RESUMEN
Hydractinia is a colonial marine hydroid that shows remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, Hydractinia symbiolongicarpus and Hydractinia echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell-type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinia's i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinia's stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from nonself.
Asunto(s)
Genoma , Hidrozoos , Animales , Hidrozoos/genética , Evolución Molecular , Transcriptoma , Células Madre/metabolismo , Masculino , Filogenia , Análisis de la Célula Individual/métodosRESUMEN
Organic polymer photocatalysts have achieved significant progress in photocatalytic hydrogen evolution, while developing the integrated organic polymers possessing the functions of photosensitizer, electron transfer mediator, and catalyst simultaneously is urgently needed and presents a great challenge. Considering that chalcogenoviologens are able to act as photosensitizers and electron-transfer mediators, a series of chalcogenoviologen-containing platinum(II)-based supramolecular polymers is designed, which exhibited strong visible light-absorbing ability and suitable bandgap for highly efficient photocatalytic hydrogen evolution without the use of a cocatalyst. The hydrogen evolution rate (HER) increases steadily with the decrease in an optical gap of the polymer. Among these "all-in-one" polymers, Se-containing 2D porous polymer exhibited the best photocatalytic performance with a HER of 3.09 mmol g-1 h-1 under visible light (>420 nm) irradiation. Experimental and theoretical calculations reveal that the distinct intramolecular charge transfer characteristics and heteroatom N in terpyridine unit promote charge separation and transfer within the molecules. This work could provide new insights into the design of metallo-supramolecular polymers with finely tuned components for photocatalytic hydrogen evolution from water.
RESUMEN
BACKGROUND: Invasive fungal disease (IFD) is a frequent complication in pediatric lung transplant recipients, occurring in up to 12% of patients in the first year. Risk factors for infection include impaired lung defenses and intense immunosuppressive regimens. While most IFD occurs from Aspergillus, other fungal conidia are continuously inhaled, and infections with fungi on a spectrum of human pathogenicity can occur. CASE REPORT: We report a case of a 17-year-old lung transplant recipient in whom Irpex lacteus and Rhodotorula species were identified during surveillance bronchoscopy. She was asymptomatic and deemed to be colonized by Irpex lacteus and Rhodotorula species following transplant. 2 years after transplantation, she developed a fever, respiratory symptoms, abnormal lung imaging, and histological evidence of acute and chronic bronchitis on transbronchial biopsy. After developing symptoms concerning for a pulmonary infection and graft dysfunction, she was treated for a presumed IFD. Unfortunately, further diagnostic testing could not be performed at this time given her tenuous clinical status. Despite the initiation of antifungal therapy, her graft function continued to decline resulting in a second lung transplantation. CONCLUSIONS: This case raises the concern for IFD in lung transplant recipients from Irpex species. Further investigation is needed to understand the pathogenicity of this organism, reduce the incidence and mortality of IFD in lung transplant recipients, and refine the approach to diagnosis and manage the colonization and isolation of rare, atypical fungal pathogens in immunocompromised hosts.
Asunto(s)
Infecciones Fúngicas Invasoras , Trasplante de Pulmón , Polyporales , Rhodotorula , Adolescente , Femenino , Humanos , Antifúngicos/uso terapéutico , Broncoscopía , Pulmón , Trasplante de Pulmón/efectos adversos , Receptores de TrasplantesRESUMEN
BACKGROUND: Alectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor indicated for ALK-mutated non-small-cell lung cancer. Recently, the association between alectinib and red cell morphological abnormalities has been reported in a few case series. This retrospective observational study aims to determine the frequency of occurrence of acanthocytosis in patients taking alectinib and to evaluate the red cell indices, biochemical markers of haemolysis and eosin-5-maleimide (EMA) binding assay results in patients receiving alectinib. METHODS: Patients who were on alectinib and had a complete blood count test performed in Queen Elizabeth Hospital Haematology Laboratory between 1 May 2021 and 31 August 2021 were included in the study. Haematological investigations that had been performed before and after the commencement of alectinib were reviewed. RESULTS: Fifty patients receiving alectinib were evaluated in this analysis. One hundred per cent of patients showed 3+ acanthocytes on the peripheral blood smears. Compared with the test results before starting alectinib, the post-alectinib blood tests showed a significantly lower haemoglobin concentration, red blood cell count and haematocrit; and a significantly higher mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and red cell distribution width. All the tested patients showed a marked reduction in EMA mean channel fluorescence compared with normal control. CONCLUSION: Our cohort revealed that alectinib caused significant acanthocytosis in all patients. Alectinib was also associated with changes in red cell indices and biochemical markers of haemolysis, compatible with a spherocytic and anisopoikilocytic morphology with haemolysis. Patients on alectinib had reduced EMA binding.
