Characterizing relationships between T-cell inflammation and outcomes in patients with high-risk neuroblastoma according to mesenchymal and adrenergic signatures.

Recent insights have identified adrenergic (ADRN) and mesenchymal (MES) cell lineages as distinct biologic cell types and T-cell inflammation as a prognostic marker in neuroblastoma. We hypothesized that elucidating unique and overlapping aspects of these biologic features could serve as novel biomarkers for informing ongoing efforts to improve therapeutic approaches for children with high-risk neuroblastoma. We identified lineage-specific, single-stranded super-enhancers to define ADRN and MES specific genes. Publicly available RNA-seq of diagnostic tumor biopsies was used in Discovery and Validation cohorts. Each tumor was assigned a relative MES score and T-cell-inflamed (TCI) score. Survival was assessed using the Kaplan-Meier method, and differences were assessed by the log-rank test. Inflammation scores were correlated with MES scores and anticorrelated with MYCN-amplification in both cohorts. Among patients with high-risk, ADRN tumors, those with TCI tumors had superior overall survival to those with non-inflamed tumors. A similar, but non-significant, trend was observed in the Validation cohort. Conversely, there was no difference according to TCI status in the MES cohort in either the Discover or Validation Cohorts. High inflammation scores were correlated with improved survival in some patients with high-risk, ADRN but not MES neuroblastoma. Our findings bolster support for further developing T-cell based immunotherapy-based approaches for children with high-risk neuroblastoma of varying MES and ADRN expression.

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Mixed epithelial and stromal tumor of the kidney: A case report in elderly male patient.

Mixed epithelial and stromal tumor (MEST) is very rare neoplasm of the kidney, commonly affecting women at menopausal age. MEST is usually considered a benign tumor with low risk of local recurrence or distance metastases. Our case presents a case of a 66 years old male patient with a complex cystic lesion of the left kidney incidentally diagnosed on urinary tract computerized scan (CT) performed for other reasons. The patient underwent a radical nephrectomy. The pathology report came back as MEST of the kidney. The present case report highlights the asymptomatic presentation of MEST as a benign renal masses.

Anesthetic Management of a Patient With Wolff-Parkinson-White Syndrome Undergoing Gynecological Robotic Surgery.

Robotic surgery provides precision and safety for minimally invasive gynecological operations but introduces unique anesthetic challenges, especially for individuals with pre-existing conditions like Wolff-Parkinson-White (WPW) syndrome. This case report addresses the anesthetic management of a 32-year-old female with WPW syndrome undergoing a myomectomy. A thorough pre-operative evaluation, including an ECG, echocardiogram, and Holter monitoring, was performed to assess the anesthetic and cardiac risks. The patient was administered a combination of loco-regional and general anesthesia, with an emphasis on neuromuscular monitoring, antiarrhythmic preparedness, and pain management to effectively manage the complexities introduced by WPW syndrome and robotic surgery. The anesthetic protocol comprised premedication with midazolam, induction using sufentanil, propofol, and rocuronium, and maintenance with desflurane, along with techniques to mitigate the effects of pneumoperitoneum and Trendelenburg positioning. Employing these strategies, the surgery concluded successfully without any anesthetic or surgical complications. The patient experienced a rapid and complete awakening, achieved optimal pain control, and was able to mobilize early, leading to her discharge 24 hours post-surgery. This case demonstrates the essential nature of customized anesthetic management for patients with WPW syndrome undergoing robotic surgery. It underscores the necessity of an exhaustive pre-operative assessment, diligent intraoperative monitoring, and active postoperative care to ensure patient safety and promote swift recovery.

Brentuximab-induced pneumonitis and organizing pneumonia: a case report with literiture review.

