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Chao-Ying Chen,1,2 Kuan-Ying Lee,3 Xavier CC Fung,4 Ji-Kang Chen,5 Yu-Chen Lai,6 Marc N Potenza,7– 12 Kun-Chia Chang,13,14 Chuan-Yin Fang,6 Amir H Pakpour,15 Chung-Ying Lin16– 20 1School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2New Taipei City Tucheng Hospital (Chang Gung Medical Foundation), Department of Pediatric Internal Medicine, New Taipei City, Taiwan; 3Department of Child and Adolescent Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 4Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong; 5Department of Social Work, Chinese University of Hong Kong, New Territories, Hong Kong; 6Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan; 7Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; 8Connecticut Mental Health Center, New Haven, CT, USA; 9Connecticut Council on Problem Gambling, Wethersfield, CT, USA; 10Child Study Center, Yale School of Medicine, New Haven, CT, USA; 11Department of Neuroscience, Yale University, New Haven, CT, USA; 12Wu Tsai Institute, Yale University, New Haven, CT, USA; 13Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan; 14Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 15Department of Nursing, School of Health and Welfare, Jönköping University, Jönköping, Sweden; 16Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 17Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 18Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 19Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 20INTI International University, Nilai, Negeri Sembilan, 71800, MalaysiaCorrespondence: Kun-Chia Chang, Department of General Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, Tainan, Taiwan, Tel +886-6-2795019 ext. 1532, Fax +886-6-2797659, Email kunchiachang0517@gmail.com Chuan-Yin Fang, Division of Colon and Rectal Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 621, Taiwan, Email 04969@cych.org.twBackground: Problematic use of internet (PUI) may have negative impacts on psychological distress and quality of life (QoL). This situation might be more profound in people with attention-deficit/hyperactivity disorder (ADHD) due to poorer behavioral control and regulatory capacity. However, there is little evidence regarding mediated effects in the associations between PUI, psychological distress, and QoL in people with ADHD.Aims: To investigate mediating effects of psychological distress in the associations of problematic smartphone use (PSPU), problematic use of social media (PUSM), and problematic gaming (PG) with QoL in individuals with ADHD.Methods and Procedures: PUI behaviors of participants with ADHD (n = 99) were assessed using the Smartphone Application-Based Addiction Scale, Bergen Social Media Addiction Scale, and Internet Gaming Disorder-Short Form. Psychological distress was assessed using the Depression, Anxiety, Stress Scale and QoL using the Kid-KINDL.Outcomes and Results: Psychological distress mediated the associations between PUI and different domains of QoL, except for self-esteem QoL. There were also positively direct effects between PG and physical QoL, PUSM and friends’ QoL, and PSPU and physical QoL.Conclusions and Implications: PUI may associate with poor QoL in people with ADHD via psychological distress. Programs on reducing PUI for people with ADHD are needed.Keywords: attention-deficit/hyperactivity disorder, ADHD, impulsive behavior, addictive behavior, internet, psychological distress, quality of life

Che-Hsing Li,1,2,&ast; Jiunn-Liang Ko,1,3,4,&ast; Yu-Ping Hsiao,5,6 Ming-Hung Tsai,7 Yen-Chein Lai,8 I-Lun Hsin,3,4 Yu-Ting Kang,3,4 Gwo-Tarng Sheu,1,3,4 Wea-Lung Lin,6,9 Ming-Fang Wu1,4,6 1Divisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; 2Graduate Program in Immunology & Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA; 3Institute of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 4CSMU Lung Cancer Research Center, Chung Shan Medical University, Taichung, 402, Taiwan; 5Division of Dermatology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan; 6School of Medicine, Chung Shan Medical University, Taichung, 402, Taiwan; 7Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, 40447, Taiwan; 8Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, 402, Taiwan; 9Department of Pathology, Chung Shan Medical University Hospital, Taichung, 402, Taiwan&ast;These authors contributed equally to this workCorrespondence: Ming-Fang WuDivisions of Medical Oncology and Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, 110, Sec. 1, Jianguo N. Road, Taichung, 40201, TaiwanTel +886-4-24739595#34711Email mfwu0111@gmail.comPurpose: Pemetrexed-based chemotherapy (Pem-C) is the first-line chemotherapy for advanced non-squamous non-small cell lung cancer (NSCLC). However, limited tumor-associated proteins in blood are available to predict pemetrexed response and/or survival.Patients and Methods: Plasma samples from three responders and three nonresponders with stage IIIB–IV NSCLC were collected prior to Pem-C and analyzed using Proteome ProfilerTM Human XL Oncology Array to detect 84 oncology-related proteins. The plasma concentrations of cathepsin S, endoglin (ENG), and matrix metalloproteinases 3 and 9 in 71 patients with advanced NSCLC treated with Pem-C were further measured using enzyme-linked immunosorbent assay based on the remarkable differences in the four proteins between responders and nonresponders in the array results.Results: Pem-C responders had significantly higher ENG levels but not the other three markers than nonresponders (mean ENG level: 27.1 ± 7.4 vs 22.3 ± 6.9, p < 0.01). High ENG concentration was correlated with improved progression-free survival (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.31– 0.86, p < 0.01) and overall survival (HR: 0.55, 95% CI: 0.32– 0.94, p < 0.05) in patients treated with Pem-C, and the ENG level was an independent factor in our cohort (HR: 0.54, 95% CI: 0.33– 0.89, p < 0.05). ENG concentration in Pem-C responders also significantly increased at the time of best response (p < 0.05).Conclusion: Cumulatively, this study reveals that ENG is correlated with Pem-C responsiveness in patients, which indicates the potential use of plasma ENG levels as a non-invasive biomarker for pemetrexed-based treatment in patients with non-squamous NSCLC.Keywords: endoglin, pemetrexed-based therapy, prognostic factor, non-squamous non-small cell lung cancer, biomarker

