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Background: miRNA‐based strategies have recently emerged as a promising therapeutic approach in several neurodegenerative diseases. Unregulated cation influx is implicated in several cellular mechanisms underlying neural cell death during ischemia. The brain constitutively active isoform of transient receptor potential melastatin 7 (TRPM7) represents a glutamate excitotoxicity‐independent pathway that significantly contributes to the pathological Ca2+ overload during ischemia. Aims: In the light of these premises, inhibition of TRPM7 may be a reasonable strategy to reduce ischemic injury. Since TRPM7 is a putative target of miRNA135a, the aim of the present paper was to evaluate the role played by miRNA135a in cerebral ischemia. Therefore, the specific objectives of the present paper were: (1) to evaluate miR135a expression in temporoparietal cortex of ischemic rats; (2) to investigate the effect of the intracerebroventricular (icv) infusion of miR135a on ischemic damage and neurological functions; and (3) to verify whether miR135a effects may be mediated by an alteration of TRPM7 expression. Methods: miR135a expression was evaluated by RT‐ PCR and FISH assay in temporoparietal cortex of ischemic rats. Ischemic volume and neurological functions were determined in rats subjected to transient middle cerebral artery occlusion (tMCAo) after miR135a intracerebroventricular perfusion. Target analysis was performed by Western blot. Results: Our results demonstrated that, in brain cortex, 72 h after ischemia, miR135a expression increased, while TRPM7 expression was parallelly downregulated. Interestingly, miR135a icv perfusion strongly ameliorated the ischemic damage and improved neurological functions, and downregulated TRPM7 protein levels. Conclusions: The early prevention of TRPM7 activation is protective during brain ischemia. [ABSTRACT FROM AUTHOR]

Trixacarus caviae is a sarcoptic mange mite infesting guinea pigs. Infestation in immunosuppressed animals produces severe dermatological problems, including alopecia, intense pruritus, hyperkeratosis and non‐dermatological issues (e.g., seizures). Treatment options are limited and include topical application of macrocyclic lactones or amitraz or injectable administration of ivermectin or doramectin. Considering the severity of the disease and the challenging treatment, the present paper aimed to determine the efficacy of oral afoxolaner in a severe case of infestation with T. caviae in a pet guinea pig. One female guinea pig was referred to the New Companion Animal Clinic due to severe dermatological problems. A clinical evaluation was done, and skin scrapings were collected and examined under the microscope. Small mites were detected and morphologically identified as T. caviae. The animal was treated with a single oral dose of 2.50 mg/kg afoxolaner, and the lesions, presence/absence of mites and intensity of pruritus were evaluated periodically until 2 months post‐treatment. A week after the medication, the lesions were milder, but pruritus was still present and was attributed to the healing process. Further examinations showed significant improvement with the complete remission of clinical signs and no mites at the microscopic examination after 4 weeks. Afoxolaner was safe and effective in this guinea pig for the treatment of T. caviae mange with no repetition needed. [ABSTRACT FROM AUTHOR]

Background: Competent clinical reasoning forms the foundation for effective and efficient clinical swallowing examination (CSE) and consequent dysphagia management decisions. While the nature of initial CSEs has been evaluated, it remains unclear how new information gathered by speech–language therapists (SLTs) throughout a patient's acute‐care journey is integrated into their initial clinical reasoning and management processes and used to review and revise initial management recommendations. Aims: To understand how SLTs' clinical reasoning and decision‐making regarding dysphagia assessment and management evolve as patients transition through acute hospital care from referral to discharge. Methods & Procedures: A longitudinal, qualitative approach was employed to gather information from two SLTs who managed six patients at a metropolitan acute‐care hospital. A retrospective 'think‐aloud' protocol was utilized to prompt SLTs regarding their clinical reasoning and decision‐making processes during initial and subsequent CSEs and patient interactions. Three types of concept maps were created based on these interviews: a descriptive concept map, a reasoning map and a hypothesis map. All concept maps were evaluated regarding their overall structure, facts gathered, types of reasoning engaged in (inductive versus deductive), types of hypotheses generated, and the diagnosis and management recommendations made following initial CSE and during subsequent dysphagia management. Outcomes & Results: Initial CSEs involved a rich process of fact‐gathering, that was predominantly led by inductive reasoning (hypothesis generation) and some application of deductive reasoning (hypothesis testing), with the primary aims of determining the presence of dysphagia and identifying the safest diet and fluid recommendations. During follow‐up assessments, SLTs engaged in increasingly more deductive testing of initial hypotheses, including fact‐gathering aimed at determining the tolerance of current diet and fluid recommendations or the suitability for diet and/or fluid upgrade and less inductive reasoning. Consistent with this aim, SLTs' hypotheses were focused primarily on airway protection and medical status during the follow‐up phase. Overall, both initial and follow‐up swallowing assessments were targeted primarily at identifying suitable management recommendations, and less so on identifying and formulating diagnoses. None of the patients presented with adverse respiratory and/or swallowing outcomes during admission and following discharge from speech pathology. Conclusions & Implications: Swallowing assessment and management across the acute‐care journey was observed as a high‐quality, patient‐centred process characterized by iterative cycles of inductive and deductive reasoning. This approach appears to maximize efficiency without compromising the quality of care. The outcomes of this research encourage further investigation and translation to tertiary and post‐professional education contexts as a clear understanding of the processes involved in reaching diagnoses and management recommendations can inform career‐long refinement of clinical skills. WHAT THIS PAPER ADDS: What is already known on the subject: SLTs' clinical reasoning processes during initial CSE employ iterative cycles of inductive and deductive reasoning, reflecting a patient‐centred assessment process. To date it is unknown how SLTs engage in clinical reasoning during follow‐up assessments of swallowing function, how they assess the appropriateness of initial management recommendations and how this relates to patient outcomes. What this paper adds to the existing knowledge: Our longitudinal evaluation of clinical reasoning and decision‐making patterns related to swallowing management in acute care demonstrated that SLTs tailored their processes to each patient's presentation. There was an emphasis on monitoring the suitability of the initial management recommendations and the potential for upgrade of diet or compensatory swallowing strategies. The iterative cycles of inductive and deductive reasoning reflect efficient decision‐making processes that maintain high‐quality clinical care within the acute environment. What are the potential or actual clinical implications of this work?: Employing efficient and high‐quality clinical reasoning is a hallmark of good dysphagia practice in maximizing positive patient outcomes. Developing approaches to understanding and making explicit clinical reasoning processes of experienced clinicians may assist SLTs of all developmental stages to provide high standards of care. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready‐to‐use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight‐for‐height z‐score ≥ −3 or mid‐upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight‐based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per‐protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (−0.9; 7.2) %] and length‐of‐stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of −10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = −1.5 (−1.8, −1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight‐based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource‐constrained contexts. Key messages: More evidence supporting the use of the nonweight‐based daily ready‐to‐use therapeutic food (RUTF) dosage for treating uncomplicated severe acute malnutrition (SAM), in specific contexts, is needed.Our real‐world prospective nonrandomized study showed that the fixed nonweight‐based daily RUTF dosage protocol is as effective as the standard weight‐based protocol for treating uncomplicated SAM in children <5 in the Afghanistan context.Our findings support the reflection of a nonweight‐based daily RUTF dosage in resource‐constrained contexts in national and global policies and guidelines to improve coverage of all children in need of treatment. [ABSTRACT FROM AUTHOR]

