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Frontiers in Oncology 2024CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well.... (Review)
Review
CAR-T cell therapy has shown remarkable promise in treating B-cell malignancies, which has sparked optimism about its potential to treat other types of cancer as well. Nevertheless, the Expectations of CAR-T cell therapy in solid tumors and non-B cell hematologic malignancies have not been met. Furthermore, safety concerns regarding the use of viral vectors and the current personalized production process are other bottlenecks that limit its widespread use. In recent years the use of gene editing technology in CAR-T cell therapy has opened a new way to unleash the latent potentials of CAR-T cell therapy and lessen its associated challenges. Moreover, gene editing tools have paved the way to manufacturing CAR-T cells in a fully non-viral approach as well as providing a universal, off-the-shelf product. Despite all the advantages of gene editing strategies, the off-target activity of classical gene editing tools (ZFNs, TALENs, and CRISPR/Cas9) remains a major concern. Accordingly, several efforts have been made in recent years to reduce their off-target activity and genotoxicity, leading to the introduction of advanced gene editing tools with an improved safety profile. In this review, we begin by examining advanced gene editing tools, providing an overview of how these technologies are currently being applied in clinical trials of CAR-T cell therapies. Following this, we explore various gene editing strategies aimed at enhancing the safety and efficacy of CAR-T cell therapy.
PubMed: 38912057
DOI: 10.3389/fonc.2024.1388475 -
Scientific Reports Jun 2024In the healthcare domain, the essential task is to understand and classify diseases affecting the vocal folds (VFs). The accurate identification of VF disease is the key...
In the healthcare domain, the essential task is to understand and classify diseases affecting the vocal folds (VFs). The accurate identification of VF disease is the key issue in this domain. Integrating VF segmentation and disease classification into a single system is challenging but important for precise diagnostics. Our study addresses this challenge by combining VF illness categorization and VF segmentation into a single integrated system. We utilized two effective ensemble machine learning methods: ensemble EfficientNetV2L-LGBM and ensemble UNet-BiGRU. We utilized the EfficientNetV2L-LGBM model for classification, achieving a training accuracy of 98.88%, validation accuracy of 97.73%, and test accuracy of 97.88%. These exceptional outcomes highlight the system's ability to classify different VF illnesses precisely. In addition, we utilized the UNet-BiGRU model for segmentation, which attained a training accuracy of 92.55%, a validation accuracy of 89.87%, and a significant test accuracy of 91.47%. In the segmentation task, we examined some methods to improve our ability to divide data into segments, resulting in a testing accuracy score of 91.99% and an Intersection over Union (IOU) of 87.46%. These measures demonstrate skill of the model in accurately defining and separating VF. Our system's classification and segmentation results confirm its capacity to effectively identify and segment VF disorders, representing a significant advancement in enhancing diagnostic accuracy and healthcare in this specialized field. This study emphasizes the potential of machine learning to transform the medical field's capacity to categorize VF and segment VF, providing clinicians with a vital instrument to mitigate the profound impact of the condition. Implementing this innovative approach is expected to enhance medical procedures and provide a sense of optimism to those globally affected by VF disease.
Topics: Humans; Vocal Cords; Machine Learning
PubMed: 38910146
DOI: 10.1038/s41598-024-64987-5 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth.
Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.
AIMS
This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth.
METHODS
Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators.
RESULTS
Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively.
CONCLUSIONS
These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.
PubMed: 38909514
DOI: 10.1016/j.clnu.2024.06.006 -
Comprehensive Psychiatry Jun 2024The activation of permissive beliefs is a cognitive mechanism through which individuals permit themselves to engage in pleasurable, yet potentially unregulated...
BACKGROUND
The activation of permissive beliefs is a cognitive mechanism through which individuals permit themselves to engage in pleasurable, yet potentially unregulated activities. Existing measures are heterogenous, focusing either on specific behaviors or on particular licensing mechanisms. The new Permissive Beliefs Questionnaire (PBQ) seeks to integrate self-licensing mechanisms from various research domains and to be applicable to different behaviors.
METHODS
Study 1 aimed at exploring the factor structure and reduce the number of items. In study 2, we used confirmatory factor analysis and tested convergent and discriminant validity in three subsamples of individuals playing videogames (n = 489), shopping online (n = 506), and drinking alcohol (n = 511). We tested the hypothesis whether individuals who experience a self-regulatory conflict show a greater expression of permissive beliefs.
