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Lian-Tao Li,1–3,* Xun Wang,4,* Wen-Tao Zhu,5,* Guo-Wei Qian,6 Dong-Sheng Pei,1,5 Jun-Nian Zheng1,2 1Cancer Institute, Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 2Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 5Department of Pathology, Xuzhou Medical University, Xuzhou 221000, People’s Republic of China; 6Department of Medical Oncology, Shanghai Sixth People’s Hospital, Shanghai 200000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Sheng Pei; Jun-Nian Zheng 84 West Huaihai Road, Xuzhou, Jiangsu, People’s Republic of ChinaTel +8605168558230Email dspei@xzhmu.edu.cn; jnzheng@xzhmu.edu.cnPurpose: DNA methylation plays major regulatory roles in gene transcription. Our previous studies confirmed that Ki-67 promoter is hypomethylated and Sp1 is a transcriptional activator of Ki-67 gene in cancer cells. However, whether Sp1-mediated transcriptional activation of Ki-67 is related to its methylation has not been studied yet.Materials and methods: In this study, we confirmed that methylated CpG binding protein 2 (MBD2) binding to methylated DNA hindered the binding of Sp1 to Ki-67 promoter and then repressed Ki-67 transcription through chromatin immunoprecipitation (ChIP) and quantitative real-time PCR (qRT-PCR). Co-immunoprecipitation (Co-IP), ChIP, methylation-specific PCR (MS-PCR) and Western blot were utilized to analyze the effects of Sp1 binding to Ki-67 promoter on its methylation status.Results: Less DNA methyltransferase 1 (DNMT1) bound to the Ki-67 promoter in MKN45 cells than in HK-2 cells. Histone acetyltransferase p300 that was recruited by Sp1 to Ki-67 promoter could attenuate the methylation level of Ki-67 promoter. Furthermore, higher expression of Sp1 and Ki-67 was related to the overall survival (OS), first progression (FP) and post-progression survival (PPS) in gastric cancer by scrutinizing bioinformatics datasets.Conclusion: Taken together, our findings suggested that hypomethylation of Ki-67 promoter enhanced the binding of Sp1, which in turn maintained hypomethylation of promoter, leading to increase Ki-67 expression in cancer cells. Sp1 and Ki-67 could act promising prognostic biomarkers for clinical diagnosis and treatment of cancer.Keywords: methylation, Ki-67, Sp1, promoter, cancer

Question: What career paths have physiotherapist researchers taken? What should career paths for physiotherapist researchers look like? Design: Observational study with questionnaire. Participants: Australian physiotherapists who had a completed a Doctor of Philosophy degree by 2006. Results: Fifty-six of 87 physiotherapists with a doctorate degree (response rate 64%) completed the questionnaire. Over half had completed the doctorate since 2000. An interest in clinical research was the strongest driver for undertaking a doctorate degree. Of the respondents, 52% worked in traditional academic roles while those who pursued other mixed clinical/research or pure research paths reported a lack of job security; 38% continued to work clinically, with a further 43% reporting they would like to but had insufficient time or a career structure that did not allow clinical work. 54% felt that the profession valued research, while 63% felt that research was valued by clinicians. The four main suggestions for improving current research career paths were: 1) develop research careers that allow mixed clinical/research and academic/clinical roles; 2) improve funding for training, particularly post-doctoral positions, and secure appropriately funded physiotherapy research positions; 3) improve co-operation between academic (university) and clinical researchers; and 4) develop more flexible research careers to accommodate private practitioner researchers and others wishing to combine clinical work with teaching and research. Conclusion: Physiotherapist researchers need broader career options and seek greater opportunity to link with clinical practice. Encouraging a vibrant research culture should foster professional excellence and enhance our reputation in the community. [ABSTRACT FROM AUTHOR]

Objective: The study was to survey the current situation and explore the relationship between pain assessment ability, palliative care core competence and palliative care practice ability among oncology nurses in mainland China., Methods: A multicenter cross-sectional study design was employed. Study data were collected in 26 tertiary hospitals among 1198 registered oncology nurses in the oncology department in Hubei province, China. A web-based survey was conducted using a stratified random integral sampling method to obtain data. All variables were measured using standardized instruments. Data was analyzed using SPSS 26.0 and AMOS 26.0 statistical software. All statistical tests were two-sided, with the significance level set at P < 0.05. The structural equation model was utilized to test the mediation effect of pain assessment ability on the pathway from palliative care core competence to palliative care practice ability., Results: The mean scores for pain assessment, core competence and practice ability were 125.68 (SD = 31.16), 76.67 (SD = 19.59) and 67.17(SD = 12.57), respectively. Pearson correlation analysis revealed significant positive correlations among the PCPS, EPCS, and Self-PAC scores of the oncology nurses (P < 0.01). The association between core competence and palliative care practice ability was mediated by pain assessment ability (ES = 0.125, 95%CI: 0.090-0.168)., Conclusions: To enhance the effectiveness of palliative care practice, managers need to strengthen the core competencies of palliative care nurses and their ability to assess patients' pain, as these two factors will promote the practical abilities of oncology nurses., (© 2024. The Author(s).)