Since its publication in 2014, L. A. Paul's book Transformative Experience has sparked many discussions in philosophy and beyond. Her main argument is that experiences we have not had before can transform us epistemically (i.e., we learn something we could not learn without the experience) and personally (i.e., our point of view changes radically). This has implications for decision theory in particular, but also for other fields. The present paper provides an overview of how transformative experiences are thought to challenge rational choice and how authors have responded to this challenge (with a focus on the epistemic transformation). Furthermore, it also shows how the concept of transformative experience has been fruitful beyond the decision‐theoretical context, with a particular focus on illness, medical treatment, and the ethical issues involved. Finally, the paper presents open questions in the literature on transformative experiences. [ABSTRACT FROM AUTHOR]

Background: Stroke profoundly affects quality of life (QOL), including loss of employment, reduced social activity, shrinking social networks and low mood. Dysgraphia (impaired writing) is a common symptom of aphasia yet is rarely targeted in rehabilitation. Recent technological advances might challenge this, since much communication is now conducted digitally through writing. The rehabilitation of writing may therefore help to address the wider consequences of stroke and aphasia. Aims: Can assistive technology (AT) training for people with dysgraphia: (1) improve written output, and are gains achieved only with AT? (2) improve reading comprehension scores, and are gains achieved only with AT? and (3) affect social participation, mood or QOL Methods and Procedures: Design A mixed‐methods, repeated measures, small group study design was adopted (qualitative outcomes will be reported elsewhere). Participants: Recruited from community settings, for example, Stroke Association communication support groups. Inclusion criteria: over 18 years old, aphasia due to stroke, acquired dysgraphia, writing more impaired than speech, fluent English prior to stroke, access to computer and Internet. Exclusion criteria: currently receiving speech and language therapy, significant cognitive impairment, neuromuscular/motor‐speech impairments/structural abnormalities, developmental dyslexia, uncorrected visual/auditory impairments. Procedures: Screening and diagnostic assessments at time T1 (first baseline). Outcome measures at T1; repeated at T2 (second baseline), T3 (end of intervention), T4 (3‐month follow up). Social participation assessment and cognitive monitoring at T2, T3, T4. Intervention: Seven–ten hours individual therapy weekly and additional email support. Participants were trained to operate Dragon NaturallySpeaking (speech to text package) and ClaroRead (read writing aloud). Outcome measures were administered on pen and paper (control) and on computer, with AT enabled only at T3, T4. Outcomes and Results: Computer narrative writing was significantly improved by AT training (Friedman's χ2 (3) = 8.27, p = 0.041), indicating a compensatory effect of AT. Though reading comprehension significantly improved in the computer condition (Friedman's χ2 (3) = 21.07, p = 0.001), gains could not be attributed to the AT. Gains were achieved only when measures were administered on the keyboard, with AT enabled. Thus, a compensatory rather than remediatory effect was suggested. Social network size significantly increased; there were no significant changes in mood/QOL. Individual success rates varied. Conclusion and Implications: The customisable AT training was acceptable to participants and resulted in significantly improved narrative writing. Compensatory AT interventions are a useful adjunct to remediatory writing interventions and may particularly support functional writing. WHAT THIS PAPER ADDS: What is already known on this subject: Writing is rarely spared in aphasia and may present as the most impaired communication modality. Yet, people with aphasia report that writing is seldom included in their rehabilitation. Many communication activities are now conducted digitally through writing, therefore rehabilitation of this is more important than ever before. This study sought to address whether an assistive technology (AT) software package can improve writing and whether any changes were compensatory or remediatory. What this study adds to existing knowledge: This group study found that AT training led to gains in written discourse and social network in people with aphasia and dysgraphia. Gains were not replicated in handwritten tasks, suggesting this was a compensatory therapeutic approach. What are the clinical implications of this work?: AT programs such as this may present speech and language therapists with a practical, pragmatic adjunct to writing or typing therapy, particularly for clients with chronic, intractable impairments for whom remediatory therapy may have a low chance of success. [ABSTRACT FROM AUTHOR]

Background and Aim: The traditional drug delivery approach involves systemic administration of a drug that could be nonspecific in targeting, low on efficacy, and with severe side‐effects. To address such challenges, the field of smart drug delivery has emerged aiming at designing and developing delivery systems that can target specific cells, tissues, and organs and have minimal off‐target side‐effects. Methods: A literature search was done to collate papers and reports about the currently available various strategies for smart nano‐inspired drug delivery. The databases searched were PubMed, Scopus, and Google Scholar. Based on selection criteria, the most pertinent and recent items were included. Results: Smart drug delivery is a cutting‐edge revolutionary intervention in modern medicines to ensure effective and safe administration of therapeutics to target sites. These hold great promise for targeted and controlled delivery of therapeutic agents to improve the efficacy with reduced side‐effects as compared to the conventional drug delivery approaches. Current smart drug delivery approaches include nanoparticles, liposomes, micelles, and hydrogels, each with its own advantages and limitations. The success of these delivery systems lies in engineering and designing them, and optimizing their pharmacokinetics and pharmacodynamics properties. Conclusion: Development of drug delivery systems that can get beyond various physiological and clinical barriers, as observed in conventionally administered chemotherapeutics, has been possible through recent advancements. Using multifunctional targeting methodologies, smart drug delivery tries to localize therapy to the target location, reduces cytotoxicity, and improves the therapeutic index. Rapid advancements in research and development in smart drug delivery provide wider and more promising avenues to guarantee a better healthcare system, improve patient outcomes, and achieve higher levels of effective medical interventions like personalized medicine. [ABSTRACT FROM AUTHOR]

This document provides abstracts of papers presented at the 2024 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics. The papers cover a wide range of topics related to clinical pharmacology and therapeutics, including the use of machine learning in predicting adverse events, the integration of brain- and blood-derived markers in antidepressant pharmacotherapy, and the use of NLP-powered topic modeling in drug repurposing. Other studies focused on the pharmacokinetics and safety of different drugs, the development of population pharmacokinetic models, and potential drug-drug interactions involving cannabidiol. These studies offer valuable insights into drug behavior and can help guide personalized treatment strategies in different populations. The document also discusses the use of computational tools and machine learning techniques to improve drug pharmacokinetics and clinical trial design. Overall, these studies contribute to our understanding of how drugs interact with the body and can inform more effective and personalized treatment approaches. [Extracted from the article]

The aptness of machine learning (ML) to learn from large datasets, discover trends, and make predictions has demonstrated its potential to metamorphose the medical field. Medical data analysis with ML algorithms can improve patient outcomes in terms of both treatment and diagnosis. This paper investigates the numerous possibilities of ML in the medical industries, including radiology, pathology, genomics, and clinical decision‐making. It also goes over the benefits and drawbacks of ML in various sectors as well as the limitations that come with its application. It illustrates the potential advantages of ML, such as better accuracy and efficiency in diagnosis and individualized treatment programs, through a review of previous studies. Lastly, it provides perspectives on prospective advancements and prospects for the discipline. This study also intends to investigate the applications of deep learning (DL) in the medical field. DL algorithms have performed exceptionally satisfactorily in several healthcare‐related fields. The main conclusions of the study are summarized, and their ramifications for the healthcare sector are discussed in this paper's conclusion. This paper intends to contribute to a greater understanding of the prevailing state of the discipline and the possibility for future developments by emphasizing the prospects of these methodologies to alter medical study and clinical practice. [ABSTRACT FROM AUTHOR]

