Search Results (108)

The uMlazi River receives effluents from wastewater work before feeding the Shongweni Dam. However, local communities are consuming fish from this dam for protein supplements. This study was undertaken to investigate the metal concentrations in the water and sediment, the general health of Coptodon rendalli and Oreochromis mossambicus, and metal bioaccumulation. Sampling was conducted during the dry (July–August) and wet seasons (November and December) in 2021. Water was sampled using acid-pre-treated sampling bottles, whereas sediment was collected using the Van Veen grab at the inflow, middle, and dam wall. Fish were collected, and their tissues were digested using aqua regia. Metal concentrations were measured using inductively coupled plasma optical emission spectroscopy (ICP-OES). This data manuscript reports the physical parameters of the water and concentrations of antimony, arsenic, cadmium, copper, iron, manganese, lead, selenium, and strontium in the water and sediment from the Shongweni Dam. Moreover, the fish morphometric data and metal concentrations observed in the muscle are also presented. This data could be used as baseline information on metal concentrations in the Shongweni Dam. Moreover, it provides insight into the potential impact of wastewater effluents on metal increases in freshwater bodies. Full article

Human corneal endothelial cell therapy has recently emerged as a novel solution to treat corneal endothelial diseases. We previously demonstrated the potential of utilizing non-cultured primary corneal endothelial cells (CEnCs) isolated from donor corneas with low endothelial cell density for simple non-cultured endothelial cell injection (SNEC-I) therapy. This study aimed to develop a robust and semi-automated approach for cell counting, characterize the extent of cellular manipulation, and evaluate the translational workflow. To address this, we evaluated manual and automated cell counting approaches and characterized the extent of manipulation of CEnCs through the analysis of cell cycle status, gene expressions, and transcriptomic profiles with single-cell RNA-sequencing. The translational feasibility and functionality of SNEC-I therapy were examined using an established rabbit model of bullous keratopathy. Manual hemocytometry and automated cell-counters exhibited comparable accuracy and reproducibility. Analysis of cell cycle status, cell cycle genes (n = 11), and transcriptomic profiles revealed close resemblance between the native corneal endothelium and its donor-matched SNEC-I-harvested cells. Successful resolution of bullous keratoplasty in the pre-clinical model supports the feasibility, efficacy, and safety of SNEC-I therapy. In conclusion, SNEC-I therapy serves as an attractive corneal endothelial therapeutic approach (from a regulatory standpoint) in view of the minimal extent of cellular manipulation. Full article

Background/Objectives: Increasing the solid-state landscape of an active pharmaceutical ingredient (API) by generating new crystalline forms (e.g., polymorphs, cyclodextrin (CD) inclusion complexes, co-crystals, and salts) can yield products with significantly enhanced biopharmaceutical properties (especially increased water solubility), thereby improving API delivery and extending its lifetime. The aim of this study was the isolation of new solid forms of the poorly water-soluble non-steroidal anti-inflammatory drug fenbufen (FBF), for which relatively few solid phases have been reported to date. Further motivation for the study is the recent finding that it has potential for repurposing to treat acute pancreatitis. Methods: Interventions for generating new solid forms of FBF included (a) polymorph screening with a variety of solvent media, (b) attempts to form solid inclusion complexes with the native cyclodextrins α-, β-, and γ-CD using various preparative methods, and (c) co-crystallization with a series of coformers to produce co-crystals and/or molecular salts. Results: No new polymorphic forms of FBF were identified, but screening with CDs resulted in isolation and characterization of a new solid inclusion complex with γ-CD. However, co-crystallization of FBF with the water-soluble coformer isonicotinamide yielded two new products, namely a 1:1 co-crystal and an unusual multi-component ionic co-crystal, whose aqueous solubility indicated significant enhancement of FBF solubility. Conclusions: Due to its extremely low water solubility, FBF presented challenges during the study aimed at modifying its crystalline form. However, two new supramolecular forms, a co-crystal and an ionic co-crystal, were isolated, the latter phase having potential for further formulation owing to its significantly enhanced solubility. Full article

