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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]

Introduction: Human peripheral blood mononuclear cells (hPBMCs) are widely used in fundamental research and clinical applications as studying their responses to in vitro activation is an effective way to uncover functional alterations and disease associated phenotypes. However, the availability of samples in large numbers at a specific time and location remains challenging, hence they often might preferably be collected and cryopreserved for later analysis. While the effect of cryopreservation on viability and cell surface expression is well established, changes in activity and cytokine secretion still lead to conflicting results as it is often measured in bulk or within the cells. Methods: Here, we used our platform for dynamic single-cell multiplexed cytokine secretion measurement and compared it to a traditional intracellular cytokine staining to quantify the effect of cryopreservation on cytokine secretion and expression of individual hPBMCs. Results: Following stimulation with LPS or anti-CD3/CD28 antibodies for up to 36 or 72 h incubation, we observed distinct alterations in cytokine responses due to cryopreservation when comparing to fresh samples, but also remarkable consistencies for some cytokines and parameters. In short, the frequencies of cytokine-secreting cells in cryopreserved samples were lower for IL-6 (LPS), IL1-b (CD3/CD28) and IFN-g (CD3/CD28), while the frequency and dynamics of IL-8 secretion were strongly impacted in all cases. We observed a large disconnect between cytokine expression and secretion for TNF-a, where the expression dramatically increased after cryopreservation, but actual secretion was, in comparison, remarkably stable. The polyfunctionality of single cells was altered by cryopreservation in specific co-secreting populations led by the effects on IL-6 or IL-8 secretion. Among immune cells, cryopreservation seemed to affect lymphocytes and monocytes differently as effects appeared early on in lymphocytes while generally observed in later time points in monocytes. Conclusion: Together, this study offers an in-depth quantitative insight into the biological behavior of immune cells in response to cryopreservation and stimulation, further providing some insights into conflicting results in the literature as well as guidelines for researchers planning to assess cytokine-secreting from frozen hPBMCs in immunological research or clinical applications. [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]

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]

High viscosity glass ionomer cements (GICs) are widely used in various clinical applications, being particularly effective in atraumatic restorative treatment (ART) due to the synergistic interaction between the material and the technique. However, the inadequate mechanical properties of GICs raise concerns regarding the predictability and longevity of these restorations in areas exposed to occlusal stress. Various modifications of the powder components have been proposed to improve the mechanical strength of GICs to withstand occlusal loading during mastication. In this in vitro study, we investigated whether the nanoparticles (NPs) added to commercially available GICs could fulfill this requirement, which would likely broaden the spectrum of their potential clinical applications. Two commercially available GIC powders (Fuji IX and Ketac Molar), modified by the addition of 5 wt.% TiO2, MgHAp100 or MgHAp1000 NPs, were incorporated into the corresponding liquid in an appropriate ratio, and the mixed cements were evaluated in terms of fracture toughness, flexural strength, Vickers microhardness and rheological tests and compared with the original material. Fuji IX containing 5 wt.% MgHAp100 NPs had lower flexural strength, while Ketac Molar with 5 wt.% TiO2 NPs showed increased fracture toughness. Vickers microhardness increased in Fuji IX following the addition of 5 wt.% TiO2 and MgHAp100 but decreased in Ketac Molar comprising 5 wt.% MgHAp100 (p < 0.05). Achieving a predictable bond between NPs and cement matrix, as well as ensuring a uniform distribution of the NPs within the cement, are critical prerequisites for enhancing the mechanical performance of the original cement. [ABSTRACT FROM AUTHOR]

Multimodal technology is poised to revolutionize clinical practice by integrating artificial intelligence with traditional diagnostic modalities. This evolution traces its roots from Hippocrates' humoral theory to the use of sophisticated AI-driven platforms that synthesize data across multiple sensory channels. The interplay between historical medical practices and modern technology challenges conventional patient–clinician interactions and redefines diagnostic accuracy. Highlighting applications from neurology to radiology, the potential of multimodal technology emerges, suggesting a future where AI not only supports but enhances human sensory inputs in medical diagnostics. This shift invites the medical community to navigate the ethical, practical, and technological changes reshaping the landscape of clinical medicine. [ABSTRACT FROM AUTHOR]

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone < 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual. [ABSTRACT FROM AUTHOR]