This paper examines cyberbullying concerning therapeutic interventions. A section on bullying and how bullying impacts the therapeutic environment is included. The author provides his definition of bullying to incorporate cyberbullying and how it is no longer a "new issue" but an evolving one. The current status of therapeutic interventions used to support victims of cyberbullying has been explored, emphasising their effectiveness in assisting those experiencing bullying. A segment has been implemented to comprehend whether practitioners fully understand the potential implications of cyberbullying on clients, whether bullying is still seen as a "rite of passage" and what the possible consequences of this could be. Peer interventions and support groups concerning cyberbullying have been referenced, including The KiVa Programme, the Shared Concern Method and The Circle of Friends Method. These have highlighted specific examples of therapeutic and nontherapeutic approaches to intervene with cyberbullying. A section on potential further training is presented for practitioners working within educational environments. Moreover, physical, psychological, sexual and relational bullying are discussed in the article when applicable, with the umbrella term "bullying" used to discuss all forms of bullying at once. The paper has uncovered two key messages: (1) cyberbullying requires more awareness in counselling and is no longer a new issue and (2) more extensive training is required to assist therapists to work with cyberbullying victims. [ABSTRACT FROM AUTHOR]

Background: Research is beginning to shed light on the practices employed by speech‐language therapists (SLTs) for the management of acquired dysarthria. However, studies that explore SLTs' satisfaction with the effectiveness of current therapies and their interest in new treatment methods for this population have not been carried out. One potential new method is neuromuscular electrical stimulation (NMES): the pool of evidence for its use in rehabilitation is increasing, yet it has not been widely explored for use with dysarthria. Aim: To extend the understanding of acquired dysarthria management practices employed by SLTs across the globe and determine their satisfaction with current therapy options. To explore their interest in using NMES with this population. Methods and Procedures: A cross‐sectional international online survey was developed and disseminated to SLTs working with adults with acquired dysarthria through international professional associations. The survey collected information on demographic characteristics, dysarthria management practices, satisfaction with treatment effectiveness and interest in and knowledge of NMES. Survey responses were analysed using descriptive and inferential statistics, and quantitative content analysis. Outcomes and Results: A total of 211 SLTs (North America, 48.8%; Europe, 36%; Asia, 8.1%; Oceania, 5.7%; Africa, 0.9%; South America, 0.5%) completed the survey in full. Management practices varied considerably. There was a clear preference for informal assessments, mainly oral‐motor examinations, focusing on body functions and structures. The majority of respondents rejected the use of non‐speech oral motor exercises as a clinical or carryover exercise. Variable satisfaction with current speech subsystem treatments was noted; however, overall, there was a general dissatisfaction. Whilst a strong interest in the use of NMES for dysarthria was evidenced, it was noted that most SLTs lacked fundamental knowledge of NMES principles and application. Conclusion: SLTs' management practices and satisfaction with acquired dysarthria treatments differed substantially. Investigations of the potential use of NMES for dysarthria treatment are of interest. WHAT THIS PAPER ADDS: What is already known on the subject: Recent country‐specific surveys have explored speech‐language therapists' (SLTs') assessment and intervention practices for acquired dysarthria. These studies indicate that although clinical management for this speech disorder mainly involves informal assessment tools and impairment‐focused treatment, communication beyond the impairment, such as the activity and participation domains, is also frequently assessed and treated. What this paper adds to existing knowledge: The majority of SLTs are dissatisfied with the overall benefits of current acquired dysarthria treatment. Phonatory, respiration and speech rate therapies are perceived to be more effective than prosody, articulation and resonance treatments. Despite a general lack of theoretical knowledge, most SLTs are interested in neuromuscular electrical stimulation treatment for acquired dysarthria. What are the potential or actual clinical implications of this work?: New, evidence‐based treatments are needed for SLTs to be confident in the effectiveness of their acquired dysarthria treatment. [ABSTRACT FROM AUTHOR]

Many believe that we ought to treat people as individuals and that this form of treatment is in some sense incompatible with treating people as members of groups. Yet, the relation between these two kinds of treatments is elusive. In this paper, we develop a novel account of the normative requirement to treat people as individuals. According to this account, treating people as individuals requires treating people as agents in the appropriate capacity. We call this the Agency Attunement Account. This view has the surprising implication that it's not only possible to fail in treating people as individuals but also possible to fail in treating people as members of groups, on the presumption that people's agency is sometimes nested in, and exercised via, agential groups. [ABSTRACT FROM AUTHOR]

Interleukin‐41 (IL‐41) is a newly discovered cytokine, named Cometin, Subfatin, meteorin‐like transcription (Metrnl), and so forth. It is widely expressed in animals and can exert its biological roles through autocrine and paracrine forms. It has functions such as anti‐inflammatory, improving body metabolism, regulating immunity, regulating fat metabolism and participates in the process of autoimmune disease or inflammatory injury. It plays an important role in psoriasis, diabetes, Crohn's disease (CD), osteoarthritis, Kawasaki disease (KD), Graves' disease, autoimmune hepatitis, infertility, obesity, sepsis, cardiovascular diseases and respiratory diseases. This paper reviews the biological functions of IL‐41, the relationship between IL‐41 and diseases, the effects of IL‐41 in the cytokine network and the possible signalling pathways. In order to explore the same target or the same drug for the treatment of different diseases from the perspective of homotherapy for heteropathy, cytokine strategies based on IL‐41 have been put forward for the precise treatment of immune diseases and inflammatory diseases. It is worth noting that IL‐41 related preparations for lung protection and smoking cessation are interesting research fields. [ABSTRACT FROM AUTHOR]

In cancer and other medical studies, time‐to‐event (eg, death) data are common. One major task to analyze time‐to‐event (or survival) data is usually to compare two medical interventions (eg, a treatment and a control) regarding their effect on patients' hazard to have the event in concern. In such cases, we need to compare two hazard curves of the two related patient groups. In practice, a medical treatment often has a time‐lag effect, that is, the treatment effect can only be observed after a time period since the treatment is applied. In such cases, the two hazard curves would be similar in an initial time period, and the traditional testing procedures, such as the log‐rank test, would be ineffective in detecting the treatment effect because the similarity between the two hazard curves in the initial time period would attenuate the difference between the two hazard curves that is reflected in the related testing statistics. In this paper, we suggest a new method for comparing two hazard curves when there is a potential treatment time‐lag effect based on a weighted log‐rank test with a flexible weighting scheme. The new method is shown to be more effective than some representative existing methods in various cases when a treatment time‐lag effect is present. [ABSTRACT FROM AUTHOR]

Summary: Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. Its prevalence is increasing with the epidemic of obesity and metabolic syndrome. MASLD progression into metabolic dysfunction‐associated steatohepatitis (MASH) and advanced fibrosis may lead to decompensated cirrhosis and development of liver‐related events, hepatocellular carcinoma and death. Monitoring disease progression is critical in decreasing morbidity, mortality, need for transplant and economic burden. Assessing for treatment response once FDA‐approved medications are available is still an unmet clinical need. Aims: To explore the most up‐to‐date literature on testing used for monitoring disease progression and treatment response Methods: We searched PubMed from inception to 15 August 2023, using the following MeSH terms: 'MASLD', 'Metabolic dysfunction‐associated steatotic liver disease', 'MASH', 'metabolic dysfunction‐associated steatohepatitis', 'Non‐Alcoholic Fatty Liver Disease', 'NAFLD', 'non‐alcoholic steatohepatitis', 'NASH', 'Biomarkers', 'clinical trial'. Articles were also identified through searches of the authors' files. The final reference list was generated based on originality and relevance to this review's broad scope, considering only papers published in English. Results: We have cited 101 references in this review detailing methods to monitor MASLD disease progression and treatment response. Conclusion: Various biomarkers can be used in different care settings to monitor disease progression. Further research is needed to validate noninvasive tests more effectively. [ABSTRACT FROM AUTHOR]

