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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.

Immune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti‐CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high‐mannose glycans into the nanobody against CD47 (HM‐nCD47) and subsequently displayed HM‐nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM‐nCD47‐CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose‐binding lectin, all synergistically activating the macrophage‐mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM‐nCD47‐CVs possessed significantly extended half‐lives and increased accumulation at the tumor site, resulting in a remarkable macrophage‐dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM‐nCD47‐CVs represent a new immunotherapeutic platform for cancer and other diseases. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer related deaths worldwide, although some patients with early‐stage disease can be cured with surgical resection. Standardised reporting of all clinically relevant pathological parameters is essential for best patient care and is also important for ongoing data collection and refinement of important pathological features that impact patient prognosis, staging and clinical care. Using the established International Collaboration on Cancer Reporting (ICCR) procedure, a representative international expert panel of nine lung pathologists as well as an oncologist was convened. Essential core elements and suggested non‐core elements were identified for inclusion in the resected lung cancer pathology data set based on predetermined levels of evidence as well as consensus expert opinion. A lung cancer histopathology reporting guide was developed that includes relevant clinical, macroscopic, microscopic and ancillary testing. Critical review and discussion of current evidence was incorporated into the new data set including changes from the 2021 World Health Organisation (WHO) Classification of Thoracic Tumours, fifth edition, new requirements for grading invasive non‐mucinous adenocarcinomas, assessment of response to neoadjuvant therapy and requirements for molecular testing in early‐stage resected lung carcinomas. This ICCR data set represents incorporation of all relevant parameters for histology reporting of lung cancer resection specimens. Routine use of this data set is recommended for all pathology reporting of resected lung cancer and it is freely available worldwide on the ICCR website (https://www.iccr‐cancer.org/datasets/published‐datasets/). Widespread implementation will help to ensure consistent and comprehensive pathology reporting and data collection essential for lung cancer patient care, clinical trials and other research. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The 22q11.2 deletion syndrome (22q11DS) is associated with a variety of neuropsychiatric outcomes that vary across deletion carriers. We adopted a dimensional approach to provide a comprehensive overview of neuropsychiatric symptom expression in adolescents with 22q11DS and further our understanding of the observed phenotypical heterogeneity.Participants were 208 adolescents with 22q11DS between 10 and 19 years old. Semi‐structured clinical interviews and IQ tests were used to quantify symptom expression on multiple symptom dimensions, some reflecting DSM‐IV diagnostic domains. We investigated symptom expression in those with and without a formal DSM‐IV classification and examined between and within symptom dimensions. We used correlation analyses to explore associations between different symptom dimensions.We demonstrated inter‐individual differences in symptom expression, both between and within neuropsychiatric symptom dimensions. On most symptom dimensions, more than 50% of adolescents expressed at least one clinically relevant symptom. In addition, a significant proportion of youth without a formal DSM‐IV diagnosis reported clinically relevant symptoms (e.g. >85% of those without an ADHD diagnosis reported ADHD symptoms). The exploratory correlation analysis indicated mostly positive correlations between symptom dimensions.The finding that most adolescents with 22q11DS express neuropsychiatric symptoms, even in the absence of a DSM‐IV classification, has substantial ramifications for guiding adequate support. Findings may spur further research into the dimensional structure of neuropsychiatric symptoms in 22q11DS and aid in uncovering mechanisms that contribute to symptom expression. Ultimately, this provides leads to improve clinical care for 22q11DS and to understand phenotypical variation in other high‐risk genetic variants. [ABSTRACT FROM AUTHOR]

ABSTRACT Disorders of somatic mosaicism (DoSMs) are rare genetic disorders arising from postzygotic alteration leading to segmental/nonsegmental disease. Current professional guidelines for standardized variant interpretation focus on germline and cancer variants, making them suboptimal for DoSM variant interpretation. The Brain Malformations Variant Curation Expert Panel (BMVCEP) modified existing guidelines to account for brain‐specific disorders of somatic mosaicism, but applicability to other DoSM presentations is limited. At Washington University in St. Louis School of Medicine, we have adopted the BMVCEP interpretation framework but suggested alterations that make it more suitable for generalized DoSM variant classification. These modifications include (1) expanding applicability beyond genes associated with brain malformations, (2) introduction of a criterion to interpret truncating variants at the C‐terminus of gain of function genes, (3) establishment of a variant allele fraction (VAF) cutoff for applying de novo criteria, and (4) demonstration that in silico prediction tools are relevant to interpretation of gain of function missense variants. Furthermore, modifications to BMVCEP guidelines reduce the number of variants classified as uncertain. The variant classification considerations that we propose have the potential to improve the accuracy of somatic variant classification, better inform clinical care, and may benefit clinical laboratories also conducting DoSM testing. [ABSTRACT FROM AUTHOR]

The success of deep learning (DL) relies heavily on training data from which DL models encapsulate information. Consequently, the development and deployment of DL models expose data to potential privacy breaches, which are particularly critical in data-sensitive contexts like medicine. We propose a new technique named DiffGuard that generates realistic and diverse synthetic medical images with annotations, even indistinguishable for experts, to replace real data for DL model training, which cuts off their direct connection and enhances privacy safety. We demonstrate that DiffGuard enhances privacy safety with much less data leakage and better resistance against privacy attacks on data and model. It also improves the accuracy and generalizability of DL models for segmentation and classification of mediastinal neoplasms in multi-center evaluation. We expect that our solution would enlighten the road to privacy-preserving DL for precision medicine, promote data and model sharing, and inspire more innovation on artificial-intelligence-generated-content technologies for medicine. [ABSTRACT FROM AUTHOR]