Vasculogenic mimicry (VM) contributes factor to the poor prognosis of malignant melanoma. Developing deoxyhypusine synthase (DHPS) inhibitors against melanoma VM is clinically essential. In this study, we optimized and synthesized a series of compounds based on the candidate structure, and the hit compound 7k was identified through enzyme assay and cell viability inhibition screening. Both inside and outside the cell, 7k's ability to target DHPS and its high affinity were demonstrated. Molecular dynamics and point mutation indicated that mutations of K329 or V129 in DHPS abolish 7k's inhibitory activity. Using PCR arrays, solid-state antibody microarrays, and angiogenesis assays investigated 7k's impact on melanoma cells to reveal that DHPS regulates melanoma VM by promoting FGFR2 and c-KIT expression. Surprisingly, 7k was discovered to inhibit MC1R-mediated melanin synthesis in the zebrafish. Pharmacokinetic evaluations demonstrated 7k's favorable properties, and xenograft models evidenced its notable anti-melanoma efficacy, achieving a TGI of 73 %. These results highlighted DHPS as key in melanoma VM formation and confirmed 7k's potential as a novel anti-melanoma agent., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest. Competing interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Research has demonstrated negative environmental impacts from in-person conferences. Nonetheless, there are benefits to in-person meetings. The 2023 American Pediatric Surgical Association (APSA) meeting was mostly attended in-person. To understand the environmental impact, this study quantifies the travel emissions generated from that meeting., Methods: The 2023 APSA meeting was held in Orlando, FL. Using a de-identified list of attendees, the distance between the attendee's home city and Orlando was determined. If ≤ 200 miles, it was assumed the attendee drove. If > 200 miles, the distance between the closest airport and Orlando International Airport was determined. Travel emissions factors represent emissions per person-mile traveled. The Environmental Protection Agency (EPA) Greenhouse Gas Inventory emissions factors for carbon dioxide (CO 2 ), methane (CH 4 ), and nitrous oxide (N 2 O) were multiplied by travel distances to determine the emissions generated from each attendee. These were aggregated to determine the total meeting travel emissions. The EPA Greenhouse Gas Equivalencies Calculator was used to convert the emissions to a relatable outcome., Results: There were 757 in-person and 135 virtual attendees. Fifty attendees drove and 707 attendees flew. This generated 267,279 kg CO 2 , 1222 gm CH 4 , and 8486 gm N 2 O; equivalent to the emissions generated from the average annual use of 60 gasoline-powered passenger vehicles in the United States., Conclusion: Based on attendance to the 2023 APSA meeting, there is a preference for meeting in-person, though the associated environmental cost should be recognized. Based on these results, APSA should consider strategies to mitigate the environmental impact of its annual meeting., Levels of Evidence: N/A., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Patients have long turned to the Internet for answers to common medical questions. As the ability to access information evolves beyond standard search engines, patients with adolescent idiopathic scoliosis (AIS) and their parents may use artificial intelligence chatbots such as ChatGPT as a new source of information., Methods: Ten frequently asked questions regarding AIS were posed to ChatGPT. The accuracy and adequacy of the responses were graded as excellent not requiring clarification, satisfactory requiring minimal clarification, satisfactory requiring moderate clarification, and unsatisfactory requiring substantial clarification., Results: ChatGPT gave one response that was excellent not requiring clarification, four responses that were satisfactory requiring minimal clarification, three responses that were satisfactory requiring moderate clarification, and two responses that were unsatisfactory requiring substantial clarification, with information about higher level, more complex areas of discussion such as surgical options being less accurate., Conclusion: ChatGPT provides answers to FAQs about AIS that were generally accurate, although correction was needed on specific surgical treatments. Patients may be at risk of developing a Dunning-Kruger effect by proxy from the superficial and sometimes inaccurate information provided by ChatGPT on more complex aspects of AIS., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Diabetes-related bone loss represents a significant complication that persistently jeopardizes the bone health of individuals with diabetes. Primary cilia proteins have been reported to play a vital role in regulating osteoblast differentiation in diabetes-related bone loss. However, the specific contribution of KIAA0753, a primary cilia protein, in bone loss induced by diabetes remains unclear. In this investigation, we elucidated the pivotal role of KIAA0753 as a promoter of osteoblast differentiation in diabetes. RNA sequencing demonstrated a marked downregulation of KIAA0753 expression in pro-bone MC3T3 cells exposed to a high glucose environment. Diabetes mouse models further validated the downregulation of KIAA0753 protein in the femur. Diabetes was observed to inhibit osteoblast differentiation in vitro, evidenced by downregulating the protein expression of OCN, OPN and ALP, decreasing primary cilia biosynthesis, and suppressing the Hedgehog signalling pathway. Knocking down KIAA0753 using shRNA methods was found to shorten primary cilia. Conversely, overexpression KIAA0753 rescued these changes. Additional insights indicated that KIAA0753 effectively restored osteoblast differentiation by directly interacting with SHH, OCN and Gli2, thereby activating the Hedgehog signalling pathway and mitigating the ubiquitination of Gli2 in diabetes. In summary, we report a negative regulatory relationship between KIAA0753 and diabetes-related bone loss. The clarification of KIAA0753's role offers valuable insights into the intricate