Background: Person‐centred services are inherently related to patients/caregivers' needs. However, the extent to which dysphagia services within Singapore meet consumer needs is largely unknown. Involving patients/caregivers in service evaluation/redesign deepens the understanding of consumer needs. This process also increases the success of implementing service enhancements through relevant and meaningful change. Aim: This study aimed to identify aspects of dysphagia services, within acute and subacute settings in Singapore, perceived as highly important and easy to change by patients/caregivers. Methods & Procedures: Using concept mapping methodology, 5 patients and 11 caregivers reflected on their experiences of receiving dysphagia care and proposed 59 unique suggestions to improve dysphagia services within Singapore. Then, each individual sorted the suggestions into groups based on similarity and rated each statement for its perceived importance and changeability for service enhancement. Data were analysed using multidimensional scaling, hierarchical cluster analysis, and bivariate analysis to generate clusters of conceptually similar suggestions and a prioritised list of suggestions for service enhancement. Results: Twelve clusters were identified, with most rated as more important than changeable for service improvement. Participants prioritised 23 (39%) of the suggestions as highly important and easy to change, and these focused on ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. Conclusion: These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients/caregivers. WHAT THIS PAPER ADDS: What is already known on this subject: Little is known about patients and caregivers' experiences and expectations of receiving dysphagia services in Singapore. Consulting them in service review and improvement deepens understanding of their needs and increases the success of implementing meaningful service enhancements. What this study adds to existing knowledge: This study shows that patients and caregivers in Singapore identified a wide range of dysphagia service issues and prioritised a list of suggestions for service improvement. They prioritised four key areas for service optimisation: ensuring effective communication among consumers and healthcare team, enhancing patients and carers' access to support at home, increasing patients and carers' access to educational resources, and improving service quality and access through technology. What are the clinical implications of this work?: This research highlights the importance of considering the consumers' perspectives in service review and redesign. Patients and caregivers in Singapore identified four prioritised areas for service enhancements. These findings provide future directions on how to develop and implement dysphagia services in Singapore to better meet the needs of patients and caregivers. [ABSTRACT FROM AUTHOR]

Objectives: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. Methods: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. Results: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second‐line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow‐up time (P = 0.19) or in the recurrence rate (P = 0.45). Conclusion: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second‐line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported. [ABSTRACT FROM AUTHOR]

Purpose: Management of children following a drowning incident is based on specific interventions which are used in the prehospital environment, the emergency department (ED) and the Paediatric Intensive Care Unit (PICU). This paper presents a review of the literature to map and describe the management and interventions used by healthcare professionals when managing a child following a drowning incident. Of specific interest was to map, synthesise and describe the management and interventions according to the different clinical domains or practice areas of healthcare professionals. Design and Methods: A traditional review of the literature was performed to appraise, map and describe information from 32 relevant articles. Four electronic databases were searched using search strings and the Boolean operators AND as well as OR. The included articles were all published in English between 2010 and 2022, as it comprised a timeline including current guidelines and practices necessary to describe management and interventions. Results: Concepts and phrases from the literature were used as headings to form a picture or overview of the interventions used for managing a child following a drowning incident. Information extracted from the literature was mapped under management and interventions for prehospital, the ED and the PICU and a figure was constructed to display the findings. It was evident from the literature that management and interventions are well researched, evidence‐informed and discussed, but no clear arguments or examples could be found to link the interventions for integrated management from the scene of drowning through to the PICU. Cooling and/or rewarming techniques and approaches and termination of resuscitation were found to be discussed as interventions, but no evidence of integration from prehospital to the ED and beyond was found. The review also highlighted the absence of parental involvement in the management of children following a drowning incident. Practice Implications: Mapping the literature enables visualisation of management and interventions used for children following a drowning incident. Integration of these interventions can collaboratively be done by involving the healthcare practitioners to form a link or chain for integrated management from the scene of drowning through to the PICU. [ABSTRACT FROM AUTHOR]

Dermatological research and education have predominantly focused on lighter skin types in the past, leading to a significant gap in knowledge and understanding of conditions in darker skin types. This has contributed to disparities in the diagnosis and treatment of diseases in patients with skin of color. In the current issue of the Journal, we highlight four papers on the epidemiology and clinics of skin of color patients but also emphasize the importance of education and research in the dermatopathology of SOC patients. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitor (TKI)‐targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistance, including on‐target mechanisms and off‐target mechanisms, as well as changes in the tumor histology and tumor microenvironment (intrinsic mechanisms). Additionally, we summarized current therapeutic approaches aiming at circumventing TKI resistance, including the development of next‐generation TKIs and combination therapies. We also discussed emerging strategies such as the use of dual‐targeted antibodies and PROteolysis Targeting Chimeras. Furthermore, we explored future directions in TKI‐targeted therapy, including the methods for detecting and monitoring drug resistance during treatment, identification of novel targets, exploration of dual‐acting kinase inhibitors, application of nanotechnologies in targeted therapy, and so on. Overall, this review provides a comprehensive overview of the challenges and opportunities in TKI‐targeted therapy, aiming to advance our understanding of resistance mechanisms and guide the development of more effective therapeutic approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

Background & Aim: Rosacea is a chronic inflammatory, multifactorial disease for which combination therapy could be an effective treatment. In this study, we evaluate the effect of the combination therapy of brimonidine 0.33% and ivermectin 1% as a single cream for the treatment of papulopustular rosacea. Method: A stable and appropriate formulation was prepared by adding the aqueous phase to the lipid phase while being stirred. The stability and physicochemical properties of the formulation were evaluated under accelerated conditions. Twelve patients (36–60 years) with mild to moderate papulopustular rosacea and a Demodex count of five or more were treated with the combination of brimonidine 0.33% and ivermectin 1% cream. Clinician's Erythema Assessment (CEA), Patients Self‐Assessment (PSA), skin erythema (ΔE) and lightness (ΔL), and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, pH, and sebum content, as well as erythema and melanin index and ultrasound parameters, were measured before treatment and 4 and 8 weeks after. Adverse drug reactions were also recorded. Results: CEA and PSA decreased significantly from 3 to 2 after 8 weeks, respectively (p‐value = 0.014 for CEA and 0.010 for PSA). ΔE and ΔL, as well as skin erythema index and TEWL improved after 8 weeks of treatment (p < 0.05). Two patients withdrew from the study in the first week because of local adverse effects; one developed flushing following treatment and left the investigation after 4 weeks and another patient withdrew from the study after 4 weeks due to deciding to become pregnant. Conclusion: Eight‐week treatment with the combination of brimonidine 0.33% and ivermectin 1% was shown to be effective for improvement of erythema and inflammatory lesions in mild to moderate papulopustular rosacea. [ABSTRACT FROM AUTHOR]

Nano‐delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral‐mimicking ternary polyplexes system for the controlled delivery of the anti‐inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44‐mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral‐mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral‐mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases. [ABSTRACT FROM AUTHOR]

As a highly organized system, endo‐lysosomes play a crucial role in maintaining immune homeostasis. However, the mechanisms involved in regulating endo‐lysosome progression and subsequent inflammatory responses are not fully understood. By screening 103 E3 ubiquitin ligases in regulating endo‐lysosomal acidification, it is discovered that lysosomal RNF13 inhibits lysosome maturation and promotes inflammatory responses mediated by endosomal Toll‐like receptors (TLRs) in macrophages. Mechanistically, RNF13 mediates K48‐linked polyubiquitination of LAMP‐1 at residue K128 for proteasomal degradation. Upon TLRs activation, LAMP‐1 promotes lysosomes maturation, which accelerates lysosomal degradation of TLRs and reduces TLR signaling in macrophages. Furthermore, peripheral blood mononuclear cells (PBMCs) from patients with rheumatoid arthritis (RA) show increased RNF13 levels and decreased LAMP‐1 expression. Accordingly, the immunosuppressive agent hydroxychloroquine (HCQ) can increase the polyubiquitination of RNF13. Taken together, the study establishes a linkage between proteasomal and lysosomal degradation mechanisms for the induction of appropriate innate immune response, and offers a promising approach for the treatment of inflammatory diseases by targeting intracellular TLRs. [ABSTRACT FROM AUTHOR]

