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Vascular endothelial cells derived from transgene-free pig induced pluripotent stem cells for vascular tissue engineering
Induced pluripotent stem cells (iPSCs) hold great promise for the treatment of cardiovascular diseases through cell-based therapies, but these therapies require extensive preclinical testing that is best done in species-in-species experiments. Pigs are a good large animal model for these tests due to the similarity of their cardiovascular system to humans. However, a lack of adequate pig iPSCs (piPSCs) that are analogous to human iPSCs has greatly limited the potential usefulness of this model system. Herein, transgene-free piPSCs with true pluripotency were generated by using reprogramming factors in an optimized pig pluripotency medium. Using an effective differentiation protocol, piPSCs were used to derive endothelial cells (ECs) which displayed EC markers and functionality comparable to native pig ECs. Further, piPSC-ECs demonstrated suitability for vascular tissue engineering, producing a tissue engineered vascular conduit (TEVC) that displayed the upregulation of flow responding markers. In an in vivo functional study, these piPSC-EC-TEVCs maintained the expression of endothelial markers and prevented thrombosis as interposition inferior vena cava grafts in immunodeficient rats. The piPSCs described in this study open up the possibility of unique preclinical species-in-species large animal modeling for the furtherance of modeling of cell-based cardiovascular tissue engineering therapies. Statement of Significance: While there has been significant progress in the development of cellularized cardiovascular tissue engineered therapeutics using stem cells, few of them have moved into clinical trials. This is due to the lack of a robust preclinical large animal model to address the high safety and efficacy standards for transplanted therapeutics. In this study, pig stem cells that are analagous to human's were created to address this bottleneck. They demonstrated the ability to differentiate into functional endothelial cells and were able to create a tissue engineered therapeutic that is analogous to a human therapy. With these cells, future experiments testing the safety and efficacy of tissue engineered constructs are possible, bringing these crucial therapeutics closer to the patients that need them.</p
Esophageal and Oropharyngeal Dysphagia: Clinical Recommendations From the United European Gastroenterology and European Society for Neurogastroenterology and Motility
Dysphagia is a prevalent symptom of the upper gastrointestinal tract causing health related consequences, impacting quality of life and is associated with global economic burden. Swallowing difficulties are classified into oropharyngeal dysphagia (OD) and esophageal dysphagia. Despite its clinical importance, dysphagia is associated with several uncertainties regarding its optimal diagnostic work-up and management, particularly, considering the progress with diagnostic modalities and technologies. A Delphi consensus was performed with experts from various disciplines who conducted a literature summary and voting process on 41 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation criteria. Consensus was reached for all the statements. The panel agreed with the definition and prevalence of esophageal and OD types. The role of endoscopy, high-resolution manometry, EndoFLIP, barium swallow and other imaging tests in evaluating esophageal dysphagia has reached overall strong agreement. Videofluoroscopic swallow study, alongside fiber-endoscopic evaluation of swallowing, as the methods of choice for the instrumental assessment of oropharyngeal dysfunction is a strong recommendation. Regarding treatment, a weak recommendation was achieved for the use of PPIs, calcium-channel blockers, nitrates, phosphodiesterase type 5 inhibitors, antidepressants or peppermint oil for the treatment of hypercontractile esophagus. A strong recommendation exists for endoscopic and surgical treatment of achalasia, while a weak recommendation is provided for other esophageal motility disorders. Regarding OD, a weak recommendation was achieved for swallow therapy, to improve swallowing mechanics, reduce symptoms, and enhance quality of life. Swallow therapy could be more effective when using validated assessment tools, consistent treatment parameters, and considering long-term follow-up. A multinational group of European experts summarized the current state of consensus on the definition, diagnosis, and management of dysphagia.</p
Bidirectional associations among positive affect, anhedonia and meaning in life during major depressive episode: ecological momentary assessment study in unipolar and bipolar individuals and healthy controls
BackgroundDiagnostic accuracy is an unmet need for major depressive disorder (MDD) and major depressive episode (MDE) in bipolar disorder. Very limited research has evaluated bipolar disorder/MDE and MDD using ecological momentary assessment (EMA) time-series data.AimsWe aimed to examine differentiating phenomenological characteristics in positive affect dynamics, and temporal relationships with pleasure towards current activity and meaning in life (MIL), among MDD, MDE/bipolar disorder and healthy controls using EMA.MethodParticipants (N = 88, mean age 28.7 years, 69% female), including individuals with MDD (n = 29) and MDE/bipolar disorder (n = 29) and healthy controls (n = 30), were assessed for positive affect, pleasure and MIL 5 times daily over a 2-week period. Multilevel modelling analysis was conducted, with estimation of first-order autoregressive model structure and time-lagged relationship between pleasure and