Introduction and importance: Brentuximab vedotin (BV) is an anti-CD30 antibody approved for various cancers, including refractory Hodgkin lymphoma (HL), anaplastic large-cell lymphoma (ALCL) among others. In general, BV has been found to be well-tolerated, with the most frequently reported side effects being peripheral neuropathy and neutropenia. BV-induced pneumonitis is extremely rare. To the best of our knowledge, this is the sixth reported instance of BV-induced lung toxicity. Case presentation: This case presents a female patient in her forties diagnosed with cutaneous T-cell lymphoma undergoing BV treatment. She developed acute hypoxic respiratory failure, ultimately, underwent a diagnostic evaluation including a computed tomography (CT) scan, which showed bilateral airspace consolidations and ground-glass opacities, suggestive of organizing pneumonia and diffuse alveolar damage. Bronchoscopy with bronchoalveolar lavage and transbronchial biopsy ruled out infection, and pulmonary lymphoma and confirmed the diagnosis of BV-induced pneumonitis. The patient had significant clinical improvement after stopping the offending agent, and starting steroids, with optimal clinical recovery at 8 weeks follow-up. Clinical discussion: Drug-related pneumonitis poses a significant concern in the management of cancer patients. Numerous chemotherapeutic agents, such as bleomycin, cyclophosphamide, methotrexate, thalidomide, and others, have been associated with pulmonary-related toxicities. These adverse effects primarily stem from direct toxicity or immunosuppression-related infections. Less commonly, immune-mediated injury may occur. Conclusion: Physicians must have a high index of suspicion for BV-induced pneumonitis, hence, early recognition with subsequent holding of the causative agent, initiation of immunosuppression with steroids, and occasionally steroid-sparing medications, prevent an otherwise fatal outcome.

The Delayed Presentation of Bilateral Subdural Hematoma Secondary to Epidural Anesthesia for Elective Vaginal Delivery: A Case Report and Review of the Literature.

Epidural anesthesia (EA) involves reaching the spinal epidural space with an anesthetic drug injection. This procedure provides pain relief during labor. Although EA can lead to some complications, subdural hemorrhage (SDH) is a rare adverse event associated with it. We report the case of a 25-year-old female patient who presented to our emergency department with a one-month history of headaches and associated blurred vision following a normal vaginal delivery with EA. She was initially treated as a case of post-dural puncture headache (PDPH), with no improvement. Finally, the diagnosis of bilateral SDH was made based on a brain MRI. She required surgical intervention, which led to a positive prognosis and a full return of normal baseline neurological functions. Only a few reports in the literature have indicated the possibility of cranial subdural hematoma formation associated with spinal or epidural analgesia. Our patient experienced a delay in her diagnosis and treatment, as SDH following EA is a rare entity. It is important to follow up with such patients and consider other possibilities when symptoms fail to resolve. Also, reporting these cases is crucial to assist clinicians in early diagnosis and treatment, and to avoid disastrous outcomes.

Accurate preoperative diagnosis of a Rathke cleft cyst with the aid of a novel classification for sellar cystic lesions and a diagnostic algorithm decision: Tools for differentiating cystic sellar lesions with a representative case.

Background: Rathke's cleft cyst (RCC) is a benign lesion in the sellar and suprasellar compartments. Similarly, pituitary adenomas can present with cystic morphology, making it a differential diagnosis when evaluating a patient with a cystic lesion in the sellar region. Surgical goals differ between RCCs and pituitary adenomas as the first can achieve remission of symptoms with cyst decompression in contrast to pituitary adenomas where complete resection would be the main goal. Imaging analysis alone may not be sufficient to define a preoperative surgical plan. The combination of imaging and conjoined use of validated tools may provide valuable insights to the clinician when defining a surgical approach. Case Description: We present a case of a 27-year-old male with a 3-month history of visual disturbances and headaches. Magnetic resonance imaging showed a cystic lesion in the sellar compartment with compression of nearby structures. The authors were able to accurately diagnose this sellar lesion as an RCC with the conjoined aid of two classifications proposed in the literature. Cyst evacuation was performed with relief of symptoms and improved visual outcomes at follow-up. Conclusion: While cystic adenomas can require total resection for cure, RCCs can show marked improvement with partial resection and evacuation of its contents. An accurate preoperative diagnosis can lead the surgeon to opt for the best surgical approach.

Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression.

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Tree demographic strategies largely overlap across succession in Neotropical wet and dry forest communities.

