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Infection and Drug Resistance 2024Accurate detection and identification of pathogens and their associated resistance mechanisms are essential prerequisites for implementing precision medicine in the...
PURPOSE
Accurate detection and identification of pathogens and their associated resistance mechanisms are essential prerequisites for implementing precision medicine in the management of Carbapenem-resistant (CRE). Among the various resistance mechanisms, the production of KPC carbapenemase is the most prevalent worldwide. Consequently, this study aims to develop a convenient and precise nucleic acid detection platform specifically for the gene.
METHODS
The initial phase of our research methodology involved developing a CRISPR/Cas12a detection framework, which was achieved by designing highly specific single-guide RNAs (sgRNAs) targeting the gene. To enhance the sensitivity of this system, we incorporated three distinct amplification techniques-polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and recombinase polymerase amplification (RPA)-into the CRISPR/Cas12a framework. Subsequently, we conducted a comparative analysis of the sensitivity and specificity of these three amplification methods when used in combination with the CRISPR/Cas12a system. Additionally, we assessed the clinical applicability of the methodologies by evaluating fluorescence readouts from 80 different clinical isolates. Furthermore, we employed lateral flow assay technology to provide a visual representation of the results, facilitating point-of-care testing.
RESULTS
Following a comparative analysis of the sensitivity and specificity of the three methods, we identified the RPA-Cas12a approach as the optimal detection technique. Our findings demonstrated that the limit of detection (LoD) of the RPA-Cas12a platform was 1 aM (~1 copy/µL) for plasmid DNA and 5 × 10³ fg/µL for genomic DNA. Furthermore, both the sensitivity and specificity of the platform achieved 100% upon validation with 80 clinical isolates.
CONCLUSION
These findings suggest that the developed RPA-Cas12a platform represents a promising tool for the cost-effective, convenient, and accurate detection of the gene.
PubMed: 38915320
DOI: 10.2147/IDR.S462088 -
European Stroke Journal Jun 2024Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on...
INTRODUCTION
Atrial fibrillation (AF) and cancer are each associated with worse outcomes in patients with acute ischemic stroke (AIS). Few studies have evaluated the impact of AF on outcomes of cancer-related stroke.
PATIENTS AND METHODS
We conducted a retrospective cross-sectional study using the 2016-2019 National Inpatient Sample, identifying all hospitalizations with diagnosis codes for cancer and AIS. The primary exposure was a diagnosis of AF. The primary outcome was in-hospital mortality. The secondary outcomes were length-of-stay and discharge to non-home locations. We used multiple logistic and linear regression models, adjusted for age, gender, race-ethnicity, and the Charlson Comorbidity Index, to examine the association between AF and study outcomes.
RESULTS
Among 150,200 hospitalizations with diagnoses of cancer and AIS (mean age 72 years, 53% male), 40,084 (26.7%) included comorbid AF. Compared to hospitalizations without AF, hospitalizations with AF had higher rates of in-hospital mortality (14.8% [95% CI, 14.0%-15.6%] vs 12.1% [95% CI, 11.6%-12.5%]) and non-home discharge disposition (83.5% [95% CI, 82.7%-84.3%] vs 75.1% [95% CI, 74.5%-75.7%]) as well as longer mean length-of-stay (8.4 days [95% CI, 8.2-8.6 days] vs 8.2 days [95% CI, 8.0-8.3 days]). In multivariable analyses, AF remained independently associated with higher odds of in-hospital mortality (adjusted odds ratio [aOR], 1.34; 95% CI, 1.24-1.46), non-home discharge disposition (aOR, 1.32; 95% CI, 1.23-1.42), and longer length-of-stay (adjusted mean difference, 13.7%; 95% CI, 10.9%-16.7%).
DISCUSSION AND CONCLUSION
In cancer-related AIS, comorbid AF is associated with worse short-term outcomes, including higher odds for in-hospital mortality, poor discharge disposition, and longer hospital stays.
PubMed: 38915252
DOI: 10.1177/23969873241263402 -
PloS One 2024In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease...
BACKGROUND
In the first year of roll-out, vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevented almost 20 million deaths from coronavirus disease 2019 (COVID-19). Yet, little is known about the factors influencing access to vaccination at the individual level within rural poor settings of low-income countries. The aim of this study was to examine determinants of vaccine receipt in rural India.