positive affect.ResultsFrom 4632 EMA observations, positive affect dynamics (inertia, variability and instability) did not differ significantly across groups (all P > 0.05). Although all groups demonstrated a bidirectional relationship between positive affect and pleasure, for MDE/bipolar disorder, both pleasuret − 1 (β = −0.11, t[51.09] = −2.31, P = 0.025) and positive affectt − 1 (β = −0.13, t[56.54] = −2.30, P = 0.025) predicted subsequent MIL less significantly than for MDD and healthy controls.ConclusionIndividuals with MDE/bipolar disorder, but not MDD, had less self-reported MIL from positive affect and pleasure. There is little evidence that emotional experience alone characterises the pathophysiology between MDD and MDE/bipolar disorder; such investigation may be limited by within-group heterogeneity. Our findings provide a new perspective on using a time-series approach beyond bimodal measures in EMA to differentiate bipolar disorder/MDE and MDD.published_or_final_versio
“Guess I’m Next to be Erased”: street art, heritage and gentrification in George Town, Malaysia
This paper builds on emerging literature documenting how street art intersects with urban heritage and processes of gentrification in rapidly urbanizing and worlding cities. In particular, it focuses on the UNESCO World Heritage City of George Town, Penang, and examines controversies over the in/formal blossoming of street art in quotidian spaces of the city (such as back lanes, alleys, and car parks) since 2012. Not only have these works brought more life to these (formerly) secluded spaces, but they have also, (un)intentionally contributed to processes of gentrification and urban renewal. In particular, the paper uses Chang’s (Citation2016) concept of gentrification aesthetics in examining the emergence of street art in George Town and its role in government efforts to revitalize the city and boost tourism revenues. The findings suggest that street art has indeed shaped processes of gentrification in George Town, attracting middle-class tourists while sidelining traditional uses of space. It also stresses that the challenges in using street art to estheticize a city, given its divergent meanings to different people, particularly in multicultural historic centers like George Town, and thus needs to be carefully cultivated and regulated to have the desired outcomes.</p
Seasonality and local nutrient loading drive changes in organic carbon in seagrass ecosystems in Hong Kong
Natural variation in environmental conditions (e.g., seasonality) modulates the ecological dynamics and functioning of seagrass ecosystems. However, these characteristics can be altered by anthropogenic-driven pressures resulting from coastal urbanization (e.g., nutrient pollution), with significant effects on ecosystem service provision, including carbon sequestration and storage. Understanding these effects is complex as seagrasses exhibit different sensitives to environmental stress and change, generating species-specific responses that vary through temporal and spatial scales. Here, we tested this hypothesis by quantifying the seasonal variation in total carbon (C%; upper sediment layer, 15 cm), total nitrogen (N%), and stable isotopes (δ13C and δ15N) in two seagrass species (i.e., Halophila ovalis and H. beccarii) in Hong Kong, one of the most urbanized coastal areas globally. The C:N ratios and δ15N values indicated seasonal differences in local nitrogen source and accumulation, resulting in increased total seagrass biomass in the wet season. Isotope results suggested belowground seagrass tissues significantly contributed towards sediment carbon, particularly in the wet season, characterized by increased nitrogen loading.published_or_final_versio
Cold atmospheric plasma combined with nanoparticles in cancer therapy
This review explores the application of cold atmospheric plasma (CAP) and nanoparticles (NPs) in cancer therapy, highlighting their potential to enhance treatment efficacy and minimize side effects. CAP generates reactive oxygen and nitrogen species that selectively induce apoptosis in cancer cells, while NPs improve drug delivery, enhance targeting precision, and reduce adverse effects on healthy tissues. By summarizing various types of NPs, including gold, silver, magnetic, and other NPs, we evaluate their individual and combined effects with CAP across different cancer models. Our findings suggest that combined CAP-NPs significantly enhance therapeutic outcomes by increasing cancer cell sensitivity and minimizing damage to surrounding tissues. This synergistic approach not only aligns with previous research on CAP's selective toxicity but also reveals new possibilities for optimizing cancer treatment through targeted NP delivery. Further clinical research is needed to establish the safety and efficacy of this combination, paving the way for novel, patient-specific treatment strategies with improved outcomes.</p
A New Classification System for Alveolar Bone Morphology around Maxillary Incisors in Adult Patients with Maxillary Protrusion