Cheng-Yu Chang,1,&ast; Chung-Yu Chen,2,3,&ast; Shih-Chieh Chang,4– 6,&ast; Yi-Chun Lai,4,5 Yu-Feng Wei7– 9 1Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan; 3College of Medicine, National Taiwan University, Taipei, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 5Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 6Department of Critical Care Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan; 7School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 8Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 9Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yu-Feng WeiDepartment of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan, No. 21, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung, 824, TaiwanTel +886-7-6150011Fax +886-7-6150927Email yufeng528@gmail.comIntroduction: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated.Methods: We enrolled patients 65 years or older with EGFR-mutated Stage IIIB–IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS).Results: From January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2– 4). Compared with patients categorized as good PS (0– 1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, < 3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS.Conclusion: In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and < 3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.Keywords: older adults, epidermal growth factor receptor tyrosine kinase inhibitor, non-small-cell lung cancer, performance status

L Leanne Lai¹, Mooi Heong Tan¹, Yen Chi Lai²¹Department of Sociobehavioral and Administrative Pharmacy, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA; ²Department of Internal Medicine, Golen Hospital, Pintong City, TaiwanBackground: The primary objective of our study was to investigate the prevalence of off-label antidepressant drug use in insomnia. The secondary objective was to compare prescribing patterns between off-label antidepressants vs hypnotics approved by the US Food and Drug Administration for insomnia, with particular emphasis on socioeconomic characteristics of patients and physicians.Methods: We undertook a secondary data analysis using the national longitudinal database from the 2006 National Ambulatory Medical Care Survey. Subjects were identified from outpatient visits in which at least one insomnia drug was prescribed. A series of weighted Chi-squared statistics was used to compare drug use for insomnia across various patient and physician characteristics. Multivariate logistic regression was conducted to identify factors associated with off-label antidepressant drug use.Results: Among 901.95 million outpatient visits that took place in the US in 2006, an estimated 30.43 million visits included at least one drug prescription for insomnia. Off-label antidepressants were prescribed significantly more frequently (45.1%) than nonbenzodiazepine z-hypnotics (43.2%) and benzodiazepines (11.7%). Insomnia prescribing patterns were significantly influenced by physician specialty and physician office settings. Pediatricians (odds ratio [OR]: 65.892; 95% confidence interval [CI]: 5.536–810.564) and neurologists (OR: 4.784; 95% CI: 2.044–11.201) were more likely to prescribe off-label antidepressants than psychiatrists. Self-paying patients were more likely to receive off-label antidepressants as treatment for insomnia than patients with private insurance (OR 2.594; 95% CI: 1.128–5.967).Conclusion: Our findings indicate significant socioeconomic disparities in the use of off-label antidepressants. Future studies might explore interventional and educational strategies to ensure well informed clinical decisions that can withstand pharmaceutical marketing strategies and diagnostic uncertainties regarding the treatment of insomnia.Keywords: insomnia, off-label drug use, antidepressants, National Ambulatory Medical Care Survey

Vibrio vulnificus is a marine bacterium causing serious septicemia and wound infection in humans. It produces an RTX toxin that can lyse a variety of cells and is important for virulence in mice. In this study, we explored the role of RTX in pathogenesis by characterizing an RTX-deficient mutant. This mutant showed an ~2-log reduction in virulence for mice infected by various routes. Survival of the mutant at the infection site and subsequent spread into the bloodstream were impaired. In mice pretreated with cyclophosphamide to deplete the neutrophils, both the virulence and survival at the infection site of this mutant were enhanced. This mutant was further shown to be more readily cleared from the macrophage-rich mouse peritoneal cavity and phagocytosed by murine macrophages. These findings suggest that the RTX of V. vulnificus is required for bacterial survival during infection by protecting the organism from phagocytosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate opioid receptor function as a basis for novel antinociceptive therapy in arthritis. METHODS: We induced human mu-opioid receptor (HuMOR) expression in arthritic joints of mice, using the feline immunodeficiency virus (FIV) vector, which is capable of stably transducing dividing, growth-arrested, and terminally differentiated cells. Male and female Col1-IL-1beta(XAT)-transgenic mice developed on a C57BL/6J background and wild-type littermates were studied. RESULTS: A single injection of FIV(HuMOR) into the temporomandibular joints of Col1-IL-1beta(XAT)-transgenic mice 1 week prior to induction of arthritis prevented the development of orofacial pain and joint dysfunction, and reduced the degree of histopathologic abnormality in the joint. In addition, FIV(HuMOR) prevented the attendant sensitization of trigeminal sensory neurons and activation of astroglia in brainstem trigeminal sensory nuclei. These effects were mediated by the transduction of primary sensory neurons via transport of FIV vectors from peripheral nerve endings to sensory ganglia, as evidenced by HuMOR expression in neuronal cell bodies located in the trigeminal ganglia, as well as in their proximal and distal nerve branches located in the main sensory and subnucleus caudalis of the brainstem and joints, respectively. The presence of MOR ligands predominantly in the descending trigeminal nucleus suggested that the observed antinociception occurred at the subnucleus caudalis. Articular chondrocytes and meniscal tissue were also infected by FIV(HuMOR), which presumably exerted an antiinflammatory effect on cartilage. CONCLUSION: Our results indicate that prophylactic therapy with MOR overexpression in joints can successfully prevent the development of pain, dysfunction, and histopathologic abnormalities in the joints in arthritis. These findings may provide a basis for the future development of spatiotemporally controlled antinociceptive and antiinflammatory therapy for arthritis. [ABSTRACT FROM AUTHOR]