METHODS
A census of a rural village in Tamil Nadu was undertaken from June 2021 to September 2022. We surveyed 775 participants from 262 households. Household-level data on socioeconomic status (SES), water, sanitation, and hygiene practices, and individual-level demographic information, travel history, and biomedical data, including anthropometry, vital signs, and comorbidities, were collected. Logistic regression models with 5-fold cross-validation were used to identify the biomedical, demographic, and socioeconomic determinants of vaccine receipt and the timing of receipt within the first 30 days of eligibility. Vaccine ineligible participants were excluded leaving 659 eligible participants. There were 650 eligible participants with complete biomedical, demographic, and socioeconomic data.
RESULTS
There were 68.0% and 34.0% of individuals (N = 650) who had received one and two vaccine doses, respectively. Participants with household ownership of a permanent account number (PAN) or ration card were 2.15 (95% CI:1.32-3.52) or 3.02 (95% CI:1.72-5.29) times more likely to receive at least one vaccine dose compared to households with no ownership of such cards. Participants employed as housewives or self-employed non-agricultural workers were 65% (95% CI:0.19-0.67) or 59% (95% CI:0.22-0.76) less likely to receive at least one vaccine dose compared to salaried workers. Household PAN card ownership, occupation and age were linked to the timing of vaccine receipt. Participants aged ≤18 and 45-60 years were 17.74 (95% CI:5.07-62.03) and 5.51 (95% CI:2.74-11.10) times more likely to receive a vaccine within 30 days of eligibility compared to 19-44-year-olds. Biomedical factors including BMI, vital signs, comorbidities, and COVID-19 specific symptoms were not consistently associated with vaccine receipt or timing of receipt. No support was found that travel history, contact with COVID-19 cases, and hospital admissions influenced vaccine receipt or timing of receipt.
CONCLUSION
Factors linked to SES were linked to vaccine receipt, more so than biomedical factors which were targeted by vaccine policies. Future research should explore if government interventions including vaccine mandates, barriers to vaccine access, or peer influence linked to workplace or targeted vaccine promotion campaigns underpin these findings.
Topics: Humans; India; COVID-19 Vaccines; Female; Male; COVID-19; Rural Population; Adult; Middle Aged; Socioeconomic Factors; Adolescent; Vaccination; SARS-CoV-2; Young Adult
PubMed: 38913614
DOI: 10.1371/journal.pone.0305819 -
International Ophthalmology Jun 2024The purpose of this study was to investigate the visual and refractive outcomes in patients with pseudoexfoliation (PXF) undergoing routine cataract surgery and to...
BACKGROUND
The purpose of this study was to investigate the visual and refractive outcomes in patients with pseudoexfoliation (PXF) undergoing routine cataract surgery and to compare the accuracy of intraocular lens (IOL) power calculation formulae.
METHODS
Retrospective case-series study from Shamir medical center, a public hospital, Israel. Medical records of patients who underwent routine cataract surgery between January 2019 and August 2021 were investigated. Postoperative visual acuity and manifest refraction were examined. The error in predicted refraction and IOL power calculation accuracy within a range of ± 0.50 to ± 1.00 diopters were compared between different IOL calculating formulae.
RESULTS
151 eyes of 151 patients ages 73.9 ± 7.1 years were included in this study- 58 eyes in the PXF group and 93 eyes in the control group. The mean absolute error (MAE) for the BUII formula was 0.63D ± 0.87 for the PXF group and 0.36D ± 0.48 for the control group (p < 0.05). The MAE for the Hill-RBF 3.0 formula was 0.61D ± 0.84 for the PXF group and 0.42D ± 0.55 for the control group (p = 0.05). There were significant differences in MAE and MedAE between PXF group and control group measures (p < 0.05). In the PXF group there were no significant differences between the different formulae.
CONCLUSIONS
There were significant differences in accuracy of IOL power calculations in all formulae between PXF group and control group measures. PXF patients show hyperopic shift from predicted refraction. Barret universal II formula had the highest proportion of eyes with absolute error in prediction below or equal to 0.50 D in both PXF and control groups.
Topics: Humans; Exfoliation Syndrome; Retrospective Studies; Aged; Female; Male; Visual Acuity; Refraction, Ocular; Lenses, Intraocular; Biometry; Aged, 80 and over; Optics and Photonics; Reproducibility of Results
PubMed: 38913082
DOI: 10.1007/s10792-024-03195-6 -
Journal of the Medical Library... Jan 2024By defining search strategies and related database exports as code/scripts and data, librarians and information professionals can expand the mandate of research data...
BACKGROUND
By defining search strategies and related database exports as code/scripts and data, librarians and information professionals can expand the mandate of research data management (RDM) infrastructure to include this work. This new initiative aimed to create a space in McGill University's institutional data repository for our librarians to deposit and share their search strategies for knowledge syntheses (KS).