Background: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. Results: The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. Conclusion: Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are a type of cell capable of regulating the immune system, as well as exhibiting self-renewal and multi-lineage differentiation potential. Mesenchymal stem cells have emerged as an essential source of seed cells for therapeutic cell therapy. It is crucial to cryopreserve MSCs in liquid nitrogen prior to clinical application while preserving their functionality. Furthermore, efficient cryopreservation greatly enhances MSCs' potential in a range of biological domains. Nevertheless, there are several limits on the MSC cryopreservation methods now in use, necessitating thorough biosafety assessments before utilizing cryopreserved MSCs. Therefore, in order to improve the effectiveness of cryopreserved MSCs in clinical stem cell treatment procedures, new technological techniques must be developed immediately. The study offers an exhaustive analysis of the state-of-the-art MSC cryopreservation techniques, their effects on MSCs, and the difficulties encountered when using cryopreserved MSCs in clinical applications. [ABSTRACT FROM AUTHOR]

Developing a clinical practice guideline (CPG) for integrating traditional Chinese medicine (TCM) and Western medicine (WM) requires the accurate identification, collation, and integration of all available evidence on TCM and WM in a comprehensive, meaningful, and resource‐efficient manner. This entails framing appropriate clinical questions, retrieving and synthesizing evidence from multiple resources, and providing concise and complete recommendations for specific diseases. However, some existing CPGs for integrating TCM and WM lack deep and organic integration. As the effective preparation of a CPG for integrating TCM and WM typically involves a complex set of principles, methodology, and steps, we believe that a cohesive, step‐by‐step guide on how to prepare a CPG for integrating TCM and WM is essential. To facilitate the design and development of a robust CPG, we present a clear and concise methodology, outlining relevant principles and procedures, supported by references for guidance. This technical specification aims to simplify the methodology for preparing a CPG for integrating TCM and WM; provide healthcare professionals and researchers with methodologically sound tools; and enhance the quality of CPGs for integrating TCM and WM. This technical specification may help elucidate this complex process, facilitate evaluation of the quality of published CPGs for integrating TCM and WM, and improve the understanding and application of recommendations for the combined and integrated use of TCM and WM in a new system. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Professional guidelines recommend molecular profiling for mismatch repair (MMR), p53, and polymerase epsilon (POLE) status in endometrial cancer (EC). However, adoption in the United States has not been documented, and barriers to the implementation of testing have not been described.In this mixed‐methods study, implementation science frameworks were used to develop a quantitative survey. Gynecologic oncologists, medical oncologists, radiation oncologists, and pathologists affiliated with NRG Oncology programs were contacted through snowball sampling and were surveyed during 2022–2023. A subset of respondents was interviewed. Statistical and thematic analyses were performed.At least 403 NRG Oncology‐affiliated providers were contacted for the survey, and 107 (26.6%) responded. Greater than 90% of respondents perceived POLE, MMR, and p53 status as important for clinical care. MMR and p53 tests were perceived as easy to obtain, but only 24.2% of respondents reported that POLE testing was moderately or very easy to obtain. Respondents from academic sites reported better access to molecular classification and perceived greater importance of molecular classification compared with respondents from community sites. In thematic analysis of 13 qualitative interviews, cost concerns were reported as large barriers to testing. Interviewees reported a desire for prospective data to guide treatment selection based on classification results.Although integrating molecular classification into standard pathologic reporting is recommended, and clinicians perceive molecular profiling in early stage EC as important, survey respondents noted significant implementation barriers. Implementation challenges that differ between community oncology and academic practice settings were identified. Strategies to improve equitable access to molecular classification of early stage EC are needed. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening syndrome of organ dysfunction, characterized by uncontrolled inflammatory response and immune dysregulation, often leading to multiple organ failure and even death. Specialized pro-resolving mediators (SPMs), which are typically thought to be formed via consecutive steps of oxidation of polyenoic fatty acids, have been shown to suppress inflammation and promote timely resolution of inflammation. They are mainly divided into four categories: lipoxins, resolvins, protectins, and maresins. The SPMs may improve the prognosis of sepsis by modulating the immune and inflammatory balance, thereby holding promise for clinical applications. However, their biosynthetic and pharmacological properties are very complex. Through a literature review, we aim to comprehensively elucidate the protective mechanisms of different SPMs in sepsis and its organ damage, in order to provide sufficient theoretical basis for the future clinical translation of SPMs. [ABSTRACT FROM AUTHOR]

Background: For renal hilar angiomyolipoma, general surgical resection is often quite challenging. The aim of this study is to evaluate the safety and efficacy of an innovative robot-assisted laparoscopic strategy that combines tumor enucleation with tumor aspiration in the treatment of renal hilar angiomyolipoma. Methods: The clinical data of 38 patients with renal hilar angiomyolipoma who went through robotic tumor enucleation combined with tumor aspiration in the Department of Urology, the Affiliated Hospital of Nanjing University Medical School, from December 2019 to December 2022 were retrospectively analyzed. The basic characteristics, the perioperative variables, intraoperative procedures, and postoperative complications were all recorded. Patients were followed up to evaluate the angiomyolipoma recurrence and the renal function by urologic CT or ultrasound and renal function tests. Results: All surgeries were successfully completed without conversion to radical nephrectomy or open surgery. One patient developed urinary extravasation 10 days after surgery, and was readmitted to the hospital for transurethral ureteral stenting considering the injury of the renal collecting system. The median operative time was 181.5 (123.8-206.3) min, the warm ischemia time was 20.0 (17.3–24.0) min, the blood loss was 125 (100.0-262.5) ml, and no patients received blood transfusion during and after surgery. The median hospitalization time was 7.0 (6.0–9.0) days, and the duration of indwelling drainage tube was 2.0 (2.0–3.0) days. The serum creatinine (Scr) on the first day, 3 months, and 6 months after surgery were 55.5 (50.8–62.8) µmol/L, 55.5 (48.0–62.0) µmol/L and 54.0 (51.8–63.5) µmol/L, respectively, and there was no significant difference compared with the preoperative level 56.0 (47.8–60.3) µmol/L. All patients were followed up after surgery, and the urinary CT scan or renal color doppler ultrasound, and renal function were reexamined. The median follow-up time of all patients was 19.0 (14.75-33.0) months, and no local recurrence of angiomyolipoma was seen in all patients. Conclusions: The surgical strategy of robot-assisted laparoscopic tumor enucleation combined with tumor aspiration is safe and effective in the treatment of renal hilar angiomyolipoma. [ABSTRACT FROM AUTHOR]