Simple Summary: This study establishes in vitro criteria for the safe and effective use of allogeneic canine mesenchymal stromal cells for potential orthopedic and therapeutic use. Allogeneic canine adipose-derived MSCs demonstrated MSC-specific characteristics and met in vitro requirements, providing a solid foundation for future in vivo research and clinical applications. Importantly, their shipping and cryobanking conditions and related procedures were also tested and validated. This validation ensures the establishment of an allogeneic canine adipose-derived mesenchymal stromal cell bank that can be used as an off-the-shelf therapy. In allogeneic MSC implantation, the cells are isolated from a donor different from the recipient. When tested, allogeneic MSCs have several advantages over autologous ones: faster cell growth, sufficient cell concentration, and readily available cells for clinics. To ensure the safe and efficient use of allogeneic MSCs in clinics, the MSCs need to be first tested in vitro. With this study, we paved the way by addressing the in vitro aspects of canine adipose-derived MSCs, considering the limited studies on the clinical use of canine cells. We isolated cAD-MSCs from canine falciform ligament fat and evaluated their viability and proliferation using an MTS assay. Then, we characterized the MSC-specific antigens using immunophenotyping and immunofluorescence and demonstrated their potential for in vitro differentiation. Moreover, we established shipping and cryobanking procedures to lead the study to become an off-the-shelf therapy. During expansion, the cells demonstrated a linear increase in cell numbers, confirming their proliferation quantitatively. The cells showed viability before and after cryopreservation, demonstrating that cell viability can be preserved. From a clinical perspective, the established shipping conditions demonstrated that the cells retain their viability for up to 48 h. This study lays the groundwork for the potential use of allogeneic cAD-MSCs in clinical applications. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide (LPS) is known to induce oxidative stress and inflammation, leading to significant damage in cardiac tissues. This study investigates the protective effects of melatonin (MLT) against LPS-induced oxidative damage, inflammation, and apoptosis in rat heart tissue. Rats were divided into four groups (n = 6 per group): control, melatonin-treated, LPS-treated, and LPS + melatonin-treated. Oxidative stress markers, including thiobarbituric acid-reactive substances (TBARSs) and advanced oxidation protein products (AOPPs), were measured. Additionally, inflammatory markers, such as interleukin-6 (IL-6) levels, inducible nitric oxide synthase (iNOS) and nitric oxide (NO) content, and apoptotic markers, caspase-3, caspase-9, and acidic DNase activity, were evaluated. LPS treatment significantly increased TBARS, AOPP, and IL-6 levels, as well as the activity of caspase-3, acidic DNase and iNOS and NO content compared to the control group. Co-treatment with melatonin significantly reduced the levels of TBARS and AOPP levels, and caspase-3 and acidic DNase activities nearly matched those of the control group, while caspse-9 was still slightly increased. Interestingly, IL-6, iNOS and NO levels were significantly decreased but did not fully match the values in the control group. Melatonin mitigates LPS-induced oxidative stress, inflammation, and apoptosis in rat heart tissue by affecting all studied parameters, demonstrating its potential as a therapeutic agent for conditions characterized by oxidative stress and inflammation. Further research is warranted to explore the clinical applications of melatonin in cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 is a popular genome editing technology, yet its clinical application is hindered by off-target effects. Many deep learning-based methods are available for off-target prediction. However, few can predict off-target activities with insertions or deletions (indels) between single guide RNA and DNA sequence pairs. Additionally, the analysis of off-target data is challenged due to a data imbalance issue. Moreover, the prediction accuracy and interpretability remain to be improved. Here, we introduce a deep learning-based framework, named Crispr-SGRU, to predict off-target activities with mismatches and indels. This model is based on Inception and stacked BiGRU. It adopts a dice loss function to solve the inherent imbalance issue. Experimental results show our model outperforms existing methods for off-target prediction in terms of accuracy and robustness. Finally, we study the interpretability of this model through Deep SHAP and teacher–student-based knowledge distillation, and find it can provide meaningful explanations for sequence patterns regarding off-target activity. [ABSTRACT FROM AUTHOR]

Glycosylase base editor (GBE) can induce C‐to‐G transversion in mammalian cells, showing great promise for the treatment of human genetic disorders. However, the limited efficiency of transversion and the possibility of off‐target effects caused by Cas9 restrict its potential clinical applications. In our recent study, we have successfully developed TaC9‐CBE and TaC9‐ABE by separating nCas9 and deaminase, which eliminates the Cas9‐dependent DNA off‐target effects without compromising editing efficiency. We developed a novel GBE called TaC9‐GBEYE1, which utilizes the deaminase and UNG‐nCas9 guided by TALE and sgRNA, respectively. TaC9‐GBEYE1 showed comparable levels of on‐target editing efficiency to traditional GBE at 19 target sites, without any off‐target effects caused by Cas9 or TALE. The TaC9‐GBEYE1 is a safe tool for gene therapy. [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]

