-
Epigenomes Oct 202323. Akirtava, C.; May, G.E.; McManus, C.J. False-Positive IRESes from Hoxa9 andOther Genes Resulting from Errors in Mam-malian 5' UTR Annotations [...].
23. Akirtava, C.; May, G.E.; McManus, C.J. False-Positive IRESes from Hoxa9 andOther Genes Resulting from Errors in Mam-malian 5' UTR Annotations [...].
PubMed: 37987304
DOI: 10.3390/epigenomes7040026 -
Research Square Oct 2023Malaria remains a public health problem in regions of northeastern India due to favourable bio-geographic transmission conditions, poor access to routine healthcare, and...
BACKGROUND
Malaria remains a public health problem in regions of northeastern India due to favourable bio-geographic transmission conditions, poor access to routine healthcare, and inadequate public health and healthcare infrastructure. This study was undertaken to better understand community members' and health workers' perceptions of malaria, as well as their knowledge, attitudes, and prevention practices related to the disease in Meghalaya state.
METHODS
The study included participants from three malaria endemic districts: West Khasi Hills, West Jaiñtia Hills, and South Garo Hills from 2019 to 2021. A total of 82 focus group discussions (FGD) with 694 community members and 63 in-depth interviews (IDI) with health personnel and traditional healers residing within the three districts were conducted. A thematic content analysis approach was employed, and NVivo12 software was utilized for data management.
RESULTS
Most participants reported a perceived reduction in malaria during recent years and attributed this to changing attitudes and behaviours in health seeking behaviour and effective government interventions. Local availability of testing and treatment, and an improved, more responsive health system contributed to changing attitudes. Long-lasting insecticidal nets (LLINs) were largely preferred over indoor residual spraying (IRS), as LLINs were perceived to be effective and more durable. Community members also reported using personal protective measures such as applying repellents, burning straw/egg trays, wearing long sleeve clothes, and applying ointments or oils to protect themselves from mosquito bites. While most participants acknowledged the role of mosquitoes in malaria transmission, other conditions that are not mosquito-borne were also attributed to mosquitoes by some participants. The communities surveyed have largely shifted from seeking traditional healers to using public facilities, although some participants reported switching between the two or using both simultaneously. Using the example of improved understanding of cerebral malaria which was previously attributed to mental illness due to 'bad spirits', participants explained how cultural and ritualistic practices had changed.
CONCLUSIONS
Our findings reveal diverse perceptions among community members regarding malaria, its prevention, practices to prevent mosquito-transmitted diseases, and their opinions about the health system. A key finding was the shift in malaria treatment seeking preferences of community members from traditional healers to the public sector. This shift highlights the changing dynamics and increasing acceptance of modern healthcare practices for malaria treatment and prevention within tribal and/or indigenous communities. By recognizing these evolving attitudes, policymakers and healthcare providers can better tailor their interventions and communication strategies to more effectively address ongoing needs and concerns as India faces the 'last mile' in malaria elimination.
PubMed: 37886590
DOI: 10.21203/rs.3.rs-3431734/v1 -
Journal of Medicinal Chemistry Mar 2024Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have emerged as a therapeutic modality to induce targeted protein degradation (TPD) by...
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have emerged as a therapeutic modality to induce targeted protein degradation (TPD) by harnessing cellular proteolytic degradation machinery. PROTACs which ligand the E3 ligase in a covalent manner have attracted intense interest; however, covalent PROTACs with a broad protein of interest (POI) scope have proven challenging to discover by design. Here, we report the structure-guided design and optimization of Von Hippel-Lindau (VHL) protein-targeted sulfonyl fluorides which covalently bind Ser110 in the HIF1α binding site. We demonstrate that their incorporation in bifunctional degraders induces targeted protein degradation of BRD4 or the androgen receptor without further linker optimization. Our study discloses the first covalent VHL ligands which can be implemented directly in bifunctional degrader design, expanding the substrate scope of covalent E3 ligase PROTACs.
