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Background: Although the prescription of physical activity in clinical care has been advocated worldwide, in the Netherlands, "Exercise is Medicine" (E = M) is not yet routinely implemented in clinical care. Methods: A set of implementation strategies was pilot implemented to test its feasibility for use in routine care by clinicians in 2 departments of a university medical center. An extensive learning process evaluation was performed, using structured mixed methods methodology, in accordance with the Reach, Effect, Adoption, Implementation, and Maintenance framework. Results: From 5 implementation strategies employed (education, E = M tool embedded in the electronic medical records, lifestyle coach situated within the department, overviews of referral options, and project support), the presence of adequate project support was a strong facilitator of the implementation of E = M. Also, the presence of the lifestyle coach within the department seemed essential for referral rate. Although clinicians appreciated the E = M tool, barriers hampered its use in practice. Conclusions: Specific implementation strategies, tailored to the setting, are effective in facilitating the implementation of E = M with specific regard to education for clinicians on E = M, deployment of a lifestyle coach within a department, and project coordination. Care providers do see a future for lifestyle coaches who are structurally embedded in the hospital, to whom they can easily refer. [ABSTRACT FROM AUTHOR]

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In VIII: clinical approaches, authors address the following themes: Evaluation, diagnosis and management I-toward a working diagnosis, Evaluation, diagnosis and management II-process steps, Interweaving integrative medicine and family medicine, Halfway-the art of clinical judgment, Seamless integration in family medicine-team-based care, Technology-uncovering stories from noise and Caring for patients with multiple long-term conditions. May readers recognise in these essays the uniqueness of a family medicine approach to care.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'IX: people and places-diverse populations and locations of care', authors address the following themes: 'LGBTQIA+health in family medicine', 'A family medicine approach to substance use disorders', 'Shameless medicine for people experiencing homelessness', '''Difficult" encounters-finding the person behind the patient', 'Attending to patients with medically unexplained symptoms', 'Making house calls and home visits', 'Family physicians in the procedure room', 'Robust rural family medicine' and 'Full-spectrum family medicine'. May readers appreciate the breadth of family medicine in these essays.

Background: Research indicates that prehabilitation is effective in optimizing physical status before surgery, although this method may be considered "aggressive" for frail elderly patients. This study aimed to evaluate whether multimodal prehabilitation decreases postoperative complications and improves functional recovery in frail elderly patients undergoing gastric cancer surgery, in comparison to usual clinical care. Methods: This study was a single-center, single-blind, randomized controlled trial. Patients over 65 years old with a Fried Frailty Index of 2 or higher, scheduled for gastric cancer surgery, were considered for inclusion. Eligible participants were randomized in a 1:1 ratio to either the intervention or control group. The intervention group underwent a 3-week multimodal prehabilitation program prior to surgery, in addition to perioperative care guided by ERAS protocols. The control group received only the latter. The primary outcome was the comprehensive complications index (CCI) measured at 30 days after surgery. Secondary outcomes included 30-day overall complications, functional walking capacity as assessed by 6-minute walking distance (6MWD) at 4 weeks postoperatively, and 3-month postoperative quality of life. This study was registered at ClinicalTrials.gov (No. NCT06510088). Results: Among the 112 eligible patients, the median age was 74 years, with 58 (52.7%) being female. No between-group difference was found in the primary outcome measure, 30-day CCI. The Median (Q1-Q3) CCI for the intervention and control groups was 0 (0-12.2) and 0 (0-22.6) (P = 0.082), while the mean (SD) CCI was 6.1 (15.8) and 9.8 (12.7), respectively (P = 0.291). Notably, the incidence of severe complications (CCI > 20) was significantly lower in the intervention group compared to the control group (11.1% vs. 25.9%, P = 0.046), particularly in terms of medical complications (12.3% vs. 29.3%, P = 0.025). Preoperatively, 27 patients (47.4%) in the intervention group exhibited an increase in the 6MWD of at least 20 m, compared to 16 patients (27.6%) in the control group (P = 0.028). At 4 weeks postoperatively, more patients in the intervention group returned to their baseline 6MWD levels (63.2% vs. 43.1%, P = 0.031). Secondary parameters of functional capacity in the postoperative period generally favored the multimodal prehabilitation approach. Conclusions: In frail elderly patients undergoing elective gastric cancer surgery, a prehabilitation program did not affect the 30-day postoperative complication rate or CCI but reduced severe complications and improved perioperative functional capacity. Trial registration: [ClinicalTrials.gov], [NCT06510088], [07/15/2024], [Retrospectively registered] [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) results from various causes, including sports‐related incidents, degenerative cervical myelopathy, traffic accidents, and falls. SCI typically leads to sensory and motor dysfunction and even paralysis. Current treatments for SCI include systemic administration of high‐dose steroids and surgical decompression and stabilization. However, excessive use of glucocorticoids may increase susceptibility to infections and systemic bleeding. The long‐term effect of surgery intervention remains unclear, with ongoing debates regarding its timing, efficacy, and safety. Therefore, innovative approaches are urgently needed to alleviate secondary injuries and promote spinal recovery. One emerging therapeutic approach for SCI is modulating the microenvironments to achieve neuroprotection and neurogenesis during recovery. Several biomaterials with favorable physicochemical properties have been developed to enhance therapeutic effects by regulating microenvironments. This Review first discusses the pathology of SCI microenvironments and then introduces biomaterials‐based regulatory strategies targeting various microenvironmental components, including anti‐inflammation, anti‐oxidation, reduction of excitotoxicity, revascularization, neurogenesis, and scar density reduction. Additionally, the research and clinical application prospects for microenvironment regulation are presented. [ABSTRACT FROM AUTHOR]

There is growing awareness and empirical support for targeting strengths and resilience when providing services to youth and families who have been impacted by adverse childhood experiences (ACE) and trauma. The purpose of this article is to highlight strengths-based, resilience-enhancing (SBRE) clinical applications that can be incorporated into ACE-informed therapeutic services. Twenty treatment components are described and organized into six main categories that chronicle the course of therapy: Relationship Development, Stabilization, Engagement, Assessment, Intervention, and Prevention. SBRE services assist youth in adaptively coping with life adversity, and acquiring the knowledge, skills, and strengths for leading psychologically healthy, resilient lives. It is hoped this article will stimulate interest from both clinicians and researchers regarding the SBRE model, which is being introduced here for the first time. [ABSTRACT FROM AUTHOR]

The article discusses a study on the bioactive mediator profile of patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA) treated with mepolizumab. The research aimed to understand variations between patients with bronchial asthma (BA) and EGPA, as well as the mechanisms of action of glucocorticoid (GC) and mepolizumab therapy. The study found differences in protein levels between BA and EGPA, with specific proteins being elevated in EGPA cases. Additionally, the study highlighted the effects of GC treatment on EGPA and the additional changes induced by mepolizumab, suggesting a multifaceted role of IL-5 in the pathogenesis of EGPA. [Extracted from the article]

Naturally occurring cell-derived extracellular vesicles (EVs) have emerged as attractive nanocarriers for drug delivery. However, production of large quantities of EVs for clinical applications in a scalable manner remains a significant challenge. This study investigated at the single cell level how sonoporation, or membrane poration produced by ultrasound-induced microbubble cavitation, impacts EV production using mouse macrophage RAW 264.7 cells stably expressing CD63-GFP as a model system. Real-time fluorescence videomicroscopy detected rapid changes in CD63-GFP, a tetraspanin family member highly enriched in intraluminal vesicles tagged with GFP, to track changes in multivesicular bodies (MVBs), which are the cellular compartments where exosomes originate within the cells. Our results revealed distinct dynamic changes in CD63-GFP intensity and distribution in RAW 264.7 cells in terms of response time and duration depending on whether the cells were directly or indirectly impacted by sonoporation, suggesting reorganization of MVBs in response to direct and indirect mechanisms resulted from the mechanical impact of ultrasound pulse on the cells. Analysis of the supernatant from sonoporation-treated RAW 264.7 cells expressing CD63-GFP demonstrated a delayed and sustained increase in the production of CD63-GFP-positive EVs. These results show the robust and detailed effect of sonoporation and reveal insights into sonoporation-induced EV release useful for guiding the application of sonoporation to enhance large-scale EV production. [ABSTRACT FROM AUTHOR]