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]

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]

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]

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]

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]

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]

Objective To explore the application effect of the “organ system-based, disease-centric” multidisciplinary integrated teaching model in the teaching of cerebrovascular diseases for five-year clinical medicine undergraduate students. Methods Two classes of five-year clinical medicine undergraduate students of grade 2019 studying in Beijing Luhe Hospital, Capital Medical University from March to May 2023 were selected as the research objects. They were randomly divided into the experimental and control groups according to different teaching models. Both groups studied the chapter on cerebrovascular diseases. The control group was taught using the traditional teaching model, while the experimental group was taught using the “organ system-based, disease-centric” multidisciplinary integrated teaching model. The assessment indicators of teaching effect included students’ test scores, students’ evaluation of the classroom teaching quality, and the evaluation on the improvement of their ability. The teaching effect was evaluated after the completion of the teaching period. Results The theoretical assessment scores [(43.90±2.36) scores vs. (41.83±3.36) scores, P=0.008], practical assessment scores [(43.67±2.16) scores vs. (41.70±3.01) scores, P=0.005], and overall scores [(87.57±3.30) scores vs. (83.53±5.43) scores, P=0.001] of the experimental group were all higher than those of the control group. Additionally, the evaluation scores of the experimental group on the classroom teaching quality (including quality requirements and overall scores) and various dimensions of the improvement of their ability (such as classroom participation, cultivation of learning interest, expansion of clinical thinking, improvement of self-learning ability, and improvement of communication and teamwork skills) were higher than those of the control group. The differences were statistically significant (all P<0.05). Conclusions The application of the “organ system-based, disease-centric” multidisciplinary integrated teaching model in the teaching of cerebrovascular diseases for five-year clinical medicine undergraduate students can improve their theoretical knowledge and clinical practice skills. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the congruence between patient assignment and established patients as well as their association with Healthcare Effectiveness Data and Information Set (HEDIS) quality performance. STUDY DESIGN: A retrospective cross-sectional analysis from January 2020 to February 2022. METHODS: The study setting is a fully integrated health care delivery system in Phoenix, Arizona. The study population includes Medicaid patients who received primary care services or were assigned to a primary care physician (PCP) at the study setting by 5 Medicaid managed care organizations (MCOs). We identified 4 possible relationships between the established patients (2 primary care visits) and the assigned patients (assigned by the MCO to the study setting): true-positive, false-positive, true-negative, and false-negative classifications. Precision and recall measures were used to assess congruence (or incongruence). Outcome measures were HEDIS quality metrics. RESULTS: A total of 100,030 Medicaid enrollees (adults and children) were established and/or assigned to the study setting from 5 separate payers. Only 15% were congruently established and assigned to the physician (true-positive). The overall precision was 21%, and the overall recall was 37%. The HEDIS quality performance was significantly higher (P< .05) for established patients for 5 of 6 metrics compared with patients who were not established. CONCLUSIONS: The vast majority of assigned patients were not treated by the assigned PCP, yet better patient outcomes were seen with an established patient. As the health system rapidly adopts value-based payments, more rigorous methodologies are essential to identify physician-patient relationships. [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]

Background: One strategy for supporting a hospital or health system's board of directors (Board), with their quality oversight responsibility is to review the organization's performance on quality measures. But for large systems, the number of measures needing review is quite burdensome and makes priority setting difficult. Our goal was to develop a scoring method that summarizes multiple quality measures together, while still maintaining the Board's opportunity to examine individual measures where there are specific concerns. Methods: We calculated an overall health system-level composite performance score using six publicly reported healthcare-associated infections reported by the Centers for Medicare and Medicaid Services on their Care Compare website [central-line associated bloodstream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), surgical site infections (SSIs) for colon surgery and abdominal hysterectomy, hospital-onset Methicillin-resistant Staphylococcus aureus bacteremia (MRSA), and hospital-onset Clostridioides difficile (C. diff)], where relative weights assigned to each infection type reflect the severity of patient harm. We also calculated a health-system composite performance target. For individual infection types, we calculated system-wide scores and targets and categorized individual hospital performance into three performance categories. Results: The health system's composite score between 2015 and 2019 ranged from a high of 1.10 to a low of 0.71. The health system's composite score in 2017–2019 was better than the composite target. Of the 34 measures used to calculate the 2019 composite score, 20 were better than internal standardized infection ratio (SIR) targets, seven were between internal targets and SIR of 1.0, and seven were worse than SIR of 1.0. Discussion: The Board communicated they find this composite score reporting approach helpful for streamlining their understanding of HAI performance, as compared to traditional approaches of reporting out individual performance measures. Approaches that streamline Board review of quality and safety performance are important as we hold Board members accountable for overseeing quality, seek greater engagement from the Board, and work to minimize measure review overload. [ABSTRACT FROM AUTHOR]