RESULTS
The final version of the PBQ consists of 12 items which represent two factors: Deserving Reward and Defensive Optimism. The PBQ exhibited robust model fit indices and internal consistencies in the three samples. Permissive beliefs were heightened among individuals intending to downregulate their gaming, shopping, or drinking behaviors as compared to individuals without this intention.
CONCLUSION
The PBQ is a valid measure of permissive beliefs for gaming, online shopping, and drinking alcohol. It serves an ecologic and psychometrically valid tool to address empirical research questions regarding the functioning of permissive beliefs. Additionally, it may be used in clinical settings to measure and raise an understanding for permissive beliefs in clients.
PubMed: 38905774
DOI: 10.1016/j.comppsych.2024.152507 -
ACS ES&T Water Jun 2024[This corrects the article DOI: 10.1021/acsestwater.2c00428.].
[This corrects the article DOI: 10.1021/acsestwater.2c00428.].
PubMed: 38903199
DOI: 10.1021/acsestwater.4c00418 -
Musculoskeletal Science & Practice Jun 2024There is a lack of qualitative research on how patients with lumbar spinal stenosis (LSS) undergoing surgery perceive their health-related quality of life (HRQOL)....
BACKGROUND
There is a lack of qualitative research on how patients with lumbar spinal stenosis (LSS) undergoing surgery perceive their health-related quality of life (HRQOL). Research that increases our understanding in this area could facilitate a biopsychosocial approach to care.
AIM
We aimed to investigate the experiences of patients with LSS undergoing decompression surgery regarding their pre- and post-surgery perceptions of HRQOL and the pre-and post-operative information and physiotherapy.
METHOD
We used a qualitative design with semi-structured interviews to perform content analysis using an inductive approach. Twelve patients (7 female, 5 male) were included post-surgery and interviewed by phone. The interviews were recorded and transcribed verbatim.
RESULTS
Four distinct categories with nine associated subcategories were identified: Patients' feelings of safety and empowerment are enhanced by healthcare professionals; Divided perceptions of information and physiotherapy in a group context; Health-related quality of life is associated with patients' perceived physical capacity; Patients' optimism and concerns influence health-related quality of life.
CONCLUSION
Both physical and psychological factors pre- and post-surgery appear to influence patients' HRQOL. Inherent optimism and feelings of empowerment in the care process appear to be important factors, regardless of physical health status. A strong patient-provider relationship is important to promote self-efficacy, which may positively affect perceived HRQOL and is in line with the generally recommended biopsychosocial approach in the treatment of people with low back pain. As qualitative studies in this area are scarce, there is a need for further studies to validate our findings.
PubMed: 38901062
DOI: 10.1016/j.msksp.2024.103124 -
PloS One 2024Early optimism saw possibilities for social media to renew democratic discourse, marked by hopes for individuals from diverse backgrounds to find opportunities to learn...
Early optimism saw possibilities for social media to renew democratic discourse, marked by hopes for individuals from diverse backgrounds to find opportunities to learn from and interact with others different from themselves. This optimism quickly waned as social media seemed to breed ideological homophily marked by "filter bubbles" or "echo chambers." A typical response to the sense of fragmentation has been to encourage exposure to more cross-partisan sources of information. But do outlets that reach across partisan lines in fact generate more civil discourse? And does the civility of discourse hosted by such outlets vary depending on the political context in which they operate? To answer these questions, we identified bubble reachers, users who distribute content that reaches other users with diverse political opinions in recent presidential elections in Brazil, where populism has deep roots in the political culture, and Canada, where the political culture is comparatively moderate. Given that background, this research studies unexplored properties of content shared by bubble reachers, specifically the quality of conversations and comments it generates. We examine how ideologically neutral bubble reachers differ from ideologically partisan accounts in the level of uncivil discourse they provoke, and explore how this varies in the context of the two countries considered. Our results suggest that while ideologically neutral bubble reachers support less uncivil discourse in Canada, the opposite relationship holds in Brazil. Even non-political content by ideologically neutral bubble reachers elicits a considerable amount of uncivil discourse in Brazil. This indicates that bubble reaching and incivility are moderated by the national political context. Our results complicate the simple hypothesis of a universal impact of neutral bubble reachers across contexts.