Introduction: Corticotomy-assisted tooth movement is commonly performed in clinics, however, its time-limited efficacy and the fear of surgery among patients significantly limit its clinical application. Hence, researchers have investigated non-invasive methods to accelerate tooth movement. However, the molecular mechanisms underlying corticotomy-assisted tooth movement are not fully understood. Methods: Micro-CT and TRAP stain were used to tooth movement and bone resorption. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages after corticotomy. Transmission electron microscopy and iron ion detection was used to evaluate ferroptosis and iron metabolism. In addition, we carried out immunohistochemistry, quantitative realtime and flow cytometry verify the effect of iron on macrophage polarization. Results: Single-cell RNA sequencing of digested alveolar bone identified a significant increase in iron metabolism-related genes post-corticotomy. Macrophages play a central role in this field. Following the dimensionality reduction of macrophages, we revealed a new developmental state via pseudotime analysis post-corticotomy. SCENIC analysis revealed that Atf3 is a key transcription factor influencing this new state. We found that Atf3+ macrophages were closely associated with osteoclasts. Moreover, cell chat revealed an increase in cellular communication between Atf3+ macrophages and other cell types after corticotomy. Discussion: These findings suggested that Atf3+ macrophages might play a key role in corticotomy-accelerated tooth movement, thus providing potential targets for drug development. [ABSTRACT FROM AUTHOR]

Cellular immunotherapy exploits the capacity of the human immune system in self-protection and surveillance to achieve the anti-tumor effects. Natural killer (NK) cells are lymphocytes of innate immune system and they display a unique inherent ability to identify and eliminate tumor cells. In this review, we first introduce the basic characteristics of NK cells in the physiological and pathological milieus, followed by a discussion of their effector function and immunosuppression in the tumor microenvironment. Clinical strategies and reports regarding NK cellular therapy are analyzed in the context of tumor treatment, especially against solid tumors. Given the widely studied T-cell therapy in the recent years, particularly the chimeric antigen receptor (CAR) T-cell therapy, we compare the technical features of NK- and T-cell based tumor therapies at the clinical front. Finally, the technical challenges and potential solutions for both T and NK cell-based immunotherapies in treating tumor malignancies are delineated. By overviewing its clinical applications, we envision the NK-cell based immunotherapy as an up-and-comer in cancer therapeutics. [ABSTRACT FROM AUTHOR]

Substance use disorders (SUDs) are highly prevalent and associated with excess morbidity, mortality, and economic costs. Thus, there is considerable interest in the early identification of individuals who may be more susceptible to developing SUDs and in improving personalized treatment decisions for those who have SUDs. SUDs are known to be influenced by both genetic and environmental factors. Polygenic scores (PGSs) provide a single measure of genetic liability that could be used as a biomarker in predicting disease development, progression, and treatment response. Although PGSs are rapidly being integrated into clinical practice, there is little information to guide clinicians in their responsible use and interpretation. In this Review, we discuss the potential benefits and pitfalls of the use of PGSs in the clinical care of SUDs, highlighting current research. We also provide suggestions for important considerations prior to implementing the clinical use of PGSs and recommend future directions for research. [ABSTRACT FROM AUTHOR]

AbstractAlzheimer’s disease is the most common form, accounting for 60–70% of 55 million dementia cases. Even though the precise pathophysiology of AD is not completely understood, clinical trials focused on antibodies targeting aggregated forms of β amyloid (Aβ) have demonstrated that reducing amyloid plaques can arrest cognitive decline in patients in the early stages of AD. In this study, we provide an overview of current research and innovations for controlled release from nano-biomaterial-assisted chimeric antigen receptor macrophage (CAR-M) therapeutic strategies targeted at AD. Nano-bio materials, such as iron-oxide nanoparticles (IONPs), can be made selectively (Hp-Hb/mannose) to bind and take up Aβ plaques like CAR-M cells. By using nano-bio materials, both the delivery and stability of CAR-M cells in brain tissue can be improved to overcome the barriers of the BBB and enhance therapeutic effects. By enhancing the targeting capabilities and stability of CAR-M cells, mRNA-loaded nano-biomaterials can significantly improve the efficacy of immunotherapy for plaque reduction in AD. This novel strategy holds promise for translating preclinical successes into clinical applications, potentially revolutionising the management of AD. [ABSTRACT FROM AUTHOR]

Background: Differentiated thyroid cancer (DTC) requires long-term follow-up due to the risk of delayed recurrence. Follow-up surveillance involves serial neck ultrasound (US) and thyroglobulin (Tg); however, the optimal frequency and diagnostic performance of neck US outside of specialized thyroid cancer centres in higher risk patients is not well defined. We sought to evaluate the diagnostic performance of US and serial Tg in advanced stage DTC. Methods: We retrospectively reviewed our thyroid cancer database for patients with stage III and IV DTC from 2006 to 2018, total thyroidectomy, and at least 2 years follow-up to assess recurrence rates. Those with hemi-thyroidectomy or anti-Tg antibodies were excluded. Diagnostic performance of US and Tg were assessed using a composite reference standard of follow-up imaging and pathology. All relevant US were reviewed by a blinded expert radiologist for uniformity. Results: Of 136 included patients (91 females, mean age 58.9), 26 (19%) had recurrence of DTC over median follow-up of 6.6 years (IQR 5.3–9.3). The sensitivity and specificity of US in diagnosing cervical recurrence were 73.3% (95% CI 0.51–0.96) and 68.3% (95% CI 0.60–0.77) based on historical reports, respectively, and 80% (95% CI 0.60-1.00) and 87.8% (95% CI 0.82–0.93) based on blinded expert review, respectively. Tg had a sensitivity of 95.5% (95% CI 0.89-1.0) and specificity of 96.2% (95% CI 0.92–0.99) in detecting cervical recurrence or distant metastases. False positive US findings on historical US and subsequent review occurred in 38 (28%) and 15 (11%) patients, respectively, while 5 (3.6%) had false positive Tg results. Conclusion: Serial Tg has better sensitivity and specificity than US for detecting recurrence of advanced stage DTC. Furthermore, re-interpretation of abnormal findings using structured US reporting with a subspecialized reader may improve diagnostic performance of US and improve its utility in clinical care. [ABSTRACT FROM AUTHOR]

