Nevin Manimala

ACS Appl Bio Mater. 2024 Jul 2. doi: 10.1021/acsabm.4c00484. Online ahead of print.

ABSTRACT

Wastewater-based epidemiology (WBE) can help mitigate the spread of respiratory infections through the early detection of viruses, pathogens, and other biomarkers in human waste. The need for sample collection, shipping, and testing facilities drives up the cost of WBE and hinders its use for rapid detection and isolation in environments with small populations and in low-resource settings. Given the ubiquitousness and regular outbreaks of respiratory syncytial virus, SARS-CoV-2, and various influenza strains, there is a rising need for a low-cost and easy-to-use biosensing platform to detect these viruses locally before outbreaks can occur and monitor their progression. To this end, we have developed an easy-to-use, cost-effective, multiplexed platform able to detect viral loads in wastewater with several orders of magnitude lower limit of detection than that of mass spectrometry. This is enabled by wafer-scale production and aptamers preattached with linker molecules, producing 44 chips at once. Each chip can simultaneously detect four target analytes using 20 transistors segregated into four sets of five for each analyte to allow for immediate statistical analysis. We show our platform’s ability to rapidly detect three virus proteins (SARS-CoV-2, RSV, and Influenza A) and a population normalization molecule (caffeine) in wastewater. Going forward, turning these devices into hand-held systems would enable wastewater epidemiology in low-resource settings and be instrumental for rapid, local outbreak prevention.

PMID:38954405 | DOI:10.1021/acsabm.4c00484

Curr Med Res Opin. 2024 Jul 2:1-10. doi: 10.1080/03007995.2024.2374510. Online ahead of print.

ABSTRACT

Background: Post-COVID-19 condition (PCC), also known as “long COVID,” is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e., reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of patients with PCC.Methods: This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption.Results: Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI).Discussions: Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.

PMID:38954402 | DOI:10.1080/03007995.2024.2374510

Ir J Med Sci. 2024 Jul 2. doi: 10.1007/s11845-024-03741-2. Online ahead of print.

ABSTRACT

OBJECTIVE: To validate the predictive performance of the THRIVE, ASTRAL, and iScore scales for clinical functional outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS).

METHODS: A total of 111 patients meeting the inclusion criteria were included in this study, with 59 (53.2%) having a good prognosis and 52 (46.8%) having a poor prognosis. MedCalc software was applied to plot receiver operating characteristic (ROC) curves, calculate the area under the curve (AUC), and compare the predictive efficacy of the three scales two by two using Delong text. Statistical significance was defined as P_c < 0.05.

RESULTS: Logistic binary regression multifactorial analysis revealed that iScore is one of the poor predictors of prognosis in patients with MT. The AUC values for the THRIVE, ASTRAL, and iScore scales in predicting prognosis after MT were found to be 0.713, 0.738, and 0.820, respectively.

CONCLUSION: The iScore is a reliable tool for assessing the poor prognosis of MT in patients with AIS.

PMID:38954327 | DOI:10.1007/s11845-024-03741-2

Musculoskelet Surg. 2024 Jul 2. doi: 10.1007/s12306-024-00846-w. Online ahead of print.

ABSTRACT

BACKGROUND: Artificial intelligence chatbot tools responses might discern patterns and correlations that may elude human observation, leading to more accurate and timely interventions. However, their reliability to answer healthcare-related questions is still debated. This study aimed to assess the performance of the three versions of GPT-based chatbots about prosthetic joint infections (PJI).

METHODS: Thirty questions concerning the diagnosis and treatment of hip and knee PJIs, stratified by a priori established difficulty, were generated by a team of experts, and administered to ChatGPT 3.5, BingChat, and ChatGPT 4.0. Responses were rated by three orthopedic surgeons and two infectious diseases physicians using a five-point Likert-like scale with numerical values to quantify the quality of responses. Inter-rater reliability was assessed by interclass correlation statistics.

RESULTS: Responses averaged “good-to-very good” for all chatbots examined, both in diagnosis and treatment, with no significant differences according to the difficulty of the questions. However, BingChat ratings were significantly lower in the treatment setting (p = 0.025), particularly in terms of accuracy (p = 0.02) and completeness (p = 0.004). Agreement in ratings among examiners appeared to be very poor.

CONCLUSIONS: On average, the quality of responses is rated positively by experts, but with ratings that frequently may vary widely. This currently suggests that AI chatbot tools are still unreliable in the management of PJI.

PMID:38954323 | DOI:10.1007/s12306-024-00846-w

Biomech Model Mechanobiol. 2024 Jul 2. doi: 10.1007/s10237-024-01856-0. Online ahead of print.

ABSTRACT

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine.

PMID:38954283 | DOI:10.1007/s10237-024-01856-0

J Occup Rehabil. 2024 Jul 2. doi: 10.1007/s10926-024-10219-6. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed the effectiveness of Individual Placement and Support (IPS), Participatory Workplace Intervention (PWI), and IPS + PWI on work participation and health of people with work disabilities.

METHODS: A randomised controlled 2 × 2 factorial trial with 120 clients and an 18-month follow-up was performed. Differences between IPS and no-IPS and between PWI and no-PWI were assessed using log-rank tests and Cox proportional hazards models.

RESULTS: In the IPS group, restricted mean survival time (RMST) for sustainable paid employment was 352 days, compared to 394 in the no-IPS group (HR = 1.47, 95% CI = 0.81-2.63). In the PWI group the RMST was 378 days, compared to 367 in the no-PWI group (HR = 0.89, 95% CI = 0.48-1.64). For the secondary outcome ‘starting any paid employment, a trial placement, or education’ RMST was significantly lower for the IPS group (222 days) than for the no-IPS group (335 days; HR = 1.85, 95% CI = 1.01-3.42). Mental health was significantly lower (worse) in the PWI group (difference -4.07, 95% CI = -7.93 to -0.22) than in the no-PWI group. For all other secondary outcomes, no statistically significant differences were found.