Asunto(s)
Carbazoles , Eritrocitos , Piperidinas , Humanos , Piperidinas/uso terapéutico , Piperidinas/farmacología , Carbazoles/farmacología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Índices de Eritrocitos/efectos de los fármacos , Adulto , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Anciano de 80 o más Años , Pruebas HematológicasRESUMEN
INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative gastroesophageal reflux disease (GERD) and erosive esophagitis (EE). The role of crural repair during LSG is still controversial. The preoperative laxity of the gastroesophageal junction (GEJ), graded by the Hill's classification, is more predictive for postoperative GERD and EE after LSG than the presence of a hiatal hernia seen on endoscopy. Thus, the authors hypothesize that a concomitant crural repair in a specific subgroup of patients with a lax GEJ (Hill's III) may reduce the incidence of postoperative GERD and EE. METHODS: A double-blinded, randomized controlled trial of patients with Hill's III GEJ undergoing LSG will be randomized to a concomitant crural repair (experimental) versus LSG alone (control). Primary outcome measures will be presence of EE at 1-year. Secondary outcome measures will include proton pump inhibitor use, postoperative complications, operative time, blood loss, quality of life, GERD and gastrointestinal symptoms. CONCLUSION: Conflicting crural repair results may be explained by differences in preoperative GEJ laxity. Patients with a frank hiatal hernia and patulous GEJ (Hill's IV) have a very high, while patients with an apposed GEJ (Hill's I, Hill's II) have a low incidence of postoperative GERD and EE respectively. Thus, the authors hypothesize that patients with a lax GEJ without frank hiatal hernia (Hill's III), might benefit from a crural repair. This study results can potentially highlight the clinical importance of preoperative endoscopic evaluation of the GEJ in all patients planned for LSG, to determine which subgroup patients may benefit from a crural repair. (Clinicaltrials.gov: NCT05330910, Registered 15-April-2022).
RESUMEN
INTRODUCTION: College transition is often regarded as the most stressful phase of life by college students. Hence, it is necessary to find ways to help them adjust more smoothly to this transition. Hope, as conceptualized by C. R. Snyder, has been widely studied as a predictor of optimal functioning and has been shown to be associated with better adjustment among college students. This study aimed to shed light on the role of hope in college transition by examining its unique reciprocal relationships with an array of important psychosocial resources and emotional well-being among first-year college students. METHODS: Data were collected from a sample of Hong Kong college freshmen (N = 433, Medianage = 18 years old, 63.7% female) at two time points. At each time point, participants completed self-reported measures tapping into their levels of hope, psychosocial resources, and emotional well-being. Psychological resources included general and academic self-efficacy, meaning in life, and optimism. Social resources included secure attachment, perceived school environment, and social support. Emotional well-being was operationalized as positive and negative emotions. Cross-lagged panel models were constructed and tested by path analyses. RESULTS: When autoregression and the effects of other variables were controlled, a greater sense of hope uniquely predicted higher levels of general and academic self-efficacy, greater presence of life meanings, more secure attachment, and more positive and fewer negative emotions. On the other hand, higher levels of meaning in life (both presence and search) and social support uniquely predicted greater hope. Academic hope and presence of life meanings reciprocally predicted one another, whereas other significant cross-lagged relationships were unidirectional. CONCLUSIONS: The findings suggest interventions that promote hope can be useful in helping college freshmen adjust to the new college environment by enhancing their psychosocial resources and emotional well-being. Such interventions would be more effective if they included elements that boost meaning in life and social support, which are expected to further enhance the perceptions of hope.
