COVID-19 Immunologic Antiviral Therapy With Omalizumab (CIAO)-a Randomized Controlled Clinical Trial.

Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.

BRD4 inhibitors broadly promote erastin-induced ferroptosis in different cell lines by targeting ROS and FSP1.

Ferroptosis, an iron-dependent form of programmed cell death, is a promising strategy for cancer treatment. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a promising target for cancer therapeutics. However, the role of BRD4 in ferroptosis is controversial and the value of the interaction between BRD4 inhibitors and ferroptosis inducers remains to be explored. Here, we found that BRD4 inhibition greatly enhanced erastin-induced ferroptosis in different types of cells, including HEK293T, HeLa, HepG2, RKO, and PC3 cell lines. Knocking down BRD4 in HEK293T and HeLa cells also promoted erastin-induced cell death. BRD4 inhibition by JQ-1 and I-BET-762 or BRD4 knockdown resulted in substantial accumulation of reactive oxygen species (ROS) in both HEK293T and HeLa cells. The effect of BRD4 inhibition on ferroptosis-associated genes varied in different cells. After using BRD4 inhibitors, the expression of FTH1, Nrf2, and GPX4 increased in HEK293T cells, while the levels of VDAC2, VDAC3, and FSP1 decreased. In HeLa cells, the expression of FTH1, VDAC2, VDAC3, Nrf2, GPX4, and FSP1 was reduced upon treatment with JQ-1 and I-BET-762. Consistently, the level of FSP1 was greatly reduced in HEK293T and HeLa cells with stable BRD4 knockdown compared to control cells. Furthermore, ChIP-sequencing data showed that BRD4 bound to the promoter of FSP1, but the BRD4 binding was greatly reduced upon JQ-1 treatment. Our results suggest that ROS accumulation and FSP1 downregulation are common mechanisms underlying increased ferroptosis with BRD4 inhibitors. Thus, BRD4 inhibitors might be more effective in combination with ferroptosis inducers, especially in FSP1-dependent cancer cells.

Buffer Chain Model for Understanding Crystallization Competition in Conjugated Polymers.

It remains challenging to comprehensively understand the packing models of conjugated polymers, in which side chains play extremely critical roles. The side chains are typically flexible and non-conductive and are widely used to improve the polymer solubility in organic solutions. Herein, a buffer chain model is proposed to describe link between conjugated backbone and side chains for understanding the relationship of crystallization competition of conductive conjugated backbones and non-conductive side chains. A longer buffer chain is beneficial for alleviating such crystallization competition and further promoting the spontaneous packing of conjugated backbones, resulting in enhanced charge transport properties. Our results provide a novel concept for designing conjugated polymers towards ordered organization and enhanced electronic properties and highlight the importance of balancing the competitive interactions between different parts of conjugated polymers.

Injectable isoniazid-loaded bone cement based on hydrazone bonds achieving long-term release and decent mechanical properties.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Monolithic PMN-39PT nanograting-assisted second harmonic generation enhancement.

Second harmonic generation plays a vital role in frequency conversion which mutually promotes the laser technology and allows the wavebands extension of new coherent source. The monolithic crystals are supposed to be a superior choice for harmonic generation due to long interaction distance, however, the phase-mismatch brought a sharp reduction in the conversion efficiency. Although birefringent phase-matching and quasi-phase-matching techniques are commonly utilized to fill the phase gap in monolithic crystals, these techniques are limited by the natural refractive index of crystal and the domain engineering, respectively. In recent years, subwavelength structures evolve as a flexible scheme to realize phase matching by engineering the geometry features of crystals. Here, structured nanogratings are designed and fabricated on a monolithic PMN-39PT (Pb(Mg1/3Nb2/3)O3-0.39PbTiO3) substrate, a novel ferroelectric crystal with promising optical prospect, for enhancing second harmonic generation, where birefringent or quasi phase-matching is hard to achieve. The nanograting-assisted second harmonic generation enhancement is observed which is not limited by the availability of thin crystalline films. Meanwhile, a boost in the second harmonic signal synchronously promotes the cascading third harmonic generation. This method may provide an alternative solution for enhanced harmonic generation on monolithic substrates and develop potential nonlinear optical materials for frequency conversion.

Detection and characterization of eravacycline heteroresistance in clinical bacterial isolates.