Topics: Nuclear Proteins; Transcription Factors; Ubiquitin-Protein Ligases; Proteolysis; Ligands; Sulfinic Acids
PubMed: 38478885
DOI: 10.1021/acs.jmedchem.3c02123 -
Methods and Protocols Sep 2023Poliomyelitis is a condition of great concern and is endemic in only two countries of the world: Pakistan and Afghanistan. Community mobilization plays a vital role in...
Poliomyelitis is a condition of great concern and is endemic in only two countries of the world: Pakistan and Afghanistan. Community mobilization plays a vital role in raising awareness and can help reduce polio vaccine refusals. The objective of this study will be to decrease polio vaccine refusals and zero-dose vaccines by motivating behavior change through the provision of conditional-collective-community-based incentives (C3Is) based on a reduction in polio vaccine refusals. The project will adopt a pretest/post-test quasi-experimental design with two intervention high-risk union councils (HRUCs) and two control union councils (UCs) of peri-urban (Karachi) and rural (Bannu) settings in Pakistan. A participatory community engagement and demand creation strategy with trust-building community mobilization with C3Is, to reduce vaccine refusals and improve polio immunization coverage in two HRUCs, will be used. These UCs will be divided into clusters based on the polio program framework and community groups will be formed in each cluster. These community groups will carry out awareness activities and will be given serial targets to reduce vaccine refusals and those who qualify will be provided C3Is. The project intends to create a replicable model that the government can integrate within health systems for long-term sustainability until the goal of eradication of poliovirus is achieved. The evaluation will be carried out by an independent data collection and analysis team at baseline and endline (after 12 months of intervention). The trial is registered with linicalTrials.gov with number NCT05721274.
PubMed: 37736966
DOI: 10.3390/mps6050083 -
Stimulus-guided adaptive transformer network for retinal blood vessel segmentation in fundus images.Medical Image Analysis Oct 2023Automated retinal blood vessel segmentation in fundus images provides important evidence to ophthalmologists in coping with prevalent ocular diseases in an efficient and...
Automated retinal blood vessel segmentation in fundus images provides important evidence to ophthalmologists in coping with prevalent ocular diseases in an efficient and non-invasive way. However, segmenting blood vessels in fundus images is a challenging task, due to the high variety in scale and appearance of blood vessels and the high similarity in visual features between the lesions and retinal vascular. Inspired by the way that the visual cortex adaptively responds to the type of stimulus, we propose a Stimulus-Guided Adaptive Transformer Network (SGAT-Net) for accurate retinal blood vessel segmentation. It entails a Stimulus-Guided Adaptive Module (SGA-Module) that can extract local-global compound features based on inductive bias and self-attention mechanism. Alongside a light-weight residual encoder (ResEncoder) structure capturing the relevant details of appearance, a Stimulus-Guided Adaptive Pooling Transformer (SGAP-Former) is introduced to reweight the maximum and average pooling to enrich the contextual embedding representation while suppressing the redundant information. Moreover, a Stimulus-Guided Adaptive Feature Fusion (SGAFF) module is designed to adaptively emphasize the local details and global context and fuse them in the latent space to adjust the receptive field (RF) based on the task. The evaluation is implemented on the largest fundus image dataset (FIVES) and three popular retinal image datasets (DRIVE, STARE, CHASEDB1). Experimental results show that the proposed method achieves a competitive performance over the other existing method, with a clear advantage in avoiding errors that commonly happen in areas with highly similar visual features. The sourcecode is publicly available at: https://github.com/Gins-07/SGAT.
Topics: Humans; Retinal Vessels; Face; Fundus Oculi
PubMed: 37598606
DOI: 10.1016/j.media.2023.102929 -
Knee Surgery & Related Research Jan 2024The present systematic review investigated the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptom state... (Review)
Review
Minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptom state (PASS) in patients who have undergone total knee arthroplasty: a systematic review.
BACKGROUND
The present systematic review investigated the minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptom state (PASS) of several frequent and established PROMs used to assess patients who have undergone TKA. This study was conducted according to the 2020 PRISMA statement.