Heatstroke is a life-threatening disease; however, no pharmacologic treatment has proven to be effective. In severe cases with multiple organ dysfunction, the mortality remains high and many patients inevitably develop permanent neurologic damage. We report a near-fatal case of exertional heatstroke with multiple organ dysfunction, including generalized convulsions, acute lung injury, and disseminated intravascular coagulation, successfully treated with induced therapeutic hypothermia (33°C [91.4°F]) by a noninvasive external cooling system. After treatment, the patient completely recovered, without any neurologic sequelae during 1 year of follow-up. To our knowledge, this is the first reported case of using therapeutic hypothermia in heatstroke. [ABSTRACT FROM AUTHOR]

Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease unrelated to the Kaposi sarcoma-associated herpesvirus/human herpesvirus type 8 (KSHV/HHV8) infection. Presently, iMCD is classified into iMCD-IPL (idiopathic plasmacytic lymphadenopathy), iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis/renal insufficiency, and organomegaly), and iMCD-NOS (not otherwise specified). The most common treatment for iMCD is using IL-6 inhibitors; however, some patients resist IL-6 inhibitors, especially for iMCD-TAFRO/NOS. Nevertheless, since serum IL-6 levels are not significantly different between the iMCD-IPL and iMCD-TAFRO/NOS cases, cytokines other than IL-6 may be responsible for the differences in pathogenesis. Herein, we performed a transcriptome analysis of cytokine storm-related genes and examined the differences between iMCD-IPL and iMCD-TAFRO/NOS. The results demonstrated that counts per million of STAT2, IL1R1, IL1RAP, IL33, TAFAIP1, and VEGFA (P < 0.001); STAT3, JAK2, MAPK8, IL17RA, IL18, TAFAIP2, TAFAIP3, PDGFA, VEGFC, CXCL10, CCL4, and CXCL13 (P < 0.01); and STAT1, STAT6, JAK1, MAPK1, MAPK3, MAPK6, MAPK7, MAPK9, MAPK10, MAPK11, MAPK12, MAPK14, NFKB1, NFKBIA, NFKBIB, NFKBIZ, MTOR, IL10RB, IL12RB2, IL18BP, TAFAIP6, TNFAIP8L1, TNFAIP8L3, CSF2RBP1, PDGFB, PDGFC, and CXCL9 (P < 0.05) were significantly increased in iMCD-TAFRO/NOS. Particularly, upregulated IL33 expression was demonstrated for the first time in iMCD-TAFRO/NOS. Thus, inflammatory signaling, such as JAK-STAT and MAPK, may be enhanced in iMCD-TAFRO/NOS and may be a cytokine storm.

A foundational machine-learning architecture is reinforcement learning, where an outstanding problem is achieving an optimal balance between exploration and exploitation. Specifically, exploration enables the agents to discover optimal policies in unknown domains of the environment for gaining potentially large future rewards, while exploitation relies on the already acquired knowledge to maximize the immediate rewards. We articulate an approach to this problem, treating the dynamical process of reinforcement learning as a Markov decision process that can be modeled as a nondeterministic finite automaton and defining a subset of states in the automaton to represent the preference for exploring unknown domains of the environment. Exploration is prioritized by assigning higher transition probabilities to these states. We derive a mathematical framework to systematically balance exploration and exploitation by formulating it as a mixed integer programming (MIP) problem to optimize the agent's actions and maximize the discovery of novel preferential states. Solving the MIP problem provides a trade-off point between exploiting known states and exploring unexplored regions. We validate the framework computationally with a benchmark system and argue that the articulated automaton is effectively an adaptive network with a time-varying connection matrix, where the states in the automaton are nodes and the transitions among the states represent the edges. The network is adaptive because the transition probabilities evolve over time. The established connection between the adaptive automaton arising from reinforcement learning and the adaptive network opens the door to applying theories of complex dynamical networks to address frontier problems in machine learning and artificial intelligence., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Purpose: Evaluate the relationship between first and second-line medication dosing and progression to refractory status epilepticus (RSE) in children., Methods: This is a retrospective analysis of prospectively collected data from September 2014 to February 2020 of children with status epilepticus (SE) who received at least two antiseizure medications (ASMs). We evaluated the risk of developing RSE after receiving a low total benzodiazepine dose (lower than 100 % of the minimum recommended dose for each benzodiazepine dose administered within 10 min) and a low first non-benzodiazepine ASM dose (lower than 100 % of the minimum recommended dose of non-benzodiazepine ASM given as the first single-dose) using a logistic regression model, adjusting for confounders such as time to ASMs. The proportion of patients receiving low first non-benzodiazepine ASM doses was calculated and a logistic regression model was used to evaluate risk factors for low dosing of the first non-benzodiazepine ASM., Results: Among 320 children, 170 (53.1 %) developed RSE, and 150 (46.9 %) responded to the first non-benzodiazepine ASM dose (non-RSE). One hundred thirty-seven (42.8 %) received a low total benzodiazepine dose, and 128 (40 %) received a low first non-benzodiazepine ASM dose. The odds of developing RSE were not higher after a low total benzodiazepine dose (OR=0.76, 95 %CI 0.47-1.23, p = 0.27) or low first non-benzodiazepine ASM dose (OR=0.85, 95 %CI 0.42-1.71, p = 0.65). Receiving a low first non-benzodiazepine ASM dose