CASE PRESENTATION
The authors, a health sciences librarian and an RDM specialist, created a repository collection of librarian-authored knowledge synthesis (KS) searches in McGill University's Borealis Dataverse collection. We developed and hosted a half-day "Dataverse-a-thon" where we worked with a team of health sciences librarians to develop a standardized KS data management plan (DMP), search reporting documentation, Dataverse software training, and howto guidance for the repository.
CONCLUSION
In addition to better documentation and tracking of KS searches at our institution, the KS Dataverse collection enables sharing of searches among colleagues with discoverable metadata fields for searching within deposited searches. While the initial creation of the DMP and documentation took about six hours, the subsequent deposit of search strategies into the institutional data repository requires minimal effort (e.g., 5-10 minutes on average per deposit). The Dataverse collection also empowers librarians to retain intellectual ownership over search strategies as valuable stand-alone research outputs and raise the visibility of their labor. Overall, institutional data repositories provide specific benefits in facilitating compliance both with PRISMA-S guidance and with RDM best practices.
Topics: Humans; Information Storage and Retrieval; Information Dissemination; Data Management; Libraries, Medical; Librarians
PubMed: 38911529
DOI: 10.5195/jmla.2024.1791 -
Endoscopy International Open Jun 2024Endoscopic through-the-scope clips (TTSC) are used for hemostasis and closure. We documented the performance of a new TTSC with anchor prongs. We conducted a...
Endoscopic through-the-scope clips (TTSC) are used for hemostasis and closure. We documented the performance of a new TTSC with anchor prongs. We conducted a prospective case series of the new TTSC in 50 patients with an indication for endoscopic clipping at three hospitals in the United States and Canada. Patients were followed for 30 days after the index procedure. Outcomes included defect closure and rate of serious adverse events (SAEs) related to the device or procedure. Fifty patients had 56 clipping procedures. Thirty-four procedures were clipping after endoscopic mucosal resection (EMR) in the colon (33) or stomach (1), 16 after polypectomy, two for hemostasis of active bleeding, and one each for fistula closure, per-oral endoscopic myotomy mucosal closure, or anchoring a feeding tube. Complete defect closure was achieved in 32 of 33 colon EMR defects and 21 of 22 other defects. All clips were placed per labeled directions for use. In 41 patients (82.0%), prophylaxis of delayed bleeding was reported as an indication for endoscopic clipping. There were three instances of delayed bleeding. There were no device-related SAEs. The only technical difficulty was one instance of premature clip deployment. A novel TTSC with anchor prongs showed success in a range of defect closures, an acceptable safety profile, and low incidence of technical difficulties.
PubMed: 38911014
DOI: 10.1055/a-2330-9803 -
Clinical Genitourinary Cancer Jun 2024Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient...
INTRODUCTION
Immune checkpoint inhibitor (ICI)-based combinations have revolutionized the management of first-line metastatic renal cell carcinoma (mRCC) by improving patient survival. Large phase 3 randomized trials assessing ICI-based combinations have reported complete response (CR) rates of 10% to 18% in the first-line setting. However, there is a scarcity of data about the effect of treatment of residual disease regarding CR rates improvement.
MATERIALS AND METHODS
We included retrospectively all consecutive mRCC patients treated in first-line setting at the Institut de Cancérologie Strasbourg Europe with an ICI-based combination involving ICI or TKI, either alone or with added local treatment of residual disease. Patients were characterized according to IMDC risk. Radiologic response was defined according to RECIST v1.1.
RESULTS
We enrolled 80 mRCC patients treated with ICI-based combinations between May 2015 and May 2022. The median age was 63 years. Regarding IMDC risk, there were 12 favourable (15%), 50 intermediate (63%), and 18 poor-risk (22%) patients. Forty-seven patients (59%) received ICI + ICI, 24 (30%) received ICI + TKI, and 9 (11%) received another ICI-based therapy. In total, 8 achieved CR (10%), 36 patients (45%) achieved partial response, 23 (29%) achieved stable disease and 12 achieved progressive disease (15%) as the best response with systemic therapy alone. By adding local treatment of residual disease, 11 additional patients (14%) achieved radiological NED. Residual disease resected sites included kidney (n = 6), lymph nodes (n = 5), lung metastases (n = 2) and liver metastases (n = 1).
CONCLUSIONS
The resection of residual disease after first-line ICI-based therapy is associated with improved CR rate (CR + NED) in patients with mRCC. These results need to be validated in prospective trial.