Asunto(s)
Esperanza , Apoyo Social , Estudiantes , Humanos , Femenino , Estudiantes/psicología , Masculino , Adolescente , Universidades , Hong Kong , Adulto Joven , Autoeficacia , Emociones , Adaptación PsicológicaRESUMEN
To reduce the mortality and morbidity associated with cancer, new cancer theranostics are in high demand and are an emerging area of research. To achieve this goal, we report the synthesis and characterization of piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives (SA1-SA7). These compounds were synthesized in good yields following a two-step protocol and characterized using multiple analytical techniques. In vitro cytotoxicity and fluorescent cellular imaging of the compounds were assessed against non-cancerous fibroblast (3T3) and breast cancer (4T1) cell lines. Although the former study indicated the safe nature of the compounds (viability = 82-95% at 1 µg/mL), imaging studies revealed that the designed probes had good membrane permeability and could disperse in the whole cell cytoplasm. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and ADME/Tox results, indicated that the compounds had the ability to target CAIX-expressing cancers. These findings suggest that piperazine-linked 1,8-naphthalimide-arylsulfonyl derivatives are potential candidates for cancer theranostics and a valuable backbone for future research.
Asunto(s)
Naftalimidas , Neoplasias , Humanos , Simulación del Acoplamiento Molecular , Piperazina , Imagen MolecularRESUMEN
Luminescent organic radicals, especially those with photoactivated circularly polarized luminescence (CPL) features, hold great significance for cutting-edge optoelectronic applications, but their development still remains a challenge. In this study, we propose a novel strategy to achieve photoactivated CPL radicals by bonding two phosphine centers within an axial chiral system, yielding a compound of R/S-5,5-bis(diphenylphosphino)-4,4'-bibenzo[d][1,3]dioxole (R/S-BDP). The photoactivated R/S-BDP molecules in polymer matrix display a robust quantum yield of 19.8 % and a dissymmetry factor (glum) of 1.2×10-4, marking this work as the first example of photoactivated CPL radicals. Furthermore, the glum is improved to 1.0×10-2 by using a liquid crystal as host. Experimental and theoretical analyses reveal that R/S-BDP molecules, endowed with double phosphine cores in axial chirality, offer a direct way for intramolecular electron transfer upon photoirradiation. This leads to the generation of radical ionic pairs, which subsequently trigger the donor-acceptor arrangement through intermolecular electron transfer, thereby resulting in stable radical emission. The extended photoactivated BDP-F exhibits a remarkably high quantum efficiency of 57.8%. Ultimately, the distinctive photo-responsive CPL radical luminescence has been successfully used for information displays and anti-counterfeiting.
RESUMEN
The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, and South America. Due to their natural characteristics as a hermaphroditic species with a high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States, as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments for reactively controlling invasive mollusc populations and proactively preventing their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in natural open-water systems was performed to evaluate molluscicides and identify the toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize the negative impact on water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners in invasive Asian clam management.
RESUMEN
BACKGROUND: Hope has been extensively studied as a predictor of college students' academic success. Most previous studies used domain-general, global hope measures to gauge the association between hope and academic performance among college students. However, a few studies have suggested that hope is domain-specific and domain-specific academic hope measures should be included in related research to better assess the influence of hope on academic outcomes. In this study, we aimed to further examine this issue to ascertain if there is value in including academic hope measures when studying the link between hope and academic outcomes in college students. METHODS: Two samples of Hong Kong college students (total N = 1321) were recruited. Each participant completed a set of self-reported online questionnaires. RESULTS: In both samples, global hope and academic hope emerged as related but separate factors in confirmatory factor analyses. Academic hope had consistently stronger unique explanatory power on academic performance and goal setting than global hope did. On the other hand, global hope explained more variance in general wellbeing than academic hope did, but its explanatory role in academic performance was not significant. CONCLUSIONS: The findings support domain-specificity and show that hope measures explain more variance in outcomes in the matched domains. Therefore, academic hope measures should more routinely be included in related research to better evaluate the role of hope in academic pursuit among college students. Possible implications for hope interventions are also discussed.