Eravacycline (ERV) has emerged as a therapeutic option for the treatment of carbapenem-resistant pathogens. However, the advent of heteroresistance (HR) to ERV poses a challenge to these therapeutic strategies. This study aimed to investigate ERV HR prevalence among common clinical isolates and further characterize ERV HR in carbapenem-resistant Klebsiella pneumoniae (CRKP). A total of 280 clinical pathogens from two centers were selected for HR and analyzed using population analysis profiling (PAP) and modified E-tests. The PAP assay revealed an overall ERV HR prevalence of 0.7% (2/280), with intermediate heterogeneity observed in 24.3% (68/280) of strains. The proportion of heteroresistant strains was 18.3% according to modified E-test results. A time-killing assay demonstrated that CRKP CFU increased significantly after 10 h of ERV treatment, contributing to the reduced bactericidal effect of ERV in vitro. Interestingly, dual treatment with ERV and polymyxin B effectively inhibited the total CFU, simultaneously reducing the required polymyxin B concentration. Furthermore, fitness cost measurements revealed a growth trade-off in CRKP upon acquiring drug resistance, highlighting fitness costs as crucial factors in the emergence of ERV HR in CRKP. Overall, the findings of the current study suggest that ERV HR in clinical strains presents a potential obstacle in its clinical application.

Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights.

While we recognize the prognostic importance of clinicopathological measures and circulating tumor DNA (ctDNA), the independent contribution of quantitative image markers to prognosis in non-small cell lung cancer (NSCLC) remains underexplored. In our multi-institutional study of 394 NSCLC patients, we utilize pre-treatment computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to establish a habitat imaging framework for assessing regional heterogeneity within individual tumors. This framework identifies three PET/CT subtypes, which maintain prognostic value after adjusting for clinicopathologic risk factors including tumor volume. Additionally, these subtypes complement ctDNA in predicting disease recurrence. Radiogenomics analysis unveil the molecular underpinnings of these imaging subtypes, highlighting downregulation in interferon alpha and gamma pathways in the high-risk subtype. In summary, our study demonstrates that these habitat imaging subtypes effectively stratify NSCLC patients based on their risk levels for disease recurrence after initial curative surgery or radiotherapy, providing valuable insights for personalized treatment approaches.

Iodine-Promoted Reductive Sulfenylation Using Ketones as Hydride Donors.

Herein, an iodine-promoted reductive sulfenylation reaction of ketones with disulfides has been developed. This method provides an approach for synthesizing unsymmetrical alkyl-alkyl and alkyl-aryl sulfides in a single step. Investigation of the reaction mechanism revealed that ketones play a dual role in this process. They react with disulfides to produce vinyl thioethers and act as effective organic hydride donors, reducing the number of vinyl thioethers that are formed in situ. This study expands the range of applications of ketones in chemical synthesis.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Strain Engineering of Twisted Bilayer Graphene: The Rise of Strain-Twistronics.

The layer-by-layer stacked van der Waals structures (termed vdW hetero/homostructures) offer a new paradigm for materials design-their physical properties can be tuned by the vertical stacking sequence as well as by adding a mechanical twist, stretch, and hydrostatic pressure to the atomic structure. In particular, simple twisting and stacking of two layers of graphene can form a uniform and ordered Moiré superlattice, which can effectively modulate the electrons of graphene layers and lead to the discovery of unconventional superconductivity and strong correlations. However, the twist angle of twisted bilayer graphene (tBLG) is almost unchangeable once the interlayer stacking is determined, while applying mechanical elastic strain provides an alternative way to deeply regulate the electronic structure by controlling the lattice spacing and symmetry. In this review, diverse experimental advances are introduced in straining tBLG by in-plane and out-of-plane modes, followed by the characterizations and calculations toward quantitatively tuning the strain-engineered electronic structures. It is further discussed that the structural relaxation in strained Moiré superlattice and its influence on electronic structures. Finally, the conclusion entails prospects for opportunities of strained twisted 2D materials, discussions on existing challenges, and an outlook on the intriguing emerging field, namely "strain-twistronics".

Erratum: Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol: Erratum.

[This corrects the article DOI: 10.7150/ijbs.20316.].

Digital inclusive finance, green technological innovation, and carbon emissions from a spatial perspective.

Based on the panel data of 276 prefecture-level cities in China from 2011 to 2020, this study explores the impact of digital inclusive finance (DIF) on carbon emissions and the intrinsic mechanism of green technological innovation from a spatial perspective by constructing a spatial econometric model, a mediating effect model, and a threshold model. The results show that DIF significantly inhibits carbon emissions, exhibiting a spatial spillover effect. The transmission mechanism from a spatial perspective shows that green technological innovation plays a partial mediating role between DIF and carbon emissions, with the mediating effect accounting for approximately 59.47%. The heterogeneity analysis suggests that the impact of DIF on the reduction of carbon emissions is more pronounced in large and medium-sized cities and eastern regions. Further discussion reveals that the carbon reduction effect of DIF is also influenced by green technological innovation and industrial structure upgrading, showing threshold effects with marginal decreases and gradual increases, respectively.