Understanding and incorporating evidence‐based veterinary medicine (EBVM) into clinical practice and research continues to pose a challenge for our profession despite over 2 decades of increasing awareness of this concept. Reasons for this include a lack of understanding of its importance to the practice of medicine, veterinary literature that often fails to adhere to evidence‐based standards, inadequate attention to teaching EBVM at the university level, and the inherent reluctance of clinicians to alter historical practice styles. For many practitioners, EBVM continues to be an abstract concept they believe requires advanced training in statistics and epidemiology resulting in them relying on less robust sources for clinical guidance. This unfortunately results in suboptimal care for our patients and delayed medical advancements for our profession. As part of the 20th anniversary of the founding of the Evidence‐Based Veterinary Medicine Association (EBVMA), we are refocusing our efforts to highlight the need for dedicated teaching of EBVM at the university level, for rigorous adherence to established research reporting guidelines, for expansion of EBVM infrastructure, and for the provision of easily accessible tools that permit clinicians to incorporate EBVM into their daily practice. As the quality of veterinary literature improves, so too will development of more effective clinical practice guidelines that ultimately can be widely adopted if they are flexible enough to support the triadic relationship between veterinarians, our clients and our patients. Ultimately, EBVM is not an end unto itself, but rather a means to improve the quality of care we provide our patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions In acute myeloid leukemia (AML), further investigation is warranted to integrate measurable residual disease (MRD) with genetic characteristics for formulating a dynamic prognostic system for predicting response and selecting appropriate postremission therapeutic strategies.The authors incorporated MRD with genetic risk classification and assessed its impact on transplantation decision making within different risk cohorts, comprising 769 patients with newly diagnosed AML across three clinical trials. Only patients who achieved complete remission (CR) within two courses of chemotherapy were selected.In the favorable‐risk and intermediate‐risk groups, patients who underwent transplantation according to the protocol experienced significant 3‐year overall survival (OS) benefits compared with those who did not (favorable‐risk group: hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.73l p = .004; intermediate‐risk group: HR, 0.53; 95% CI, 0.33–0.85; p = .008). In the intermediate‐risk group, early detection of MRD positivity, even after the initial course of chemotherapy, was associated with a significantly elevated cumulative incidence of relapse (47.2% vs. 36.0%; p = .009) and a notable extension of OS with allogeneic hematopoietic stem cell transplantation (HR, 0.47; 95% CI, 0.28–0.79; p = .004). Conversely, patients who achieved MRD negativity at either of the two time points had comparable OS in the favorable‐risk and intermediate‐risk groups, regardless of whether they underwent transplant or not. In the adverse‐risk group, allogeneic hematopoietic stem cell transplantation led to improvements in OS irrespective of MRD status (HR, 0.51; 95% CI, 0.38–0.69; p < .001).Early clearance of MRD demonstrated significant prognostic value, particularly for patients in the favorable‐risk and intermediate‐risk groups. Positive MRD status after two courses of intensive chemotherapy were associated with a higher relapse rate and inferior OS, necessitating allogeneic hematopoietic stem cell transplantation. [ABSTRACT FROM AUTHOR]

Background: In recent years, limited studies have evaluated the development of cultural awareness, sensitivity, skills, communication and competence among nursing students using different models and curricula. Objectives: This study aimed to evaluate the effectiveness of a new internationally developed curriculum for transcultural nursing education. Methods: This mixed methods study was conducted on nursing students (n = 83) who attended a transcultural nursing course from 2021 to 2022 during the fall semester. A paired samples test was used to compare total scores, and the related-samples Wilcoxon signed-rank test was used to compare subscale scores. Results: The vast majority (94.0%) of the participants mentioned Islam as their religion. Turkish was the mother tongue of 91.6% of them, while 10.8% were able to speak English and 6.0% were able to speak Kurdish fluently. The mean score for the achievement of cultural competence subdimension posttest was significantly greater (p < 0.001). Posttest mean scores for challenges and barriers in providing culturally competent care subdimensions were significantly lower (p = 0.003). The mean score on the culturally sensitive communication subdimension pretest was 21.00 ± 4.76, and the mean score on the posttest increased to 23.02 ± 6.05, which was a statistically significantly greater difference (p = 0.024). According to the qualitative results of our study, five main themes were analyzed: transcultural nursing as an opportunity, transcultural nursing as a didactic process, transcultural nursing as a professional field, transcultural care as a safe environment, and transcultural care as an obligation. Conclusions: In this study, after a semester of continuing education, nursing students developed respect for cultural diversity, cultural competence, and culturally sensitive communication. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) is an independent risk factor of poor prognosis in hepatocellular carcinoma (HCC) and can be used to guide the diagnosis and treatment of HCC. The immune system serves as an integral role in the incidence and progression of HCC. However, the molecular biology correlation between MVI and tumor immunity and the value of combining the two parameters to predict patient prognosis and HCC response to treatment remain to be evaluated. Results: In this study, we used univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis to establish the MVI and immune-related gene index (MIRGPI) including eight genes. We demonstrated that the MIRGPI was an independent risk factor in predicting the prognosis of HCC. Subsequently, our research established a nomogram model combining pathologic characteristics and verified its good clinical application value. In addition, our study found that the TP53 gene had a higher mutation frequency and a lower degree of immune infiltration in the high-risk group. The low-risk group had higher sensitivity to immunotherapy, sorafenib, and TACE treatment, and the high-risk group had higher sensitivity to common chemotherapeutic agents. Finally, SEMA3C was found to facilitate the proliferation, migration and invasive ability of HCC by in vitro and in vivo experiments, and its mechanism may be associated with the activation of the NF-Κb/EMT signaling pathway. Conclusions: In summary, the MIRGPI signature we developed is a reliable marker for the prediction of prognosis and treatment response, and is important for the prognostic assessment and individualized treatment of HCC. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To review in utero transfers (IUT), their antenatal optimisation strategies including predictive testing and outcomes in a large region in the UK.All IUT requests received by regional transport service in the UK, over a 12‐month period, were reviewed gathering information on gestation at referral, antenatal corticosteroid use, tocolysis, magnesium sulphate, predictive test use (and result if applicable) and delivery outcome at 48 h. The reason for transfer was also collated to determine capacity issues.Only 22.9% of women transferred delivered within 48 h of transfer, with only 76% of eligible women receiving antenatal steroids. The overall use of predictive testing was low, in 23.5% of all referrals. Approximately 19.8% of women presenting at 30 weeks gestation or more received predictive testing while only 26.5% of women at risk of extreme preterm delivery had a predictive test, and 40.7% of all IUT requests were for capacity reasons.More predictive testing with accurate approaches to predicting imminent preterm labour and delivery needs to be incorporated into clinical care to reduce the number of inappropriate IUTs. Appropriate antenatal optimisation to improve outcomes should be offered to women undergoing an IUT. Capacity remains problematic leading to a significant number of transfers. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) cells express sialylated Lewis antigens (sLe), crucial for metastasis via E‐selectin binding. However, these glycoepitopes lack cancer specificity, and E‐selectin‐targeted glycoproteins remain largely unknown. Here, we established a framework for identifying metastasis‐linked glycoproteoforms. More than 70% of CRC tumors exhibited overexpression of sLeA/X, yet without discernible associations with metastasis or survival. However, The Cancer Genome Atlas (TCGA) analysis unveiled differing expression patterns of sLeA/X‐related glycogenes correlating with disease severity, indicating context‐dependent regulation by distinct glycosyltransferases. Deeper exploration of metastatic tumor sialoglycoproteome identified nearly 600 glycoproteins, greatly expanding our understanding of the metastasis‐related glycoproteome. These glycoproteins were linked to cell adhesion, oncogenic pathways, and neuroendocrine functions. Using an in‐house algorithm, the secretin receptor (SCTR) emerged as a top‐ranked targetable glycoprotein. Tumor screening confirmed SCTR's association with poor prognosis and metastasis, with N‐glycosylation adding cancer specificity to this glycoprotein. Prognostic links were reinforced by TCGA‐based investigations. In summary, SCTR, a relatively unknown CRC glycoprotein, holds potential as a biomarker of poor prognosis and as an E‐selectin ligand, suggesting an unforeseen role in disease dissemination. Future investigations should focus on this glycoprotein's biological implications for clinical applications. [ABSTRACT FROM AUTHOR]