Motivation Polygenic scoring is an approach for estimating an individual's likelihood of a given outcome. Polygenic scores are typically calculated from genome-wide association study (GWAS) summary statistics and individual-level genotype data for the target sample. Going from genotype to interpretable polygenic scores involves many steps and there are many methods available, limiting the accessibility of polygenic scores for research and clinical application. Additional challenges exist for studies in ancestrally diverse populations. We have implemented the leading polygenic scoring methodologies within an easy-to-use pipeline called GenoPred. Results Here, we present the GenoPred pipeline, an easy-to-use, high-performance, reference-standardized, and reproducible workflow for polygenic scoring. It requires minimal inputs and offers various configuration options to cater to a range of use cases. GenoPred implements a comprehensive set of analyses, including genotype and GWAS quality control, target sample ancestry inference, polygenic score file generation using a range of leading methods, and target sample scoring. GenoPred standardizes the polygenic scoring process using reference genetic data, providing interpretable polygenic scores. The pipeline is applicable to GWAS and targets data from any population within the reference, facilitating studies of diverse ancestry. GenoPred is a Snakemake pipeline with associated Conda software environments, ensuring reproducibility. We apply the pipeline to UK Biobank data demonstrating the pipeline's simplicity, efficiency, and performance. The GenoPred pipeline provides a novel resource for polygenic scoring, integrating a range of complex processes within an easy-to-use framework. GenoPred widens access to the leading polygenic scoring methodology and their application to studies of diverse ancestry. Availability and implementation Freely available on the web at https://github.com/opain/GenoPred. [ABSTRACT FROM AUTHOR]

Background: Oncocytic thyroid carcinoma (OTC) was previously considered a variant of follicular thyroid carcinoma (FTC) but has recently been reclassified as a separate form of thyroid cancer. This study aimed to demonstrate that FTC and OTC are fundamentally distinct entities that can potentially be differentiated preoperatively through cytology and/or molecular testing. Methods: A retrospective chart review of patients diagnosed with FTC and OTC operated upon at two university health centers from January 2016 to September 2023 (n = 3219) was conducted. Molecular testing results were correlated with histopathologic diagnosis. Results: Fifty patients met the inclusion criteria. FTC was identified in 27 (54.0%) patients, and OTC in 23 (46.0%) patients. Patients with OTC were older (61.8 years) than FTC patients (51.2 years) (p = 0.013). Moreover, aggressive tumors were found in 39.1% (9/23) of OTCs compared to 11.1% (3/27) of FTCs (p = 0.021). Amongst Bethesda category III and IV nodules, 17 out of 20 (85.0%) OTC cytology reports demonstrated an oncocytic subtype compared to only 5 out of 24 FTC cytology reports (20.8%) (p = 0.002). On molecular testing, the EIF1AX alteration was exclusively present in OTCs while the PAX8/PPARy and PTEN alterations were exclusively found in FTCs. Copy number alterations (CNAs) were found to be more prevalent in OTC (66.7%) compared to FTC (33.3%), and they were not indicative of tumor aggressiveness. Within the OTC group, all three patients who had a TP53 alteration were diagnosed with aggressive cancer. Lastly, the OTCs exhibited a higher frequency of multiple alterations on molecular testing (66.7%) compared to FTCs (33.3%). Conclusion: To our knowledge, this is the largest study to date comparing the clinical application of abnormalities found on molecular testing for FTC and OTC. It further demonstrates the distinct clinicopathological and molecular characteristics of OTC. [ABSTRACT FROM AUTHOR]