mechanisms underlying diabetic bone complications., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi-omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure-based design, synthesis, and activity screening yielded the hit compound GL-1 as a DHPS inhibitor. Notably, GL-1 directly inhibits DHPS binding to eIF5A, whereas GC-7 cannot. Based on the clarification of the mode of action of GL-1 on DHPS, it is found that GL-1 can promote the accumulation of intracellular Cu 2+ to induce apoptosis, and antibody microarray analysis shows that GL-1 inhibits the expression of several cytokines. GL-1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL-1 for clinical melanoma therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda, was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4 ± 0.55 µm in diameter. The octospores were oval and measured 2.3 × 1.5 μm (fresh) and 1.96 × 1.17 μm (fixed). The isofilar polar filament was coiled with 9-10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora, but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pseudorabies virus is a swine alpha-herpesvirus. We demonstrated that alpha-herpesvirus infection downregulates HSF1, a master transcription factor in the heat shock response. The serine/threonine protein kinase activity of late viral protein UL13 is indispensable for HSF1 depletion and phosphorylation, and UL13 does not degrade HSF1 posttranslationally but inhibits the HSF1 mRNA level. Importantly, UL13 increased HSF1 activity even though it reduced HSF1 mRNA. Furthermore, viral replication markedly decreased in the HSF1 knockout cell line or in the presence of an HSF1-specific inhibitor. Interestingly, HSF1 knockout accelerated the activation of NF-κB and p38MAPK. The K96 loci of UL13 are important to induce high levels of IL-6, TNF-α, and IL-β cytokines while playing a crucial role in promoting mild interstitial pneumonia, liver necrosis, and severe inflammatory cell infiltration in the footpad. Thus, UL13 steers the heat shock response to promote viral replication and the inflammatory response. IMPORTANCE: PRV is a ubiquitous pathogen that infects a variety of mammals, such as pigs, ruminants, carnivores, and rodents as well as human beings, causing enormous economic losses in the swine industry. Here, we employed PRV as a model to determine the relationship between α-herpesvirus and the inflammatory response. Overall, our findings indicated that PRV infection inhibits the level of HSF1 mRNA via the serine/threonine protein kinase activity of UL13. Additionally, we discovered that HSF1 was involved in NF-κB activation upon PRV infection. PRV UL13 orchestrates the level of HSF1 mRNA, HSF1 protein phosphorylation, and priming of the inflammatory response. Our study reveals a novel mechanism employed by UL13 serine/threonine protein kinase activity to promote the inflammatory response, providing novel clues for therapy against alpha-herpesvirus infection., Competing Interests: Declaration of competing interest We declare no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Myeloid-derived growth factor (MYDGF) is a cytokine that exhibits a variety of biological functions. This study focused on utilizing BL21(DE3) strain engineering and fermentation strategies to achieve high-level expression of soluble human MYDGF (hMYDGF) in Escherichia coli. Initially, the E. coli expressing strain BL21(DE3) was engineered by deleting the IpxM gene and inserting the GROEL/S and Trigger factor genes. The engineered E. coli strain BL21(TG)/pT-MYDGF accumulated 3557.3 ± 185.6 μg/g and 45.7 ± 6.7 mg/L of soluble hMYDGF in shake flask fermentation, representing a 15.6-fold increase compared to the control strain BL21(DE3)/pT-MYDGF. Furthermore, the yield of hMYDGF was significantly enhanced by optimizing the fermentation conditions. Under optimized conditions, the 5L bioreactor yielded up to 2665.8 ± 164.3 μg/g and 407.6 ± 42.9 mg/L of soluble hMYDGF. The results indicate that the implementation of these optimization strategies could enhance the ratio and yield of soluble proteins expressed by E.coli, thereby meeting the demands of industrial production. This study employed sophisticated strategies to lay a solid foundation for the industrial application of hMYDGF., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent years have witnessed the explosive development of highly sensitive smart sensors based on conductive polymer foam materials. However, the design and development of multifunctional polymeric foam composites as smart sensors applied in complex solvent and oil environments remain a critical challenge. Herein, we design and synthesize vinyl-terminated polytrifluoropropylmethylsiloxane through anionic ring-opening polymerization to fabricate fluorosilicone rubber foam (FSiRF) materials with nanoscale wrinkled surfaces and reactive Si-H groups via a green and rapid chemical foaming strategy. Based on the strong adhesion between FSiRF materials and consecutive oxidized ketjen black (OKB) nano-network, multifunctional FSiRF nanocomposites were prepared by a dip-coating strategy followed by fluoroalkylsilane modification. The optimized F-OKB@FSiRF nanocomposites exhibit outstanding mechanical flexibility in wide-temperature range (100 cycle compressions from -20 to 200 °C), structure stability (no detached particles after being immersed into various aqueous solutions for up to 15 days), surface superhydrophobicity (water contact angle of 154° and sliding angle of ∼7°), and tunable electrical conductivity (from 10 -5 to 10 -2 S m -1 ). Additionally, benefiting from the combined actions of multiple lines of defense (low surface energy groups, physical barriers, and "shielding effect"), the F-OKB@FSiRF sensor presents excellent anti-swelling property and high sensitivity in monitoring both large-deformation and tiny vibrations generated by knocking the beaker, ultrasonic action, agitating, and sinking objects in weak-polar or nonpolar solvents. This work conceivably provides a chemical strategy for the fabrication of multifunctional polymeric foam nanocomposite materials as smart sensors for broad applications.