was independently associated with having received a low total benzodiazepine dose (OR=1.65, 95 %CI 1.01-2.70, p = 0.04)., Conclusion: For most patients, dosing variability in first and second-line medications for SE was not the sole clinical feature predicting progression to RSE in this cohort of benzodiazepine-resistant patients. Identification of additional modifiable clinical biomarkers that predict progression to RSE is needed. Though lower ASM doses did not predict RSE in this model, the administration of ASMs at doses likely to prevent RSE remains crucial in SE treatment., Competing Interests: Declaration of competig interest TL is part of pending patent applications to detect and predict seizures and to diagnose epilepsy. He receives research support from the NIH, the Epilepsy Research Fund, and Epitel. He received research grants from Sage, Lundbeck, Eisai, Upsher-Smith, Mallinckrodt, Pfizer, and MIKU in the past. He served as a consultant for Engage and Upsher Smith, in the past., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: National Comprehensive Cancer Network guidelines suggest chest CT when gastrointestinal stromal tumors are larger than 2 cm. We evaluate the value of screening the chest region during initial and follow-up CT., Method: Single institution retrospective analysis of GIST cancer registry for patients diagnosed between May 2010 and November 2019 with tumor > 2 cm. We collected the patient demographics and clinical data; reviewed all CT scans of the chest region and recorded the lung nodules. Patients were grouped into lung nodule group and non-nodule group. Categorical variables were compared with the Chi square test and continuous variables with the Mann-Whitney U test. The survival probability was determined from Kaplan-Meier survival analysis and log-rank test for comparing differences., Results: The final cohort included 382 patients (median age 61 years-old [interquartile range: 52-71]) and grouped into non-nodule group (n = 284) and lung nodule group (n = 98). The frequency of the CT scan was more in lung nodule group (8 [5-12]) than in non-nodule group (4 [2-9], p < 0.001). The lung nodule group had more CT including the chest region (6 [3-10] vs 3 [1-7], p < 0.001). In progressive lung nodules (8/98 [8 %]), only one patient had confirmed lung metastasis from GIST (1/382 [3 %]). There was no difference in overall survival between nodule groups (p = 0.12)., Conclusions: GIST patients with tumors larger than 2 cm have extremely low risk for lung metastasis. Routine inclusion of chest CT scan in staging and follow up is unnecessary., 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 B.V. All rights reserved.)

Skeletal muscle is a highly adaptable tissue, finely tuned by various physiological and pathological factors. Whilst the pivotal role of skeletal muscle in overall health is widely acknowledged, unravelling the underlying molecular mechanisms poses ongoing challenges. Protein ubiquitylation, a crucial post-translational modification, is involved in regulating most biological processes. This widespread impact is achieved through a diverse set of enzymes capable of generating structurally and functionally distinct ubiquitin modifications on proteins. The complexity of protein ubiquitylation has presented significant challenges in not only identifying ubiquitylated proteins but also characterising their functional significance. Mass spectrometry enables in-depth analysis of proteins and their post-translational modification status, offering a powerful tool for studying protein ubiquitylation and its biological diversity: an approach termed ubiquitylomics. Ubiquitylomics has been employed to tackle different perspectives of ubiquitylation, including but not limited to global quantification of substrates and ubiquitin linkages, ubiquitin site recognition and crosstalk with other post-translational modifications. As the field of mass spectrometry continues to evolve, the usage of ubiquitylomics has unravelled novel insights into the regulatory mechanisms of protein ubiquitylation governing biology. However, ubiquitylomics research has predominantly been conducted in cellular models, limiting our understanding of ubiquitin signalling events driving skeletal muscle biology. By integrating the intricate landscape of protein ubiquitylation with dynamic shifts in muscle physiology, ubiquitylomics promises to not only deepen our understanding of skeletal muscle biology but also lay the foundation for developing transformative muscle-related therapeutics. This review aims to articulate how ubiquitylomics can be utilised by researchers to address different aspects of ubiquitylation signalling in skeletal muscle. We explore methods used in ubiquitylomics experiments, highlight relevant literature employing ubiquitylomics in the context of skeletal muscle and outline considerations for experimental design., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Carbapenem-resistant Enterobacter cloacae complex is a significant global healthcare threat, particularly carbapenemase-producing Enterobacter hormaechei (CPEH). From January 2017 to January 2021, twenty-two CPEH isolates from a regional teaching hospital in central Taiwan were identified with the carriage of carbapenemase genes bla KPC-2 , bla IMP-8 , and predominantly bla OXA-48 . Over 80% of these CPEH strains clustered into the high-risk ST78 lineage, carrying a bla OXA-48 IncL plasmid (pOXA48-CREH), nearly identical to the endemic plasmid pOXA48-KP in ST11 Klebsiella pneumoniae . This OXA-48-producing ST78 lineage disseminated clonally from 2018 to 2021 and transferred pOXA48-CREH to ST66 and ST90 E. hormaechei . An IMP-8-producing ST78 strain harbouring a bla IMP-8 -carrying pIncHI2 plasmid appeared in 2018, and by late 2020, a KPC-2-producing ST78 strain was identified after acquiring a novel bla KPC-2 -carrying IncFII plasmid. These findings suggest that the high-risk ST78 lineage of E . hormaechei has emerged as the primary driver behind the transmission of CPEH . ST78 has not only acquired various carbapenemase-gene-carrying plasmids but has also facilitated the transfer of pOXA48-CREH to other lineages. Continuous genomic surveillance and targeted interventions are urgently needed to control the spread of emerging CPEH clones in hospital settings.