Secondary tropical forests play an increasingly important role in carbon budgets and biodiversity conservation. Understanding successional trajectories is therefore imperative for guiding forest restoration and climate change mitigation efforts. Forest succession is driven by the demographic strategies-combinations of growth, mortality and recruitment rates-of the tree species in the community. However, our understanding of demographic diversity in tropical tree species stems almost exclusively from old-growth forests. Here, we assembled demographic information from repeated forest inventories along chronosequences in two wet (Costa Rica, Panama) and two dry (Mexico) Neotropical forests to assess whether the ranges of demographic strategies present in a community shift across succession. We calculated demographic rates for >500 tree species while controlling for canopy status to compare demographic diversity (i.e., the ranges of demographic strategies) in early successional (0-30 years), late successional (30-120 years) and old-growth forests using two-dimensional hypervolumes of pairs of demographic rates. Ranges of demographic strategies largely overlapped across successional stages, and early successional stages already covered the full spectrum of demographic strategies found in old-growth forests. An exception was a group of species characterized by exceptionally high mortality rates that was confined to early successional stages in the two wet forests. The range of demographic strategies did not expand with succession. Our results suggest that studies of long-term forest monitoring plots in old-growth forests, from which most of our current understanding of demographic strategies of tropical tree species is derived, are surprisingly representative of demographic diversity in general, but do not replace the need for further studies in secondary forests.

Combined endoscopic transorbital and transnasal approach for the management of a solitary plasmacytoma of the sphenoid bone: A case report and literature review.

Background: Parasellar plasmacytomas are rare neurosurgical entities. Intrinsic characteristics of these tumors, such as adjacent bone erosion and symptoms resulting from invasion and mass effect, may lead to the possibility of a solitary extramedullary plasmacytoma (SEP) as a differential diagnosis. Case Description: We present the case of a 39-year-old male with a 1-month history of bilateral decreased visual acuity, retroocular pulsating pain, and chromatic vision loss. A computed tomography scan of the head revealed a parasellar lesion causing chiasmatic compression, as well as clival, orbital, sphenoidal, and ethmoidal invasion. A combined transorbital and endonasal endoscopic approach was found suitable, and gross total resection was achieved. Histological analysis of the lesion established the diagnosis of a SEP. After radiotherapy, a new magnetic resonance imaging was performed, revealing a recurrence of the lesion with a high grade of invasion. The patient was treated with palliative radiotherapy, as surgical resection did not seem feasible. Conclusion: Surgical resection and radiotherapy may achieve remission of these lesions; however, recurrence rates remain high despite any treatment modality. Patients with this condition must be followed up with a multidisciplinary team due to the high risk of multiple myeloma progression.

Incomplete recovery of tree community composition and rare species after 120 years of tropical forest succession in Panama.

Determining how fully tropical forests regenerating on abandoned land recover characteristics of old-growth forests is increasingly important for understanding their role in conserving rare species and maintaining ecosystem services. Despite this, our understanding of forest structure and community composition recovery throughout succession is incomplete, as many tropical chronosequences do not extend beyond the first 50 years of succession. Here, we examined trajectories of forest recovery across eight 1-hectare plots in middle and later stages of forest succession (40-120 years) and five 1-hectare old-growth plots, in the Barro Colorado Nature Monument (BCNM), Panama. We first verified that forest age had a greater effect than edaphic or topographic variation on forest structure, diversity and composition and then corroborated results from smaller plots censused 20 years previously. Tree species diversity (but not species richness) and forest structure had fully recovered to old-growth levels by 40 and 90 years, respectively. However, rare species were missing, and old-growth specialists were in low abundance, in the mid- and late secondary forest plots, leading to incomplete recovery of species composition even by 120 years into succession. We also found evidence that dominance early in succession by a long-lived pioneer led to altered forest structure and delayed recovery of species diversity and composition well past a century after land abandonment. Our results illustrate the critical importance of old-growth and old secondary forests for biodiversity conservation, given that recovery of community composition may take several centuries, particularly when a long-lived pioneer dominates in early succession. Abstract in Spanish is available with online material.