Radiotheranostics is a rapidly growing approach in personalized medicine, merging diagnostic imaging and targeted radiotherapy to allow for the precise detection and treatment of diseases, notably cancer. Radiolabeled antibodies have become indispensable tools in the field of cancer theranostics due to their high specificity and affinity for cancer‐associated antigens, which allows for accurate targeting with minimal impact on surrounding healthy tissues, enhancing therapeutic efficacy while reducing side effects, immune‐modulating ability, and versatility and flexibility in engineering and conjugation. However, there are inherent limitations in using antibodies as a platform for radiopharmaceuticals due to their natural activities within the immune system, large size preventing effective tumor penetration, and relatively long half‐life with concerns for prolonged radioactivity exposure. Antibody engineering can solve these challenges while preserving the many advantages of the immunoglobulin framework. In this review, the goal is to give a general overview of antibody engineering and design for tumor radiotheranostics. Particularly, the four ways that antibody engineering is applied to enhance radioimmunoconjugates: pharmacokinetics optimization, site‐specific bioconjugation, modulation of Fc interactions, and bispecific construct creation are discussed. The radionuclide choices for designed antibody radionuclide conjugates and conjugation techniques and future directions for antibody radionuclide conjugate innovation and advancement are also discussed. [ABSTRACT FROM AUTHOR]

Background: Severe bacterial infections can trigger acute lung injury (ALI) and acute respiratory distress syndrome, with bacterial pathogen‐associated molecular patterns (PAMPs) exacerbating the inflammatory response, particularly in COVID‐19 patients. Cyclic‐di‐GMP (CDG), one of the PAMPs, is synthesized by various Gram‐positve and Gram‐negative bacteria. Previous studies mainly focused on the inflammatory responses triggered by intracellular bacteria‐released CDG. However, how extracellular CDG, which is released by bacterial autolysis or rupture, activates the inflammatory response remains unclear. Methods: The interaction between extracellular CDG and myeloid differentiation protein 2 (MD2) was investigated using in vivo and in vitro models. MD2 blockade was achieved using specific inhibitor and genetic knockout mice. Site‐directed mutagenesis, co‐immunoprecipitation, SPR and Bis‐ANS displacement assays were used to identify the potential binding sites of MD2 on CDG. Results: Our data show that extracellular CDG directly interacts with MD2, leading to activation of the TLR4 signalling pathway and lung injury. Specific inhibitors or genetic knockout of MD2 in mice significantly alleviated CDG‐induced lung injury. Moreover, isoleucine residues at positions 80 and 94, along with phenylalanine at position 121, are essential for the binding of MD2 to CDG. Conclusion: These results reveal that extracellular CDG induces lung injury through direct interaction with MD2 and activation of the TLR4 signalling pathway, providing valuable insights into bacteria‐induced ALI mechanisms and new therapeutic approaches for the treatment of bacterial co‐infection in COVID‐19 patients. [ABSTRACT FROM AUTHOR]

Maturation of the secondary antibody repertoire requires class‐switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high‐affinity antibodies. Following immune response or infection within the body, activation of T cell‐dependent and T cell‐independent antigens triggers the activation of activation‐induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper‐IgM syndrome, Waldenström macroglobulinemia, hyper‐IgD syndrome, selective IgA deficiency, hyper‐IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to investigate the impact of treatment on the quality of life of patients with chronic oral mucosal diseases. Specifically, the study aimed to determine how treatment affects the changes in the quality of life of these patients. Methods: This descriptive study involved 220 patients diagnosed with chronic oral mucosal lesions. Data were collected using the Chronic Oral Mucosal Disease Questionnaire, validated for use in Persian/Farsi. The study population was selected through convenience sampling. Data analysis employed descriptive statistical methods, including frequency and percentage distribution tables, graphs, measures of central tendency, and dispersion. Additionally, confidence intervals were utilized for the studied ratios and indices. Results: Among the study population, 129 (58.6%) were male and 91 (41.4%) were female. The mean quality of life, as assessed by the utilized questionnaire, was 61.9 ± 13.2. The results indicated that females and unemployed individuals reported lower quality of life compared to males and employed individuals, respectively, with a statistically significant difference (p < 0.05). Conclusion: In the population studied the quality of life of patients with chronic mucous membrane diseases was influenced by various factors, including gender, income, employment, and place of residence. [ABSTRACT FROM AUTHOR]

Background: CBT is an effective treatment for depression, but access varies across the United Kingdom. Online CBT increases access. The INTERACT platform was designed to support patient engagement in CBT, enabling therapists to deliver high‐intensity CBT via typed instant messaging and allowing patients and therapists access to an integrated online library of resources during and between sessions. Methods: The INTERACT trial aimed to evaluate this integrated approach to delivering CBT for primary care patients with depression. A nested qualitative study was conducted within the trial. Interviews were conducted with 20 patients who received the intervention, 9 therapists who delivered it and 3 therapist supervisors. Data were analysed using thematic analysis. Results: The combination of receiving support from a therapist and having access to integrated online CBT resources enabled patients to better manage their depression. Platform benefits included the opportunity to review transcripts to clarify how to complete homework tasks and track progress in managing their depression. The typing process allowed reflection and a focused discussion. However, less could be covered than during an in‐person session, which reduced therapists' expectations around goal setting. Patients who did not complete therapy struggled with the typing and found the CBT approach too demanding. Conclusion: Findings highlight the importance of establishing patient and therapist goals and expectations about what can be achieved in CBT mediated by typing. Some patients are comfortable communicating via typing and are motivated to utilise online resources in between sessions. Exploring the benefits and challenges of typed CBT with patients will enable them to make an informed choice about referral for this novel approach to therapy. Patient or Public Contribution: Patients, service users and members of the public were involved in the study design and management. Substantial pilot work gathered stakeholder feedback and informed the design of the intervention, before undertaking the RCT. Coauthor P.L. is a service user representative co‐applicant and member of the management group responsible for developing the intervention and the trial. Two PPI members sit on the Independent Steering Committee. PPI members provided valuable feedback on the study resources and documents. [ABSTRACT FROM AUTHOR]

Objective: To review the existing literature on the application of computational fluid dynamics methods to study nasal particle deposition and to summarize and analyze the factors affecting nasal particle deposition in order to provide theoretical references for the development of future transnasal drug delivery devices and the prevention of respiratory‐related diseases. Data Source: PubMed and CNKI databases. Methods: A search of all current literature (up to and including February 2023) was conducted. Search terms related to the topic of factors influencing nasal particle deposition were identified, and queries were conducted to identify relevant articles. Results: Both the properties of the particles themselves and the environmental conditions external to the particles can affect particle deposition in the nasal cavity, with particle deposition showing a positive correlation with particle size, particle density, and airflow velocity, with increasing subject age leading to a decrease in deposition, and with the relationship between airflow temperature and humidity still requiring more research to further explore. Conclusions: With the popularity of computational fluid dynamics, more and more scholars have applied computational fluid dynamics technology to explore the influence of different parameters on particle deposition. By summarizing and analyzing the influence law of various factors on deposition, it can provide a theoretical basis for the future development and application of transnasal drug delivery devices and the prevention of respiratory‐related diseases, which makes a significant contribution to the optimization of clinical disease prevention and treatment. Level of Evidence: NA. [ABSTRACT FROM AUTHOR]