The glutamatergic signaling pathway, which is mediated by N-methyl-D-aspartate (NMDA) receptors, is crucial for osteoblast differentiation and bone function. Dextromethorphan (DXM), a widely used antitussive, is a noncompetitive antagonist of the NMDA receptor. However, the effects of DXM on osteoblast and bone regeneration remain unclear. The present study investigated the effects of DXM on osteogenesis in vitro and in vivo. A MC3T3-E1 preosteoblast cell line was treated with varying concentrations of DXM. Real-time-quantitative polymerase chain reaction (RT-qPCR) and Western-blot analysis were performed to evaluate the expression of osteogenesis-related runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), collagen type 1α (Col-1α), and alkaline phosphatase (ALP) after DXM treatment. Zebrafish embryos were incubated with DXM, which had potential to affect the ossification of the vertebrae and skull, and analyzed using calcein staining. Furthermore, we used a rat calvarial defect model to assess the effects of DXM on bone regeneration by using microcomputed tomography. The results indicate that DXM inhibited extracellular mineralization, ALP activity, and the expression of osteogenic markers, namely RUNX2, OSX, OCN, Col-1α, and ALP, in MC3T3-E1 cells. DXM suppressed skeleton ossification in zebrafish and affected bone regeneration in rats with calvarial defects. However, the mineral density of the regenerated bones did not differ significantly between the DXM and control groups. The present study demonstrated that DXM negatively affects the osteogenic function of osteoblasts, leading to impaired skeletal development and bone regeneration. Thus, clinicians should consider the negative effects of DXM on bone regeneration., (© 2024 Wiley Periodicals LLC.)

Objective: Previous studies have shown that the incidence of peptic ulcer disease (PUD) exhibits seasonal variations. This study aimed to investigate the seasonal variation in PUD incidence in Taiwan, which spans both tropical and subtropical regions, using a nationwide database., Methods: A cross-sectional study was conducted using real-world claims data from Taiwan, which includes a representative sample of 2 million individuals. Patients hospitalised with a primary diagnosis of PUD between 2001 and 2019 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for gastric ulcers (GUs), duodenal ulcers (DUs) and unspecified peptic ulcers. Descriptive statistics were used to present the seasonal variations in PUD incidence. Patients' gender, age, PUD type, geographical region and non-steroidal anti-inflammatory drugs (NSAIDs) usage across the four seasons (spring, summer, fall, winter) were compared using Pearson's χ 2 test., Results: Among the 13 022 patients, new-onset PUD cases varied annually, peaking at 771 cases in 2004 and reaching a low of 614 cases in 2018. PUD incidence was higher in males than in females, and more common in elderly individuals aged ≥65 (59.5%). GU had the highest prevalence (56.1%), followed by DU (36.3%) and unspecified ulcers (7.7%). PUD incidence peaked in winter (26.8%), followed by spring (25.1%), fall (24.2%) and summer (23.9%). This seasonal trend was consistent across gender and age groups, with no significant impact on latitude, NSAID usage or PUD type., Conclusion: Across the tropical and subtropical regions of Taiwan, seasonal variation in PUD incidence is observed with the highest rates occurring in winter, regardless of age or sex. However, NSAID usage tends to obscure this trend. The seasonal variation in DU incidence showed no significant differences between north and south Taiwan, suggesting that factors other than temperature may affect DU incidence compared with their effect on GU incidence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Compare the efficacy and procedural efficiency of central vascular plug-assisted portal vein embolization (PVE) with absolute ethanol compared to selective PVE., Materials and Methods: Between 2016 and 2023, patients who underwent ipsilateral percutaneous transhepatic PVE were included. Selective PVE involves serial cannulation and embolization of portal veins. Central vascular plug-assisted PVE involves deploying a vascular plug at the main portal vein with embolization. Recorded data includes patient demographics, disease diagnosis, volumetry, embolization procedure, biliary drainage, surgery, and measures of future liver remnant hypertrophy (relative hypertrophy, degree of hypertrophy, and kinetic growth rate)., Results: The cohort comprised of 30 patients (cohort mean age 64±9 years old, females n=14) of which 17 (57%) patients underwent central vascular plug-assisted PVE. Indications for PVE were predominately (87%, 26/30) due to bile duct cancer. Volumetric changes between central vascular plug-assisted PVE and selective PVE were not different between the two groups (DH 13%±5 vs 11%±4, p=0.21; and KGR 3%/week ± 2 vs 2%/week ± 2, p=0.27, respectively). Overall procedure times were shorter for central vascular plug-assisted PVE (45±20 minutes vs 112±34 minutes; p<0.001). Two adverse events occurred in selective PVE, while none in central vascular plug-assisted PVE. There was no difference in rates of surgery or no surgery for both methods (p=0.07)., Conclusion: Central vascular plug-assisted PVE with absolute ethanol effectively induced FLR hypertrophy, and significantly reduced procedure times due to faster embolization and simpler technique., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: Postpartum depression (PPD) is a major mental health issue affecting 10%-15% of women globally. This meta-analysis synthesized updated evidence on sub-anesthetic ketamine/esketamine's efficacy in preventing PPD., Methods: Randomized controlled trials (RCTs) comparing ketamine/esketamine to a placebo for PPD prevention were searched without language restriction. Primary outcomes were PPD risk at 1- and 4-6-week postpartum. Secondary outcomes included the difference in depression scores and risk of adverse events. Trial sequential analysis (TSA) was conducted to validate the reliability., Results: A meta-analysis of 22 RCTs (n = 3,463) showed that ketamine/esketamine significantly decreased PPD risk at 1- (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.3-0.57) and 4-6-week (RR, 0.47; 95%CI, 0.35-0.63) follow-ups. Consistently, participants receiving ketamine/esketamine had lower depression-related scores at 1- (standardized