Asunto(s)
Esperanza , Estudiantes , Humanos , Femenino , Masculino , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Adulto Joven , Universidades , Hong Kong , Adulto , Rendimiento Académico/psicología , Rendimiento Académico/estadística & datos numéricos , Encuestas y Cuestionarios/normas , Éxito Académico , Adolescente , ObjetivosRESUMEN
If some inferences require cognitive effort, could that mean, that all of them do? The scalar term "some" has long fascinated academics from various backgrounds, as it can be interpreted either purely semantically, as "some and possibly all", or pragmatically, as "some and not all". The pragmatic reading implies the generation of what is called a scalar implicature. While scientific investigation of such implicatures has given rise to many potential explanations of the "pragmatic enrichment" phenomenon behind them, the debate between the two dominant frameworks-the literal-first and the default accounts-has not convincingly been settled. With the birth of a new interdisciplinary field, appropriately dubbed experimental pragmatics, the last 20 years have led to a substantial amount of new empirical data on scalar implicatures. In this ongoing investigation, the loading and measuring of Working Memory has become an important experimentation tool, as it allows to test the contrasting hypotheses with regard to the cognitive effort of implicature generation, which are made by the two main theoretical accounts. The current systematic review evaluates the relevant literature until March 08, 2022 in an attempt to shed light on the role of Working Memory in implicature derivation. A comprehensive search, and two-step review procedure yielded a sample of 18 studies, containing data of 23 relevant experiments. Findings were bundled in a narrative synthesis and combined through two separate meta-analyses. Our results support the literal-first account, by showing that the derivation of scalar implicatures is a cognitively effortful process that is sensitive to changes in the available Working Memory resources. However, as the reported effects are relatively weak and capricious, we argue that the development of more sophisticated paradigms and eventually, stronger theories within the field, will be crucial in order to both fully understand the current results and set-up fruitful future research.
Asunto(s)
Memoria a Corto Plazo , Lectura , Humanos , Proyectos de Investigación , CogniciónRESUMEN
Despite total knee arthroplasty (TKA) being the gold standard for end-stage knee osteoarthritis, 20% of patients remain dissatisfied. Robotic-assisted arthroplasty promises unparalleled control of the accuracy of bone cuts, implant positioning, control of gap balance, and resultant hip-knee-ankle (HKA) axis. Patients underwent clinical and radiological assessments, including knee CT scans and patient-reported outcome measures (PROMs), preoperatively. Follow-up assessments were conducted at 2 weeks, 6 weeks, and 3 months post-operatively, with imaging repeated at 6 weeks. A total of 155 patients underwent robotic-assisted TKA and have completed 3 months of follow-up. Mean pre-operative HKA axis was 7.39 ± 5.52 degrees varus, improving to 1.34 ± 2.22 degrees varus post-operatively. Restoration of HKA axis was 0.76 ± 1.9 degrees from intra-operative planning (p < 0.0005). Implant placement accuracy in the coronal plane was 0.08 ± 1.36 degrees (p = 0.458) for the femoral component and 0.71 ± 1.3 degrees (p < 0.0005) for the tibial component. Rotational alignment mean deviation was 0.39 ± 1.49 degrees (p = 0.001). Most patients (98.1%) had ≤ 2 mm difference in extension-flexion gaps. PROM scores showed improvement and exceeded pre-operative scores by 6 weeks post-surgery. Robotic-assisted knee arthroplasty provides precise control over traditionally subjective factors, demonstrating excellent early post-operative outcomes.Level of evidence Prospective observational study-II.
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Procedimientos Quirúrgicos Robotizados , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Medición de Resultados Informados por el Paciente , Anciano de 80 o más Años , Resultado del Tratamiento , Recuperación de la Función , Articulación de la Rodilla/cirugía , Estudios ProspectivosRESUMEN
An 18-year-old male with multiple endocrine neoplasm type 1 (MEN1) syndrome presented with hyperparathyroidism. Parathyroidectomy was performed. Patient complained of bone pain afterwards, multiple imaging modalities revealed features of osteitis fibrosa cystica and biochemical profile showed features of hungry bone syndrome. Incidental suspicious pancreatic lesion was initially revealed by 18F-FDG PET/CT scan while MRI further characterized the possibility of insulinoma. Ultimately, the patient was diagnosed of MEN1 syndrome by genetic test. This case report demonstrates the utilization of various imaging modalities such as ultrasound, Tc99m-sestamibi parathyroid scintigraphy, bone scintigraphy, CT, PET/CT and MRI, which leads to ultimately the diagnosis of MEN1 syndrome.
RESUMEN
The development of high-performance electrocatalysts for energy conversion reactions is crucial for advancing global energy sustainability. The design of catalysts based on their electronic properties (e.g., work function) has gained significant attention recently. Although numerous reviews on electrocatalysis have been provided, no such reports on work function-guided electrocatalyst design are available. Herein, a comprehensive summary of the latest advancements in work function-guided electrocatalyst design for diverse electrochemical energy applications is provided. This includes the development of work function-based catalytic activity descriptors, and the design of both monolithic and heterostructural catalysts. The measurement of work function is first discussed and the applications of work function-based catalytic activity descriptors for various reactions are fully analyzed. Subsequently, the work function-regulated material-electrolyte interfacial electron transfer (IET) is employed for monolithic catalyst design, and methods for regulating the work function and optimizing the catalytic performance of catalysts are discussed. In addition, key strategies for tuning the work function-governed material-material IET in heterostructural catalyst design are examined. Finally, perspectives on work function determination, work function-based activity descriptors, and catalyst design are put forward to guide future research. This work paves the way to the work function-guided rational design of efficient electrocatalysts for sustainable energy applications.