Difluprednate (DFP) (difluoroprednisolone butyrate acetate, or DFBA) ophthalmic emulsion 0.05% (Durezol®) was the first potent corticosteroid to be approved for both postoperative pain and inflammation in 2008. In June 2012, it was approved for the treatment of endogenous anterior uveitis. It is a synthetic difluorinated prednisolone derivative that was originally developed in Japan as a dermatologic ointment. The glucocorticoid binding affinity of its active metabolite was demonstrated to be 56 times stronger than prednisolone. Experimental models showed that it reached the anterior and posterior segments of the eye quickly, via both transcorneal and noncorneal (conjunctiva and sclera) absorption routes. Its clinical applications have been expanded to treat patients with uveitic macular edema and anterior scleritis. Case reports and case series also describe its use in some forms of posterior uveitis and in non-uveitic entities. Elevated intraocular pressure and acceleration of cataract formation are the main concerns with DFP as with all corticosteroids. Because IOP elevation is particularly pronounced in the pediatric age group, IOP is to be closely monitored at every visit in children. High incidence of cataract formation and progression was also documented in children, thus necessitating vigilant follow-up of children on chronic treatment. This review aims to give a comprehensive and up-to-date overview of difluprednate’s pharmacological properties, clinical applications, safety profiles, and alternative delivery methods. [ABSTRACT FROM AUTHOR]

Background: The value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development. Methods: A 12-month "accelerator" award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research. Results: Sixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement. Conclusions: In general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted. Plain English Summary: Patient and public involvement (PPI) in the development of funding applications to deliver clinical trials is desirable, but the PPI activities and processes involved at this early, "pre-award" stage are rarely reported. In the current paper we describe such activities during a 12-month project to develop a grant proposal for a substantive, international clinical trial. Three PPI partners were co-recipients of "seed funding" to conduct the 12-month Accelerator project, an additional 22 PPI partners being subsequently recruited to co-develop the funding application for the trial, entitled the "Rheumatoid Arthritis Prevention: catalysing PlatfORm Trial (RAPPORT)." PPI partners contributed through meetings, email discussions and the completion of feedback forms. The PPI processes used in the project were evaluated by 16 of the PPI partners using an anonymous online feedback form. The form asked about the areas covered by the UK Standards for Public Involvement. PPI partners indicated that PPI in RAPPORT was done well in relation to all areas of the UK Standards. PPI partners felt they were heard, and their input valued, and that the communication was effective. Furthermore, they appreciated online format of the PPI activities, the flexible levels of involvement offered and the support from staff with expertise in both research and PPI. Some areas for potential improvement in future initiatives were also identified, which are discussed alongside challenges to co-development of projects during the "pre-award" stage in general, and the benefit of seed funding to support effective PPI. [ABSTRACT FROM AUTHOR]

Objective: Artificial intelligence (AI) is revolutionizing healthcare, but less is known about how it may facilitate methodological innovations in research settings. In this manuscript, we describe a novel use of AI in summarizing and reporting qualitative data generated from an expert panel discussion about the role of electronic health records (EHRs) in implementation science. Materials and methods: 15 implementation scientists participated in an hour-long expert panel discussion addressing how EHRs can support implementation strategies, measure implementation outcomes, and influence implementation science. Notes from the discussion were synthesized by ChatGPT (a large language model—LLM) to generate a manuscript summarizing the discussion, which was later revised by participants. We also surveyed participants on their experience with the process. Results: Panelists identified implementation strategies and outcome measures that can be readily supported by EHRs and noted that implementation science will need to evolve to assess future EHR advancements. The ChatGPT-generated summary of the panel discussion was generally regarded as an efficient means to offer a high-level overview of the discussion, although participants felt it lacked nuance and context. Extensive editing was required to contextualize the LLM-generated text and situate it in relevant literature. Discussion and conclusions: Our qualitative findings highlight the central role EHRs can play in supporting implementation science, which may require additional informatics and implementation expertise and a different way to think about the combined fields. Our experience using ChatGPT as a research methods innovation was mixed and underscores the need for close supervision and attentive human involvement. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the protective effects of anisodamine (654-1/654-2) against acute kidney injury (AKI) in LPS-induced septic shock rats and explore its molecular mechanisms. Methods: 56 rats were randomly divided into 8 groups: control, LPS, LPS + 654-1, and LPS + 654-2 (1.25, 2.5 and 5 mg/kg). The model was evaluated by monitoring MAP, HR, and plasma LD levels. ELISA and biochemical assay kits were used to measure the levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and kidney injury markers (BUN and CRE). Additionally, RNA-seq and bioinformatic analysis were performed to explore the mechanism of action of 654-1/654-2, and verification was conducted by western blotting and RT-PCR. Results: 654-1/654-2 significantly restored the levels of MAP, HR, and plasma LD in septic shock rats. Furthermore, 654-1/654-2 (5 mg/kg) effectively ameliorated LPS-induced kidney structural damage and exhibited a dose-dependent reduction in levels of inflammatory cytokines and kidney injury markers. In addition, RNA-seq, WB, and RT-PCR analyses revealed that 654-1/654-2 exerted its effects by inhibiting the expressions of the NF-κB and MAPK pathways and activating the Pi3K/Akt/Bcl-2 signaling pathway, thereby mitigating AKI. Discussion: This study suggested that 654-1/654-2 could alleviate AKI in septic shock rats by improving inflammation invasion and cell apoptosis. Notably, 654-1/654-2 collectively suppressed inflammation response through the p38/JNK/AP-1/NF-κB pathway. Additionally, 654-1 promotes survival signaling via the Pi3K/Akt/Bcl-2 pathway, whereas 654-2 reduces apoptosis through the P53/Bax pathway. These findings provided a theoretical basis for the clinical application of 654-1/654-2 in treating organ damage caused by septic shock. [ABSTRACT FROM AUTHOR]

The skull has long been an obstacle for transcranial ultrasound therapy and neuromodulation, leading to waveform distortion and focal points misalignment. In this work, we propose a dual-focus transcranial ultrasound focusing method for ex vivo human skulls to bridge this barrier, which is demonstrated by using a 2 MHz single-element transducer placed outside the occipital bone, coupled to a 3D-printed acoustic holographic lens. The experimental results show that the proposed method allows for achieving high-precision single- and dual-focus ultrasound focusing through human skulls with the maximum target registration error less than one wavelength in water. The in-target ratio spans a range from 72% to 92%, with an average of 80.7%, while the out-of-target ratio varies from 0% to 43.9%, with an average of 18.3%. Additionally, the focal spots are substantially free of the skull-induced distortion, closely matching the ideal ones, and maintain a clearly identifiable circular focus shape. The method opens up a route toward the subsequent applications in clinical research and may enable to implement transcranial ultrasound therapy and neuromodulation. [ABSTRACT FROM AUTHOR]

β-nicotinamide mononucleotide (NMN) is a naturally occurring biologically active nucleotide widely present in organisms and an inherent substance in the human body. As a critical intermediate in synthesizing coenzyme I (NAD+), it widely participates in multiple biochemical reactions in the human body and is closely related to immunity, metabolism, and other factors. In recent years, NMN has rapidly developed and made significant progress in medicine, food, and healthcare. However, there is currently a lack of comprehensive reports on the research progress of NMN, as well as exploration and analysis of the current research achievements and progress of NMN. Therefore, this review is based on retrieving relevant research on NMN from multiple databases at home and abroad, with the retrieval time from database establishment to 20 May 2024. Subsequently, literature search, reading, key information extraction, organization, and summarization were conducted with the aim of providing a comprehensive and in-depth analysis of the characteristics, metabolic pathways, pharmacological effects, progress in human clinical trials, and wide applications of NMN in drug development and food applications. Furthermore, it offers personal insights into NMN's potential future developments and advancements to present the current development state and existing challenges comprehensively. Ultimately, this review aims to provide guidance and serve as a reference for the future application, innovation, and progression of NMN research. [ABSTRACT FROM AUTHOR]