Objective: Closure surgery of patent foramen ovale (PFO) has been found to effectively control cryptogenic stroke and migraine, but it is uncertain whether PFO closure could also alleviate epileptic seizures. This study aims to observe the therapeutic effect of PFO closure on epileptic seizures. Methods: Since July 11th, 2017, in the neurology department of West China Hospital, Sichuan University, Chengdu, we have been regularly monitoring patients with epilepsy who have undergone PFO closure. The patient's clinical information, such as frequency, duration, and severity of seizures, before and after surgery was recorded in detail as well as postoperative safety events. Results: Of the 31 epilepsy patients who confirmed PFO observed (27 cases were drug‐resistant epilepsy, 87.10%), average age of surgery was 23.74 years, and 12 cases were female (38.71%). After one‐year follow‐up, 26 patients (83.87%) achieved remission of seizure frequency, and 22 of whom (70.97%) experienced a remission of more than 50%. Additionally, compared to before surgery, 22 cases (70.97%) reported a decrease in the average seizure duration, and 20 cases (64.52%) reported a reduction in seizure severity. In the seizure indicators of frequency, average duration and severity, significant differences were identified between preoperative and postoperative comparisons with all test p values were <0.05. Furthermore, no serious safety events were reported except for one patient who briefly reported chest pain, and all patients expressed effective PFO closure. Significance: The PFO closure has been shown for the first time to result in a significant reduction in the frequency, duration, and severity of seizures. Patients with drug‐resistant epilepsy and PFO with a large shunt are ideal candidates for undergoing PFO closure. Plain Language Summary: Since PFO closure was found to have a good therapeutic effect on cryptogenic stroke and migraine, it has become a credible complementary therapy for the treatment of neurological diseases, and drug‐resistant epilepsy with PFO is expected to become the next target disease that PFO closure could significantly improve. [ABSTRACT FROM AUTHOR]

Background: Postherpetic neuralgia (PHN) is a classic chronic condition with multiple signs of peripheral and central neuropathy. Unfortunately, the pathogenesis of PHN is not well defined, limiting clinical treatment and disease management. Objective: To describe the peripheral and central pathological axes of PHN, including peripheral nerve injury, inflammation induction, central nervous system sensitization, and brain functional and structural network activity. Methods: A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the pathogenesis of PHN, including peripheral and central pathological axes. Results: Currently, due to the complexity of the pathophysiological mechanisms of PHN and the incomplete understanding of the exact mechanism of neuralgia. Conclusion: It is essential to conduct in‐depth research to clarify the origins of PHN pathogenesis and explore effective and comprehensive therapies for PHN. [ABSTRACT FROM AUTHOR]

Background: Cancer remains a formidable global health challenge, currently affecting nearly 20 million individuals worldwide. Due to the absence of universally effective treatments, ongoing research explores diverse strategies to combat this disease. Recent efforts have concentrated on developing combined drug regimens and targeted therapeutic approaches. Objective: This study aimed to investigate the anticancer efficacy of a conjugated drug system, consisting of doxorubicin and cisplatin (Dox‐Cis), encapsulated within niosomes and modified with MUC‐1 aptamers to enhance biocompatibility and target specific cancer cells. Methods: The chemical structure of the Dox‐Cis conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Liquid Chromatography Quadrupole Time‐of‐Flight Mass Spectrometry (LC‐Q‐TOF/MS). The zeta potential and morphological parameters of the niosomal vesicles were determined through Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). In vitro assessments of cell viability and apoptosis were conducted on MUC‐1 positive HeLa cells and MUC‐1 negative U87 cells. Results: The findings confirmed the successful conjugation of Dox and Cis within the niosomes. The Nio/Dox‐Cis/MUC‐1 formulation demonstrated enhanced efficacy compared to the individual drugs and their unencapsulated combination in both cell lines. Notably, the Nio/Dox‐Cis/MUC‐1 formulation exhibited greater effectiveness on HeLa cells (38.503 ± 1.407) than on U87 cells (46.653 ± 1.297). Conclusion: The study underscores the potential of the Dox‐Cis conjugate as a promising strategy for cancer treatment, particularly through platforms that facilitate targeted drug delivery to cancer cells. This targeted approach could lead to more effective and personalized cancer therapies. [ABSTRACT FROM AUTHOR]

Extracellular vesicles have gained wide momentum as potential therapeutics for osteoarthritis, a highly prevalent chronic disease that still lacks an approved treatment. The membrane‐bound vesicles are secreted by all cells carrying different cargos that can serve as both disease biomarkers and disease modifiers. Nonetheless, despite a significant peak in research regarding EVs as OA therapeutics, clinical implementation seems distant. In addition to scalability and standardization challenges, researchers often omit to focus on and consider the proper tropism of the vesicles, the practicality and relevance of their source, their low native therapeutic efficacy, and whether they address the disease as a whole. These considerations are necessary to better understand EVs in a clinical light and have been comprehensively discussed and ultimately summarized in this review into a conceptualized framework termed the nanodiamond concept. Future perspectives are also discussed, and alternatives are presented to address some of the challenges and concerns. [ABSTRACT FROM AUTHOR]

Background and Aims: Behçet's disease is a chronic, multisystemic, and relapsing inflammatory disorder. It lacks a permanent cure, the focus of treatment is on mitigating symptoms, decreasing the frequency and severity of relapses, and preventing life‐threatening complications. This study aims to report the experience of a single center in managing patients with Behçet's disease and discuss the treatment outcomes. Methods: This study was a retrospective case series conducted over 2 years. All cases were clinically diagnosed according to the International Criteria for Behçet's Disease. The extracted data were demographics, family history, clinical findings, criteria scores, treatment, and outcomes. Results: A total of 31 patients were included, consisting of 13 males (42%) and 18 females (58%). Most cases were over the age of 30, and both genders were nearly equally distributed among age groups. The most commonly affected site was the oral cavity, observed in 96.77% of cases. Genital, cutaneous, and vascular involvements were more common in males, while females were more likely to have oral, ocular, and musculoskeletal involvements. For various treatment regimens, oral, cutaneous, vascular, and musculoskeletal involvements showed complete response in all cases. Among cases with genital involvement, complete response was achieved in seven cases (41.2%), while four cases (23.5%) showed only partial response, and six cases (35.3%) experienced recurrence. In cases with ocular involvement, only partial responses were observed. Conclusion: Oral, cutaneous, vascular, and musculoskeletal involvements may have a higher likelihood of a complete response to treatment regimens. However, genital involvement may be the most recurrent manifestation, followed by ocular involvement. Key points: The incidence of the disease varies widely across different regions. The risk factors include family history, exposure to environmental factors, and genetic predisposition. Its diagnosis is challenging because the symptoms are not always concomitant and there are no specific diagnostic tests. The focus of treatment is on mitigating symptoms, decreasing the frequency and severity of relapses, and preventing life‐threatening complications. [ABSTRACT FROM AUTHOR]

The induction of regulated cell death (RCD) through photo/ultrasound sensitization therapeutic agents has gained significant attention as a vital approach to combat drug resistance in tumors. Aggregation‐induced emission (AIE) therapeutic agents generate reactive oxygen species through photo/ultrasound activation, which can synergize with RCD inducers or directly induce RCD, ultimately resulting in the death of tumor cells. The presented comprehensive review delves into recent advancements in AIE therapeutic agents designed to trigger RCD or synergize with RCD inducers, encompassing apoptosis, necroptosis, pyroptosis, immunogenic cell death, autophagy, ferroptosis, and cuproptosis. Additionally, the intricate regulatory mechanisms through which activatory‐AIE therapeutics influence distinct RCD pathways are examined. A forward‐looking perspective on future developments and pertinent challenges within this exciting realm is presented, anticipating the continued evolution of activatable AIE therapeutics as a transformative approach to enhance tumor therapy. [ABSTRACT FROM AUTHOR]