CONCLUSION: No statistically significant differences were observed in the duration until starting sustainable employment between IPS and no-IPS, and between PWI and no-PWI. The duration until starting any paid employment, a trial placement, or education was shorter in the IPS group than in the no-IPS group, but further research should explore whether this also increases sustainable employment in the longer term.

PMID:38954248 | DOI:10.1007/s10926-024-10219-6

Interdiscip Sci. 2024 Jul 2. doi: 10.1007/s12539-024-00621-2. Online ahead of print.

ABSTRACT

To elucidate the genetic basis of complex diseases, it is crucial to discover the single-nucleotide polymorphisms (SNPs) contributing to disease susceptibility. This is particularly challenging for high-order SNP epistatic interactions (HEIs), which exhibit small individual effects but potentially large joint effects. These interactions are difficult to detect due to the vast search space, encompassing billions of possible combinations, and the computational complexity of evaluating them. This study proposes a novel explicit-encoding-based multitasking harmony search algorithm (MTHS-EE-DHEI) specifically designed to address this challenge. The algorithm operates in three stages. First, a harmony search algorithm is employed, utilizing four lightweight evaluation functions, such as Bayesian network and entropy, to efficiently explore potential SNP combinations related to disease status. Second, a G-test statistical method is applied to filter out insignificant SNP combinations. Finally, two machine learning-based methods, multifactor dimensionality reduction (MDR) as well as random forest (RF), are employed to validate the classification performance of the remaining significant SNP combinations. This research aims to demonstrate the effectiveness of MTHS-EE-DHEI in identifying HEIs compared to existing methods, potentially providing valuable insights into the genetic architecture of complex diseases. The performance of MTHS-EE-DHEI was evaluated on twenty simulated disease datasets and three real-world datasets encompassing age-related macular degeneration (AMD), rheumatoid arthritis (RA), and breast cancer (BC). The results demonstrably indicate that MTHS-EE-DHEI outperforms four state-of-the-art algorithms in terms of both detection power and computational efficiency. The source code is available at https://github.com/shouhengtuo/MTHS-EE-DHEI.git .

PMID:38954231 | DOI:10.1007/s12539-024-00621-2

Pediatr Surg Int. 2024 Jul 2;40(1):166. doi: 10.1007/s00383-024-05739-4.

ABSTRACT

PURPOSE: To report our experience with laparoscopic repair of anterior congenital diaphragmatic hernia (CDH) using extracorporeal subcutaneous knot tying and to define recurrence risk factors.

METHODS: This retrospective unicentric study included children who underwent laparoscopic repair of anterior CDH without patch, using extracorporeal knot tying of sutures passed through the full thickness of the abdominal wall (2013-2020). A systematic review of the literature with meta-analysis was performed using the MEDLINE database since 2000.

RESULTS: Eight children were included (12 months [1-183]; 10.6 kg [3.6-65]). Among the two patients with Down syndrome, one with previous cardiac surgery had a recurrence at 17 months postoperatively. In our systematic review (26 articles), among the 156 patients included, 10 had a recurrence (none with patch). Recurrence was statistically more frequent in patients with Down syndrome (19.4%) than without (2.5%) (p < 0.0001), and when absorbable sutures were used (50%) instead of non-absorbable sutures (5.3%) (p < 0.0001).

CONCLUSION: Laparoscopic repair of anterior CDH without patch was a safe and efficient surgical approach in our patients. The use of a non-absorbable prosthetic patch should be specifically discussed in anterior CDH associated with Down syndrome and/or in case of previous cardiac surgery to perform a diaphragmatic tension-free closure.

PMID:38954216 | DOI:10.1007/s00383-024-05739-4

Biochem Genet. 2024 Jul 2. doi: 10.1007/s10528-024-10873-8. Online ahead of print.

ABSTRACT

Sarcomas are malignant tumors that may metastasize and the course of the disease is highly aggressive in children and young adults. Because of the rare incidence of sarcomas and the heterogeneity of tumors, there is a need for non-invasive diagnostic and prognostic biomarkers in sarcomas. The aim of the study was to investigate the level of miR-218-5p in peripheral blood and tumor tissue samples of Ewing’s sarcoma, osteosarcoma, spindle cell sarcoma patients, and healthy controls, and assessed whether the corresponding molecule was a diagnostic and prognostic biomarker. The study was performed patients (n = 22) diagnosed and treated with Ewing’s sarcoma and osteosarcoma and in a control group of 22 healthy children who were matched for age, gender, and ethnicity with the patient group. The expression level of miR-218-5p in RNA samples from peripheral blood and tissue samples were analyzed using the RT-PCR and the expression level of miR-218-5p was evaluated by comparison with the levels in patients and healthy controls. The expression level of miR-218-5p was found to be statistically higher (3.33-fold, p = 0.006) in pediatric patients with sarcomas and when the target genes of miR-218-5p were investigated using the bioinformatics tools, the miR-218-5p was found as an important miRNA in cancer. In this study, the miR-218-5p was shown for the first time to have been highly expressed in the peripheral blood and tumor tissue of sarcoma patients. The results suggest that miR-218-5p can be used as a diagnostic and prognostic biomarker in sarcomas and will be evaluated as an important therapeutic target.

PMID:38954213 | DOI:10.1007/s10528-024-10873-8

Biochem Genet. 2024 Jul 2. doi: 10.1007/s10528-024-10868-5. Online ahead of print.

ABSTRACT

Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (β⁰) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

PMID:38954212 | DOI:10.1007/s10528-024-10868-5