Radiotherapy, a traditional cancer treatment, not only controls local tumor growth but also potentially induces immunogenic cell death, initiating systemic immune responses. However, radiotherapy resistance and immunosuppressive tumor microenvironments often limit the potency of radiation‐induced anti‐tumor immune responses, rendering them insufficient for clinical applications. Consequently, trimetallic nanoparticles are constructed with dual enzymatic activity, AuBiCu‐distearoyl phosphoethanolamine‐PEG nanoparticles (AuBiCu‐PEG NPs), to synergistically improve radiotherapy resistance through X‐ray deposition, hypoxia alleviation, and ferroptosis and cuproptosis induction. This approach promotes radiotherapy‐induced immunogenic cell death and boosts anti‐tumor immune responses. Furthermore, AuBiCu‐PEG NPs effectively reversed radiation‐induced upregulation of programmed cell death 1 ligand 1 (PD‐L1), inhibit tumor immune evasion, and reshaped the immune microenvironment. Non‐invasive and real‐time longitudinal monitoring of nanoparticle accumulation in tumors can be achieved using spectral computed tomography (CT) and photoacoustic (PA) imaging. In summary, the designed AuBiCu‐PEG NPs serve as promising nanoplatforms for immune microenvironment remodeling and can be used in multimodal molecular imaging‐guided ferroptosis‐cuproptosis‐enhanced radiotherapy. [ABSTRACT FROM AUTHOR]

Following a systematic review of quality indicators employed in the evaluation of clinical care for individuals with HIV and AIDS, we performed “an exploratory study” that aims to assess the clinical significance and practical applicability of these indicators from the perspective of health care professionals (HCPs) specialising in HIV and AIDS care. Twenty-five HCPs filled out two questionnaires. From the initial list of 88 quality indicators, 50 were identified as the most relevant and useful in HIV and AIDS clinical care. Analysis was conducted on the individual indicators, and the outcomes were categorised into seven domains for clinical relevance and practical usefulness. Health care professionals deemed the functional organisational structure and the therapy domain to have the most pertinent and useful indicators among the seven different clinical domains, followed by the prevention domain. [ABSTRACT FROM AUTHOR]

Microscopic examination of cells in their tissue context has been the driving force behind diagnostic histopathology over the past two centuries. Recently, the rise of advanced molecular biomarkers identified through single cell profiling has increased our understanding of cellular heterogeneity in cancer but have yet to significantly impact clinical care. Spatial technologies integrating molecular profiling with microenvironmental features are poised to bridge this translational gap by providing critical in situ context for understanding cellular interactions and organization. Here, we review how spatial tools have been used to study tumor ecosystems and their clinical applications. We detail findings in cell-cell interactions, microenvironment composition, and tissue remodeling for immune evasion and therapeutic resistance. Additionally, we highlight the emerging role of multi-omic spatial profiling for characterizing clinically relevant features including perineural invasion, tertiary lymphoid structures, and the tumor-stroma interface. Finally, we explore strategies for clinical integration and their augmentation of therapeutic and diagnostic approaches. Gong et al. review how spatial tools have been used to study tumor ecosystems and their clinical applications. They discuss findings in spatial cancer biology, highlight the emerging role of multi-omic spatial profiling for characterizing clinically relevant features, and explore strategies for clinical integration and their augmentation of therapeutic and diagnostic approaches. [ABSTRACT FROM AUTHOR]

Point-of-care ultrasound (POCUS) has increasingly been used by neonatal providers in neonatal intensive care units in the United States. However, there is a lack of literature addressing the complexities of POCUS coding and billing practices in the United States. This article describes the coding terminology and billing process especially those relevant to neonatal POCUS. We elucidate considerations for neonatal POCUS billing framework and workflow integration. Directions on image storage and supporting documentation to facilitate efficient reimbursement, compliance with billing regulations, and appeal to insurance claim denial are discussed. Key Points Code neonatal POCUS procedure precisely allows accurate reimbursement and reduced errors in billing. Document details to support medical necessity and reimbursement claims effectively. Adhere to regulations to avoid audits, denials, and ensure proper reimbursement. [ABSTRACT FROM AUTHOR]

The limited accessibility of mental healthcare providers highlights the need for innovative approaches to provide effective and efficient care. Digital mental health applications (DMHAs) can improve patient access to evidence-based treatments and reduce burden on the healthcare system. Here, we examined the provider and patient barriers and facilitators to integration of DMHAs in a healthcare system. Patients (n = 57) and providers (n = 100) were recruited from a large healthcare system over five months. Participants completed a survey assessing attitudes towards DMHAs, and perceived facilitators and barriers to adoption and utilization of DMHAs in mental healthcare. DMHA credibility was a key facilitator for provider adoption, while usability and accessibility were identified as key facilitators for patient utilization. Provider barriers included patient cost/provider reimbursement, limited knowledge, perceived limits to credibility, patient outcome enhancement, and personalization of DMHAs for patient needs. Patients identified privacy concerns as the top barrier for using DMHAs. The self-report survey nature of this study, modest sample size, and majority of sample identifying as White and upper middle class make results subject to biases and limitations. Given the potential of DMHAs to address disparities in access to mental healthcare, more research is needed including populations who are at greatest risk. Findings provide new insights to inform the development of intervention strategies to improve the integration of DMHAs within healthcare systems. Additional research examining key stakeholders at different levels of care is critical to address barriers, optimize facilitators, and develop roadmaps for best-practice use in healthcare systems. • DMHA credibility, usability, and accessibility are important facilitators to adoption and use. • Barriers include concerns related to cost/reimbursement, DMHA knowledge, credibility, benefit, personalization, and privacy. • Provider/patient discrepancies around timing of DMHA integration in stepped-care models require further exploration. • Findings can help inform development of roadmaps for best-practice use of DMHAs in healthcare systems. [ABSTRACT FROM AUTHOR]