Purpose: To evaluate how both annual surgeon and facility volume affect the cost and outcomes of anterior cruciate ligament reconstruction surgery. We also aimed to identify trends in how surgeon caseload predicts graft selection., Methods: The 2014 State Ambulatory and Surgical Database from Florida was used. Every case with Current Procedural Terminology code 29888 ("Arthroscopic anterior cruciate ligament reconstruction") was selected. Surgeon and facility identifiers were used to separate high- and low-volume groups, defined as >25 cases for surgeons and >125 cases for facilities. Univariate analysis was performed for patient demographics and surgical characteristics. Multivariate analysis was performed on significant factors to determine how these variables impact cost and odds of allograft usage, postoperative admission, and meniscal repair., Results: There were 7905 cases performed between January 1, 2014, and December 31, 2014 after excluding same-year revisions. High-volume surgeons had $6155 lower total charges, were 1.949 times more likely to use an autograft, and had 54.5% lower odds of postoperative admission (all P < .001). They were also 1.196 times more likely to perform a meniscal repair (P = .017). In patients younger than 18, low-volume surgeons were 3.7 times more likely to use an allograft (P < .001). Concomitant multiligamentous procedures were also performed at greater rates in the high-volume group. Postoperative admission added $18,698, and allografts added $9174 (both P < .001)., Conclusions: We found that high-volume surgeons were more likely to perform a meniscal repair and less likely to have their patients admitted postoperatively, which was the second largest cost driver of anterior cruciate ligament reconstruction. They were also significantly less likely to use an allograft, especially in patients younger than the age of 18 years. High-volume surgeons had lower costs despite greater rates of concomitant procedures., Level of Evidence: III, retrospective cohort study., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Objective: Sleep stages can provide valuable insights into an individual's sleep quality. By leveraging movement and heart rate data collected by modern smartwatches, it is possible to enable the sleep staging feature and enhance users' understanding about their sleep and health conditions., Method: In this paper, we present and validate a recurrent neural network based model with 23 input features extracted from accelerometer and photoplethysmography sensors data for both healthy and sleep apnea populations. We designed a lightweight and fast solution to enable the prediction of sleep stages for each 30-s epoch. This solution was developed using a large dataset of 1522 night recordings collected from a highly heterogeneous population and different versions of Samsung smartwatch., Results: In the classification of four sleep stages (wake, light, deep, and rapid eye movements sleep), the proposed solution achieved 71.6 % of balanced accuracy and a Cohen's kappa of 0.56 in a test set with 586 recordings., Conclusion: The results presented in this paper validate our proposal as a competitive wearable solution for sleep staging. Additionally, the use of a large and diverse data set contributes to the robustness of our solution, and corroborates the validation of algorithm's performance. Some additional analysis performed for healthy and sleep apnea population demonstrated that algorithm's performance has low correlation with demographic variables., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Sergio Tufik reports financial support was provided by Associação Fundo de Incentivo à Pesquisa. Monica L. Andersen reports financial support was provided by Fundação de Amparo à Pesquisa do Estado de São Paulo. Monica L. Andersen reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. Sergio Tufik reports financial support was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We sought to evaluate the ability of ChatGPT, an AI-powered online chatbot, to answer frequently asked questions (FAQs) regarding slipped capital femoral epiphysis (SCFE)., Methods: Seven FAQs regarding SCFE were presented to ChatGPT. Initial responses were recorded and compared with evidence-based literature and reputable online resources. Responses were subjectively rated as "excellent response requiring no further clarification," "satisfactory response requiring minimal clarification," "satisfactory response requiring moderate clarification," or "unsatisfactory response requiring substantial clarification.", Results: ChatGPT was frequently able to provide satisfactory responses that required only minimal clarification. One response received an excellent rating and required no further clarification, while only 1 response from ChatGPT was rated unsatisfactory and required substantial clarification., Conclusions: ChatGPT is able to frequently provide satisfactory responses to FAQs regarding SCFE while appropriately reiterating the importance of always consulting a medical professional., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate ChatGPT responses to common questions patients have regarding anterior cruciate ligament (ACL) reconstruction., Methods: Ten frequently asked questions regarding ACL tears and ACL reconstruction were chosen from the frequently asked questions found on the websites of major institutions. These were presented to ChatGPT and responses were rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," "satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification.", Results: Four responses were satisfactory, requiring minimal clarification, 3 were satisfactory, requiring moderate clarification, 2 were unsatisfactory, and 1 was excellent, requiring no clarification., Conclusions: As hypothesized, ChatGPT provided generally accurate information to common questions around ACL reconstruction. Although clarification often was needed, responses were satisfactory for providing generalized information about ACL tears and ACL reconstruction., Clinical Relevance: ChatGPT is a promising avenue for patients to learn about general background information regarding ACL reconstruction, although questions specific to any planned operation need to be addressed directly with an orthopaedic provider., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.E.V. reports a relationship with Arthrex that includes: speaking and lecture fees. J.G.C. reports a relationship with Smith & Nephew Inc that includes: speaking and lecture fees. All other authors (L.T.L., M.A.S., J.M.A.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes., Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD., Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA)., Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set., Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Gao, Li, Hu, Ling, Jia, Chen, Meng and Jiang.)