METHODS
In September 2023, PubMed, Web of Science, and Embase were accessed with no time constraint All clinical studies investigating tools to assess the clinical relevance of PROMs used to evaluate patients having received TKA were accessed. Only studies which evaluated the MCID, PASS, or SCB were eligible. The PROMs of interest were the Forgotten Joint Score-12 (FJS-12), the Oxford Knee Score (OKS), the Knee Injury and Osteoarthritis Outcome Score (KOOS) and its related subscales activity of daily living (ADL), pain, quality of life (QoL), sports and recreational activities, and symptoms, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, the Knee Society Score (KSS) and related function score, and the Short Form-12 (SF-12) and Short Form-36 (SF-36).
RESULTS
Data from 29,737 patients were collected. The overall risk of bias was low to moderate. The great variability of thresholds for MCID, SCB and PASS between questionnaires but also between investigated aspects was noted, whereby MCIDs for the SF-36 appear lower than for knee-specific questionnaires.
CONCLUSION
Despite its critical role from a patient's perspective, the dimension of SCB is still neglected in the literature. Moreover, thresholds for the different concepts need to be condition-specific. We encourage authors to specifically report such data in future studies and to adhere to previously reported definitions to allow future comparison. Level of evidence Level IV, systematic review and meta-analysis.
PubMed: 38212863
DOI: 10.1186/s43019-024-00210-z -
JFMS Open Reports 2023An 8-year-old male neutered domestic shorthair cat presented collapsed and was subsequently diagnosed with a pericardial effusion based on ultrasound imaging. A...
CASE SUMMARY
An 8-year-old male neutered domestic shorthair cat presented collapsed and was subsequently diagnosed with a pericardial effusion based on ultrasound imaging. A laboratory analysis of pericardial fluid revealed a septic pericardial effusion and further diagnostics, including abdominal ultrasound and fluid analysis, revealed a concurrent hepatic abscess. Bacterial isolation and identification from both septic foci revealed . Therapeutic measures included a combination of medical and surgical intervention, the latter including a pericardiectomy, cholecystectomy, liver lobectomy and splenectomy.
RELEVANCE AND NOVEL INFORMATION
Septic pericarditis is one of the least reported causes of feline pericardial effusion. This case report describes bacterial pericarditis in a cat, suspected to be derived from a hepatic abscess via haematological spread. In this case, a favourable response was achieved with both surgical and medical management.
PubMed: 38035151
DOI: 10.1177/20551169231208896 -
Nature Communications Aug 20233D orthogonal woven composites are receiving increasing attention with the ever-growing market of composites. A current challenge for these materials' development is how...
3D orthogonal woven composites are receiving increasing attention with the ever-growing market of composites. A current challenge for these materials' development is how to improve their damage tolerance in orthogonal and layer-to-layer structures under extreme loads. In this paper, a damage reduction strategy is proposed by combining structural and electromagnetic properties. An integrated experimental platform is designed combining a power system, a drop-testing machine, and data acquisition devices to investigate the effects of pulse current and impact force on woven composites. Experimental results demonstrate that pulse current can effectively reduce delamination damage and residual deformation. A multi-field coupled damage model is developed to analyze the evolutions of temperature, current and damage. Parallel current-carrying carbon fibers that cause yarns to be transversely compressed enhance the mechanical properties. Moreover, the microcrack formation and extrusion deformation in yarns cause the redistribution of local current among carbon fibers, and its interaction with the self-field produces an obvious anti-impact effect. The obtained results reveal the mechanism of damage reduction and provide a potential approach for improving damage tolerance of these composites.
PubMed: 37598238
DOI: 10.1038/s41467-023-40752-6 -
Computers in Biology and Medicine Aug 2023This work presents an open-source software pipeline to create patient-specific left atrial models with fibre orientations and a fibrDEFAULTosis map, suitable for...