Accurate segmentation of thyroid nodules in ultrasound images is crucial for the diagnosis of thyroid cancer and preoperative planning. However, the segmentation of thyroid nodules is challenging due to their irregular shape, blurred boundary, and uneven echo texture. To address these challenges, a novel Mamba- and ResNet-based dual-branch network (MRDB) is proposed. Specifically, the visual state space block (VSSB) from Mamba and ResNet-34 are utilized to construct a dual encoder for extracting global semantics and local details, and establishing multi-dimensional feature connections. Meanwhile, an upsampling–convolution strategy is employed in the left decoder focusing on image size and detail reconstruction. A convolution–upsampling strategy is used in the right decoder to emphasize gradual feature refinement and recovery. To facilitate the interaction between local details and global context within the encoder and decoder, cross-skip connection is introduced. Additionally, a novel hybrid loss function is proposed to improve the boundary segmentation performance of thyroid nodules. Experimental results show that MRDB outperforms the state-of-the-art approaches with DSC of 90.02% and 80.6% on two public thyroid nodule datasets, TN3K and TNUI-2021, respectively. Furthermore, experiments on a third external dataset, DDTI, demonstrate that our method improves the DSC by 10.8% compared to baseline and exhibits good generalization to clinical small-scale thyroid nodule datasets. The proposed MRDB can effectively improve thyroid nodule segmentation accuracy and has great potential for clinical applications. [ABSTRACT FROM AUTHOR]

Spinal medical image segmentation is critical for diagnosing and treating spinal disorders. However, ambiguity in anatomical boundaries and interfering factors in medical images often cause segmentation errors. Current deep learning models cannot fully capture the intrinsic data properties, leading to unstable feature spaces. To tackle the above problems, we propose Verdiff-Net, a novel diffusion-based segmentation framework designed to improve segmentation accuracy and stability by learning the underlying data distribution. Verdiff-Net integrates a multi-scale fusion module (MSFM) for fine feature extraction and a noise semantic adapter (NSA) to refine segmentation masks. Validated across four multi-modality spinal datasets, Verdiff-Net achieves a high Dice coefficient of 93%, demonstrating its potential for clinical applications in precision spinal surgery. [ABSTRACT FROM AUTHOR]

Wound healing is a complex and precisely regulated process that encompasses multiple stages, including inflammation, anti-inflammation, and tissue repair. It involves various cells and signaling molecules, with macrophages demonstrating a significant degree of plasticity and playing a crucial regulatory role at different stages. In recent years, the use of biomaterials, which include both natural and synthetic polymers or macromolecules, has proliferated for the purpose of enhancing wound healing. This review summarizes how these diverse biomaterials promote wound healing by modulating macrophage behavior and examines the broader implications of these modulations. Additionally, we discuss the limitations associated with the clinical application of immunomodulatory biomaterials and propose potential solutions. Finally, we look towards future developments in the design of immunomodulatory biomaterials intended to enhance wound healing. [ABSTRACT FROM AUTHOR]

Human amniotic membrane (hAM), the innermost placental layer, has unique properties that allow for a multitude of clinical applications. It is a common misconception that birth-derived tissue products, such as dual-layered dehydrated amnion–amnion graft (dHAAM), are similar regardless of the manufacturing steps. A commercial dHAAM product, Axolotl Biologix DualGraft™, was assessed for biological and mechanical characteristics. Testing of dHAAM included antimicrobial, cellular biocompatibility, proteomics analysis, suture strength, and tensile, shear, and compressive modulus testing. Results demonstrated that the membrane can be a scaffold for fibroblast growth (cellular biocompatibility), containing an average total of 7678 unique proteins, 82,296 peptides, and 96,808 peptide ion variants that may be antimicrobial. Suture strength results showed an average pull force of 0.2 N per dHAAM sample (equating to a pull strength of 8.5 MPa). Tensile modulus data revealed variation, with wet samples showing 5× lower stiffness than dry samples. The compressive modulus and shear modulus displayed differences between donors (lots). This study emphasizes the need for standardized processing protocols to ensure consistency across dHAAM products and future research to explore comparative analysis with other amniotic membrane products. These findings provide baseline data supporting the potential of amniotic membranes in clinical applications. [ABSTRACT FROM AUTHOR]