Background: Exosomes, nano-sized extracellular vesicles, have emerged as a promising tool for the diagnosis and treatment of various intractable diseases, including chronic wounds and cancers. As our understanding of exosomes continues to grow, their potential as a powerful therapeutic modality in medicine is also expanding. This systematic review aims to examine the progress of exosome-based clinical trials and provide a comprehensive overview of the therapeutic perspectives of exosomes. Methods: This systematic review strictly follows PRISMA guidelines and has been registered in PROSPERO, the International Prospective Register of Systematic Reviews. It encompasses articles from January 2000 to January 2023, sourced from bibliographic databases, with targeted search terms targeting exosome applications in clinical trials. During the screening process, strict inclusion and exclusion criteria were applied, including a focus on clinical trials utilizing different cell-derived exosomes for therapeutic purposes. Results: Among the 522 publications initially identified, only 10 studies met the stringent eligibility criteria after meticulous screening. The selection process involved systematically excluding duplicates and irrelevant articles to provide a transparent overview. Conclusion: According to our systematic review, exosomes have promising applications in a variety of medical fields, including cell-free therapies and drug delivery systems for treating a variety of diseases, especially cancers and chronic wounds. To ensure safety, potency, and broader clinical applications, further optimization of exosome extraction, loading, targeting, and administration is necessary. While cell-based therapeutics are increasingly utilizing exosomes, this field is still in its infancy, and ongoing clinical trials will provide valuable insights into the clinical utility of exosomes. [ABSTRACT FROM AUTHOR]

Tumor-associated carbohydrate antigens (TACAs) provide a special class of tumor-specific antigens that show promising applications in cancer immunotherapy. However, the weak immunogenicity and structural complexity of TACAs are obstacles to their clinical application. Here, based on a fast and low-cost purification strategy for oligosaccharide synthesis, the synthesis of tumour-associated carbohydrate antigens Globo H and mannobiose which resembles repeat unit of mannan was achieved. To enhance the immunogenicity and multivalent effect, Globo H and mannobiose were covalently attached to degradable polymer backbones. 2D spindle-like lamellar micelle and globular micelle were obtained from glycopolymer through a solvent-exchange method of self-assembly. The glyconanoparticle showed good biocompatibility and degradability. Immunological functions of these glyconanoparticles such as stimulation of BMDC to cause upregulation of inflammatory factors were preliminarily explored. [ABSTRACT FROM AUTHOR]

Polyethyleneimine (PEI), as a widely used polymer material in the field of gene delivery, has been extensively studied for modification and shielding to reduce its cytotoxicity. However, research aimed at preparing degradable PEI is scarce. In this work, the hydrogen peroxide (H2O2) oxidation method was used to introduce degradable amide groups in the PEI and a series of oxidized PEI22k (oxPEI22k) with different degrees of oxidation were synthesized by regulating the dosage of H2O2. The relationship between the oxidation degree of oxPEI22k and the gene transfection efficiency of oxPEI22k was studied in detail, confirming that the oxPEI22k with oxidation degrees of 16.7% and 28.6% achieved improved transfection efficiency compared to unmodified PEI. These oxPEI22k also proved reduced cytotoxicity and improved degradability. Further, this strategy was extended to the synthesis of low-molecular-weight oxPEI1.8k. The oxPEI1.8k with suitable oxidation degree also achieved improved transfection efficiency and reduced cytotoxicity. In brief, this work provided high-efficiency and low-cytotoxicity degradable gene delivery carriers by regulating the oxidation degree of PEI, which was of great significance for promoting clinical applications of PEI. [ABSTRACT FROM AUTHOR]

Background: Comparing outcomes across different health measurement tools is essential where various patient-reported outcome measures (PROMs) are used. In spinal surgery, where recent studies show that over 30 different PROMs are applied, this need becomes even more pressing. Although several statistical transformations between the Oswestry Disability Index (ODI) and the PROMIS Profile 29 have been proposed, validation studies on conversion equations and cross-walk tables remain limited. In this study, we examined the agreement between observed ODI scores and those predicted from the PROMIS Profile 29 in a large sample of patients with low back pain, collected from routine clinical care. Methods: We compared the performance of regression and linking models at both the individual and group levels. Using Bland–Altman plots, we assessed the mean difference, 95% limits of agreement, root mean squared error (RMSE), and standardized mean differences (Cohen's d) between predicted and observed ODI scores. Results: While group-level agreement was satisfactory, with negligible effect sizes, individual prediction accuracy was relatively poor. Additionally, regression models showed inconsistent performance across the ODI score range, though incorporating more domains marginally improved predictions. Conclusions: The equipercentile linking approach demonstrated stable agreement across all ODI scores, making it the preferred method. Future regression models should account for nonlinear relationships between PROMs to enhance prediction accuracy. [ABSTRACT FROM AUTHOR]

The development of effective biomaterials for tissue regeneration has led to the exploration of blood derivatives such as leucocyte- and platelet-rich fibrin (L-PRF). A novel variant, Albumin-Enriched Platelet-Rich Fibrin (Alb-PRF), has been introduced to improve structural stability and bioactivity, making it a promising candidate for bone regeneration. This study aimed to evaluate Alb-PRF's capacity for cytokine and growth factor release, along with its effects on the proliferation, differentiation, and mineralization of human osteoblasts in vitro. Alb-PRF membranes were analyzed using histological, scanning electron microscopy, and fluorescence microscopy techniques. Cytokine and growth factor release was quantified over seven days, and osteoinductive potential was evaluated with MG-63 osteoblast-like cells. Structural analysis showed Alb-PRF as a biphasic, highly cellularized material that releases lower levels of inflammatory cytokines and higher concentrations of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) compared to L-PRF. Alb-PRF exhibited higher early alkaline phosphatase activity and in vitro mineralization (p < 0.05) and significantly increased the OPG/RANKL mRNA ratio (p < 0.05). These results indicate that Alb-PRF has promising potential as a scaffold for bone repair, warranting further in vivo and clinical assessments to confirm its suitability for clinical applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is the ninth most commonly diagnosed form of cancer in both sexes worldwide and the fifth in Europe. The most common form, non-muscle-invasive bladder cancer, is highly prevalent with high recurrence rates and has wide range of outcomes that is partially due to the variability in the treatment delivered. Therefore, some recommendations have been done by the European Association of Urology to standardize their management. Several quality control indicators have been proposed to monitor the adherence of urologists and hospitals to these recommendations. A quality control indicator program has been initiated in the hospitals that are a part of the Flemish Hospital Network in June 2013 using a specific prospective registry. We have recently published the first analysis of these quality control indicators, which showed significant differences between the hospitals. Before publishing the second analysis with more patients and additional quality control indicators, we aimed to describe the characteristics of the cohort in this study. Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non–muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk–KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL–NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL–NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry's real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332). [ABSTRACT FROM AUTHOR]

