the educational intervention was effective in improving breast cancer screening behavior.

PMID:37593730 | PMC:PMC10427920 | DOI:10.3389/fpubh.2023.1123888