The integration of biomaterials in medical applications triggers the foreign body response (FBR), a multi-stage immune reaction characterized by the formation of foreign body giant cells (FBGCs). Originating from the fusion of monocyte/macrophage lineage cells, FBGCs are pivotal participants during tissue-material interactions. This review provides an in-depth examination of the molecular processes during FBGC formation, highlighting signaling pathways and fusion mediators in response to both exogenous and endogenous stimuli. Moreover, a wide range of material-specific characteristics, such as surface chemical and physical properties, has been proven to influence the fusion of macrophages into FBGCs. Multifaceted biological activities of FBGCs are also explored, with emphasis on their phagocytic capabilities and extracellular secretory functions, which profoundly affect the vascularization, degradation, and encapsulation of the biomaterials. This review further elucidates the heterogeneity of FBGCs and their diverse roles during FBR, as demonstrated by their distinct behaviors in response to different materials. By presenting a comprehensive understanding of FBGCs, this review intends to provide strategies and insights into optimizing biocompatibility and the therapeutic potential of biomaterials for enhanced stability and efficacy in clinical applications. As a hallmark of the foreign body response (FBR), foreign body giant cells (FBGCs) significantly impact the success of implantable biomaterials, potentially leading to complications such as chronic inflammation, fibrosis, and device failure. Understanding the role of FBGCs and modulating their responses are vital for successful material applications. This review provides a comprehensive overview of the molecules and signaling pathways guiding macrophage fusion into FBGCs. By elucidating the physical and chemical properties of materials inducing distinct levels of FBGCs, potential strategies of materials in modulating FBGC formation are investigated. Additionally, the biological activities of FBGCs and their heterogeneity in responses to different material categories in vivo are highlighted in this review, offering crucial insights for improving the biocompatibility and efficacy of biomaterials. [Display omitted] [ABSTRACT FROM AUTHOR]

The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. STING agonists have shown potential in enhancing immune responses, particularly in tumors resistant to traditional therapies. This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, and delivery methods remain obstacles to their broader clinical use. Ongoing research and innovation are essential to overcoming these hurdles. STING agonists could play a transformative role in cancer treatment, particularly for patients with hard-to-treat malignancies, by harnessing the body's immune system to target and eliminate cancer cells. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common autoimmune disease characterized primarily by persistent synovial inflammation and joint destruction. In recent years, ferroptosis, as a novel form of cell death, has garnered widespread attention due to its critical role in various diseases. This review explores the potential mechanisms of ferroptosis in RA and its relationship with the pathogenesis of RA, systematically analyzing the regulatory role of ferroptosis in synovial cells, chondrocytes, and immune cells. We emphasize the evaluation of ferroptosis-related pathways and their potential as therapeutic targets, including the development and application of inhibitors and activators. Although ferroptosis shows some promise in RA treatment, its dual role and safety issues in clinical application still require in-depth study. Future research should focus on elucidating the specific mechanisms of ferroptosis in RA pathology and developing more effective and safer therapeutic strategies to provide new treatment options for RA patients. [ABSTRACT FROM AUTHOR]

In recent years, with the aggravation of aging, the incidence of neurodegenerative diseases is increasing year by year, and the prognosis of patients is poor. Functional Near-Infrared Spectroscopy (fNIRS) is a new and non-invasive neuroimaging technology, which has been gradually deepened in the application research of neurodegenerative diseases by virtue of its unique neurooxygen signal brain functional imaging characteristics in monitoring the disease condition, making treatment plans and evaluating the treatment effect. In this paper, the mechanism of action and technical characteristics of fNIRS are briefly introduced, and the application research of fNIRS in different neurodegenerative diseases is summarized in order to provide new ideas for future related research and clinical application. [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]

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-1ß, IL-6, and TNF-a) 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]

Cell-derived extracellular vesicles (EVs), which carry diverse biomolecules such as nucleic acids, proteins, metabolites, and lipids reflecting their cell of origin, are released under both physiological and pathological conditions. EVs have been demonstrated to mediate cell-to-cell communication and serve as biomarkers. EV-associated DNA (EV-DNA) comprises genomic and mitochondrial DNA (i.e., gDNA and mtDNA) fragments. Some studies have revealed that EV-DNA can represent the full nuclear genome and mitochondrial genome of parental cells. Furthermore, DNA fragments loaded into EVs are stable and can be transferred to recipient cells to regulate their biological functions. In this review, we summarized and discussed EV-DNA research advances with an emphasis on EV-DNA detection at the population-EV and single-EV levels, gene transfer-associated biological functions, and clinical applications as biomarkers for disease liquid biopsy. We hope that this review will provide potential directions or guidance for future EV-DNA investigations. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of human mortality worldwide. Despite Western medicine having made encouraging results in the clinical management of CVD, the morbidity, mortality, and disability rates of the disease remain high. Modern pharmacology has confirmed that traditional Chinese medicine (TCM), characterized by its multi-component, multi-target, and integrity, plays a positive and important role in the prevention and treatment of various CVDs in China, which has notable advantages in stabilizing disease, improving heart function, and enhancing the quality of life. Importantly, TCM is gradually being accepted by the international community due to its low cost, high safety, versatile bioactivity, and low toxicity. Unfortunately, comprehensive studies on the therapeutic effect of TCM on CVD and its mechanisms are very limited, which may restrict the clinical application of TCM in CVD. Therefore, this review is performed to analyze the pathogenesis of CVD, including inflammatory response, oxidative stress, mitochondrial dysfunction, pyroptosis, ferroptosis, dysbiosis of gut microbiota, etc. Moreover, we summarized the latest progress of TCM (formulas, extracts, and compounds) in curing CVD according to published literature from 2018 to 2023, as well as its mechanisms and clinical evidence. In conclusion, this review is expected to provide useful information and reference for the clinical application of TCM in the prevention and treatment of CVD and further drug development of CVD. [ABSTRACT FROM AUTHOR]