Cabozantinib in patients with unresectable and progressive metastatic phaeochromocytoma or paraganglioma (the Natalie Trial): a single-arm, phase 2 trial.

BACKGROUND: Metastatic phaeochromocytomas and paragangliomas (MPPGs) are orphan diseases. Up to 50% of MPPGs are associated with germline pathogenic variants of the SDHB gene. These tumours and many non-familial MPPGs exhibit a phenotype that is characterised by abnormal angiogenesis. We aimed to assess the activity and safety of cabozantinib, an antiangiogenic multi-tyrosine kinase inhibitor, in patients with MPPGs. METHODS: The Natalie Trial is a single-arm, phase 2 clinical trial being conducted at The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients aged 18 years or older with histologically confirmed, progressive, and unresectable MPPGs, with an Eastern Cooperative Oncology Group performance status of 0-2, were treated with oral cabozantinib 60 mg/day. The primary endpoint was the investigator-assessed overall response rate per the Response Evaluation Criteria in Solid Tumours version 1.1 criteria. All outcomes were assessed in all evaluable participants who received any amount of study treatment. The trial is registered with ClinicalTrials.gov (NCT02302833) and is active but not recruiting. FINDINGS: From March 10, 2015, to May 11, 2021, 17 patients (13 male participants and four female participants) were enrolled. The median follow-up was 25 months (IQR 18-49). The overall response rate was 25·0% (95% CI 7·3-52·4; four of 16 patients). Seven grade 3 adverse events were reported in six patients, including single cases of hand-and-foot syndrome, hypertension, rectal fistula, QT prolongation, and asymptomatic hypomagnesaemia, and two cases of asymptomatic elevations of amylase and lipase. There were no grade 4 adverse events and no patient died on-study. INTERPRETATION: Cabozantinib shows promising activity in patients with MPPGs. FUNDING: Team NAT Foundation, Margaret Cazalot, and Clarence P Cazalot.

High-Specific-Activity 131I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma.

PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease (SDHB, VHL, RET); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA-131I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.

Opening the black box: explainable deep-learning classification of wood microscopic image of endangered tree species.

BACKGROUND: Traditional method of wood species identification involves the use of hand lens by wood anatomists, which is a time-consuming method that usually identifies only at the genetic level. Computer vision method can achieve "species" level identification but cannot provide an explanation on what features are used for the identification. Thus, in this study, we used computer vision methods coupled with deep learning to reveal interspecific differences between closely related tree species. RESULT: A total of 850 images were collected from the cross and tangential sections of 15 wood species. These images were used to construct a deep-learning model to discriminate wood species, and a classification accuracy of 99.3% was obtained. The key features between species in machine identification were targeted by feature visualization methods, mainly the axial parenchyma arrangements and vessel in cross section and the wood ray in tangential section. Moreover, the degree of importance of the vessels of different tree species in the cross-section images was determined by the manual feature labeling method. The results showed that vessels play an important role in the identification of Dalbergia, Pterocarpus, Swartzia, Carapa, and Cedrela, but exhibited limited resolutions on discriminating Swietenia species. CONCLUSION: The research results provide a computer-assisted tool for identifying endangered tree species in laboratory scenarios, which can be used to combat illegal logging and related trade and contribute to the implementation of CITES convention and the conservation of global biodiversity.

Pectate lyase genes from Radopholus similis and their application in pathotype identification.

Radopholus similis is a destructive, migratory, and endophytoparasitic nematode. It has two morphologically indistinguishable pathotypes (or physiological races): banana and citrus pathotypes. At present, the only reliable method to differentiate the two pathotypes is testing the infestation and parasitism of nematodes on Citrus spp. via inoculation. However, differences in inoculation methods and conditions adopted by different researchers complicate obtaining consistent results. In this study, the parasitism and pathogenicity of 10 R. similis populations on rough lemon (Citrus limon) seedlings and the tropism and invasion of rough lemon roots were tested. It revealed that populations SWK, GJ, FZ, GZ, DBSR, and YJ were citrus pathotypes, which showed parasitism and pathogenicity on rough lemon and could invade rough lemon roots, whereas populations XIN, ML, HN6, and HL were banana pathotypes, having no parasitism and pathogenicity on rough lemon and they did not invade the rough lemon roots. Four pectate lyase genes (Rs-pel-2, Rs-pel-3, Rs-pel-4, and Rs-pel-5) belonging to the Class III family from these populations were amplified and analysed. The gene Rs-pel-3 could be amplified from six citrus pathotype populations and was stably expressed in the four developmental stages of the nematode, whereas it could not be amplified from the four banana pathotypes. Rs-pel-3 expression may be related to the parasitism and pathogenicity of R. similis on rough lemon. Hence, it can be used as a molecular marker to distinguish between banana and citrus pathotypes and as a target gene for the molecular identification of these two pathotypes. KEY POINTS: • Four pectate lyase genes (Rs-pels) from Radopholus similis were cloned and analysed. • The expression of Rs-pels is different in two pathotypes of Radopholus similis. • A molecular identification method for two pathotypes of Radopholus similis using pectate lyase gene Rs-pel-3 as the target gene was established.