Topics: Social Media; Politics; Humans; Brazil; Canada; Public Opinion; Communication
PubMed: 38900724
DOI: 10.1371/journal.pone.0304564 -
Frontiers in Neurology 2024Spinal Muscular Atrophy (SMA) is an inherited neuromuscular disorder characterized by progressive muscle weakness and atrophy, resulting from the degeneration of motor... (Review)
Review
Spinal Muscular Atrophy (SMA) is an inherited neuromuscular disorder characterized by progressive muscle weakness and atrophy, resulting from the degeneration of motor neurons in the spinal cord. A critical aspect of SMA is its impact on respiratory function. As the disease progresses, respiratory muscles, in particular intercostal muscles, become increasingly affected, leading to breathing difficulties and respiratory failure. Without intervention, many children with SMA type 1 die from respiratory failure before their second year of life. While assisted ventilation has improved survival, it often results in ventilator dependence. The development of new SMN-augmenting therapies has renewed optimism, but their long-term impact on respiratory function is uncertain, and non-invasive respiratory support remains an important part of SMA management. Despite the importance of respiratory support in SMA, knowledge regarding sleep disorders in this population is limited. This review aims to synthesize existing literature on sleep and sleep-related breathing disorders in patients with SMA, with a focus on SMA type 1. We summarize evidence of sleep-disordered breathing and respiratory failure in SMA, as well as outcomes and survival benefits associated with non-invasive or invasive ventilation with or without pharmacological therapies. We also discuss current knowledge regarding the effects of novel disease-modifying therapies for SMA on respiratory function and sleep. In conclusion, optimal care for children with SMA requires a multidisciplinary approach that includes neurology and respiratory specialists. This review highlights the importance of monitoring sleep and respiratory function in SMA, as well as the potential benefits and challenges associated with assisted ventilation combined with new therapies.
PubMed: 38895692
DOI: 10.3389/fneur.2024.1299205 -
Cancers May 2024Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The... (Review)
Review
Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The prognosis of patients with advanced, unresectable HCC has historically been poor. However, with the emergence of immunotherapy, specifically immune checkpoint inhibitors (ICIs), there is reason for optimism. Nevertheless, ICIs do not come without risk, especially when administered in patients with HCC, given their potential underlying poor hepatic reserve. Given their novelty in the management of HCC, there are few studies to date specifically investigating ICI-related side effects on the liver in patients with underlying HCC. This review will serve as a guide for clinicians on ICIs' role in the management of HCC and their potential side effect profile. There will be a discussion on ICI-related hepatotoxicity, the potential for hepatitis B and C reactivation with ICI use, the potential for the development of autoimmune hepatitis with ICI use, and the risk of gastrointestinal bleeding with ICI use. As ICIs become more commonplace as a treatment option in patients with advanced HCC, it is imperative that clinicians not only understand the mechanism of action of such agents but also understand and are able to identify hepatic-related side effects.
PubMed: 38893164
DOI: 10.3390/cancers16112042 -
Journal of Psychosocial Rehabilitation... 2024Severe mental health conditions (SMHCs) significantly contribute to the global disease burden. In low-and-middle-income countries (LMICs) like South Africa, the...
Severe mental health conditions (SMHCs) significantly contribute to the global disease burden. In low-and-middle-income countries (LMICs) like South Africa, the long-term impact of SMHCs on individuals and their families is serious. However, mental health services focus on clinical recovery, with little attention given to the personal recovery needs of mental health service users (MHSUs) and their caregivers. The CHIME framework outlines five domains characterising personal recovery: connectedness, hope and optimism about the future, identity, meaning in life, and empowerment. This qualitative, descriptive study sought insights from male MHSUs and their caregivers on their perspectives of personal recovery from SMHCs. Four male MHSUs and three of their caregivers were purposively selected from Cape Flats communities in the Western Cape. Data were collected using visual participatory methods, including photovoice, life graphs, community maps, and photo-elicitation interviews with MHSUs. In addition, semi-structured interviews were held with caregivers. Data were thematically analysed, and two main themes emerged: Finding meaningful participation and affirming agency. These themes describe how diverse contextual, socioeconomic, political, demographic, cultural, and spiritual factors help and hinder personal recovery. MHSUs and their caregivers sought support from mental health non-profit organisations (MH-NPOs) because of stigmatising attitudes from their communities. MH-NPOs provided MHSUs with long-term relational support and opportunities to build their capacities which helped them access living, learning, working and socialising opportunities. Understanding the diverse needs of MHSUs and including MH-NPOs in scaling up community-based mental health services in LMICs will enable more accessible services that support personal recovery.
PubMed: 38887754
DOI: 10.1007/s40737-023-00341-8