Operable non-small cell lung cancer (NSCLC) has been traditionally managed with surgical resection, often followed by adjuvant chemotherapy with or without radiotherapy. However, disease recurrence still occurs approximately 50% of the time. Most recently, (neo) adjuvant/perioperative systemic therapy has evolved to include checkpoint inhibitor therapy and targeted therapies that have proved successful in advanced disease settings. We provide a comprehensive review of the trials investigating neoadjuvant, adjuvant, and perioperative systemic therapies in resectable lung cancer, including a discussion on surrogate survival endpoints. We review the management of N2 disease, the utility of circulating tumor DNA (ctDNA) in determining the risk and benefit from systemic therapy in operable NSCLC, as well as future directions of investigation. Full article

The rapid advancements in artificial intelligence (AI) have significantly transformed various domains, including education, by introducing innovative tools that reshape teaching and learning processes. This research investigates the perceptions and attitudes of students towards the use of AI tools in their academic activities, focusing on constructs such as perceived usefulness, the perceived ease of use, security and privacy concerns, and both positive and negative attitudes towards AI. On the basis of Technology Acceptance Model (TAM) and the General Attitudes towards Artificial Intelligence Scale (GAAIS), this research seeks to identify the factors influencing students’ behavioral intentions and actual adoption of AI tools in educational settings. A structured survey was administered to students at Multimedia University, Malaysia, capturing their experiences and opinions on widely used AI tools such as ChatGPT, Quillbot, Grammarly, and Perplexity. Hypothesis testing was used to evaluate the statistical significance of relationships between the constructs and behavioral intention and actual use of the AI tools. The findings reveal a high level of engagement with AI tools among University students, primarily driven by their perceived benefits in enhancing academic performance, improving efficiency, and facilitating personalized learning experiences. The findings also uncover significant concerns related to data security, privacy, and the potential over-reliance on AI tools, which may hinder the development of critical thinking and problem-solving skills. Full article

Background and Objectives: Traditionally, full-thickness skin defects (FTSDs) are covered with split-thickness skin grafts (STSGs). This usually provides an epidermal coverage but entails a high risk of hypertrophic scarring mainly due to the absence of the dermal layer. The Novosorb^® Biodegradable Temporising Matrix (BTM) is a novel synthetic dermal substitute that has been used for the reconstruction of various complex and/or large defects in our center. The aim of this article is to evaluate the clinical performance of the BTM as a synthetic dermal substitute for complex FTSD reconstruction in a European context. Materials and methods: This case series focused on the treatment of complex FTSDs with the BTM. After wound debridement, the BTM was applied according to a defined protocol. Once adequate vascularization was observed, the sealing membrane was removed and the neo-dermis was covered with STSGs. Patient demographics, comorbidities, wound defect localization and etiology, wound bed preparations, time of BTM application and removal, time to complete wound healing after STSG, complications, and HTS formation were recorded. Results: The BTM was used to treat FTSDs in six patients with complex wounds from degloving (3), burns (1), ulcerations (1), and necrotizing fasciitis (1). Successful integration occurred in five cases (83%), with one partial integration. The BTM remained in situ for an average of 20.7 days before delamination and STSG coverage. No major complications occurred, though one case had hypergranulation with secondary STSG infection. Two patients were lost to follow-up, while the remaining four had excellent aesthetic and functional outcomes with good-quality scars. Conclusions: Within the limits of this small and heterogeneous case series, the BTM appears to be a promising option for the reconstruction of complex FTSDs of varying etiologies. Its successful integration in most cases and limited complication rate support its clinical potential. However, given this study’s retrospective design and limited sample size, further prospective studies are required to validate these findings and assess long-term outcomes. Full article