This work presents an open-source software pipeline to create patient-specific left atrial models with fibre orientations and a fibrDEFAULTosis map, suitable for electrophysiology simulations, and quantifies the intra and inter observer reproducibility of the model creation. The semi-automatic pipeline takes as input a contrast enhanced magnetic resonance angiogram, and a late gadolinium enhanced (LGE) contrast magnetic resonance (CMR). Five operators were allocated 20 cases each from a set of 50 CMR datasets to create a total of 100 models to evaluate inter and intra-operator variability. Each output model consisted of: (1) a labelled surface mesh open at the pulmonary veins and mitral valve, (2) fibre orientations mapped from a diffusion tensor MRI (DTMRI) human atlas, (3) fibrosis map extracted from the LGE-CMR scan, and (4) simulation of local activation time (LAT) and phase singularity (PS) mapping. Reproducibility in our pipeline was evaluated by comparing agreement in shape of the output meshes, fibrosis distribution in the left atrial body, and fibre orientations. Reproducibility in simulations outputs was evaluated in the LAT maps by comparing the total activation times, and the mean conduction velocity (CV). PS maps were compared with the structural similarity index measure (SSIM). The users processed in total 60 cases for inter and 40 cases for intra-operator variability. Our workflow allows a single model to be created in 16.72 ± 12.25 min. Similarity was measured with shape, percentage of fibres oriented in the same direction, and intra-class correlation coefficient (ICC) for the fibrosis calculation. Shape differed noticeably only with users' selection of the mitral valve and the length of the pulmonary veins from the ostia to the distal end; fibrosis agreement was high, with ICC of 0.909 (inter) and 0.999 (intra); fibre orientation agreement was high with 60.63% (inter) and 71.77% (intra). The LAT showed good agreement, where the median ± IQR of the absolute difference of the total activation times was 2.02 ± 2.45 ms for inter, and 1.37 ± 2.45 ms for intra. Also, the average ± sd of the mean CV difference was -0.00404 ± 0.0155 m/s for inter, and 0.0021 ± 0.0115 m/s for intra. Finally, the PS maps showed a moderately good agreement in SSIM for inter and intra, where the mean ± sd SSIM for inter and intra were 0.648 ± 0.21 and 0.608 ± 0.15, respectively. Although we found notable differences in the models, as a consequence of user input, our tests show that the uncertainty caused by both inter and intra-operator variability is comparable with uncertainty due to estimated fibres, and image resolution accuracy of segmentation tools.
Topics: Humans; Atrial Fibrillation; Reproducibility of Results; Heart Atria; Magnetic Resonance Imaging; Fibrosis; Predictive Value of Tests
PubMed: 37301099
DOI: 10.1016/j.compbiomed.2023.107009 -
Family Medicine Nov 2023Implementing a structured activity to encourage exercise in children may be a strategy with benefits. We evaluated pulmonary function in elementary school children...
BACKGROUND AND OBJECTIVES
Implementing a structured activity to encourage exercise in children may be a strategy with benefits. We evaluated pulmonary function in elementary school children participating in a school-based exercise program called The Daily Mile.
METHODS
During the fall semester, we implemented The Daily Mile program in one elementary school and compared pulmonary function in children in the intervention school pre- and postintervention to children in a control school in the same community. The primary outcomes were forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1% (the FEV1/FVC ratio).
RESULTS
The children in the control school showed no significant change in FEV1% during the semester (P=.06). On the other hand, children in the intervention school showed a significant improvement in FEV1% during the same semester (P=.001). This effect was consistent even when stratifying by asthma and sports participation.
CONCLUSIONS
The Daily Mile has benefits for pulmonary function in children. Although family physicians should continue to encourage their patients to have a healthy lifestyle, a more effective approach may be to encourage schools to adopt a program that teachers oversee and administer in a structured way.
Topics: Child; Humans; Asthma; Exercise; Forced Expiratory Volume; Vital Capacity; Exercise Therapy
PubMed: 37540535
DOI: 10.22454/FamMed.2023.976789