RESUMEN
Cancer is one of the major noncommunicable diseases, responsible for millions of deaths every year worldwide. Though various cancer detection and treatment modalities are available today, many deaths occur owing to its late-stage detection and metastatic nature. Noninvasive detection using luminescence-based imaging tools is considered one of the promising techniques owing to its low cost, high sensitivity, and brightness. Moreover, these tools are unique and valuable as they can detect even the slightest changes in the cellular microenvironment. To achieve this, a fluorescent probe with strong tumor uptake and high spatial and temporal resolution, especially with high water solubility, is highly demanded. Recently, several water-soluble molecules with emission windows in the visible (400-700 nm), first near-infrared (NIR-I, 700-1000 nm), and second near-infrared (NIR-II, 1000-1700 nm) windows have been reported in literature. This review highlights recently reported water-soluble small organic fluorophores/dyes with applications in cancer diagnosis and therapeutics. We systematically highlight and describe the key concepts, structural classes of fluorophores, strategies for imparting water solubility, and applications in cancer therapy and diagnosis, i.e., theragnostics. We discuss examples of water-soluble fluorescent probes based on coumarin, xanthene, boron-dipyrromethene (BODIPY), and cyanine cores. Some other emerging classes of dyes based on carbocyclic and heterocyclic cores are also discussed. Besides, emerging molecular engineering methods to obtain such fluorophores are discussed. Finally, the opportunities and challenges in this research area are also delineated.
Asunto(s)
Colorantes Fluorescentes , Neoplasias , Solubilidad , Agua , Colorantes Fluorescentes/química , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/diagnóstico , Agua/química , Imagen ÓpticaRESUMEN
2D conjugated metal-organic frameworks (c-MOFs) have emerged as promising materials for (opto)electronic applications due to their excellent charge transport properties originating from the unique layered-stacked structures with extended in-plane conjugation. The further advancement of MOF-based (opto)electronics necessitates the development of novel 2D c-MOF thin films with high quality. Cu-HHHATN (HHHATN: hexahydroxyl-hexaazatrinaphthylene) is a recently reported 2D c-MOF featuring high in-plane conjugation, strong interlayer π-π stacking, and multiple coordination sites, while the production of its thin-film form has not yet been reported. Herein, large-area Cu-HHHATN thin films with preferential orientation, high uniformity, and smooth surfaces are realized by using a convenient layer-by-layer growth method. Flexible photodetectors are fabricated, showing broadband photoresponse ranging from UV to short-wave infrared (370 to 1450 nm). The relatively long relaxation time of photocurrent, which arises from the trapping of photocarriers, renders the device's synaptic plasticity similar to that of biological synapses, promising its use in neuromorphic visual systems. This work demonstrates the great potential of Cu-HHHATN thin films in flexible optoelectronic devices for various applications.
RESUMEN
OBJECTIVES: The study aimed to evaluate the frequency of incidental suspicious lesions detected by flourine-18 fluorodeoxyglucose PET/computed tomography ( 18 F-FDG PET/CT) scans done for staging or restaging in adult cancer patients. We further determined the detection rate of synchronous and metachronous malignancies in these suspicious lesions after further investigations. MATERIALS AND METHODS: This retrospective analysis evaluated the consecutive patients with 18 F-FDG PET/CT scans done in Queen Elizabeth Hospital (QEH), Hong Kong between July 2021 and June 2022. The adult cancer patients who underwent staging or restaging 8 F-FDG PET/CT were included while the remaining were excluded. Patients' demographics, primary cancer type, tumor markers, and pathological analyses for the incidental suspicious lesions were reviewed to establish the detection rate of synchronous and metachronous malignancies. RESULTS: A total of 2054 patients fulfilled inclusion criteria with age ranging from 18 to 93â years old. Out of the 2054 patients, 304 (14.8%) were found to have incidental suspicious lesions. Of these, 206 patients (67.8%) underwent further investigations including pathological analyses. Subsequently, 84 of these 206 patients (40.8%) had pathologically proven synchronous or metachronous malignancies. CONCLUSION: The detection rate of incidental suspicious lesions in adult cancer patients who underwent 18 F-FDG PET/CT scans for staging or restaging was 14.8% and the rate of synchronous and metachronous malignancies in these suspicious lesions was 40.8%. The treatment plan of these patients may potentially be altered, which should be included in the cost-benefit analysis of using this imaging modality.
Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias Primarias Secundarias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Masculino , Femenino , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Primarias Secundarias/diagnóstico por imagen , Adulto Joven , Adolescente , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias/diagnóstico por imagenRESUMEN
Background: Patients with hematological malignancy are at high risk of invasive fungal infections (IFIs). Diagnosis is challenging, which can lead to overtreatment. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety, but modifying prescribing behavior is difficult. We aimed to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary hemato-oncology center in the United Kingdom. Methods: We studied adults receiving treatment for acute leukemia at our center between 1 April 2019 and 14 October 2022. We developed a reproducible method to analyze routinely collected data on antifungal therapy episodes in a widely used electronic health record system. We report antifungal use in days of therapy stratified by level of diagnostic confidence, as defined by consensus diagnostic guidelines (European Organisation for Research and Treatment of Cancer/Mycoses Study Group). Results: Two hundred ninety-eight patients were included in the analysis; 21.7% of inpatient antifungal use occurred in cases of proven/probable IFI. Substantial antifungal use occurred in the absence of strong evidence of infection in patients receiving high-intensity first-line chemotherapy or approaching death (81.0% and 77.9%, respectively). Approximately 33% of high-resolution computed tomography (HRCT) reports were indeterminate for IFI. Indeterminate reports were around 8 times more likely to be followed by a new antifungal therapy episode than a negative report. Conclusions: Antifungal stewardship remains challenging in the absence of reliable diagnostics, particularly in more unwell patients. The proportion of antifungal therapy given for proven/probable infection is a new metric that will likely be useful to target antifungal stewardship programs. The thoracic HRCT report is an important contributor to diagnostic uncertainty.
RESUMEN
Biocompatible synthetic supramolecular systems have shed light on biomedical and tissue-regenerative material applications. The intrinsic functional applicability, tunability, and stimuli-responsiveness of synthetic supramolecular systems allow one to develop various multicontrolled supramolecular assemblies in aqueous media. However, it remains highly challenging to use state-of-the-art supramolecular assemblies of photoresponsive amphiphiles controlled by multiple stimulations in fabricating macroscopic materials. Herein, we demonstrate a stiff-stilbene amphiphile (SA) multicontrolled supramolecular assembling system that comprises two different charged end groups. The excellent photoswitchabilities of SA in both organic and aqueous media are demonstrated. Furthermore, multiple stimuli, i.e., light, pH, and counterions, are applied to control the supramolecular assembling behaviors, which are monitored by circular dichroism spectroscopy and electron microscopies. This multicontrolled supramolecular system can be systematically assembled into macroscopic soft functional scaffolds, whose structural parameters are investigated by electron microscopies and X-ray diffraction techniques, suggesting the large aspect ratio of SA nanostructures assembled into macroscopic soft scaffolds. The fabricated soft functional scaffold is highly biocompatible for photocontrolled biotarget encapsulation/release selectively, as well as a cell-material interface for diverse cells' attachment. This new synthetic multicontrolled soft functional material provides a new strategy toward the development of next-generation controllable and biocompatible soft functional materials.
RESUMEN
Delivering bioactive proteins into cells without carriers presents significant challenges in biomedical applications due to limited cell membrane permeability and the need for targeted delivery. Here, we introduce a novel carrier-free method that addresses these challenges by chemically modifying proteins with an acid-responsive cell-penetrating peptide (CPP) for selective intracellular delivery within tumours. Cytochrome C, a protein known for inducing apoptosis, served as a model for intracellular delivery of therapeutic proteins for cancer treatment. The CPP was protected with 2,3-dimethyl maleic anhydride (DMA) and chemically conjugated onto the protein surface, creating an acid-responsive protein delivery system. In the acidic tumour microenvironment, DMA deprotects and exposes the positively charged CPP, enabling membrane penetration. Both in vitro and in vivo assays validated the pH-dependent shielding mechanism, demonstrating the modified cytochrome C could induce apoptosis in cancer cells in a pH-selective manner. These findings provide a promising new approach for carrier-free and tumour-targeted intracellular delivery of therapeutic proteins for a wide range of potential applications.