Background: During the ongoing global pandemic of COVID-19, the association between hyperglycemia and COVID-19 infection has emerged as a notable concern. Therefore, finding effective methods to manage hyperglycemia in patients with COVID-19 is crucial., Objective: To introduce the clinical pharmacists participating in multidisciplinary collaborative whole hospital blood glucose management mode, and to explore its effect on blood glucose control in patients with coronavirus disease 2019 infection and complicated with hyperglycemia., Methods: Patients with COVID-19 treated at Nanjing Drum Tower Hospital from December 2022 to January 2023 were assigned to routine diagnosis and treatment group and whole hospital blood glucose management group according to the blood glucose management plan received by patients. The groups were compared in regards to their adherence to management advice, blood glucose levels, fluctuation, inflammation-related indicators, medical service-related indicators, and incidence of hypoglycemia and adverse events., Results: After 5 days of glucose management, both groups showed a decrease in fasting and postprandial blood glucose. Postprandial blood glucose in the whole hospital glucose management group was significantly lower than the routine group (P < 0.05). The whole hospital glucose management group showed a significant increase in compliance rate, improved inflammation-related indicators, and higher detection rates for hemoglobin and islet function (P < 0.05). Implementation rates for medical orders and treatment plans were also higher in the whole hospital group (P < 0.05). There was no significant difference in incidence of adverse events., Conclusions: Multidisciplinary blood glucose management is highly recommended for patients with COVID-19 who have hyperglycemia due to its effectiveness, standardization, safety, and improvement of inflammation indicators., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study., Approach and Results: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings., Conclusions: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Artificial intelligence (AI) may benefit pediatric healthcare, but it also raises ethical and pragmatic questions. Parental support is important for the advancement of AI in pediatric medicine. However, there is little literature describing parental attitudes toward AI in pediatric healthcare, and existing studies do not represent parents of hospitalized children well., Methods: We administered the Attitudes toward Artificial Intelligence in Pediatric Healthcare, a validated survey, to parents of hospitalized children in a single tertiary children's hospital. Surveys were administered by trained study personnel (11/2/2021-5/1/2022). Demographic data were collected. An Attitudes toward Artificial Intelligence in Pediatric Healthcare score, assessing openness toward AI-assisted medicine, was calculated for seven areas of concern. Subgroup analyses were conducted using Mann-Whitney U tests to assess the effect of race, gender, education, insurance, length of stay, and intensive care unit (ICU) admission on AI use., Results: We approached 90 parents and conducted 76 surveys for a response rate of 84%. Overall, parents were open to the use of AI in pediatric medicine. Social justice, convenience, privacy, and shared decision-making were important concerns. Parents of children admitted to an ICU expressed the most significantly different attitudes compared to parents of children not admitted to an ICU., Conclusions: Parents were overall supportive of AI-assisted healthcare decision-making. In particular, parents of children admitted to ICU have significantly different attitudes, and further study is needed to characterize these differences. Parents value transparency and disclosure pathways should be developed to support this expectation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The impact of dietary saturated fatty acids (SFAs) on breast cancer risk may vary depending on their carbon chain lengths, attributable to the discrepancy in their dietary sources and biological activities. The associations between SFA subgroups classified by chain length and breast cancer risk remain controversial. In this case-control study, we aimed to investigate the association between the dietary intake of SFA subgroups, classified by chain lengths, and odds of breast cancer in China. This study included 1661 cases of breast cancer (confirmed as primary and histologically) and 1674 frequency-matched controls. Face-to-face interviews were used to collect basic information, while dietary intake information was obtained by a food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). All SFA subgroups were inversely associated with odds of breast cancer. The adjusted ORs (95% CIs) were 0.78 (0.61-0.99) for medium-chain SFAs, 0.50 (0.31-0.83) for long even-chain SFAs, 0.69 (0.54-0.88) for long odd-chain, and 0.67 (0.48-0.95) for very long-chain SFAs, respectively. In the restricted cubic spline (RCS) models, a non-linear M-shaped association was observed between long odd-chain SFAs and odds of breast cancer ( P non-linearity = 0.007). However, the associations of medium-chain SFAs, long even-chain SFAs, and very long-chain SFAs did not reach statistical significance ( P non-linearity > 0.05). No significant interactions were observed between all these four subgroups of SFAs and menopausal status or BMI. Our findings emphasize the significance of elucidating the associations of dietary SFAs according to chain lengths, providing insights into the etiology as well as the potential benefits of SFA-rich food intake in reducing the risk of breast cancer. Further prospective cohort studies and intervention studies are warranted to confirm these findings and identify the underlying mechanisms of the association between dietary SFAs and breast cancer.