OBJECTIVE: To develop a new alveolar bone morphology classification for maxillary incisors in patients with maxillary protrusion, and to investigate the association of alveolar morphology with skeletal patterns and alveolar bone defects following retraction. METHODS: A retrospective study of CBCT scans was performed for 250 patients with maxillary protrusion. The morphology of alveolar bone around maxillary incisors was classified into four types: A1 (upright maxillary incisor in thin alveolar bone), A2 (lingually inclined maxillary incisor in thin alveolar bone), B1 (upright maxillary incisor in thick alveolar bone) and B2 (lingually inclined maxillary incisor in thick alveolar bone). The association of alveolar types with different skeletal patterns and the incidence of post-treatment alveolar bone defects were analysed. RESULTS: For maxillary incisors in patients with maxillary protrusion, A1 was the most common alveolar type (33.4%), followed by A2 (28.5%), B1 (22.1%) and B2 (16.0%). Types B1 (34.4%) and A2 (42.2%) were the most common in maxillary central and lateral incisors, respectively. In high angle patients, A2 and A1 were the most common types for maxillary lateral (49.6%) and central incisors (41.2%), respectively. Additionally, types A1 and A2 were at greater risk of severe lingual dehiscence. CONCLUSION: This is the first alveolar bone morphology classification for maxillary incisors in patients with maxillary protrusion. The alveolar types exhibited a significant association with skeletal patterns and the incidence of alveolar bone defects after retraction
Roles of unmet supportive care needs, supportive cancer care service disruptions, and COVID-19–related perceptions in psychological distress among recently diagnosed breast cancer survivors in Hong Kong
Introduction: Receiving a cancer diagnosis and living with breast cancer can be particularly stressful during pandemic situations. This study examined how cancer care service disruptions, unmet supportive care needs (SCNs), and coronavirus disease 2019 (COVID-19)–related perceptions were associated with psychological distress among Hong Kong breast cancer survivors (BCS) during the COVID-19 pandemic. Methods: A total of 209 female BCS diagnosed since January 2020 (ie, the start of the COVID-19 pandemic in Hong Kong) were recruited from the Hong Kong Breast Cancer Registry to complete a cross-sectional survey measuring the aforementioned variables. Results: Multivariable logistic regression analysis indicated that unmet physical/daily living needs (odds ratio [OR]=1.03; P=0.002), unmet psychological needs (OR=1.06; P<0.001), and perceived severity of COVID-19–related health consequences in BCS (OR=1.67; P=0.02) were significantly associated with moderate-to-severe psychological distress. However, cancer treatment/supportive care service disruptions, fear of COVID-19, and unmet SCNs in patient care/health system information/sexual domains were not significant contributors (P=0.77-0.89). Conclusion: Half of the BCS in Hong Kong experienced substantial psychological distress during the pandemic. Survivors with higher levels of unmet SCNs in physical/daily living and psychological domains, as well as those with greater perceived severity of COVID-19–related health consequences, were more likely to experience moderate-to-severe psychological distress. These findings suggest that efforts to address specific unmet SCNs and risk perceptions are important for reducing psychological distress among BCS during pandemic situations
Economic inequality and corruption as social determinants of health: An empirical analysis across 136 countries (2001–2020)
This study examines the compounded effects of corruption and economic inequality on public health outcomes across 136 countries from 2001 to 2020. By employing panel regression analysis with fixed effects on data from Transparency International's Corruption Perceptions Index, the World Inequality Database's post-tax income Gini coefficient, and health indicators from the World Bank, the study reveals that corruption and inequality independently worsen health outcomes. More importantly, their interaction exacerbates these effects, highlighting a structural synergy that restricts access to essential health resources and disproportionately harms already vulnerable populations. The findings indicate that this compounded impact is most severe in low- and lower-middle-income countries, where systemic governance failures intersect with structural inequities to undermine health systems. Robustness checks using alternative health indicators and econometric methods strengthen the validity of the conclusions. By emphasizing the systemic interplay between governance and economic structures, this study challenges reductionist approaches to public health that overlook broader structural determinants. The results underscore the urgent need for integrated policy interventions targeting both corruption and inequality to mitigate health disparities and advance global health equity. These findings call for a global rethinking of governance and economic priorities in addressing structural health inequities.published_or_final_versio
Band Gap Engineering and Electronic Property Modulation of β-Ga2O3 through Bi2O3 Alloying
Bismuth (Bi) has recently emerged as a promising dopant for engineering the valence band of Ga2O3 to enable p-type doping. This study investigates the structural, electronic and optical effects of Bi incorporation in the ternary oxide (BixGa1−x)2O3 (x = 0 to 0.08) using a combination of experiments and densityfunctional theory (DFT) calculations. Alloying Ga2O3 with Bi2O3 induces an upward shift of 0.37 eV in the valence band maximum (VBM) while preserving the monoclinic crystal structure. The band gap decreases from 4.97 to 4.57 eV, and the electrical conductivity of the (BixGa1−x)2O3 films reduces by over 2 orders of magnitude as the Bi fraction increases. This conductivity reduction is attributed to greater electron carrier compensation arising from the VBM upshift and a larger effective electron mass. Enhanced defect-related luminescence is observed in (BixGa1−x)2O3, in agreement with DFT calculations showing that the presence of nearby Bi atoms reduces the formation energy of Ga vacancies from 3.69 to 1.43 eV. These findings highlight the potential of Bi2O3 alloying for band structure engineering in Ga2O3 to facilitate p-type doping.</p