mean difference [SMD], -0.94; 95%CI, -1.26 to -0.62) and 4-6-week (SMD, -0.89; 95%CI, -1.25 to -0.53) follow-ups. Despite potential publication bias, TSA confirmed the evidence's reliability. Subgroup analysis showed that ketamine/esketamine's preventive effect on 1-week PPD was consistent, regardless of administration timing, type of agents, or total dosage (<0.5 vs. ≥0.5 mg/kg). For the 4-6-week period, PPD risk was favorably reduced only with postoperative administration or the use of esketamine, with the total dosage having no observed influence. Participants on ketamine/esketamine experienced more frequency of hallucinations (RR, 4.77; 95%CI, 1.39-16.44) and dizziness (RR, 1.36; 95%CI, 1.02-1.81)., Conclusion: Our findings advocate for the postoperative administration of low-dose ketamine/esketamine to avert PPD, which needed additional research for confirmation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Microsatellite instable (MSI) gastric cancers exhibit reduced lymph node (LN) metastasis and improved survival compared to microsatellite stable (MSS) counterparts. However, to our longstanding observation, clinical N-staging (cN) is frequently overestimated in MSI cases. The clinical implications and underlying mechanisms of this discrepancy warrant further investigation., Materials and Methods: We conducted a comprehensive review of clinicopathological data from a 141 MSI and 1119 MSS gastric cancer patients. Expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 were assessed using qPCR and immunohistochemistry. High-parameter flow cytometry was employed to analyze subsets of CD8+ T cells within the tumors., Results: Multivariate analysis revealed that MSI status was an independent prognostic factor, alongside the LN ratio and AJCC8 pathology staging. MSI gastric cancers exhibited a reduced LN ratio, particularly at advanced T-staging, compared to MSS counterparts, while maintaining an equivalent LN yield. Overestimation of cN by computed tomography preoperatively was frequent in MSI gastric cancers but was more commonly underestimated in MSS counterparts. VEGF-C and VEGFR-3 expression were lower in MSI tumors. MSI gastric cancers showed an increased total number of CD8+ T cells, albeit with a lower proportion of effector memory cells expressing CD45RA (EMRA) and CD8+ CXCR4+ T cells, compared to MSS counterparts., Conclusion: Frequent overestimation of clinical N-staging in MSI gastric cancers is associated with VEGF-C signaling and CD8+ T-cell dynamics and should be cautiously interpreted, as it might misguide therapeutic options., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: We sought to examine the effects of acute seizures and respiratory derangement on the cardiac electrical properties reflected on the electrocardiogram (ECG); and to analyze their potential interactions with a diagnosis of epilepsy in children., Methods: Emergency center (EC) visits with seizure or epilepsy diagnostic codes from 1/2011-12/2013 were included if they had ECG within 24 h of EC visit. Patients were excluded if they had pre-existing cardiac conditions, ion channelopathy, or were taking specific cardiac medications. Control subjects were 1:1 age and gender matched. Abnormal ECG was defined as changes in rhythm, PR, QRS, or corrected QT intervals; QRS axis or morphology; ST segment; or T wave morphology from normal standards. We identified independent associations between clinical factors and abnormal ECG findings using multivariable logistic regression modeling., Results: Ninety-five children with epilepsy presented to the EC with seizures, respiratory distress, and other concerns. Three hundred children without epilepsy presented with seizures. There was an increased prevalence of minor ECG abnormalities in children with epilepsy (49 %) compared to the control subjects (29 %) and those without epilepsy (36 %). Epilepsy (OR: 1.61, 95 %CI: 1.01-2.6), need for supplemental oxygen (OR 3.06, 95 % CI: 1.45-6.44) or mechanical ventilation (OR: 2.5, 95 % CI: 1.03-6.05) were independently associated with minor ECG abnormalities. Secondary analyses further demonstrated an independent association between level of respiratory support and ECG abnormalities only in the epilepsy group., Significance: Independent association of increased respiratory support with minor ECG abnormalities suggests a potential respiratory influence on the hearts of children with epilepsy., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to disclose. We confirm that we have read journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The Baylor College of Medicine Institutional Review Board approved the study with waiver of consent (H-34453)., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To establish reference values for SPPB score as well as test performances among Taiwanese community-dwelling older adults., Methods: Participants included 847 older adults. The total scores and three subtest scores for the SPPB and the registered time to complete the walk and five-repetition sit-to-stand (STS) tests were determined and compared between sex and age (65-74, 75-84, and ≥85 years) groups., Results: The mean SPPB total score was 10.9 in women and 10.5 in men. SPPB scores did not differ by sex, regardless of age group. However, the walk test (p = .030) and STS test (p = .008) timings were longer for men than for women in the 65-74-year-old group. The ≥85-year-old men achieved a lower balance score than did the 65-74-year-old men (p = .027)., Conclusions: Population-specific SPPB reference values contribute to assessments of physical function and facilitate cross-cultural comparisons of physical performance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Comprehensive next-generation sequencing (NGS) of non-small-cell lung cancer specimens can identify oncogenic driver mutations and their corresponding targeted therapies. Plasma cell-free DNA (cfDNA) genotyping is easy to perform; however, false negatives cannot be overlooked. We explored malignant pleural effusion (MPE), a rich source of cfDNA, as a non-inferior alternative to tumor tissues for genotyping., Methods: We conducted a prospective trial including 39 patients with newly diagnosed stage IV lung adenocarcinoma who presented with MPE. Tissue tests matching hotspot variants, including EGFR, ALK, and ROS1, were compared with the AlphaLiquid100 of PE-cfDNA., Results: Among the 39 PE-cfDNA samples successfully