Category: Statistics

Appl Immunohistochem Mol Morphol. 2024 Mar 1. doi: 10.1097/PAI.0000000000001189. Online ahead of print.

ABSTRACT

The use of chemotherapy has improved the overall treatment of breast cancer, which is frequently administered in the form of neoadjuvant chemotherapy (NAC). Apoptosis is an established cell stress response to NAC in preclinical models; however, there is limited understanding of its role in clinical cancer, specifically, its contribution to favorable pathologic responses in breast cancer therapy. Here, we aimed to characterize the change in protein expression of 3 apoptosis-associated biomarkers, namely, BCL-XL, MCL-1, and BAX in breast cancer in response to NAC. For this, we utilized a set of 68 matched invasive breast cancer FFPE samples that were collected before (pre) and after (post) the exposure to NAC therapy that were characterized by incomplete pathologic response. Immunohistochemistry (IHC) analysis suggested that most of the samples show a decrease in the protein expression of all 3 markers following exposure to NAC as 90%, 69%, and 76% of the matched samples exhibited a decrease in expression for BCL-XL, MCL-1, and BAX, respectively. The median H-score of BCL-XL post-NAC was 150/300 compared with 225/300 pre-NAC (P value <0.0001). The median H-score of MCL-1 declined from 200 pre-NAC to 160 post-NAC (P value <0.0001). The median H-score of BAX protein expression decreased from 260 pre-NAC to 190 post-NAC (P value <0.0001). There was no statistically significant association between the expression of these markers and stage, grade, and hormone receptor profiling (luminal status). Collectively, our data indicate that the expression of apoptosis regulatory proteins changes following exposure to NAC in breast cancer tissue, developing a partial pathologic response.

PMID:38426376 | DOI:10.1097/PAI.0000000000001189

J Cosmet Dermatol. 2024 Mar 1. doi: 10.1111/jocd.16235. Online ahead of print.

ABSTRACT

BACKGROUND: Acne vulgaris is a common inflammatory disease associated with various sequelae after skin lesion remission. Acne erythema has been considered simple erythema or a vascular lesion; however, because the understanding of this disease has improved, acne erythema is currently considered an early scar with erythematous components.

AIMS: This study evaluated the efficacy of using both a 595-nm pulsed dye laser (PDL) and 1565-nm nonablative fractional laser (NAFL) for the treatment of erythematous scars caused by acne.

METHODS: Ninety patients with acne scars were equally randomized to two groups. Group A (n = 45) received treatment with the NAFL. Group B (n = 45) received treatment with the PDL and NAFL. Each patient underwent one treatment session and 4 weeks of follow-up.

RESULTS: Qualitative (χ² = 12.415; p < 0.05) and quantitative (t = 2.675; p < 0.05) scores of Groups A and B were determined using a global scarring grading system and exhibited statistically significant differences. The quantitative score of Group A was higher than that of Group B (6.67 ± 3.46 vs. 4.98 ± 2.44). The erythema areas of the groups differed significantly after treatment, with Group B exhibiting more notable score improvements (5.00 [3.10, 7.10] vs. 2.80 [1.65, 4.60]; Z = 3.072; p < 0.05). The erythema regression rate of Group B (88.9%) was significantly higher than that of Group A (66.7%) (χ² = 20.295; p < 0.001). Adverse events, including redness and swelling (86.6%), scabbing (78.8%), and purpura (36.6%), occurred within 7 days for 86.6% of patients.

CONCLUSIONS: The combined use of the PDL and NAFL is safe and effective for erythematous acne scars.

PMID:38426374 | DOI:10.1111/jocd.16235

Bioinformatics. 2024 Feb 29:btae119. doi: 10.1093/bioinformatics/btae119. Online ahead of print.

ABSTRACT

MOTIVATION: MetaCerberus is a massively parallel, fast, low memory, scalable annotation tool for inference gene function across genomes to metacommunities. MetaCerberus provides an elusive HMM/HMMER-based tool at a rapid scale with low memory. It offers scalable gene elucidation to major public databases, including KEGG (KO), COGs, CAZy, FOAM, and specific databases for viruses, including VOGs and PHROGs, from single genomes to metacommunities.

RESULTS: MetaCerberus is 1.3x as fast on a single node than eggNOG-mapper v2 on 5x less memory using an exclusively HMM/HMMER mode. In a direct comparison, MetaCerberus provides better annotation of viruses, phages, and archaeal viruses than DRAM, Prokka, or InterProScan. MetaCerberus annotates more KOs across domains when compared to DRAM, with a 186x smaller database, and with 63x less memory. MetaCerberus is fully integrated for automatic analysis of statistics and pathways using differential statistic tools (i.e., DESeq2 and edgeR), pathway enrichment (GAGE R), and pathview R. MetaCerberus provides a novel tool for unlocking the biosphere across the tree of life at scale.