Nitrate-dependent anaerobic methane oxidation coupled to Fe(III) reduction as a source of ammonium and nitrous oxide.

'Candidatus Methanoperedens nitroreducens' is an archaeal methanotroph with global importance that links carbon and nitrogen cycles and great potential for sustainable operation of wastewater treatment. It has been reported to mediate the anaerobic oxidation of methane through a reverse methanogenesis pathway while reducing nitrate to nitrite. Here, we demonstrate that 'Ca. M. nitroreducens' reduces ferric iron forming ammonium (23.1 %) and nitrous oxide (N2O, 46.5 %) from nitrate. These results are supported with the upregulation of genes coding for proteins responsible for dissimilatory nitrate reduction to ammonium (nrfA), N2O formation (norV, cyt P460), and multiple multiheme c-type cytochromes for ferric iron reduction. Concomitantly, an increase in the N2O-reducing SJA-28 lineage and a decrease in the nitrite-reducing 'Candidatus Methylomirabilis oxyfera' are consistent with the changes in 'Ca. M. nitroreducens' end products. These findings demonstrate the highly flexible physiology of 'Ca. M. nitroreducens' in anaerobic ecosystems with diverse electron acceptor conditions, and further reveals its roles in linking methane oxidation to global biogeochemical cycles. 'Ca. M. nitroreducens' could significantly affect the bioavailability of nitrogen sources as well as the emission of greenhouse gas in natural ecosystems and wastewater treatment plants.

SIRT4 promotes neuronal apoptosis in models of Alzheimer's disease via the STAT2-SIRT4-mTOR pathway.

Alzheimer's disease (AD) is the leading cause of dementia and presents a considerable disease burden. Its pathology involves substantial neuronal loss, primarily attributed to neuronal apoptosis. Although sirtuin 4 (SIRT4) has been implicated in regulating apoptosis in various diseases, the role of SIRT4 in AD pathology remains unclear. The study employed APP/PS1 mice as an animal model of AD and amyloid-ß (Aß)1-42-treated HT-22 cells as an AD cell model. SIRT4 expression was determined by quantitative real-time polymerase chain reaction, western blot, and immunofluorescence. A Sirt4 knockdown model was established by intracranial injection of lentivirus-packaged sh-SIRT4 and cellular lentivirus transfection. Immunohistochemistry and flow cytometry were used to examine Aß deposition in mice and apoptosis, respectively. Protein expression was assessed by western blot analysis. The UCSC and JASPAR databases were used to predict upstream transcription factors of SIRT4. Subsequently, the binding of transcription factors to SIRT4 was analyzed using a dual-luciferase assay and chromatin immunoprecipitation. SIRT4 expression was upregulated in both APP/PS1 mice and Aß-treated HT-22 cells in comparison to their respective control groups. Sirt4 knockdown in animal and cellular models of AD resulted in reduced apoptosis, decreased Aß deposition, and amelioration of learning and memory impairments in mice. Mechanistically, SIRT4 modulates apoptosis via the mTOR pathway and is negatively regulated by the transcription factor signal transducer and activator of transcription 2 (STAT2). Our study findings suggest that targeting the STAT2-SIRT4-mTOR axis may offer a new treatment approach for AD.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Enchondroma on Bone Scan and PSMA PET/CT in a Patient With Prostate cancer.

ABSTRACT: A 54-year-old man with Gleason 9 prostate cancer with reported nodal and skeletal metastases was referred to us. Outside hospital reports described abnormal left proximal humerus activity on bone scan concerning for metastasis; however, concurrent PSMA PET/CT did not show activity in this lesion. Further review of the PET/CT images revealed characteristic features of enchondroma in the left humeral lesion.