Aims: The aim of this study was to characterize the influence of social deprivation on the rate of complications, readmissions, and revisions following primary total shoulder arthroplasty (TSA), using the Social Deprivation Index (SDI). The SDI is a composite measurement, in percentages, of seven demographic characteristics: living in poverty, with < 12 years of education, single-parent households, living in rented or overcrowded housing, households without a car, and unemployed adults aged < 65 years., Methods: Patients aged ≥ 40 years, who underwent primary TSA between 2011 and 2017, were identified using International Classification of Diseases (ICD)-9 Clinical Modification and ICD-10 procedure codes for TSA in the New York Statewide Planning and Research Cooperative System database. Readmission, reoperation, and other complications were analyzed using multivariable Cox proportional hazards regression controlling for SDI, age, ethnicity, insurance status, and Charlson Comorbidity Index., Results: A total of 17,698 patients with a mean age of 69 years (SD 9.6), of whom 57.7% were female, underwent TSA during this time and 4,020 (22.7%) had at least one complication. A total of 8,113 patients (45.8%) had at least one comorbidity, and the median SDI in those who developed complications 12 months postoperatively was significantly greater than in those without a complication (33 vs 38; p < 0.001). Patients from areas with higher deprivation had increased one-, three-, and 12-month rates of readmission, dislocation, humeral fracture, urinary tract infection, deep vein thrombosis, and wound complications, as well as a higher three-month rate of pulmonary embolism (all p < 0.05)., Conclusion: Beyond medical complications, we found that patients with increased social deprivation had higher rates of humeral fracture and dislocation following primary TSA. The large sample size of this study, and the outcomes that were measured, add to the literature greatly in comparison with other large database studies involving TSA. These findings allow orthopaedic surgeons practising in under-served or low-volume areas to identify patients who may be at greater risk of developing complications., Competing Interests: S. S. Shah is a paid consultant for Exactech, unrelated to this study; a board/committee member of the American Academy of Orthopaedic Surgeons, the American Orthopaedic Society for Sports Medicine, and the Arthroscopy Association of North America; and an editorial/governing board member of Arthroscopy. A. I. Cruz Jr. is a board/committee member of the Pediatric Orthopaedic Society of North America and Pediatric Research in Sports Medicine (PRiSM)., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Background: Newer minimally invasive techniques have supplanted laparotomy and thoracotomy for management of hiatal hernias. Limited data exists on outcomes after robotic hiatal hernia repair without mesh despite the increasing popularity of this approach. We report our high-volume experience with durable robotic hiatal hernia repair with gastric fundoplication without mesh., Methods: A retrospective review was conducted on patients with type I-IV hiatal hernias who underwent an elective robotic-assisted repair from 2016 to 2019 using a novel technique of approximating the hiatus with running barbed absorbable (V-loc TM ) suture and securing it with interrupted silk sutures. Main outcomes included length of stay, readmission rate, and recurrence rate., Results: A total of 144 patients were reviewed. The average age of the patient was 61 years. Most of the patients were female [95 females (66%) to 49 males], and the average body mass index (BMI) was 29.96 kg/m 2 . The average operating time was 173 minutes (standard deviation 62 minutes). The average length of stay in the hospital was 2 days, and 89% of patients went home within the first 3 days. Ten patients (6.9%) were readmitted within 30 days, there were no mortalities in 30 days, and there were 6 (4.2%) recurrences on follow up requiring reoperation., Conclusions: Elective robotic hiatal hernia repair with fundoplication and primary closure of the hiatus with V-loc TM and nonabsorbable suture without mesh is safe and effective. The robotic approach has similar operative times, lengths of stay, and complications compared to nationally published data on laparoscopic hiatal hernia repairs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-753/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Cerebral small vessel disease (CSVD) is a significant contributor to stroke, intracerebral hemorrhages, and vascular dementia, particularly in the elderly. Early diagnosis remains challenging. This study aimed to develop and validate a novel nomogram for the early diagnosis of cerebral small vessel disease (CSVD). We focused on integrating cerebrovascular risk factors and blood biochemical markers to identify individuals at high risk of CSVD, thus enabling early intervention., Methods: In a retrospective study conducted at the neurology department of the Affiliated Hospital of Hebei University from January 2020 to June 2022, 587 patients were enrolled. The patients were randomly divided into a training set (70%, n = 412) and a validation set (30%, n = 175). The nomogram was developed using multivariable logistic regression analysis, with variables selected through the Least Absolute Shrinkage and Selection Operator (LASSO) technique. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA)., Results: Out of 88 analyzed biomarkers, 32 showed significant differences between the CSVD and non-CSVD groups. The LASSO regression identified 12 significant indicators, with nine being independent clinical predictors of CSVD. The AUC-ROC values of the nomogram were 0.849 (95% CI: 0.821-0.894) in the training set and 0.863 (95% CI: 0.810-0.917) in the validation set, indicating excellent discriminative ability. Calibration plots demonstrated good agreement between predicted and observed probabilities in both sets. DCA showed that the nomogram had significant clinical utility., Conclusions: The study successfully developed a nomogram predictive model for CSVD, incorporating nine clinical predictive factors. This model offers a valuable tool for early identification and risk assessment of CSVD, potentially enhancing clinical decision-making and patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li and Li.)