Colorectal cancer remains a leading cause of cancer-related deaths worldwide, with early detection and removal of polyps being critical in preventing disease progression. Automated polyp segmentation, particularly in colonoscopy images, is a challenging task due to the variability in polyp appearance and the low contrast between polyps and surrounding tissues. In this work, we propose an edge-enhanced network (EENet) designed to address these challenges by integrating two novel modules: the covariance edge-enhanced attention (CEEA) and cross-scale edge enhancement (CSEE) modules. The CEEA module leverages covariance-based attention to enhance boundary detection, while the CSEE module bridges multi-scale features to preserve fine-grained edge details. To further improve the accuracy of polyp segmentation, we introduce a hybrid loss function that combines cross-entropy loss with edge-aware loss. Extensive experiments show that the EENet achieves a Dice score of 0.9208 and an IoU of 0.8664 on the Kvasir-SEG dataset, surpassing state-of-the-art models such as Polyp-PVT and PraNet. Furthermore, it records a Dice score of 0.9316 and an IoU of 0.8817 on the CVC-ClinicDB dataset, demonstrating its strong potential for clinical application in polyp segmentation. Ablation studies further validate the contribution of the CEEA and CSEE modules. [ABSTRACT FROM AUTHOR]

Background and Purpose: To our knowledge, there is currently no research on telerehabilitation concerning artists. This study aims to assess the feasibility, acceptability, and effectiveness of utilizing video‐based telerehabilitation in physiotherapy among artists during the COVID‐19 pandemic. Methods: Fifty‐one artists who accessed virtual physiotherapy between November 2020 and February 2022 at a healthcare center that provides specialized healthcare services to artists of all disciplines who reside or work in Ontario, Canada were asked to complete a 26‐item online questionnaire about their experience with virtual physiotherapy. Results: The 51 respondents were from a range of artistic disciplines, with the largest portion being musicians (n = 22; 43%). Of the respondents, 86% (n = 44) felt the virtual physiotherapy met their expectations in therapeutic benefits, 78% (n = 40) were confident in performing all the exercises that the physiotherapist demonstrated on the virtual platform, 80% (n = 41) did not run into many technological challenges when booking or attending virtual sessions, and 54% (n = 20) reported similar treatment outcomes between virtual and in‐person sessions. Although artists liked the convenience of accessing physiotherapy from home, 53% (n = 17) of respondents rated the lack of physical contact as a major limitation in telerehabilitation. Conclusion: Telerehabilitation for artists during the COVID‐19 pandemic has shown potential to be an effective and viable alternative to in‐person physiotherapy, as demonstrated by high satisfaction levels and comparable treatment outcomes, especially when public health restrictions were in place. Future research can explore hybrid models (mix of in‐person and virtual sessions) in physiotherapy to meet the needs for physical contact during sessions. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are highly heterogeneous, and different EV subpopulations from various origins mediate different biological effects. The separation of different subpopulations of EVs from mixtures is critical but challenging. Epididymosomes are secreted by the epididymal epithelium and play a key role in sperm maturation and function. However, limited access to human epididymal tissue and epididymal fluid has hampered further study of epididymosomes and their potential clinical applications. Here, we established a novel strategy based on flow cytometry sorting to isolate human CD63‐positive epididymosomes from ejaculate. We identified CD52, a membrane‐located protein expressed exclusively in the epididymis, as the sorting marker for human epididymosomes. Then, CD63‐positive epididymosomes were isolated from human semen using a flow cytometry sorting instrument and concentrated. Additionally, we observed that isolated CD63‐positive epididymosomes improved sperm function more than other CD63‐positive seminal EV subpopulations did, demonstrating the successful isolation of a subpopulation of epididymosomes from human semen and their potential application in the clinic. [ABSTRACT FROM AUTHOR]

The automatic video recognition of depression is becoming increasingly important in clinical applications. However, traditional depression recognition models still face challenges in practical applications, such as high computational costs, the poor application effectiveness of facial movement features, and spatial feature degradation due to model stitching. To overcome these challenges, this work proposes a lightweight Time-Context Enhanced Depression Detection Network (TCEDN). We first use attention-weighted blocks to aggregate and enhance video frame-level features, easing the model's computational workload. Next, by integrating the temporal and spatial changes of video raw features and facial movement features in a self-learning weight manner, we enhance the precision of depression detection. Finally, a fusion network of 3-Dimensional Convolutional Neural Network (3D-CNN) and Convolutional Long Short-Term Memory Network (ConvLSTM) is constructed to minimize spatial feature loss by avoiding feature flattening and to achieve depression score prediction. Tests on the AVEC2013 and AVEC2014 datasets reveal that our approach yields results on par with state-of-the-art techniques for detecting depression using video analysis. Additionally, our method has significantly lower computational complexity than mainstream methods. [ABSTRACT FROM AUTHOR]