Objective: To apply the 2019 joint American Academy of Neurology (AAN) and American Headache Society (AHS) quality measures for headache management to a cohort of neurology resident physicians and then assess outcomes related to guideline adherence. Background: The optimization of headache management is essential to reduce both the individual and systemic impact of these disorders. In 2014, the AAN developed 10 quality measures for evidence‐based management of patients with headache. A workgroup updated and condensed its headache quality measures in 2019, narrowing the set to six measurements, four of which would primarily focus on the management of migraine and two of which would address the management of cluster headache. Methods: This quality improvement study was conducted using a pretest‐posttest study design. A pre‐intervention survey based on retrospective analysis of five clinic notes for adherence to the measures was designed and distributed to all neurology residents (n = 32) at a large, academic tertiary referral center. The intervention included the creation of an electronic medical record template to aid residents in following the measures during clinical encounters, as well as the provision of direct feedback based on pre‐intervention results. Finally, a post‐intervention survey was distributed for completion based on notes written during the intervention period. Analysis was limited to migraine, given the low percentage of cluster headache seen in clinic. Results: An increase in adherence was seen in three of the four migraine‐related quality measures, with the Use of Abortive Medications for Migraine and Documentation of Counseling on Modifiable Lifestyle and Chronification Factors demonstrating statistically significant improvements (75.8% to 88.0% [p = 0.013] and 83.9% to 94.0% [p = 0.029] adherence, respectively). For secondary outcomes, the increase in the utilization of appropriate diagnostic criteria (82.6% to 93.2%, p = 0.018) was significant, and the self‐assessed confidence rating for adherence to guidelines was significant (p < 0.001). Conclusions: This study provides evidence that the quality improvement intervention led to increased adherence to the AAN and AHS migraine‐related measures. It is anticipated that increased adherence may lead to improved patient outcomes. Plain Language Summary: In 2019, the American Academy of Neurology and the American Headache Society worked together to create a set of quality measures to guide clinicians in the care of patients with headache; however, we do not know if these guidelines are being followed. This study aimed to see if resident neurologists at a large academic medical center would better follow these guidelines if they were part of a standardized electronic medical record template. Overall, this study showed that applying the headache quality measures in a real clinical setting is feasible and can improve best‐care practices. [ABSTRACT FROM AUTHOR]

Although significant progress has been made, there is still an urgent need to develop more effective therapies for neurodegenerative diseases (NDs). Recently, mitophagy activation has garnered significant interest as a potential therapeutic target for NDs. There have been advances in understanding how mitophagy functions and its specificity in different cell types, particularly in the central nervous system (CNS). Recent mechanistic insights, combined with the disease-relevant models, enable the rational design and development of mitophagy-activating drugs for the CNS. Mitophagy, the selective degradation of mitochondria, is impaired in many neurodegenerative diseases (NDs), resulting in an accumulation of dysfunctional mitochondria and neuronal damage. Although enhancing mitophagy shows promise as a therapeutic strategy, the clinical significance of mitophagy activators remains uncertain due to limited understanding and poor representation of mitophagy in the central nervous system (CNS). This review explores recent insights into which mitophagy pathways to target and the extent of modulation necessary to be therapeutic towards NDs. We also highlight the complexities of mitophagy in the CNS, highlighting the need for disease-relevant models. Last, we outline crucial aspects of in vitro models to consider during drug discovery, aiming to bridge the gap between preclinical research and clinical applications in treating NDs through mitophagy modulation. [ABSTRACT FROM AUTHOR]

Purpose: Evidence surrounding swallowing impairment in sporadic inclusion body myositis (IBM) is based on nonstandardized and nonvalidated assessment methods. We investigated (a) IBM’s impact on swallowing function and oral intake status using well-tested assessment frameworks; (b) changes in swallowing over time; and (c) age, sex, and swallowing impairment severity’s influence on oral intake status. Method: We conducted a secondary analysis of Modified Barium Swallow Impairment Profile (MBSImP) and Functional Oral Intake Scale (FOIS) data from 13 patients with IBM (seven females; Mage = 60.2 [±13.6] years) and 13 ageand sex-matched healthy controls. We compared MBSImP Overall Impression (OI), Oral Total (OT), Pharyngeal Total (PT), and FOIS scores between groups. Specific to the IBM cohort, we analyzed repeated OT and PT scores and calculated whether age, sex, and OT and PT scores predicted FOIS scores. Results: The IBM cohort demonstrated poorer OI scores across six swallowing components than healthy controls (each p < .05). Unlike OT scores (p = .84), PT (p = .033) and FOIS (p < .001) scores were worse in the IBM cohort. Repeated OI scores revealed changes in three swallowing components (each p < .05), but repeated OT (p = .16) and PT (p = .30) scores did not significantly change. Age, sex, and OT and PT scores did not influence FOIS scores (each p > .05). Conclusions: Pharyngeal impairments were most prominent in the IBM cohort, and their oral intake status was adversely affected. Our preliminary data showcase the application of robust assessment methods to investigate swallowing function in IBM, enhancing standardization and comparability across studies. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine formula granules (TCMFGs) are the advanced dosage forms of the single traditional Chinese herbal decoction pieces, which are widely used for clinical treatment in China. With the clinical application of TCMFG, Erchen decoction (ECD), a classic traditional Chinese medicine (TCM) formula treating phlegm–dampness syndrome, is treated as TCM formula granules instead of herb decoction pieces. However, the chemical profiles and chemical consistency between TCM formula granules ECD and herbal decoction pieces are still unclear. To clarify the chemical profiles in TCM formula granules ECD, the ultra‐high performance liquid chromatography‐Q‐Exactive Orbitrap tandem mass spectrometry technology was used to characterize the chemical profiles of TCM formula granules ECD, and nine characteristic chemical components were further determined. Our exciting finding indicated that a total of 64 components were quantified and glycyrrhizic acid, hesperidin, liquiritigenin, and nobiletin were found to be the major compounds in TCM formula granules ECD and might be the pharmacodynamic material basis of ECD for phlegm–dampness syndrome treatment. The study is to explore the chemical profile and the major compounds quantitatively analysis of TCM formula granules ECD for the first time, which provides a valuable knowledge for the quality control and clinical application on TCM formula granules ECD. [ABSTRACT FROM AUTHOR]

Background: Recent advancements in anomaly detection have paved the way for novel radiological reading assistance tools that support the identification of findings, aimed at saving time. The clinical adoption of such applications requires a low rate of false positives while maintaining high sensitivity. Purpose: In light of recent interest and development in multi pathology identification, we present a novel method, based on a recent contrastive self‐supervised approach, for multiple chest‐related abnormality identification including low lung density area ("LLDA"), consolidation ("CONS"), nodules ("NOD") and interstitial pattern ("IP"). Our approach alerts radiologists about abnormal regions within a computed tomography (CT) scan by providing 3D localization. Methods: We introduce a new method for the classification and localization of multiple chest pathologies in 3D Chest CT scans. Our goal is to distinguish four common chest‐related abnormalities: "LLDA", "CONS", "NOD", "IP" and "NORMAL". This method is based on a 3D patch‐based classifier with a Resnet backbone encoder pretrained leveraging recent contrastive self supervised approach and a fine‐tuned classification head. We leverage the SimCLR contrastive framework for pretraining on an unannotated dataset of randomly selected patches and we then fine‐tune it on a labeled dataset. During inference, this classifier generates probability maps for each abnormality across the CT volume, which are aggregated to produce a multi‐label patient‐level prediction. We compare different training strategies, including random initialization, ImageNet weight initialization, frozen SimCLR pretrained weights and fine‐tuned SimCLR pretrained weights. Each training strategy is evaluated on a validation set for hyperparameter selection and tested on a test set. Additionally, we explore the fine‐tuned SimCLR pretrained classifier for 3D pathology localization and conduct qualitative evaluation. Results: Validated on 111 chest scans for hyperparameter selection and subsequently tested on 251 chest scans with multi‐abnormalities, our method achieves an AUROC of 0.931 (95% confidence interval [CI]: [0.9034, 0.9557], p$ p$‐value < 0.001) and 0.963 (95% CI: [0.952, 0.976], p$ p$‐value < 0.001) in the multi‐label and binary (i.e., normal versus abnormal) settings, respectively. Notably, our method surpasses the area under the receiver operating characteristic (AUROC) threshold of 0.9 for two abnormalities: IP (0.974) and LLDA (0.952), while achieving values of 0.853 and 0.791 for NOD and CONS, respectively. Furthermore, our results highlight the superiority of incorporating contrastive pretraining within the patch classifier, outperforming Imagenet pretraining weights and non‐pretrained counterparts with uninitialized weights (F1 score = 0.943, 0.792, and 0.677 respectively). Qualitatively, the method achieved a satisfactory 88.8% completeness rate in localization and maintained an 88.3% accuracy rate against false positives. Conclusions: The proposed method integrates self‐supervised learning algorithms for pretraining, utilizes a patch‐based approach for 3D pathology localization and develops an aggregation method for multi‐label prediction at patient‐level. It shows promise in efficiently detecting and localizing multiple anomalies within a single scan. [ABSTRACT FROM AUTHOR]