The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) is increasing at a rapid pace and is becoming an increasingly important consideration in clinical care. Epidemiological data from multiple countries indicate that the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibits regional, site-specific, and gender-based variations. While the genetics and pathogenesis of some GEP NEN, particularly pancreatic NENs, have been investigated, there are still many mechanisms that require further investigation. The management of GEP NEN is diverse, but surgery remains the primary option for most cases. Peptide receptor radionuclide therapy (PRRT) is an effective treatment, and several clinical trials are exploring the potential of immunotherapy and targeted therapy, as well as combination therapy. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Diabetes distress (DD) refers to the emotional and behavioural challenges associated with managing this demanding chronic disease over time. DD is alarmingly common and it has a significant impact on self‐management behaviours and clinical outcomes. Thus, there is growing recognition that DD is a pressing problem that deserves careful attention in clinical care. Translating the application of validated DD assessment and intervention protocols from the research to the clinical setting, however, presents challenges that require a reconsideration of some common assumptions about what DD is, how prevalent it is, how it presents itself clinically, how it might best be assessed and by whom.We employed data from six large‐scale studies using five common DD measures. Using these data, we review and challenge several common assumptions about DD.These data suggest that, because of its relative ubiquity, DD should not be viewed as a ‘co‐morbidity’ or ‘complication’ of diabetes and it should not be seen as a mental health/illness ‘condition’. Furthermore, we argue that DD assessment should: (1) be accepted as a standard part of comprehensive diabetes care, (2) occur regularly using broad rather than brief screening measures and (3) be addressed directly by diabetes clinicians, rather than exclusively by behavioural specialists.The results form the basis of a series of suggestions to enhance the translation, adoption and implementation of DD knowledge derived from the research setting directly into the real world of clinical care. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodResultsConclusionsThe aim of this study was to compare and analyze the clinical effects of endoscopic submucosal dissection (ESD) and endoscopic band electrocision ligation (EEL) in the removal of gastric submucosal tumors (SMTs).We analyzed the clinical data of 130 patients with gastrointestinal SMTs (diameter ≤10 mm) who underwent endoscopic resection, including 62 cases in the EEL group and 68 in the ESD group, and compared indicators such as surgical time, intraoperative and postoperative complications, postoperative hospital stay, and surgical cost, between the EEL and ESD group.EEL surgery time (8.9 ± 1.1 min) was significantly shorter than the ESD group (62.3 ± 2.8 min) (p < .05), EEL surgery cost (5126.8 ± 26.5 yuan) was significantly lower than the ESD group (15721.3 ± 39.6 yuan) (p < .05), and intraoperative blood loss was also markedly lower in the EEL group (5.6 ± 1.7 ml) compared to the ESD group (42.3 ± 3.5 ml) (p < .05). There was no statistically significant difference in postoperative hospitalization time or postoperative complication incidence between the two groups (p > .05).In treating gastric muscular, mucosal, or submucosal tumors with a diameter of less than 10 mm, the EEL surgical method was superior to the ESD surgical method in terms of surgical time, intraoperative blood loss, and cost. There was no difference in hospital stay and postoperative complication rate between the two methods, which was worthy of clinical application. [ABSTRACT FROM AUTHOR]

Background: Homocysteine (HCY) is a sulfur-containing amino acid that is an independent or important risk factor for the occurrence of many chronic diseases and is one of the most important indicators for determining health risks. However, existing HCY detection methods do not meet the requirements of clinical diagnosis. Therefore, there is an urgent need to establish new detection methods to meet the needs of clinical detection. Results: In this study, we used the principle of competitive method to establish a new method for the determination of HCY in human serum using a chemiluminescent enzyme immunoassay in conjunction with a chemiluminescent assay instrument that uses magnetic microparticles as the solid phase of the immunoreaction. The established method achieved satisfactory results in terms of minimum detection limit, specificity, accuracy, and clinical application. The limit of detection was 0.03 ng/mL. The intra-assay coefficient of variation (CV) was 1.94–5.05%, the inter-assay CV was 2.29–6.88%, and the recovery rate was 88.60–93.27%. Cross-reactivity with L-cysteine ranged from 0.0100 to 0.0200 μmol/L, and cross-reactivity with glutathione ranged from 0.0100 to 0.200 μmol/L, all of which were less than the limit of detection (LoD) of this method. The linear factor R of this method was greater than 0.99. Conclusions: In summary, the developed method showed a good correlation with the product from Abbott. A total of 996 clinical patients with cardiovascular diseases were evaluated using the method developed in this study. [ABSTRACT FROM AUTHOR]

Summary Cellular metabolism influences all aspects of cellular function and is crucial for overall organismal health. Metabolic disorders related to cardiovascular health can lead to cardiovascular diseases (CVDs). Moreover, associated comorbidities may also damage cardiovascular metabolism, exacerbating CVD and perpetuating a vicious cycle. Given the prominent role of metabolic alterations in CVD, metabolomics has emerged as an imperative technique enabling a comprehensive assessment of metabolites and metabolic architecture within the body. Metabolite profile and metabolic pathways help to deepen and broaden our understanding of complex genomic landscape and pathophysiology of CVD. Here in this review, we aim to overview the experimental and clinical applications of metabolomics in pathogenesis, diagnosis, prognosis, and management of various CVD plus future perspectives and limitations. [ABSTRACT FROM AUTHOR]