Fuchs Endothelial Corneal Dystrophy (FECD) is a corneal endothelial disease that causes microenvironment alterations and endothelial cell loss, which leads to vision impairment. It has a high global prevalence, especially in elderly populations. FECD is also one of the leading indications of corneal transplantation globally. Currently, there is no clearly defined canonical pathway for this disease, and it has been proposed that the combinatorial effects of genetic mutations and exogenous factors cause FECD. Clinical studies and observations have provided valuable knowledge and understanding of FECD, while preclinical studies are essential for gaining insights into disease progression and mechanisms for the development and testing of regenerative medicine therapies. In this review, we first introduce the proposed genetic and molecular pathologies of FECD. Notably, we discuss the impact of abnormal extracellular matrix deposition (guttata), endothelial-to-mesenchymal transition, cell senescence, and oxidative stress on the pathology and etiology of FECD. We review and summarize the in vitro cell models, ex vivo tissues, and in vivo animal models used to study FECD. The benefits and challenges of each model are also discussed. Full article

The SARS-CoV-2 pandemic has increased healthcare waste (HCW) across the globe, giving rise to new challenges such as illegal dumping of medical waste, and an increased risk to hazardous waste exposure such as blood and body fluids that could cause diseases. The study aimed to determine factors associated with SARS-CoV-2 infection among employees handling medical waste in selected healthcare risk waste (HCRW) facilities in Johannesburg, South Africa. The pilot study followed a cross-sectional design, where self-administered questionnaires were used to collect data on occupation-related risk factors for SARS-CoV-2 among HCW handlers working in waste generation, transportation, and final disposal. A total of 33 participants selected from eight HCRW facilities participated in the study. The analysis showed that 21.9% (n = 7) of the HCW handlers who participated in the study reported a positive test result for COVID-19, while 78.1% (n = 26) reported a negative test result for COVID-19. The logistic regression analysis showed that repeated handling of HCW (COR: 1.50, 95% CI: 1.00–2.25) and not having sufficient hand washing facilities (COR: 1.13: 95% CI: 1.04–1.24) increased the odds of SARS-CoV-2 infection; however, these factors were not significant as risks for SARS-CoV-2. In the multivariable analysis, not being trained on personal protective equipment (PPE) use (AOR: 1.25, 95% CI: 1.00–1.58) increased the odds of SARS-CoV-2 infection, while having 3-6 years of experience in medical waste handling significantly lowered the odds of occupation-related SARS-CoV-2 infection by 33% (AOR: 0.67, 95% CI: 0.48–0.95). These preliminary findings show that factors such as the accessibility of handwashing facilities, training on the use of PPE, years of work experience, and repeated contact with medical waste may play a role in modifying the odds of SARS-CoV-2 infection among HCW handlers. A study with a larger sample size is needed to comprehensively quantify occupation related risk factors associated with communicable disease infections among HCW handlers. Full article

Background: The diagnosis and treatment of cancer are associated with substantial physical, psychological, and social morbidity for most patients. Distress can be seen as an unpleasant experience of an emotional, psychological, social, or spiritual nature that interferes with the ability to cope with cancer treatment. Purpose: The aim was to understand patients’ experiences of distress in their context and to analyze and interpret the findings. Method: An explorative, descriptive qualitative study was conducted among cancer patients receiving treatment and care at rural hospitals in Limpopo. A face-to-face individual interview was conducted to determine the participants’ cancer-related experiences and quality of life. Thematic analysis was conducted following Tesch’s method, and the themes developed were subjected to a triangulation process to ensure the validity and rigor of the findings. Findings: The participants revealed experiences of symptomatic distress resulting in biopsychosocial distress such as pain, fatigue, emotional distress related to prognosis and uncertainty about the future, psychosocial distress related to a lack or absence of support, financial instability, and poor self-esteem. Conclusions: Cancer patients face many challenges during their treatment journey. Participants were drained by anxiety and uncertainty of the cancer trajectory and required psychosocial support. The oncology team must provide supportive preventive measures for side effects management and culture-sensitive psychotherapy at an early stage to improve their quality of life. Full article