Background: Poly L‐lactic acid (PLLA) can stimulate fibrous tissue regeneration to exert a filling effect. However, severe inflammatory reactions and unsatisfactory effects remain a concern. Objective: Herein, we describe the mechanism of action, efficacy, and safety of PLLA microspheres in suspension (PLLA‐b‐PEG/HA) for facial contouring and soft tissue augmentation. Methods: PLLA‐b‐PEG/HA, ssynthesized by copolymerization with ethylene glycol, were suspended in hyaluronic acid (HA). Physiological verification was performed using scanning electron microscopy and X‐ray computed tomography. PLLA‐b‐PEG/HA were subcutaneously injected into the dorsal region of 4‐month‐old rabbits. Ultrasound assessed volumetric capacity at 3 days and 1, 2, 4, and 12 weeks. The inflammatory response, collagen production, and HA degradation were evaluated. A retrospective case series of 10 patients who received PLLA‐b‐PEG/HA injections was conducted to assess long‐term efficacy and safety. Results: PLLA‐b‐PEG exhibited a spherical structure with a smooth surface (20–45 μm diameter). In rabbits, implant site volume increased within 4 weeks, gradually decreasing thereafter. Fibrous capsules, microvessel density, and new collagen fiber formation progressively increased at 4, 12, and 26 weeks after injection. Clinical data demonstrated significant improvements in face contouring at months 3 and 12 after injection. All patients showed improved internal contours based on the Global Aesthetic Improvement Scale. After 12 months, 90% of the patients retained good shaping and support effects with minimal adverse reactions. Conclusions: PLLA‐b‐PEG/HA demonstrated superior biocompatibility and facial regeneration potential, with outstanding dual collagen‐stimulating properties. The clinical efficacy and safety of PLLA‐b‐PEG/HA have been validated and established as a promising therapeutic option. [ABSTRACT FROM AUTHOR]

Background: Associations between intraoperative hypotension (IOH) and various postoperative outcomes were shown in retrospective trials using a variety of different definitions of IOH. This complicates the comparability of these trials and makes clinical application difficult. Information about the best performing definitions of IOH regarding 30-day mortality, hospital length of stay (hLOS), and postanesthesia care unit length of stay (PACU-LOS) is missing. Methods: A retrospective cohort trial was conducted using data from patients undergoing noncardiothoracic surgery. We split the obtained dataset into two subsets. First, we used one subset to choose the best fitting definitions of IOH for the outcomes 30-day mortality, hLOS, and PACU-LOS. The other subset was used to independently assess the performance of the chosen definitions of IOH. Results: The final cohort consisted of 65,454 patients. In the shaping subset, nearly all tested definitions of IOH showed associations with the three outcomes, where the risk of adverse outcomes often increased continuously with decreasing MAP. The best fitting definitions were relative time with a MAP (mean arterial pressure) of <80 mmHg for 30-day mortality, lowest MAP for one minute for hLOS, and lowest MAP for one cumulative minute for PACU-LOS. Testing these three definitions of IOH in the independent second subset confirmed the associations of IOH with 30-day mortality, hLOS, and PACU-LOS. Conclusions: Using a data-driven approach, we identified the best fitting definitions of IOH for 30-day mortality, hLOS, and PACU-LOS. Our results demonstrate the need for careful selection of IOH definitions. Clinical trial number: n/a, EC #2245/2020 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of comprehensive nursing intervention in pelvic floor and bladder function recovery post-cervical cancer surgery. Method: This was a retrospective study. A total of 120 patients with cervical cancer undergoing radical surgery at Tangshan People's Hospital from June 2021 to June 2023 were randomly divided into two groups (n=60 cases each group). The control group received routine nursing intervention, while the study group was provided with comprehensive nursing intervention. Comparative analysis was conducted on clinical indicators, postoperative complications, bladder and pelvic floor function recovery, and patient satisfaction before and after intervention in both groups. Result: In the study group, ambulation time, gastrointestinal function recovery, duration of postoperative drainage tube placement, oral diet resumption time, duration of postoperative vaginal bleeding, and length of hospital stay were significantly shorter than in the control group (all p< 0.05). Bladder function recovery in the study group was superior to that in the control group (p< 0.05). The study group showed lower scores for anorectal disorders, urogenital disorders, and pelvic organ prolapse than the control group (p< 0.05, respectively). Patient satisfaction was 100% in the study group and 85% in the control group, suggesting a statistically significant difference between the two groups (p< 0.05). Conclusion: Comprehensive nursing intervention deserve to be promoted as it can accelerate postoperative clinical recovery, reduce the incidence of surgical complications, improve pelvic floor and bladder function post-cervical cancer surgery, and enhance patient satisfaction with care. [ABSTRACT FROM AUTHOR]

To outline the current status of Shock Wave Lithotripsy (SWL) in stone treatment and the changes in the mode of application after the COVID-19 pandemic along with critical factors affecting the clinical practice of this particular procedure. This study targeted national and international urology experts who could share and contribute their experiences and perspectives on SWL practices after COVID-19 era. Approximately 650 urology specialists were invited to participate in the survey based study via Google Forms. Participation was voluntary and 398 of the invited participants completed the survey, yielding an acceptable response rate of approximately 61.23%. This survey highlights significant findings that shed light on the changes in clinical SWL applications. Nearly half of SWL procedures are performed by technicians or nurses instead of experienced urologists, potentially affecting the proper application and outcomes of the procedure. SWL seemed to be applied on a guideline (GL) indications based manner by the majority of the participants. Fluoroscopy remains still as the most commonly used method for radiological assessment, underscoring the necessity to teach sonography applications to younger urologists. Key reasons for the limited clinical application of SWL include the absence of lithotripters in the departments, high lithotriptor costs and significantly lower reimbursement rates compared to PNL and fURS modalities. Finally, an increase in SWL utilization rates has been observed post-COVID-19, highlighting its certain advantages realized during this period. These findings provide important insights into the role of SWL in stone treatment and the main factors influencing its clinical application practices. Although the popularity of SWL in the management of urinary stones is being stated to decline particularly in the last two decades, data obtained in this survey emphasized well that it is still a viable option especially for stones smaller than 15 mm. Our findings highlight the enduring relevance of SWL in contemporary stone therapy protocols in the context of COVID-19, where outpatient, non-invasive procedures are preferred. In addition to the consideration of certain factors affecting the rate of its application in clinical practice, to achieve high success rates with minimal complications in SWL, strategic patient selection and adherence to procedure guidelines seem to be crucial. [ABSTRACT FROM AUTHOR]

The development, application, and benchmarking of artificial intelligence (AI) tools to improve diagnosis, prognostication, and therapy in neuro-oncology are increasing at a rapid pace. This Policy Review provides an overview and critical assessment of the work to date in this field, focusing on diagnostic AI models of key genomic markers, predictive AI models of response before and after therapy, and differentiation of true disease progression from treatment-related changes, which is a considerable challenge based on current clinical care in neuro-oncology. Furthermore, promising future directions, including the use of AI for automated response assessment in neuro-oncology, are discussed. [ABSTRACT FROM AUTHOR]

In recent years, bispecific antibodies (BsAbs) have emerged as a promising therapeutic strategy against tumors. BsAbs can recruit and activate immune cells, block multiple signaling pathways, and deliver therapeutic payloads directly to tumor sites. This review provides a comprehensive overview of the recent advances in the development and clinical application of BsAbs for the treatment of solid tumors. We discuss the different formats, the unique mechanisms of action, and the clinical outcomes of the most advanced BsAbs in solid tumor therapy. Several studies have also analyzed the clinical progress of bispecific antibodies. However, this review distinguishes itself by exploring the challenges associated with bispecific antibodies and proposing potential solutions. As the field progresses, BsAbs hold promise to redefine cancer treatment paradigms and offer new hope to patients with solid tumors. [ABSTRACT FROM AUTHOR]