sequenced, 32 (82.1%) had a PE cell-block tumor content of < 10%. Standard tissue or cell-block testing for EGFR, ALK, and ROS1 identified 20 mutations (51.3%), whereas PE cfDNA identified 25 mutations (64.1%). Five EGFR mutations were observed in PE cfDNA but not in Cobas EGFR owing to coverage or insufficient tumor content issues. The overall rate of oncogenic mutations identified in the PE cfDNA was 92.3%, and the mutation distribution was as follows: even with a very low cfDNA input, high detection rates could be achieved. Otherwise, most patients harbored co-mutations. Comparison of pleural fluid NGS with traditional testing revealed differences in accuracy. We also followed up with patients with EGFR-sensitizing mutations who had a treatment response rate of 97.2% after 3 months., Conclusions: Genotyping of MPE supernatant cfDNA is feasible in clinical practice, in addition to plasma and tumor testing, to improve diagnostic yield and extend patients' benefit from targeted therapies., (© 2024. The Author(s).)

All known forms of life are composed of cells, whose boundaries are defined by lipid membranes that separate and protect cell contents from the environment. It is unknown how the earliest forms of life were compartmentalized. Several models have suggested a role for single-chain lipids such as fatty acids, but the membranes formed are often unstable, particularly when made from shorter alkyl chains (≤C 8 ) that were probably more prevalent on prebiotic Earth. Here we show that the amino acid cysteine can spontaneously react with two short-chain (C 8 ) thioesters to form diacyl lipids, generating protocell-like membrane vesicles. The three-component reaction takes place rapidly in water using low concentrations of reactants. Silica can catalyse the formation of protocells through a simple electrostatic mechanism. Several simple aminothiols react to form diacyl lipids, including short peptides. The protocells formed are compatible with functional ribozymes, suggesting that coupling of multiple short-chain precursors may have provided membrane building blocks during the early evolution of cells., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-13C]pyruvate and [1-13C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

New-onset refractory status epilepticus (NORSE) is a devastating clinical condition that often leads to severe disability. Intrathecal dexamethasone (IT-DEX) has been reported to improve refractory status epilepticus. We present an 11-year-old female with anti-GAD 65 encephalitis presenting as NORSE who had minimal response to standard anti-seizure medications and first-line immunotherapies. The patient received 6 doses of IT-DEX in conjunction with rituximab which correlated with subsequent decreased neuroinflammation, reduced seizure burden and aided in weaning anesthetic infusions. Our case with literature review suggests IT-DEX may be utilized as an early intervention in those with refractory status epilepticus from various etiologies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rationale: Caustic substance ingestion is an emergency and life-threatening condition as it leads to tissue damage, acidosis, and multiorgan failure. This study presents a case report of hydrochloric acid ingestion and notably dark-red urine output due to acute tubular necrosis., Patient Concerns: A 59-year-old male presented with attempted suicide by ingesting 500 mL of hydrochloric acid (37%), and complained of severe abdominal pain and shortness of breath. Upon arrival, his vital signs showed a temperature of 34.3°C, blood pressure of 104/77 mm Hg, a pulse rate of 135 beats per minute, and the Glasgow Coma Scale E4V2M6. Following Foley catheter insertion, dark, bloody urine resulting from acute tubular necrosis was observed. His creatinine level was 1.1 mg/dL, and urinalysis showed 38 red blood cells per high-power field. Arterial blood gas analysis revealed metabolic acidosis., Diagnoses: The patient's condition rapidly deteriorated in the emergency room, revealing diffuse circumferential ulceration with necrosis in the esophagus (Zargar score grade 3b). An exploratory laparotomy was performed for acidosis with intractable shock, revealing up to 1500 mL of bloody ascites, and ischemic changes with loss of peristalsis throughout the small bowel to the cecum., Interventions: Esophagostomy with T-tube insertion was performed. Notably, stomach necrosis with perforation was identified, prompting a surgical consultation for primary perforation closure., Outcomes: During the operation, the patient experienced hemodynamic instability. The family confirmed the "Do Not Resuscitate" status, and he died in a critical state., Lessons: For corrosive injuries, early endoscopy was crucial in assessing the extent of the damage and guiding treatment in this patient. It is essential to perform an early endoscopic examination in cases of acute nephrotoxic tubular necrosis following hydrochloric acid ingestion. Surgical intervention is warranted if necrosis is detected in the corrosive tissue., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Escalating energy demands of self-independent on-skin/wearable electronics impose challenges on corresponding power sources to offer greater power density, permeability, and stretchability. Here, a high-efficient breathable and stretchable monolithic hybrid triboelectric-piezoelectric-electromagnetic nanogenerator-based electronic skin (TPEG-skin) is reported via sandwiching a liquid metal mesh with two-layer topological insulator-piezoelectric polymer composite nanofibers. TPEG-skin concurrently extracts biomechanical energy (from body motions) and electromagnetic radiations (from adjacent appliances), operating as epidermal power sources and whole-body self-powered sensors. Topological insulators with conductive surface states supply notably enhanced triboelectric and piezoelectric effects, endowing TPEG-skin with a 288 V output voltage (10 N, 4 Hz), ∼3 times that of state-of-the-art devices. Liquid metal meshes serve as breathable electrodes and extract ambient electromagnetic pollution (±60 V, ±1.6 µA cm -2 ). TPEG-skin implements self-powered physiological and body motion monitoring and system-level human-machine interactions. This study provides compatible energy strategies for on-skin/wearable electronics with high power density, monolithic device integration, and multifunctionality., (© 2024 Wiley‐VCH GmbH.)