PATIENT SUMMARY
In recent years, the advent of immunotherapy has radically changed the management of patients with metastatic kidney cancer. Approximately 10% to 18% of these patients using immune checkpoint inhibitor (ICI)-based combinations no longer have detectable disease on CT scans (complete response). There are currently few data on the use of treatment of residual disease to increase the number of patients in complete response. In this retrospective study, the complete response rate with ICI-based treatment was 10%. When local treatment was added, the number of patients with a complete response increased to 24%. This strategy could increase the number of patients with a prolonged complete response in the future.
PubMed: 38909529
DOI: 10.1016/j.clgc.2024.102134 -
Journal of Experimental Child Psychology Jun 2024The mechanisms underlying the developing sense of bodily self are debated. Whereas some scholars stress the role of sensory factors, others propose the importance of...
The mechanisms underlying the developing sense of bodily self are debated. Whereas some scholars stress the role of sensory factors, others propose the importance of contextual factors. By manipulating multisensory stimulation and social familiarity with the other person, we explored two factors that are proposed to relate to young children's developing sense of bodily self. Including an adult sample allowed us to investigate age-related differences of the malleability of the bodily self. To this end, the study implemented an enfacement illusion with children (N = 64) and adults (N = 33). Participants were exposed to one trial with synchronous interpersonal multisensory stimulation and one trial with asynchronous interpersonal multisensory stimulation-either with a stranger or with the mother as the other person. A self-recognition task using morph videos of self and other and an enfacement questionnaire were implemented as dependent measures. Results revealed evidence for the presence of the enfacement effect in children in both measures. The identity of the other person had a significant effect on the self-recognition task. Contrary to our hypothesis, the effect was significantly smaller in the caregiver condition. No significant differences between children and adults emerged. Our results demonstrate the role of both multisensory stimulation and contextual-here social familiarity-factors for the construction and development of a bodily self. The study provides developmental science with a novel approach to the bodily self by showing the validity of the self-recognition task in a child sample. Overall, the study supports proposals that the sense of bodily self is malleable early in development.
PubMed: 38909521
DOI: 10.1016/j.jecp.2024.105990 -
NeuroImage. Clinical Jun 2024AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated...
INTRODUCTION
AD and CVD, which frequently co-occur, are leading causes of age-related cognitive decline. We assessed how demographic factors, socioeconomic status (SES) as indicated by education and occupation, vascular risk factors, and a range of biomarkers associated with both CVD (including white matter hyperintensities [WMH], diffusion MRI abnormalities, infarctions, and microbleeds) and AD (comprising amyloid-PET and tau-PET) collectively influence cognitive function.
METHODS
In this cross-sectional population study, structural equation models were utilized to understand these associations in 449 participants (mean age (SD) = 74.5 (8.4) years; 56% male; 7.5% cognitively impaired).
RESULTS
(1) Higher SES had a protective effect on cognition with mediation through the vascular pathway. (2) The effect of amyloid directly on cognition and through tau was 11-fold larger than the indirect effect of amyloid on cognition through WMH. (3) There is a significant effect of vascular risk on tau deposition.
DISCUSSION
The utilized biomarkers captured the impact of CVD and AD on cognition. The overall effect of vascular risk and SES on these biomarkers are complex and need further investigation.
PubMed: 38909419
DOI: 10.1016/j.nicl.2024.103634 -
Nature Communications Jun 2024Given limited institutional resources, low-income populations often rely on social networks to improve their socioeconomic outcomes. However, it remains in question...
Given limited institutional resources, low-income populations often rely on social networks to improve their socioeconomic outcomes. However, it remains in question whether small-scale social interactions could affect large-scale economic inequalities in under-resourced contexts. Here, we leverage population-level data from one of the poorest South African settings to construct a large-scale, geographically defined, inter-household social network. Using a multilevel network model, we show that having social ties in close geographic proximity is associated with stable household asset conditions, while geographically distant ties correlate to changes in asset allocation. Notably, we find that localised network interactions are associated with an increase in wealth inequality at the regional level, demonstrating how macro-level inequality may arise from micro-level social processes. Our findings highlight the importance of understanding complex social connections underpinning inter-household resource dynamics, and raise the potential of large-scale social assistance programs to reduce disparities in resource-ownership by accounting for local social constraints.
Topics: Humans; South Africa; Socioeconomic Factors; Social Networking; Poverty; Family Characteristics; Income; Male; Female; Social Support; Social Interaction
PubMed: 38909070
DOI: 10.1038/s41467-024-49607-0