Objectives: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. Methods: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. Results: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. Conclusions: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases. [ABSTRACT FROM AUTHOR]

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike–wave activation in sleep (DEE‐SWAS) and epileptic encephalopathy with spike–wave activation in sleep (EE‐SWAS). Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE‐SWAS or EE‐SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE‐SWAS and EE‐SWAS. Brain‐specific gene co‐expression analysis was performed for D/EE‐SWAS genes. Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE‐SWAS and 13/47 (28%) with EE‐SWAS. A genetic etiology was identified in 31/91 (34%). D/EE‐SWAS genes were highly co‐expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE‐SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE‐SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE‐SWAS. Interpretation: DEE‐SWAS and EE‐SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE‐SWAS and EE‐SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932–943 [ABSTRACT FROM AUTHOR]

To establish whether there are geographic differences in treatments and outcomes for patients with kidney cancer (KC) in England which could potentially be improved by the creation of national guidelines. A multidisciplinary group convened by the charity Kidney Cancer UK developed Quality Performance Indicators (QPIs) for the treatment of KC. Adherence to these QPIs was reported for all patients with a histological diagnosis of KC diagnosed in England between 2017 and 2018. Utilising data extracted from national datasets, logistic and linear probability models were used to estimate geographic variation in the delivery of surgery and systemic anti-cancer therapy at Cancer Alliance and NHS trust levels. Results were adjusted for a priori confounders, including age at diagnosis, area deprivation of residence, and Charlson Comorbidity Index. Differences in overall survival are reported. The cohort comprised 18,640 tumours in 18,421 patients. Of tumours diagnosed, median patient age was 68 (interquartile range 58–77) years and 63.4% were in males. When stratified by Cancer Alliance, the proportions of T1a/T1b/N0/M0 KC that had radical nephrectomy (RN), nephron sparing surgery or ablation ranged from 53.3% (95% CI [48.7, 57.8]) to 80.3% (95% CI [73.0, 86.0]). For stage T1b-3 cancers, the proportion that received RN ranged from 65.6% (95% CI [60.3, 70.5]) to 77.3% (95% CI [72.1, 81.7]). Patients with M0 (n = 12,365) and M1 KC (n = 3312) at diagnosis had 24-month survival of 87.5% and 25.1%, respectively. Of patients diagnosed with M1 KC, 50.3% received systemic anti-cancer therapy, ranging from 39.7% (95% CI [33.7, 46.1]) to 70.7% (95% CI [59.6, 79.8]) between Cancer Alliances. The six-month survival of these patients was 77.4% compared to 27.6% for those that did not receive SACT. These major geographical differences in surgical and systemic therapy practice have led to national guideline development. • Analysis of 18,421 patients with Kidney Cancer presenting in England 2017–18. • Marked variations between Cancer Alliances in rates of surgery for primary kidney cancer. • Systemic anti-cancer therapy improves outcomes in metastatic kidney cancer patients. • Significant variations between Cancer Alliances in systemic anti-cancer therapy use. • Low rates of clinical trial recruitment. [ABSTRACT FROM AUTHOR]

• pCLE enables real-time, cellular-level endometriosis detection during surgery. • Optical biopsies correlate highly with histopathology, enhancing surgical accuracy. • pCLE advances minimally invasive diagnostic practices in gynecology. • Development of a pCLE atlas supports improved diagnostic reliability and surgeon training. To validate probe-based Confocal Laser Endomicroscopy (pCLE) as a method in assessing endometriosis during conventional and robot-assisted laparoscopy. Pilot study, including five women in Hospital Moriah, São Paulo, Brazil. During laparoscopic procedures, pCLE was used to assess endometriosis lesions, complemented by subsequent histological evaluations. 214 optical biopsies were performed. These assessments contributed to the development of a comparative atlas, which was used by surgeons to respond to a questionnaire to identify specific cellular structures related to endometriosis in selected confocal images. The patients had an average age of 35, exhibiting predominant symptoms like dysmenorrhea and dyspareunia. Despite varied familiarity with pCLE, surgeons demonstrated positive acceptance of the method, with 63.1% recommending its use for intraoperative diagnosis. The technique was particularly noted for its ability to provide real-time, detailed images aiding the identification of endometriosis and associated structures like adipocytes and vascularization, with average evaluation scores exceeding 8 of 10. This study underscores pCLE's potential as a transformative diagnostic tool in minimally invasive gynecological surgery. It highlights the feasibility and initial acceptance among surgeons, emphasizing the need for further improvements in device durability and cost-effectiveness. pCLE promises significant advancements in the diagnosis and management of endometriosis, suggesting a future direction for clinical applications and technological refinement. [ABSTRACT FROM AUTHOR]

Cancer research has become increasingly complex over the past few decades as knowledge of the heterogeneity of cancer cells, their proliferative ability, and their tumor microenvironments has become available. Although conventional therapies remain the most compelling option for cancer treatment to date, immunotherapy is a promising way to harness natural immune defenses to target and kill cancer cells. Cell-mediated drug delivery systems (CDDSs) have been an active line of research for enhancing the therapeutic efficacy and specificity of cancer immunotherapy. These systems can be tailored to different types of immune cells, allowing immune evasion and accumulation in the tumor microenvironment. By enabling the targeted delivery of therapeutic agents such as immune stimulants, cytokines, antibodies, and antigens, CDDSs have improved the survival of some patients with cancer. This review summarizes the research status of CDDSs, with a focus on their underlying mechanisms of action, biology, and clinical applications. We also discuss opportunities and challenges for implementation of CDDSs into mainstream cancer immunotherapy. Cell-mediated drug delivery systems leverage the unique biodistribution of erythrocytes, immune cells or stem cells to deliver biomolecules specifically to sites of interest, which provide a new hope for cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Cancer immunotherapy, as an emerging cancer treatment approach, harnesses the patient's own immune system to effectively prevent tumor recurrence or metastasis. However, its clinical application has been significantly hindered by relatively low immune response rates. In recent years, metal-based biomaterials have been extensively studied as effective immunomodulators and potential tools for enhancing anti-tumor immune responses, enabling the reversal of immune suppression without inducing toxic side effects. This review introduces the classification of bioactive metal elements and summarizes their immune regulatory mechanisms. In addition, we discuss the immunomodulatory roles of biomaterials constructed from various metals, including aluminum, manganese, gold, calcium, zinc, iron, magnesium, and copper. More importantly, a systematic overview of their applications in enhancing immunotherapy is provided. Finally, the prospects and challenges of metal-based biomaterials with immunomodulatory functions in cancer immunotherapy are outlined. Cancer immunotherapy, as an emerging cancer treatment approach, harnesses the patient's own immune system to effectively prevent tumor recurrence or metastasis. However, its clinical application has been significantly hindered by relatively low immune response rates. In recent years, metal-based biomaterials have been extensively studied as effective immunomodulators and potential tools for enhancing anti-tumor immune responses, enabling the reversal of immune suppression without inducing toxic side effects. This review introduces the classification of bioactive metal elements and summarizes their immune regulatory mechanisms. In addition, we discuss the immunomodulatory roles of biomaterials constructed from various metals, including aluminum, manganese, gold, calcium, zinc, iron, magnesium, and copper. More importantly, a systematic overview of their applications in enhancing immunotherapy is provided. Finally, the prospects and challenges of metal-based biomaterials with immunomodulatory functions in cancer immunotherapy are outlined. [Display omitted] [ABSTRACT FROM AUTHOR]