As frontline cells, the precise recruitment of neutrophils is crucial for resolving inflammation and maintaining the homeostasis of the organism. Increasing evidence suggests the pivotal role of neutrophil chemotaxis in cancer progression and metastasis. Here, we collected clinical data and peripheral blood samples from patients with tumours to examine the alterations in the neutrophil quantity and chemotactic function using the Cell Chemotaxis Analysis Platform (CCAP). Transcriptome sequencing data of pan-cancer were obtained from The Cancer Genome Atlas (TCGA). Using the least absolute shrinkage and selection operator (LASSO) Cox regression model, we selected a total of 29 genes from 155 neutrophil- and chemotaxis-related genes to construct the ChemoScore model. Meanwhile, nomogram-based comprehensive model was established for clinical application. Furthermore, immunofluorescence (IF) staining was employed to assess the relationship between the neutrophils infiltrating and the survival outcomes of tumours. In this observational study, the chemotactic function of neutrophils was notably diminished in patients. The establishment and validation of ChemoScore suggested neutrophil chemotaxis to be a risk factor in most tumours, whereby higher scores were associated with poorer survival outcomes and were correlated with various immune cells and malignant biological processes. Moreover, IF staining of tumour tissue substantiated the adverse correlation between neutrophil infiltration and the survival of patients with lung adenocarcinoma (P = 0.0002) and colon adenocarcinoma (P = 0.0472). Taken together, patients with tumours demonstrated a decrease in chemotactic function. ChemoScore potentially prognosticates the survival of patients with tumours. Neutrophil chemotaxis provides novel directions and theoretical foundations for anti-tumour treatment. [ABSTRACT FROM AUTHOR]

Intracellular oligonucleotide delivery possesses unparalleled potential for precise regulation of pathogenic gene expression and alteration of cell destiny. However, limited by its feeble resistance against humoral environment, hindered intracellular transportation, and lysosomal phagocytosis, oligonucleotide therapy remains a formidable challenge. The discovery of cationic peptides has provided innovative insights for the effective delivery of oligonucleotides, yet the stable, efficient, and convenient assembly of peptides and oligonucleotides remains an elusive goal, referred to as the "Holy Grail" challenge in the field. Addressing this challenge, it has pioneered the development of a straightforward and highly efficient engineering carrier‐free covalent peptide‐oligonucleotide nano‐conjugates (PONs) through a mild click reaction. Notably, this PONs can realize self‐assemble into nanoparticles under amphiphilic electrostatic interactions, which exhibits significant RNase resistance and surprisingly effective intracellular oligonucleotide delivery as well as lysosomal escape. Based on this strategy, a PONs named CPP‐(DOPA)6‐miRNA‐223 is synthesized, which demonstrates rapid and effective cellular uptake, swift lysosomal escape in macrophage, remarkable accumulation in inflammatory regions and excellent therapeutic effect in an inflammatory arthritis model. Therefore, this work may provide a breakthrough for the clinical application of all oligonucleotide delivery therapies and expanding the applications in gene therapy. [ABSTRACT FROM AUTHOR]

Monitoring the status of grafts and the occurrence of postoperative complications, such as rejection, is crucial for ensuring the success and longterm survival of organ transplants. Traditional histopathological examination, though effective, is an invasive procedure and poses risks of complications, making frequent use impractical. In recent years, graft-derived cell-free DNA (gd-cfDNA) has emerged as a promising non-invasive biomarker. It not only provides early warnings of rejection and other types of graft injury but also offers important information about the effectiveness of immunosuppressive therapy and prognosis. gd-cfDNA shows potential in the monitoring of organ transplants. The early, real-time information on graft injury provided by gd-cfDNA facilitates timely individualized treatment and improves patient outcomes. However, the progress of research on gd-cfDNA varies across different organs. Therefore, this article will comprehensively review the application and findings of gd-cfDNA in monitoring various solid organs, discussing the advantages, limitations, and some future research directions to aid in its clinical application. [ABSTRACT FROM AUTHOR]

Aim: Tacrolimus, an immunosuppressant used to prevent organ rejection in renal transplant patients, exhibits high inter-patient variability, necessitating therapeutic drug monitoring. Early post-transplant tacrolimus exposure in Hispanics is understudied. Although genotypic information is linked to pharmacokinetic differences, its clinical application remains limited. This study aimed to use a real-world data-driven, pharmacokinetic model-based approach for tacrolimus in Hispanics to determine a suitable initial dose and design an optimal dose titration strategy by simulations to achieve plasma trough concentration target levels of 10-12 ng/mL at the earliest. Methods: Sparse concentration-time data of tacrolimus were obtained from electronic medical records for self-identified Hispanic subjects following renal transplant. Rich pharmacokinetic literature data was leveraged to estimate structural pharmacokinetic model parameters, which were then fixed in the current analysis. Only apparent clearance was estimated with the sparse tacrolimus data and potential covariates were identified. Simulations of various starting doses and different dose titration strategies were then evaluated. Results: The analysis included 121 renal transplant patients with 2,215 trough tacrolimus concentrations. A two-compartment transit absorption model with allometrically scaled body weight and time-varying hematocrit on apparent clearance adequately described the data. The estimated apparent clearance was 13.7 L/h for a typical patientweighing 70 kg and at 30%hematocrit, demonstrating a 40% decrease in clearance compared to other patient populations. Model based simulations indicated the best initial dose for the Hispanic population is 0.1mg/kg/day. The proposed titration strategy, with three dose adjustments based on trough levels of tacrolimus, increased the proportion of patients within the target range (10-12 ng/mL) more than 2.5-fold and decreased the proportion of patients outside the therapeutic window by 50% after the first week of treatment. Conclusion: Hispanic renal transplant population showed an estimated 40% decrease of apparent clearance in the typical patient compared to other populations with similar characteristics. The proposed dose adjustment attained the target range rapidly and safely. This study advocates for tailored tacrolimus dosing regimens based on population pharmacokinetics to optimize therapy in Hispanic renal transplant recipients. [ABSTRACT FROM AUTHOR]

