Nevin Manimala

Bioinformatics. 2024 Jul 1:btae425. doi: 10.1093/bioinformatics/btae425. Online ahead of print.

ABSTRACT

MOTIVATION: Spatial proteomics can reveal the spatial organization of immune cells in the tumor immune microenvironment. Relating measures of spatial clustering, such as Ripley’s K or Besag’s L, to patient outcomes may offer important clinical insights. However, these measures require pre-specifying a radius in which to quantify clustering, yet no consensus exists on the optimal radius which may be context-specific.

RESULTS: We propose a SPatial Omnibus Test (SPOT) which conducts this analysis across a range of candidate radii. At each radius, SPOT evaluates the association between the spatial summary and outcome, adjusting for confounders. SPOT then aggregates results across radii using the Cauchy combination test, yielding an omnibus p-value characterizing the overall degree of association. Using simulations, we verify that the type I error rate is controlled and show SPOT can be more powerful than alternatives. We also apply SPOT to an ovarian and lung cancer study.

AVAILABILITY: An R package and tutorial is provided at https://github.com/sarahsamorodnitsky/SPOT.

PMID:38950184 | DOI:10.1093/bioinformatics/btae425

Microb Genom. 2024 Jul;10(7). doi: 10.1099/mgen.0.001267.

ABSTRACT

Lactobacillus species are common inhabitants of the ‘healthy’ female urinary and vaginal communities, often associated with a lack of symptoms in both anatomical sites. Given identification by prior studies of similar bacterial species in both communities, it has been hypothesized that the two microbiotas are in fact connected. Here, we carried out whole-genome sequencing of 49 Lactobacillus strains, including 16 paired urogenital samples from the same participant. These strains represent five different Lactobacillus species: L. crispatus, L. gasseri, L. iners, L. jensenii, and L. paragasseri. Average nucleotide identity (ANI), alignment, single-nucleotide polymorphism (SNP), and CRISPR comparisons between strains from the same participant were performed. We conducted simulations of genome assemblies and ANI comparisons and present a statistical method to distinguish between unrelated, related, and identical strains. We found that 50 % of the paired samples have identical strains, evidence that the urinary and vaginal communities are connected. Additionally, we found evidence of strains sharing a common ancestor. These results establish that microbial sharing between the urinary tract and vagina is not limited to uropathogens. Knowledge that these two anatomical sites can share lactobacilli in females can inform future clinical approaches.

PMID:38949867 | DOI:10.1099/mgen.0.001267

J Ethn Subst Abuse. 2024 Jul 1:1-16. doi: 10.1080/15332640.2024.2369328. Online ahead of print.

ABSTRACT

In Greenland, where addiction-related concerns significantly affect well-being, research has explored alcohol’s impact on health and mortality. However, no studies have focused on mortality among those who received addiction treatment. This study investigates whether individuals treated for addiction in Greenland experience elevated mortality rates compared to the general population. The study encompassed individuals receiving addiction treatment through the national system between 2012 and December 31, 2022. Data on treatment were sourced from the National Addiction Database, and Statistics Greenland. Person-years at risk were calculated and used to estimate crude mortality rates (CMRs). Adjusted standardized mortality rates (SMRs), accounting for age, sex, and calendar year, were estimated using an indirect method based on observed and expected deaths. Of the 3286 in treatment, 53.9% were women, with a median age of 37. About a third had undergone multiple treatment episodes, and 60.1% received treatment in 2019 or later. The cohort was followed for a median of 2.89 years, yielding 12,068 person-years. The overall CMR was 7.79 deaths per 1000 person-years, with a SMR of 1.42 (95% confidence interval: 1.15; 1.74). Significantly, SMRs differed by age at treatment entry, with younger groups exhibiting higher SMRs (p value = .021). This study found that individuals seeking treatment for addiction problems in Greenland had a higher mortality rate than the general population. Importantly, these SMRs were substantially lower than those observed in clinical populations in other countries.

PMID:38949863 | DOI:10.1080/15332640.2024.2369328

Angew Chem Int Ed Engl. 2024 Jul 1:e202410219. doi: 10.1002/anie.202410219. Online ahead of print.

ABSTRACT

Pd(II)-based low-symmetry coordination cages possessing anisotropic cavities are of great interest. The common strategies employed to achieve such cages utilize either more than one type of symmetrical ligands (e.g., Laa, Lbb, etc.) or only one type of unsymmetrical ligand (e.g., Lab). To significantly enhance the anisotropy, we have designed two unsymmetrical bidentate ligands i.e., Lab and Lcd, aiming a low-symmetry Pd2Lab2Lcd2-type cage. It was accomplished by high-fidelity integrative self-sorting of two different low-symmetry cages having Pd2Lab4 and Pd4Lcd8-type architectures (homoleptic complexes of the designed ligands). Structural constraints and geometry complementarity in the ligand design drive the non-statistical exclusive self-assembly of the Pd2Lab2Lcd2-type cage. By taking advantage of the complemental geometries between ligands, a low-symmetry Pd2Lab2Lcc2-type cage was also obtained. Heteromeric completive self-sorting of three homoleptic assemblies (Pd2Lab4, Pd4Lcc8 and Pd4Lcd8-type cages) into an exclusive mixture of Pd2Lab2Lcd2 and Pd2Lab2Lcc2-type mixed ligated assemblies was demonstrated through cage-to-cage transformations.