Introduction: Hearing loss is a chronic health condition that rises sharply with age. The way people respond to and cope with health conditions is influenced by their capacity to perform illness and treatment‐related work. The aim was to explore the cumulative burdens of living with hearing loss and the resources mobilised to ease the burdens. Methods: A qualitative design was used with semi‐structured interviews (online or in‐person) with participants recruited through audiology services and nonclinical services, such as lip‐reading classes. Forty‐six participants with hearing loss aged between 16 and 96 years were interviewed. An abductive approach, informed by May et al.'s burden of treatment theory, was used to analyse the data. Results: The illness burden involved participants working to make sense of their hearing loss, engaging in emotional work in response to changes in sound, social interactions and identity and coping with the daily frustrations required to communicate with others. Abandonment and uncertainty characterised the treatment burden; participants engaged in emotional work to adjust to hearing technology and deal with the uncertainty of how their hearing might progress. To ameliorate the burdens, participants drew on internal resources (psychological, health literacy, cognitive) and external resources (social support, financial, information, technology). Conclusions: The workload of hearing loss appears largely devolved to the patient and is not always visible. Our work indicates the need to widen approaches in audiological care through the implementation of lifeworld‐led care, family‐centred care and peer support to build support for those with hearing loss. Patient or Public Contribution: We developed the project in consultation with members of the public who have lived experience of hearing loss recruited through Aston University and volunteer links to audiology services. We also consulted people more likely to be affected by hearing loss adults including adults with learning disabilities, older adults in residential care and people from South Asia (Bangladeshi, Indian and Pakistani communities). These individuals commented on the study aims, interview schedule and participant recruitment practices. One of our co‐authors (expert by experience) contributed to the development and interpretation of themes and preparation of the final manuscript. [ABSTRACT FROM AUTHOR]

Objectives: Olfactory training (OT) has emerged as a first-line therapeutic approach to the management of olfactory dysfunction. Conventional OT (COT) involves the systematic home-based exposure to four distinct odors. Previous research has demonstrated that immersive OT (IOT) involving full-body exposure to dozens of distinct odors could also improve overall olfactory function. This study compared IOT and COT in terms of efficacy. Methods: A total of 60 patients were enrolled and assigned to three groups. The IOT group (n = 25) underwent immersive exposure to 64 odors once daily in a specialized theater. COT participants (n = 17) sniffed four typical odors in a set of four jars twice daily at home. A control group (n = 18) underwent passive observation. Olfactory function was assessed before and after training. Results: Significant improvements in composite threshold-discrimination-identification (TDI) scores were observed after training in both the IOT (mean difference = 2.5 ± 1.1. p = .030) and COT (mean difference = 4.2 ± 1.3, p = .002) groups. No changes were observed in the control group. A significantly higher proportion of patients in the COT group (41%) presented improvements of clinical importance (TDI =5.5) compared to the controls (p = .018). The improvements attained in the IOT group (20%) were less pronounced (p = .38). Conclusion: While IOT did not exhibit the same efficacy as COT in restoring olfactory function, it still demonstrated promising outcomes. Future efforts to advance olfactory recovery should focus on cross-modal integration. [ABSTRACT FROM AUTHOR]

Despite progression in advanced treatments for malignant tumors, surgery remains the primary treatment intervention, which removes a large portion of firm tumor tissues; however, the postoperative phase poses a possible risk for provincial tumor recurrence and metastasis. Consequently, the prevention of tumor recurrence and metastasis has attracted research attention. In this review, we summarized the postoperative treatment strategies for various tumors from both basic research and clinical perspectives. We delineated the underlying factors contributing to the recurrence of malignant tumors with a substantial prevalence rate, related molecular mechanisms of tumor recurrence post‐surgery, and related means of monitoring recurrence and metastasis after surgery. Furthermore, we described relevant therapeutic approaches for postoperative tumor recurrence, including chemotherapy, radiation therapy, immunotherapy, targeted therapy, and photodynamic therapy. This review focused on the emerging technologies used for postoperative tumor treatment in recent years in terms of functional classification, including the prevention of postoperative tumor recurrence, functional reconstruction, and monitoring of recurrence. Finally, we discussed the future development and deficiencies of postoperative tumor therapy. To understand postoperative treatment strategies for tumors from clinical treatment and basic research and further guide the research directions for postoperative tumors. [ABSTRACT FROM AUTHOR]

A medical tool is a general instrument intended for use in the prevention, diagnosis, and treatment of diseases in humans or other animals. Nowadays, sensors are widely employed in medical tools to analyze or quantify disease‐related parameters for the diagnosis and monitoring of patients' diseases. Recent explosive advancements in sensor technologies have extended the integration and application of sensors in medical tools by providing more versatile in vivo sensing capabilities. These unique sensing capabilities, especially for medical tools for surgery or medical treatment, are getting more attention owing to the rapid growth of minimally invasive surgery. In this review, recent advancements in sensor‐integrated medical tools are presented, and their necessity, use, and examples are comprehensively introduced. Specifically, medical tools often utilized for medical surgery or treatment, for example, medical needles, catheters, robotic surgery, sutures, endoscopes, and tubes, are covered, and in‐depth discussions about the working mechanism used for each sensor‐integrated medical tool are provided. [ABSTRACT FROM AUTHOR]

Toll‐like receptors (TLRs) are inflammatory triggers and belong to a family of pattern recognition receptors (PRRs) that are central to the regulation of host protective adaptive immune responses. Activation of TLRs in innate immune myeloid cells directs lymphocytes to produce the most appropriate effector responses to eliminate infection and maintain homeostasis of the body's internal environment. Inappropriate TLR stimulation can lead to the development of general autoimmune diseases as well as chronic and acute inflammation, and even cancer. Therefore, TLRs are expected to be targets for therapeutic treatment of inflammation‐related diseases, autoimmune diseases, microbial infections, and human cancers. This review summarizes the recent discoveries in the molecular and structural biology of TLRs. The role of different TLR signaling pathways in inflammatory diseases, autoimmune diseases such as diabetes, cardiovascular diseases, respiratory diseases, digestive diseases, and even cancers (oral, gastric, breast, colorectal) is highlighted and summarizes new drugs and related clinical treatments in clinical trials, providing an overview of the potential and prospects of TLRs for the treatment of TLR‐related diseases. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation‐specific homologous factor (EHF), a member of the E26 transformation‐specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma‐associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor‐associated macrophages (TAMs) through the C‐C motif chemokine 2/C‐C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co‐expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF‐mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2‐TAMs to inhibit EHF‐driven CCA development. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are released by all cells and contribute to cell‐to‐cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans. The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well‐designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso‐responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model‐based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it. [ABSTRACT FROM AUTHOR]