Introduction: The use of artificial intelligence (AI), particularly machine learning and predictive analytics, has shown great promise in health care. Despite its strong potential, there has been limited use in health care settings. In this systematic review, we aim to determine the main barriers to successful implementation of AI in healthcare and discuss potential ways to overcome these challenges., Methods: We conducted a literature search in PubMed (1/1/2001-1/1/2023). The search was restricted to publications in the English language, and human study subjects. We excluded articles that did not discuss AI, machine learning, predictive analytics, and barriers to the use of these techniques in health care. Using grounded theory methodology, we abstracted concepts to identify major barriers to AI use in medicine., Results: We identified a total of 2,382 articles. After reviewing the 306 included papers, we developed 19 major themes, which we categorized into three levels: the Technical/Algorithm, Stakeholder, and Social levels (TASS). These themes included: Lack of Explainability, Need for Validation Protocols, Need for Standards for Interoperability, Need for Reporting Guidelines, Need for Standardization of Performance Metrics, Lack of Plan for Updating Algorithm, Job Loss, Skills Loss, Workflow Challenges, Loss of Patient Autonomy and Consent, Disturbing the Patient-Clinician Relationship, Lack of Trust in AI, Logistical Challenges, Lack of strategic plan, Lack of Cost-effectiveness Analysis and Proof of Efficacy, Privacy, Liability, Bias and Social Justice, and Education., Conclusion: We identified 19 major barriers to the use of AI in healthcare and categorized them into three levels: the Technical/Algorithm, Stakeholder, and Social levels (TASS). Future studies should expand on barriers in pediatric care and focus on developing clearly defined protocols to overcome these barriers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ischemic stroke occurs when the arteries supplying blood to the brain are narrowed or blocked, inducing damage to brain tissue due to a lack of blood supply. One effective way to reduce brain damage and alleviate symptoms is to reopen blocked blood vessels in a timely manner and reduce neuronal damage. To achieve this, researchers have focused on identifying key cellular signaling pathways that can be targeted with drugs. These pathways include oxidative/nitrosative stress, excitatory amino acids and their receptors, inflammatory signaling molecules, metabolic pathways, ion channels, and other molecular events involved in stroke pathology. However, evidence suggests that solely focusing on protecting neurons may not yield satisfactory clinical results. Instead, researchers should consider the multifactorial and complex mechanisms underlying stroke pathology, including the interactions between different components of the neurovascular unit. Such an approach is more representative of the actual pathological process observed in clinical settings. This review summarizes recent research on the multiple molecular mechanisms and drug targets in ischemic stroke, as well as recent advances in novel therapeutic strategies. Finally, we discuss the challenges and future prospects of new strategies based on the biological characteristics of stroke., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro . A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.

The aim of this study was to clarify the response characteristics of Chinese cabbage pakchoi ( Brassica chinensis L.) under two particle size (100 nm and 1000 nm) polystyrene microplastic (PS-MPs) stress conditions. This study can provide a theoretical basis and experimental reference for the interpretation of the physiological and ecological mechanism of microplastic pollution and the bioremediation of microplastic-contaminated soil. Hydroponic experiments were carried out to study the effects of two particle sizes (100 nm and 1000 nm) of PS-MPs on growth, photosynthetic physiology, antioxidant enzyme activities, nutritional quality, anatomical structure, and canopy temperature in Chinese cabbage pakchoi. The results showed that PS-MPs stress significantly inhibited the growth and development of Chinese cabbage pakchoi. When PS-MPs stress was increased, the phenotypic indicators were significantly reduced. Meanwhile, PS-MPs stress significantly enhanced the oxidative stress response of Chinese cabbage pakchoi, such as the activities of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) and the content of malondialdehyde (MDA) in leaves. Such a change tended to decrease the thickness of fenestrated and leaf and spongy tissues. Moreover, PS-MPs stress significantly increased the canopy population temperature of the Chinese cabbage pakchoi leaves. Microplastic stress had obvious inhibitory effects and toxic damage on the growth, development, and physical and chemical properties of Chinese cabbage pakchoi.