PMID:38949846 | DOI:10.1002/anie.202410219

JAMA Neurol. 2024 Jul 1. doi: 10.1001/jamaneurol.2024.2044. Online ahead of print.

ABSTRACT

IMPORTANCE: Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population.

OBJECTIVE: To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023.

EXPOSURES: Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies.

MAIN OUTCOMES AND MEASURES: The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes.

RESULTS: In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%).

CONCLUSIONS AND RELEVANCE: These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

PMID:38949838 | DOI:10.1001/jamaneurol.2024.2044

Dent Med Probl. 2024 May-Jun;61(3):353-362. doi: 10.17219/dmp/158835.

ABSTRACT

BACKGROUND: Despite the superiority of glass-ionomer cements (GICs) over composites in treating white spot lesions (WSLs), there is still a concern about their preventive and antibacterial properties. Efforts have been made to improve the strength of their bond to demineralized enamel, fluoride release and antibacterial properties by adding nanoparticles of chitosan, which seems to be a promising method.

OBJECTIVES: The aim of the present study was to assess the antibacterial effect, the microshear bond strength (μSBS) to enamel at the WSL area, and the fluoride and nano-chitosan release after modifying the polyacrylic acid liquid phase of a traditional GIC with different nano-chitosan volumes.

MATERIAL AND METHODS: A total of 120 samples were prepared, and then divided into 4 groups (n = 30): G1 – non-modified GIC, which served as a control group, while G2, G3 and G4 were modified with different nano-chitosan volumes (50%, 100% and 150%, respectively). Microshear bond strength was assessed using a universal testing machine (UTM) after storage in distilled water for 24 h. Fluoride and nanochitosan release was measured with the use of spectrophotometers at different time points (initially, and at 1 h, 24 h, 48 h, 72 h, 1 week, 2 weeks, 3 weeks, and 6 weeks) after storage in distilled water. The antibacterial effect against the Streptococcus aureus strain was assessed with the agar diffusion test. The data was statistically analyzed.

RESULTS: After 24-hour storage, G2 recorded a slight, yet non-significant, increase in the μSBS values (4.1 ±0.94 MPa) as compared to G1 (3.9 ±1.30 MPa). With regard to fluoride release, the amount recorded for G1 was significantly greater at the end of the 24-hour storage period (0.70 ±0.30 μmf/cm2) than modified nano-chitosan GIC groups; G1 was followed by G4 (0.54 ±0.34 μmf/cm2). The highest amount of nano-chitosan release after 24-hour storage was noted for G3 (0.85 ±0.00 μmf/cm2). The highest inhibition zone value was recorded for G2.

CONCLUSIONS: Glass-ionomer cement modified with 50% nano-chitosan was shown to positively affect μSBS and the antibacterial effect, while modification with 150% nano-chitosan significantly increased fluoride release.

PMID:38949834 | DOI:10.17219/dmp/158835

JPEN J Parenter Enteral Nutr. 2024 Jul;48(5):562-570. doi: 10.1002/jpen.2647.

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thrombosis. They often need parenteral nutrition (PN) requiring intravenous access for prolonged periods. We assessed the risk of deep vein thrombosis (DVT) associated with peripherally inserted central catheters (PICCs) and tunneled catheters for patients with IBD receiving home PN (HPN).

METHODS: Using the Cleveland Clinic HPN Registry, we retrospectively studied a cohort of adults with IBD who received HPN between June 30, 2019 and January 1, 2023. We collected demographics, catheter type, and catheter-associated DVT (CADVT) data. We performed descriptive statistics and Poisson tests to compare CADVT rates among parameters of interest. We generated Kaplan-Meier graphs to illustrate longevity of CADVT-free survival and a Cox proportional hazard model to calculate the hazard ratio associated with CADVT.

RESULTS: We collected data on 407 patients, of which, 276 (68%) received tunneled catheters and 131 (32%) received PICCs as their initial catheter. There were 17 CADVTs with an overall rate of 0.08 per 1000 catheter days, whereas individual rates of DVT for PICCs and tunneled catheters were 0.16 and 0.05 per 1000 catheter days, respectively (P = 0.03). After adjusting for age, sex, and comorbidity, CADVT risk was significantly higher for PICCs compared with tunneled catheters, with an adjusted hazard ratio of 2.962 (95% CI=1.140-7.698; P = 0.025) and adjusted incidence rate ratio of 3.66 (95% CI=2.637-4.696; P = 0.013).

CONCLUSION: Our study shows that CADVT risk is nearly three times higher with PICCs compared with tunneled catheters. We recommend tunneled catheter placement for patients with IBD who require HPN infusion greater than 30 days.

PMID:38949827 | DOI:10.1002/jpen.2647

JAMA Netw Open. 2024 Jul 1;7(7):e2424099. doi: 10.1001/jamanetworkopen.2024.24099.

NO ABSTRACT

PMID:38949815 | DOI:10.1001/jamanetworkopen.2024.24099

JAMA Netw Open. 2024 Jul 1;7(7):e2419258. doi: 10.1001/jamanetworkopen.2024.19258.

ABSTRACT

IMPORTANCE: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns.

OBJECTIVE: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results.

EXPOSURES: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign.

MAIN OUTCOMES AND MEASURES: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex.

RESULTS: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination.

CONCLUSIONS AND RELEVANCE: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

PMID:38949812 | DOI:10.1001/jamanetworkopen.2024.19258