The proven efficacy of immunotherapy in fighting tumors has been firmly established, heralding a new era in harnessing both the innate and adaptive immune systems for cancer treatment. Despite its promise, challenges such as inefficient delivery, insufficient tumor penetration, and considerable potential toxicity of immunomodulatory agents have impeded the advancement of immunotherapies. Recent endeavors in the realm of tumor prophylaxis and management have highlighted the use of living biological entities, including bacteria, oncolytic viruses, and immune cells, as a vanguard for an innovative class of live biotherapeutic products (LBPs). These LBPs are gaining recognition for their inherent ability to target tumors. However, these LBPs must contend with significant barriers, including robust immune clearance mechanisms, cytotoxicity and other in vivo adverse effects. Priority must be placed on enhancing their safety and therapeutic indices. This review consolidates the latest preclinical research and clinical progress pertaining to the exploitation of engineered biologics, spanning bacteria, oncolytic viruses, immune cells, and summarizes their integration with combination therapies aimed at circumventing current clinical impasses. Additionally, the prospective utilities and inherent challenges of the biotherapeutics are deliberated, with the objective of accelerating their clinical application in the foreseeable future. This abstract graphic takes concerted action with abstract section and illustrates the engineered live oncolytic biotherapeutics (microbe/virus/cells) from preclinical research to clinical progress. [Display omitted] [ABSTRACT FROM AUTHOR]

Immunotherapy is a rapidly developing and effective strategy for cancer therapy. Among various immunotherapy approaches, peptides have garnered significant attention due to their potent immunomodulatory effects. In particular, melittin emerged as a promising candidate to enhance cancer immunotherapy by inducing immunogenic cell death, promoting the maturation of antigen-presenting cells, activating T cells, enhancing the infiltration and cytotoxicity of effector lymphocytes, and modulating macrophage phenotypes for relieving immunosuppression. However, the clinical application of melittin is limited by poor targeting and systemic toxicity. To overcome these challenges, melittin has been incorporated into biomaterials and related nanotechnologies, resulting in extended circulation time in vivo , improved targeting, reduced adverse effects, and enhanced anti-cancer immunological action. This review provides an in-depth analysis of the immunomodulatory effects of melittin-incorporated nanomedicines and examines their development and challenges for clinical cancer immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to develop a set of nursing‐sensitive quality indicators for acute poisoning in emergency departments. Design: A two‐round e‐Delphi study was conducted from July to November 2023. Methods: Subject‐matter experts from 19 tertiary hospitals across four provinces of China participated in the survey. Potential indicators identified through a literature review were rated on a 5‐point Likert scale and comments solicited. Descriptive statistics were used to demonstrate convergence of expert opinion, and consensus was reached in two rounds. Weights of each indicator were determined by analytic hierarchy process. There were 20 expert responses in Round 1 and 18 in Round 2. Results: After two rounds, experts reached a consensus on definitions, calculation formulas, and data collection methods for these indicators. Three primary and 11 secondary indicators were included in the final nursing‐sensitive quality indicators for acute poisoning in the emergency department. Conclusion: A set of indicators about acute poisoning care, applicable to the Chinese context, was developed in collaboration with emergency nurse specialists. Implications for the Profession and Patient Care: The lack of supervision of the nursing quality for acute poisoning leads to great variability in clinical practice in different medical institutions. The results can help in their standardization in China and in other countries lacking regulation. Our study also offers nursing managers a concrete and operable evaluation tool for quality supervision. Normative nursing behaviours are conducive to increase safety and enhance patients' experience of medical treatment. Impact: The indicators identified in this study closely approach clinical practice and exhibit the characteristics of sensitivity and practicality. Although developed in the Chinese healthcare system, there is potential for adoption or adaption in other healthcare settings. Reporting Method: This study was reported in line with the Conducting and REporting of DElphi studies (CREDE) guidance on Delphi studies. Patient or Public Contribution: No patient or public contribution in this study. Contribution to the Wider Global Clinical Community: The nursing quality of acute poisoning in emergency departments remains a growing attention, but the relevant assessment tools are lack. This study provides a set of nursing‐sensitive quality indicators for acute poisoning to guide the quality monitoring of nursing managers. Study recommendations have broad applicability to all healthcare professionals who are engaged in emergency nursing. [ABSTRACT FROM AUTHOR]

The development of microRNA (miRNA)-based biomarkers has gained significant attention due to their potential diagnostic, prognostic and therapeutic applications. However, the reproducibility of miRNA biomarker research faces unique challenges, primarily due to the influence of pre-analytical and analytical factors. The absence of standardized procedures contributes to inconsistencies across studies, alongside challenges in reference gene selection, data analysis methods and miRNA profiling platforms. Inter-laboratory comparison trials, or ring trials, offer a strategic approach to address technical and biological variability in miRNA biomarker studies. These trials promote standardization, identify sources of variability and strengthen the correlation between miRNAs and clinical outcomes. Despite their underutilization in miRNA biomarker research, ring trials represent a valuable tool for enhancing reproducibility and expediting the translation of miRNA-based biomarkers into clinical applications. [ABSTRACT FROM AUTHOR]

Aim: To examine the personal experiences and perceptions of people with dark skin tones and their carers, in relation to pressure injury. Design: Qualitative study using semi‐structured interviews. Methods: Twenty‐two interviews with people with dark skin tone and/or their family carers, who were known to and visited by community nurses for pressure area management or who had been identified as being at high risk for developing a pressure injury were carried out. Results: Thematic analysis of the interview transcripts revealed that skin discolouration towards a darker hue than usual was the commonest symptom identified by participants as a sign of altered skin integrity and potential pressure damage. Four main overarching themes were revealed through comprehensive analysis of the transcripts: (1) indicators of pressure injury; (2) experienced symptoms of pressure damage; (3) trust in healthcare workers; and (4) improving care for populations with dark skin tones. Conclusion: The findings from this study clearly present how early‐stage pressure damage is identified among people with dark skin tones. Implications for the Profession and/or Patient Care: These findings have the potential to reduce health inequality by influencing and informing clinical policies and strategies in practice. Findings could also lead to the development of patient‐informed educational strategies for nurses and health workers which will enable the early identification of pressure ulcers among people with dark skin tones. Further research is needed to better understand health disparities in relation to preventable patient safety harm. Impact: The findings demonstrate the importance of engaging with and listening to the stories and experiences of people living with pressure damage to help in the early recognition of pressure injuries. Reporting Method: The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines for qualitative research were followed. Patient or Public Contribution: A project steering group reviewed information sheets for participants and checked the interview questions were relevant and suitable. [ABSTRACT FROM AUTHOR]

Tumor vaccine therapy offers significant advantages over conventional treatments, including reduced toxic side effects. However, it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods. Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors, thereby limiting their clinical efficacy. In this study, we developed a nanoparticle-based tumor vaccine, OVA@HA-PEI, utilizing ovalbumin (OVA) as the presenting antigen and hyaluronic acid (HA) and polyethyleneimine (PEI) as adjuvants and carriers. This formulation significantly enhanced the proliferation of immune cells and cytokines, such as CD3, CD8, interferon- γ , and tumor necrosis factor- α , in vivo, effectively activating an immune response against B16–F10 tumors. In vivo fluorescence flow cytometry (IVFC) has already become an effective method for monitoring circulating tumor cells (CTCs) due to its direct, noninvasive, and long-term detection capabilities. Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1 (PD-1) antibody. The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone. Additionally, this combination therapy substantially reduced the number of CTCs in vivo, increased the clearance rate of CTCs by the immune system, and slowed tumor progression. These findings greatly enhance the clinical application prospects of IVFC and tumor vaccines. [ABSTRACT FROM AUTHOR]

Summary: Obesity represents a major public health emergency worldwide, and its etiology is shaped by a complex interplay of environmental and genetic factors. Over the last decade, polygenic risk scores (PRS) have emerged as a promising tool to quantify an individual's genetic risk of obesity. The field of PRS in obesity genetics is rapidly evolving, shedding new lights on obesity mechanisms and holding promise for contributing to personalized prevention and treatment. Challenges persist in terms of its clinical integration, including the need for further validation in large‐scale prospective cohorts, ethical considerations, and implications for health disparities. In this review, we provide a comprehensive overview of PRS for studying the genetics of obesity, spanning from methodological nuances to clinical applications and challenges. We summarize the latest developments in the generation and refinement of PRS for obesity, including advances in methodologies for aggregating genome‐wide association study data and improving PRS predictive accuracy, and discuss limitations that need to be overcome to fully realize its potential benefits of PRS in both medicine and public health. [ABSTRACT FROM AUTHOR]