Introduction: Surgical site occurrences (SSO), including surgical site infection, dehiscence, and incisional hernia, are complications following laparotomy. SSO rates in premature neonates are poorly understood. We hypothesize that SSO rates are higher among extremely low birth weight (ELBW) infants compared to very low birth weight (VLBW) infants and strive to determine the optimal abdominal closure method for these infants., Methods: We conducted a prospective observational study of infants < 1.5 kg (kg) undergoing laparotomy at two institutions from 1/1/2020 to 5/1/2022. Patients were grouped by weight and closure; SSO rates were computed and the association tested using Fisher's exact test., Results: We identified 59 patients and 104 total operations. At initial surgery, 37 patients weighed < 1 kg (ELBW); 22 patients weighed 1-1.5 kg (VLBW). Complication rate for ELBW was 6(16%) vs. 2(9%) in VLBW, but not significant (p = 0.45). More complications followed a single-layer compared to a two-layer closure (18 vs. 2), but not significant (p = 0.30)., Conclusions: SSO rates are higher for ELBW infants undergoing laparotomy, and fewer complications follow two-layer closure. However, these findings did not reach statistical significance. Further studies are needed to identify modifiable factors to reduce postoperative complications in these infants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis are poorly understood. We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers., Methods: Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age. A good prognosis was defined as survival with native liver and total bilirubin (TB) < 85.5 μmol/L, while a poor prognosis was defined as either liver transplantation, death from liver failure, or TB ≥ 85.5 μmol/L at the last follow-up., Results: We found that the concentrations of two poly-hydroxylated bile acids, tauro-2β,3α,7α,12α-tetrahydroxylated bile acid (THBA) and glyco-hyocholic acid (GHCA), were significantly increased in patients with good prognosis compared to those with poor prognosis [area under curve (AUC) = 0.836 and 0.782, respectively] in the discovery cohort. The same trend was also observed in the molar ratios of GHCA to glyco- chenodeoxycholic acid (GCDCA) and tetrahydroxylated bile acid (THCA) to tauro-chenodeoxycholic acid (TCDCA) (both AUC = 0.836). A validation cohort confirmed these findings. Notably, tauro-2β,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00% (92.31% sensitivity and 83.33% specificity); GHCA at > 607.69 nmol/L was associated with native liver survival [hazard ratio: 13.03, 95% confidence interval (CI): (2.662-63.753), P = 0.002]., Conclusions: We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients. Enhanced hydroxylation of bile acids may result in better clinical outcomes., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Background: We propose a new deep learning model to identify unnecessary hemoglobin (Hgb) tests for patients admitted to the hospital, which can help reduce health risks and healthcare costs., Methods: We collected internal patient data from a teaching hospital in Houston and external patient data from the MIMIC III database. The study used a conservative definition of unnecessary laboratory tests, which was defined as stable (i.e., stability) and below the lower normal bound (i.e., normality). Considering that machine learning models may yield less reliable results when trained on noisy inputs containing low-quality information, we estimated prediction confidence to assess the reliability of predicted outcomes. We adopted a "select and predict" design philosophy to maximize prediction performance by selectively considering samples with high prediction confidence for recommendations. Our model accommodated irregularly sampled observational data to make full use of variable correlations (i.e., with other laboratory test values) and temporal dependencies (i.e., previous laboratory tests performed within the same encounter) in selecting candidates for training and prediction., Results: The proposed model demonstrated remarkable Hgb prediction performance, achieving a normality AUC of 95.89% and a Hgb stability AUC of 95.94%, while recommending a reduction of 9.91% of Hgb tests that were deemed unnecessary. Additionally, the model could generalize well to external patients admitted to another hospital., Conclusions: This study introduces a novel deep learning model with the potential to significantly reduce healthcare costs and improve patient outcomes by identifying unnecessary laboratory tests for hospitalized patients., (© 2023. The Author(s).)

Multiple biomarker detection is crucial for early clinical diagnosis, and it is significant to achieve the simultaneous detection of multiple biomarkers with the same nanomaterial. In this work, the hairpin DNA strands were selectively modified on the surface of gold nanorods (AuNRs) to construct two kinds of nanoprobes by rational design. When in the presence of dual microRNAs, AuNRs were assembled to form end-to-end (ETE) and side-by-side (SBS) dimers. Compared with a single AuNR, the dark-field scattering intensity and red color percentage variation of dimers were extremely distinguished, which could be developed for dual microRNA detection by combining the red color percentage and scattering intensity with the data processing method of principal component analysis to construct a two-dimensional analysis method. Especially, the fraction of AuNR dimers presented a linear relationship with the amount of microRNAs. Based on this, microRNA-21 and microRNA Let-7a in breast cancer cells were detected with the detection limits of 1.72 and 0.53 fM, respectively. This method not only achieved the sensitive detection of dual microRNAs in human serum but also realized the high-resolution intracellular imaging, which developed a new way for the oriented assembly of nanomaterials and biological detection in living cells.

Right ventricular clot-in-transit (CIT) is a rare finding in venous thromboembolic disease and carries a high mortality rate. Its optimal treatments have yet to be established in the literature. Here we describe the usage of a suction-based catheter, the INARI FlowTriever® system (INARI Medical Inc.) to successfully retrieve a CIT from the right ventricle of a patient with coronavirus disease 2019 acute respiratory distress syndrome on veno-veno extracorporeal membrane oxygenation., (© 2022 Wiley Periodicals LLC.)

Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS., Approach and Results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001)., Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases.)