Introduction: The ketogenic diet (KD) is widely used for weight management by reducing appetite, enhancing fat oxidation, and facilitating weight loss. However, the high content of total and saturated fats in a conventional KD may elevate low-density lipoprotein (LDL)-cholesterol levels, a known risk factor for cardiovascular diseases, highlighting the need for healthier alternatives. This study aimed to investigate the effect of a newly developed Healthy Ketogenic Diet (HKD) versus an Energy-Restricted Diet (ERD) on weight loss and metabolic outcomes among adults with obesity. Methods: Multi-ethnic Asian adults (n = 80) with body mass index ≥ 27.5 kg/m² were randomized either to HKD (n = 41) or ERD (n = 39) for 6 months. Both groups followed an energy-restricted healthy diet, emphasizing on reducing saturated and trans fats. The HKD group additionally limited net carbohydrate intake to no more than 50 g per day. Dietary adherence was supported via the Nutritionist Buddy app with dietitian coaching. The primary outcome was weight change from baseline at 6 months. Secondary outcomes included weight change at 3 months and 1 year, along with changes in metabolic profiles. Data were analyzed using linear regression with an intention-to-treat approach. Results: The HKD group achieved significantly greater mean weight loss at 6 months than the ERD group (−7.8 ± 5.2 kg vs. −4.2 ± 5.6 kg, p = 0.01). The mean weight loss percentage at 6 months was 9.3 ± 5.9% and 4.9 ± 5.8% for the HKD and ERD groups, respectively (p = 0.004). Improvements in metabolic profiles were also significantly better in the HKD group [glycated hemoglobin (−0.3 ± 0.3% vs. −0.1 ± 0.2%, p = 0.008), systolic blood pressure (−7.7 ± 8.9 mmHg vs. −2.6 ± 12.2 mmHg, p = 0.005), and aspartate transaminase (−7.6 ± 15.5 IU/L vs. 0.6 ± 11.5 IU/L, p = 0.01)], with no increase in LDL-cholesterol (−0.12 ± 0.60 mmol/L vs. −0.04 ± 0.56 mmol/L, p = 0.97) observed in either group. Conclusions: The HKD was more effective than the ERD in promoting weight loss and improving cardiometabolic outcomes without elevation in LDL-cholesterol. It can be recommended for therapeutic intervention in patients with obesity. Full article

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease, primarily affecting the middle-aged to elderly population. Among its nonmotor symptoms, cognitive decline (CD) is a precursor to dementia and represents a critical target for early risk assessment and diagnosis. Accurate CD prediction is crucial for timely intervention and tailored management of at-risk patients. This study used machine learning (ML) techniques to predict the CD risk over five-year in early-stage PD. Methods: Data from the Early Parkinson’s Disease Longitudinal Singapore (2014 to 2018) was used to predict CD defined as a one-unit annual decrease or a one-unit decline in Montreal Cognitive Assessment over two consecutive years. Four ML methods—AutoScore, Random Forest, K-Nearest Neighbors and Neural Network—were applied using baseline demographics, clinical assessments and blood biomarkers. Results: Variable selection identified key predictors of CD, including education year, diastolic lying blood pressure, diastolic standing blood pressure, systolic lying blood pressure, Hoehn and Yahr scale, body mass index, phosphorylated tau at threonine 181, total tau, Neurofilament light chain and suppression of tumorigenicity 2. Random Forest was the most effective, achieving an AUC of 0.93 (95% CI: 0.89, 0.97), using 10-fold cross-validation. Conclusions: Here, we demonstrate that ML-based models can identify early-stage PD patients at high risk for CD, supporting targeted interventions and improved PD management. Full article