In June–July 2022, the Randomization Working Group () conducted an online survey on the current practices in the application of randomization in clinical trials. Of 145 unique respondents, 137 (94.5%) identified themselves as statisticians. The majority of respondents were from academia and pharmaceutical companies. Permuted block randomization, with or without stratification, was the most frequently chosen method of randomization for RCTs. Interactive Web-Based Response Systems (IWRS) and "in-house" or a combination of "in-house and outsourced" randomization models were found to be most common in practice. Over 80% of respondents perceived some challenges to adoption of new randomization methods that may have more desirable properties. Over 80% of respondents identified opportunities for improving current practice, including education/training, development of standards/guidance on randomization, and adoption of validated software for generating randomization sequences. In summary, practitioners acknowledge the pivotal role of randomization in clinical trials. There are some perceived challenges to successful implementation of randomization, and there are opportunities for improving practice. [ABSTRACT FROM AUTHOR]

According to SAMHSA (2023), approximately 16,600,000 American adults and teens reported having serious thoughts of suicide in 2022. While suicide prevention has primarily focused on suicide deaths and attempts, we contend that suicidal ideation (SI) deserves more in-depth investigation and should be an essential intervention target on its own. In support of this point, we provide three examples of ways to improve specificity in understanding of SI through the study of controllability of SI, the language used to assess SI, and measuring SI in real time. We also consider qualitative work on the content of SI, its treatment, and definitional considerations. We thus call for an increased general focus on SI within research, clinical care, and policy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical efficacy of 3D-printed fusion cage implantation in treating cervical spondylotic myelopathy. Methods: A retrospective analysis was performed on 52 patients with single-segment cervical spondylotic myelopathy who received anterior cervical discectomy and fusion in Affiliated Hospital of Beihua University from July 2019 to July 2022. They were divided into the 3D group and the control group. Afterward, the perioperative indicators were compared between the two groups. Meanwhile, the Japanese Orthopaedic Association (JOA) scores, Visual analogue scale (VAS) and neck disability index (NDI) were recorded pre-operation and one-year post-operation. Evaluate the fusion rate of two group of intervertebral fusion cages. Results: The JOA score and NDI of the two groups of patients were significantly improved compared to pre-operation (P<0.05), and the JOA score, JOA score improvement rate, and NDI of the 3D group were better than the control group (P<0.05), the VAS scores were significantly improved compared to pre-operation(P<0.05), but there was no statistically significant difference between the groups (P>0.05). The intervertebral height, angle, and cervical Cobb angle of the two groups of patients were significantly improved compared to pre-operation (P<0.05), and the improvement of intervertebral height, angle, and cervical Cobb angle in the 3D group was better than the control group (P<0.05). Conclusion: The clinical efficacy of 3D printed intervertebral fusion cage placement in the treatment of cervical spondylotic myelopathy may be reliable, and it would be better than traditional intervertebral fusion cages in maintaining the height, angle, cervical Cobb angle, and fusion rate of the intervertebral space. [ABSTRACT FROM AUTHOR]

Patients with neurological illnesses have many palliative care needs that need to be addressed in the outpatient clinical setting. This review discusses existing models of care delivery, including services delivered by neurology teams, palliative care specialists, telehealth, and home-based programs. We review the existing literature that supports these services and ongoing limitations that continue to create barriers to necessary clinical care for this vulnerable patient population. [ABSTRACT FROM AUTHOR]

The field of neuro-oncology has seen significant advances that have allowed the expansion of the therapeutic armamentarium. Nevertheless, overall outcomes have not improved significantly particularly for high-grade tumors. The relative rarity of these pathologies in the pediatric population limits the capacity to design large-scale, multicenter, randomized clinical trials. The emergence of precision medicine as a direct result of better, more widespread genetic and molecular testing affords clinicians the possibility of envisioning new clinical trial paradigms. Each patient becomes their own singular trial receiving the most tailored treatment at every stage of their disease while serving as their own controls. Although limitations still exist for the widespread adoption of these technologies and incorporation into standard clinical care, the prospect of being able to offer directed therapies and monitor disease progression based on single-patient testing represents a much-needed paradigm shift in neuro-oncology. [ABSTRACT FROM AUTHOR]

To provide an overview of the I‐CAH Registry. Following the successful roll‐out of the I‐DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I‐CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I‐CAH Registry are important tools for all stakeholders involved in the care of people with CAH. [ABSTRACT FROM AUTHOR]

Background: Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I‐CAH, https://sdmregistries.org/) was established to enable insights into CAH management and outcomes, yet its global adoption by endocrine centres remains unclear. Design: We sought (1) to assess current practices amongst clinicians managing patients with CAH in the United Kingdom and Ireland, with a focus on choice of glucocorticoid, monitoring practices and screening for associated co‐morbidities, and (2) to assess use of the I‐CAH registry. Measurements: We designed and distributed an anonymised online survey disseminated to members of the Society for Endocrinology and Irish Endocrine Society to capture management practices in the care of patients with CAH. Results: Marked variability was found in CAH management, with differences between general endocrinology and subspecialist settings, particularly in glucocorticoid use, biochemical monitoring and comorbidity screening, with significant disparities in reproductive health monitoring, notably in testicular adrenal rest tumours (TARTs) screening (p =.002), sperm banking (p =.0004) and partner testing for CAH (p <.0001). Adoption of the I‐CAH registry was universally low. Conclusions: Differences in current management of CAH continue to exist. It appears crucial to objectify if different approaches result in different long‐term outcomes. New studies such as CaHASE2, incorporating standardised minimum datasets including replacement therapies and monitoring strategies as well as longitudinal data collection, are now needed to define best‐practice and standardise care. [ABSTRACT FROM AUTHOR]