AVAILABILITY: MetaCerberus is written in Python and distributed under a BSD-3 license. The source code of MetaCerberus is freely available at https://github.com/raw-lab/metacerberus compatible with Python 3 and works on both Mac OS X and Linux. MetaCerberus can also be easily installed using bioconda: mamba create -n metacerberus -c bioconda -c conda-forge metacerberus.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38426351 | DOI:10.1093/bioinformatics/btae119

J Natl Cancer Inst. 2024 Feb 29:djae052. doi: 10.1093/jnci/djae052. Online ahead of print.

ABSTRACT

BACKGROUND: Foreign-born (FB) populations in the US have significantly increased, yet cancer trends remain unexplored. Survey-based Population-Adjusted Rate Calculator (SPARC) is a new tool for evaluating nativity differences in cancer mortality.

METHODS: Using SPARC, we calculated 3-year (2016-2018) age-adjusted mortality rates (AAMRs) and rate ratios (RRs) for common cancers by sex, age group, race/ethnicity, and nativity. Trends by nativity were examined for the first time for 2006-2018. Traditional cancer statistics draw populations from decennial censuses. However, nativity-stratified populations are from the American Community Surveys, thus involve sampling errors. To rectify this, SPARC employed bias-corrected estimators. Death counts came from the National Vital Statistics System.

RESULTS: AAMRs were higher among US-born (UB) populations across nearly all cancer types, with the largest UB- FB difference observed in lung cancer among Black females (RR = 3.67, 95%CI = 3.37-4.00). The well-documented White-Black differences in breast cancer mortality existed mainly among UB women. For all cancers combined, descending trends were more accelerated for the UB compared to the FB in all race/ethnicity groups with changes ranging from -2.6% per year in UB Black males to stable (non-significant) among FB Black females. Pancreas and liver cancers were exceptions with increasing, stable, or decreasing trends depending on nativity and race/ethnicity. Notably, FB Black males and FB Hispanic males did not show a favorable decline in colorectal cancer mortality.

CONCLUSIONS: While all groups show beneficial cancer mortality trends, those with higher rates in 2006 have experienced sharper declines. Persistent disparities between the UB and the FB, especially among Black people, necessitate further investigation.

PMID:38426333 | DOI:10.1093/jnci/djae052

Dev Psychopathol. 2024 Mar 1:1-14. doi: 10.1017/S0954579424000518. Online ahead of print.

ABSTRACT

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children’s susceptibility to the effects of maternal depression on telomere dynamics in early life.

PMID:38426330 | DOI:10.1017/S0954579424000518

Circ Heart Fail. 2024 Mar 1:e010896. doi: 10.1161/CIRCHEARTFAILURE.123.010896. Online ahead of print.

ABSTRACT

BACKGROUND: Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

METHODS: Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication.

RESULTS: Sixty metabolites (hazard ratios range, 0.79-1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19-1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017-0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (P<0.05).

CONCLUSIONS: Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.

PMID:38426319 | DOI:10.1161/CIRCHEARTFAILURE.123.010896

Semin Ophthalmol. 2024 Mar 1:1-6. doi: 10.1080/08820538.2024.2324074. Online ahead of print.

ABSTRACT

PURPOSE: To assess the feasibility of the clinical use of a novel Virtual Reality (VR) training software designed to be used for active vision therapy in amblyopic patients by determining its preliminary safety and acceptance on the visual function of healthy adults.

METHODS: Pilot study enrolling 10 individuals (3 men, 7 women, mean age: 31.8 ± 6.5 years) with a best-corrected visual acuity (BCVA) of ≥ .90 (decimal) in both eyes were evaluated before and after 20 minutes of exposure to the NEIVATECH VR system using the HTC Vive Pro Eye head mounted display. Visual function assessment included near (40 cm) and distance (6 m) cover test (CT), stereopsis, binocular accommodative facility (BAF), near point of convergence (NPC), near point of accommodation (NPA), accommodative-convergence over accommodation (AC/A) ratio and positive and negative fusional vergences. Safety was assessed using the VR Sickness Questionnaire (VRSQ) and acceptance using the Technology Acceptance Model ;(TAM). Changes in all these variables after VR exposure were analyzed.