Background: Since the discovery that Histone deacetylase inhibitors (HDCAi) could enhance radiation response, a number of HDACi, mainly pan-HDAC inhibitors, have been studied either as monotherapy or in combination with X-ray irradiation or chemotherapeutic drugs in the management of breast cancer. However, studies on the combination of HDACi and proton radiation remain limited. CUDC-101 is a multitarget inhibitor of Histone deacetylases (HDACs), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2). In this paper, the effectiveness of CUDC-101 in enhancing radiation response to both proton and X-ray irradiation was studied. Methods: MCF-7, MDA-MB-231, and MCF-10A cell lines were pre-treated with CUDC-101 and exposed to 148 MeV protons, and X-rays were used as reference radiation. Colony survival, γ-H2AX foci, apoptosis, and cell cycle analysis assays were performed. Results: γ-H2AX foci assays showed increased sensitivity to CUDC-101 in the MDA-MB-231 cell line compared to the MCF-7 cell line. In both cell lines, induction of apoptosis was enhanced in CUDC-101 pre-treated cells compared to radiation (protons or X-rays) alone. Increased apoptosis was also noted in CUDC-101 pre-treated cells in the MCF-10A cell line. Cell cycle analysis showed increased G2/M arrest by CUDC-101 mono-treatment as well as combination of CUDC-101 and X-ray irradiation in the MDA-MB-231 cell line. Conclusions: CUDC-101 effectively enhances response to both proton and X-ray irradiation, in the triple-negative MDA-MB-231 cell line. This enhancement was most notable when CUDC-101 was combined with proton irradiation. This study highlights that CUDC-101 holds potential in the management of triple-negative breast cancer as monotherapy or in combination with protons or X-ray irradiation. Full article

Background: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (³²P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following ³²P implantation, using contrast-enhanced EUS (CE-EUS). Methods: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and ³²P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time–intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. Results: A total of 20 patients underwent ³²P implantation, with 15 completing 12-week follow-up. The technical success of ³²P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5–38.75) pre-implantation to 24 mm (IQR 16–26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08–54.35). This increased to 46.85 (IQR 35.05–76.6; p = 0.007) and 66.3 (IQR 54.7–76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8–12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. Conclusion: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed ³²P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted. Full article

Toceranib phosphate (toceranib) is approved for canine mast cell tumor treatment. However, no long-term response to toceranib in canine HSTCL has been reported. Here, we describe a case of a 10-year-old castrated mixed-breed dog that presented with a 3-month history of weight loss, polydipsia, and polyuria. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and splenomegaly with multiple diffuse splenic hypoechoic nodules. On day 21, a cholecystectomy was performed to remove the obstruction, followed by a liver biopsy and splenectomy. Cytology of the spleen and liver showed many small lymphocytes with intracytoplasmic granules (sGLs). Splenic and hepatic infiltration of neoplastic CD3/granzyme B-positive small cells and lymphocytic cholecystitis with granzyme B-negative small cells were noted. T-cell receptor gene clonal rearrangements were observed in the liver tissues. The dog was diagnosed with a hepatosplenic T-cell lymphoma (HSTCL) of sGLs concurrent with lymphocytic cholecystitis. The icterus resolved after surgery, but there was progressive elevation of liver enzyme levels. Toceranib was administered from day 39, resulting in decreased liver enzyme levels, and the dog remained in good condition. The dog stayed in remission after toceranib administration and survived for 460 days. Toceranib should be considered an effective treatment option for canine HSTCL. Full article

In this study, AlSi12 alloy samples were produced via the selective laser melting (SLM) technique to produce high-density components with complex and customized parts for railway applications. Nonetheless, the production of dense samples necessitates the optimization of production process parameters. As a statistical design of the experimental method, response surface methodology was applied to optimize different combinations of SLM parameters. The outcomes were analyzed via analysis of variance (ANOVA) and signal-to-noise(S/N) ratios. The relationship between the hardness response to the process parameters (scanning speed and laser power) for determining the optimal processing conditions were examined. A hardness value of 133 HV was obtained. The process parameters were successfully optimized and the relationship between the parameters and the structures of the fabricated samples were reported. Full article