Objective: To summarize the clinical characteristics and imaging manifestations of patients with nonketotic hyperglycemic hemichorea (NH‐HC) and to explore the possible pathogenesis, diagnosis. and treatment of the disease in order to improve the understanding of this disease and avoid misdiagnosis. Methods: Retrospective analysis was performed on the case data of five patients with NH‐HC admitted to our hospital in recent years. The patients were treated in the department of endocrinology, department of neurology, and department of neurosurgery in our hospital, respectively. Meanwhile, relevant literatures were consulted for further learning. Results: NH‐HC is usually presented as a triad of nonketotic hyperglycemia, lateral chorea, and typical imaging manifestations of head magnetic resonance imaging or computed tomography, but the clinical manifestations are not the same, and imaging features may also be different, presenting a diversified trend in clinical practice. All five patients were given glucose‐lowering drugs and improved with or without combination of drugs to control symptoms of chorea. Conclusion: NH‐HC is a rare complication of diabetes, characterized by hyperglycemia and hemichorea. How to identify the extreme situation and make fast judgment is a top priority. Timely and correct control of blood glucose is the key to the treatment, and when necessary, application of dopamine receptor antagonists in patients with combination therapy can accelerate improvement of the clinical symptoms. The prognosis of NH‐HC is good, the clinician should strengthen comprehensive understanding of this disease to avoid missed diagnosis or misdiagnosis and enable patients to get more timely and effective treatment. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is caused by a third copy of chromosome 21. Alzheimer's disease (AD) is a neurodegenerative condition characterized by the deposition of amyloid‐beta (Aβ) plaques and neurofibrillary tangles in the brain. Both disorders have elevated Aβ, tau, dysregulated immune response, and inflammation. In people with DS, Hsa21 genes like APP and DYRK1A are overexpressed, causing an accumulation of amyloid and neurofibrillary tangles, and potentially contributing to an increased risk of AD. As a result, people with DS are a key demographic for research into AD therapeutics and prevention. The molecular links between DS and AD shed insights into the underlying causes of both diseases and highlight potential therapeutic targets. Also, using biomarkers for early diagnosis and treatment monitoring is an active area of research, and genetic screening for high‐risk individuals may enable earlier intervention. Finally, the fundamental mechanistic parallels between DS and AD emphasize the necessity for continued research into effective treatments and prevention measures for DS patients at risk for AD. Genetic screening with customized therapy approaches may help the DS population in current clinical studies and future biomarkers. [ABSTRACT FROM AUTHOR]

Background: Vitiligo is a kind of refractory, autoimmune locally, or systemically generalized depigmentation spots caused by the disappearance of melanocyte function in the skin. Acupuncture and related therapies are extensively utilized for treating vitiligo in China. The objective of this study is to succinctly encapsulate and meticulously assess the methodological and reporting caliber of systematic reviews (SRs) pertaining to acupuncture and associated therapeutic approaches, while concurrently offering an all‐encompassing body of evidence elucidating their efficacy and safety in the treatment of vitiligo. Methods: We performed an electronic literature search in eight databases to identify SRs that evaluated the efficacy of acupuncture therapy for vitiligo. The Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) tool was used to evaluate the methodological and reporting quality of these SRs. The preferred reporting items for SRs and meta‐analyses were followed according to PRISMA (2020) guidelines. Additionally, the risk of bias in systematic reviews (ROBIS) was assessed to evaluate potential bias. The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Results: This study included 10 SRs and assessed a total of 13 outcome measures, all of which were published before June 2023. Acupuncture therapy was more effective than control conditions for the treatment of Vitiligo. The AMSTAR‐2 results indicated a critical deficiency in the methodological quality of all SRs, with items 7 and 16 demonstrating notably low quality. The reporting quality of the included SRs according to PRISMA was deemed unsatisfactory, with significant reporting flaws identified in the areas of Protocol and registration, Risk of bias across studies, Study selection, and Limitations. According to the ROBIS assessment, 5 out of the total number of SRs (50.00%) were found to have a high risk of bias. Out of the total of 62 outcomes evaluated using the GRADE framework, 9 outcomes (14.51%) exhibited high‐quality evidence, 20 outcomes (32.26%) demonstrated moderate‐quality evidence, 19 outcomes (30.65%) presented low‐quality evidence, while 14 outcomes (22.58%) indicated very low‐quality evidence. Conclusions: This overview shows that Acupuncture therapy was more effective than the control treatment for Vitiligo. Nevertheless, given the subpar methodological quality of the reviews, we recommend conducting studies with stricter designs, larger sample sizes, and improved methodological and reporting quality to yield more robust evidence. [ABSTRACT FROM AUTHOR]

Biosimilars are biological drugs created from living organisms or that contain living components. They share an identical amino‐acid sequence and immunogenicity. These drugs are considered to be cost‐effective and are utilized in the treatment of cancer and other endocrine disorders. The primary aim of biosimilars is to predict biosimilarity, efficacy, and treatment costs; they are approved by the Food and Drug Administration (FDA) and have no clinical implications. They involve analytical studies to understand the similarities and dissimilarities. A biosimilar manufacturer sets up FDA‐approved reference products to evaluate biosimilarity. The contribution of next‐generation sequencing is evolving to study the organ tumor and its progression with its impactful therapeutic approach on cancer patients to showcase and target rare mutations. The study shall help to understand the future perspectives of biosimilars for use in gastro‐entero‐logic diseases, colorectal cancer, and thyroid cancer. They also help target specific organs with essential mutational categories and drug prototypes in clinical practices with blood and liquid biopsy, cell treatment, gene therapy, recombinant therapeutic proteins, and personalized medications. Biosimilar derivatives such as monoclonal antibodies like trastuzumab and rituximab are common drugs used in cancer therapy. Escherichia coli produces more than six antibodies or antibody‐derived proteins to treat cancer such as filgrastim, epoetin alfa, and so on. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma (EHE) is a rare vascular neoplasm with a clinical behaviour that falls between a benign hemangioma and a high-grade angiosarcoma. Pleural EHE is exceptionally rare, and its prognosis is grim, with most patients experiencing survival of less than 1 year. Here, we present a case of pleural EHE in a 45-year-old woman with a month-long history of right-sided pleuritic chest pain. Chest computed tomography revealed consolidation, atelectasis of the right lung, right pleural thickening, and pleural effusion. She underwent video-assisted thoracoscopic surgery for decortication and was diagnosed with conclusively pleural EHE, showing a CAMTA1 rearrangement. Paclitaxel treatment, administered once weekly on days 1, 8 and 15 of a 28-day cycle, resulted in a stable disease after 12 cycles. Managing patients with pleural EHE is challenging because there are still no established standard treatments. Our case achieved 11-month progression-free survival following paclitaxel treatment. [ABSTRACT FROM AUTHOR]

Background: The development of prototypes capable of intervening in the area of rehabilitation in physical therapy clinical practice activities that were previously carried out in a traditional way, that is, manually, demonstrates how technology is having an impact on professional careers such as physiotherapy. Objective: The purpose of this study is to present a comprehensive examination of various technologies employed in the facilitation of patient rehabilitation, with a focus on their potential integration within the clinical practice of physical therapists. Methods: We conducted a systematic search in four electronic databases (CINAHL, Embase, PEDro, and PubMed) for research on rehabilitation technologies. The eligible studies should demonstrate a clear utilization of technology in various aspects of the clinical approach to the rehabilitation process and have been published between 2000 and 2021 in either Portuguese or English. Results: A total of 18 articles that satisfied the selection criteria were included in the study. The studies were classified into four distinct categories of rehabilitation technologies, which were determined by the specific characteristics of the technology employed and its integration with the therapeutic approach to rehabilitation. These categories include digital technologies, artificial intelligence and/or robotics, virtual technologies, and hybrid technologies. Implications on Physiotherapy Practice: Rehabilitation technologies possess the capacity to effectively facilitate clinical activities performed by physical therapy professionals, including injury prevention, movement monitoring, and coordination of rehabilitation programs, with minimal or negligible intervention from the physical therapist. Further research is required to ascertain the precise capabilities of various technologies in collaborating with physiotherapists to deliver comprehensive care for patients' physical well‐being, encompassing both therapeutic and preventive approaches. Trial Registration: PROSPERO registration number CRD42020222288 [ABSTRACT FROM AUTHOR]