RESULTS: Short-term exposure to the NEIVATECH VR system only induced statistically significant changes in distance phoria (p = .016), but these changes were not clinically relevant. No significant changes were observed in VRSQ oculo-motricity and disorientation scores after exposure (p = .197 and .317, respectively). TAM scores showed a good acceptance of the system in terms of perceived enjoyment and perceived ease of use, although some concerns were raised in relation to the intention-to-use domain.

CONCLUSION: Exposure to the NEIVATECH VR system does not seem to adversely affect the visual function in healthy adults and its safety and acceptance profile seems to be adequate for supporting its potential use in other populations, such as amblyopic patients.

PMID:38426308 | DOI:10.1080/08820538.2024.2324074

Turk J Haematol. 2024 Mar 1. doi: 10.4274/tjh.galenos.2024.2023.0469. Online ahead of print.

ABSTRACT

OBJECTIVE: Calprotectin (CLP), S100A6, and High Mobility Group Nucleosome-Binding Protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to inve stigate the relationship of serum CLP, S100A6, and HMGN1 levels with clinical and laboratory findings in Multiple Myeloma (MM) patients and their role in the pathogenesis of MM.

MATERIALS AND METHODS: We measured serum CLP, S100A6, and HMGN1 levels in 55 newly diagnosed patients and 32 healthy controls (HC).

RESULTS: We determined significantly decreased serum CLP, S100A6 ve HMGN1 levels in MM patients compared to HC (p=0.012, p=0.001, p=0.030, respectively). ROC analysis was used to determine a diagnostic cut-off value for serum CLP, S100A6 and HMGN1; the cut off value for CLP was <98 ng/ml (AUC = 0.663, 95% CI 0.554-0.761, p=0.009), S100A6 was <1174.5 pg/ml (AUC = 0.706, 95% CI 0.598-0.799, p=0.001), and HMGN1 was <440.18 pg/ml (AUC = 0.640, 95% CI 0.530-0.740, p:0.03). CLP level was found to be statistically significantly in light chain MM patients ( 91.58±22.57) higher than in heavy chain MM patients (79.42±15.83) (p=0.03). A negative correlation was observed between CLP and M protein, IgG, globulin, and beta 2 microglobulin (correlation coefficient: -0,361; -0,370; -0,279; -0,300, p=0,024, p=006, p=0,04, p=0,0033).

CONCLUSION: In this study, we found that serum CLP, S100A6, and HMGN1 levels were statistically lower in newly diagnosed MM patients compared to HC. These results suggest that CLP may binds to the paraprotein produced by heavy chain MM in the blood and therefore its blood levels are found to be low. Additionally, low levels of HMGN1, which is involved in DNA repair, suggest that HMGN1 may contribute to the complex genetic abnormalities found in MM.

PMID:38426298 | DOI:10.4274/tjh.galenos.2024.2023.0469

Pediatrics. 2024 Mar 1:e2023063447. doi: 10.1542/peds.2023-063447. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Approximately half of youth suicides involve firearms. The promotion of safe firearm storage in the home through lethal means counseling reduces suicide risk. We aimed to increase the documentation of firearm access and storage among children presenting to the emergency department (ED) with suicidal ideation or self-injury to 80% within 13 months.

METHODS: We conducted a multidisciplinary quality improvement initiative to improve the documentation of firearm access and storage among children <18 years old seen in the ED for suicidal ideation or self-injury. The baseline period was February 2020 to September 2021, and interventions occurred through October 2022. Interventions included adding a templated phrase about firearm access to psychiatric social work consult notes and the subsequent modification of the note to include all firearm storage elements (ie, locked, unloaded, separate from ammunition). Statistical process control and run charts were generated monthly to monitor the documentation of firearm access and storage, which was measured through a review of keyword snippets extracted from note text.

RESULTS: We identified 2158 ED encounters for suicidal ideation or self-injury during the baseline and intervention periods. Documentation of firearm access increased from 37.8% to 81.6%, resulting in a centerline shift. Among families who endorsed firearm access, the documentation of firearm storage practices increased from 50.0% to 78.0%, resulting in a centerline shift.

CONCLUSIONS: The modification of note templates facilitated increased documentation of firearm access and storage practices for children with suicidal ideation in the ED. Future studies should assess whether improved documentation is associated with improved storage practices and reductions in firearm suicides after ED encounters.

PMID:38426287 | DOI:10.1542/peds.2023-063447

Eur J Anaesthesiol. 2024 Apr 1;41(4):257-259. doi: 10.1097/EJA.0000000000001965. Epub 2024 Mar 6.

NO ABSTRACT

PMID:38426253 | DOI:10.1097/EJA.0000000000001965