Background: Temporomandibular disorders (TMDs) may be an 'idiom' of psychological distress in Confucian heritage cultures (CHCs)., Objectives: This systematic review/meta-analysis estimated the prevalence of TMDs in CHCs and compared the differences in TMD occurrence between time periods and age groups. Additionally, the associated biopsychosocial risk factors were also examined., Methods: The study protocol was developed a priori following the PRISMA guidelines and Joanna Briggs Institute systematic review methodology (CRD42021245526). Electronic searches of seven databases were conducted from January 2002 to Dec 2021. Reference lists of identified studies were hand-searched for additional articles. Study selection, quality assessment, and data extraction were done. Meta-analysis was performed using the RevMan 5.4 software., Results: Forty-eight articles were included in the systematic review. Overall prevalences were: TMDs-15% (95% CI: 15-16%); TMD pain-8% (95% CI: 7-9%); TMJ sounds-24% (95% CI: 21-27%); and TMJ locking-7% (95% CI: 1-13%). While TMD prevalence appeared to have declined from 2002 to 2011 to 2012-2021, the occurrence of TMD pain, TMJ sounds, and locking increased marginally or remained constant. TMD prevalence in children/adolescents was 18% (95% CI: 14-22%) and 17% (95% CI: 16-18%) among adults. Significant associations between TMDs and bruxism/psychological distress/education levels were specified by 73%/90%/88% of the relevant studies., Conclusions: TMDs are prevalent in CHCs and a slight increase in TMD pain (2%) and TMJ sounds (8%) were discerned over the past two decades. TMDs are related to a myriad of biopsychosocial variables, particularly psychological distress, and these factors must be addressed within the cultural context of patients., (© 2024 John Wiley & Sons Ltd.)

Background: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Early detection of allograft injury is important to delay or prevent irreversible damage., Purpose: To investigate the feasibility of hyperpolarized (HP) [1- 13 C]pyruvate MRI for assessing kidney allograft metabolism., Study Type: Prospective., Subjects: 6 participants (mean age, 45.2 ± 12.4 years, 2 females) scheduled for kidney allograft biopsy and 5 patients (mean age, 59.6 ± 10.4 years, 2 females) with renal cell carcinoma (RCC)., Field Strength/sequence: 3 Tesla, T2-weighted fast spin echo, multi-echo gradient echo, single shot diffusion-weighted echo-planar imaging, and time-resolved HP 13 C metabolite-selective imaging., Assessment: Five of the six kidney allograft participants underwent biopsy after MRI. Estimated glomerular filtration rate (eGFR) and urine protein-to-creatine ratio (uPCR) were collected within 4 weeks of MRI. Kidney metabolism was quantified from HP [1- 13 C]pyruvate MRI using the lactate-to-pyruvate ratio in allograft kidneys and non-tumor bearing kidneys from RCC patients., Statistical Tests: Descriptive statistics (mean ± standard deviation)., Results: Biopsy was performed a mean of 9 days (range 5-19 days) after HP [1- 13 C]pyruvate MRI. Three biopsies were normal, one showed low-grade fibrosis and one showed moderate microvascular inflammation. All had stable functioning allografts with eGFR > 60 mL/min/1.73 m 2 and normal uPCR. One participant who did not undergo biopsy had reduced eGFR of 49 mL/min/1.73 m 2 and elevated uPCR. The mean lactate-to-pyruvate ratio was 0.373 in participants with normal findings (n = 3) and 0.552 in participants with abnormal findings (n = 2). The lactate-to-pyruvate ratio was highest (0.847) in the participant with reduced eGFR and elevated uPRC. Native non-tumor bearing kidneys had a mean lactate-to-pyruvate ratio of 0.309., Data Conclusion: Stable allografts with normal findings at biopsy showed lactate-to-pyruvate ratios similar to native non-tumor bearing kidneys, whereas allografts with abnormal findings showed higher lactate-to-pyruvate ratios.