Determinar en que medida los bosques tropicales que se regeneran en tierras abandonadas recuperan las características de los bosques primarios es cada vez más importante para comprender su papel en la conservación de especies raras y el mantenimiento de los servicios ecosistémicos. A pesar de ello, nuestro entendimiento sobre la recuperación de la estructura del bosque y la composición de la comunidad a lo largo de la sucesión es incompleta, ya que muchas cronosecuencias tropicales no van más allá de los primeros 50 años de sucesión. En este estudio, investigamos las trayectorias de recuperación del bosque en ocho parcelas de 1 hectárea en estadíos medios y tardíos de la sucesión forestal (40­120 años) y cinco parcelas de 1 hectárea de bosque primario, en el Monumento Natural Barro Colorado (MNBC), Panamá. En primer lugar, verificamos que la edad del bosque tenía un mayor efecto que la variación edáfica o topográfica en la estructura, diversidad y composición del bosque y luego corroboramos los resultados de parcelas más pequeñas estudiadas 20 años antes. La diversidad de especies arbóreas, pero no la riqueza de especies, y la estructura forestal se habían recuperado completamente hasta alcanzar los niveles de bosque primario a los 40 y 90 años, respectivamente. Sin embargo, los bosques secundarios carecían de especies raras y presentaban una escasa abundancia de especies especialistas del bosque antiguo, lo que condujo a una recuperación incompleta de la composición de especies, incluso a 120 años de sucesión. También encontramos pruebas de que el predominio de un pionero longevo en las primeras etapas de la sucesión provocó una alteración de la estructura forestal y retrasó la recuperación de la diversidad y composición de especies más allá de un siglo después el abandono de las tierras. Nuestros resultados ilustran la importancia crítica de los bosques primarios y secundarios más antiguos para la conservación de la biodiversidad, dado que la recuperación de la composición de la comunidad puede llevar varios siglos, especialmente cuando un pionero longevo domina en la sucesión temprana.

Simultaneous spine extradural and intradural teratomas in a pediatric patient: A rare presentation with insights in the flawed migration of germ cells theory.

Spinal teratomas are infrequent lesions in the pediatric population. These lesions can be extradural, intradural or intramedullary. We present a case of an 8-month-old boy that was assessed for underdevelopment of motor milestones. The neurologic examination revealed hyporeflexia, decreased sensation and flaccid paraplegia. MRI of the spine revealed two simultaneous and independent lesions in the extradural and intradural compartment. A laminectomy was performed for the T4-T7 vertebrae with total resection of both lesions. The histopathological analysis confirmed both lesions to be mature cystic teratomas. At the 1-year follow-up, the patient remained with no recovery of neurological function. A debate takes place regarding the etiology of formation of these lesions in the spine. The simultaneous presentation of two independent lesions in this patient could contribute to define the flawed migration of germ cells theory as the etiology for formation of teratomatous lesions in the spine.

Multiparameter screen optimizes immunoprecipitation.

Immunoprecipitation (IP) coupled with mass spectrometry effectively maps protein-protein interactions when genome-wide, affinity-tagged cell collections are used. Such studies have recorded significant portions of the compositions of physiological protein complexes, providing draft 'interactomes'; yet many constituents of protein complexes still remain uncharted. This gap exists partly because high-throughput approaches cannot optimize each IP. A key challenge for IP optimization is stabilizing in vivo interactions during the transfer from cells to test tubes; failure to do so leads to the loss of genuine interactions during the IP and subsequent failure to detect. Our high-content screening method explores the relationship between in vitro chemical conditions and IP outcomes, enabling rapid empirical optimization of conditions for capturing target macromolecular assemblies.

Quality of Life Assessment in Women With Breast Cancer in Nineveh, Iraq.

Background Due to earlier detection and improved treatment and examinations, there has been a rise in the survival rate of patients with breast cancer (BC). It is imperative to examine the health-related quality of life (QoL) of these patients, as it can aid healthcare professionals and authorities in comprehending the variables that influence quality of life. Unfortunately, there is a dearth of information on the subject of women in Nineveh. In Nineveh, a study sought to delve into the quality of life experienced by women undergoing treatment or on follow-up for breast cancer at Mosul Oncology and Nuclear Medicine Hospital. Specifically, researchers wanted to see how age and treatment impacted the QoL of these women. Methods A cross-sectional study was conducted on 212 women with BC. Clinico-pathological-, social-, disease-, and treatment-related characteristics were reviewed. The Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire was used for assessing QoL in this study. Results The overall FACT-B score was 75.7 (SD=19.99). Around 36.3% (n=77) of women with BC suffered from a lack of energy, and 39% (n=83) could not meet the needs of their families. The mean score of emotional well-being was the lowest among the FACT-B subscales. Patients aged 60 years and older had significantly worse QoL than younger patients (less than 60 years), and patients receiving chemotherapy had poor QoL. During the chemotherapy period, 51.4% (n=77) of patients were bothered by the side effects of treatment; 43.8% (n=65) suffered from pain; 35.3% (n=53) had nausea; and 39.1% (n=58) felt ill. Conclusions Patients with breast carcinoma who are older tend to experience a lower quality of life, according to the findings of a recent study. Interestingly, those who undergo systemic chemotherapy have a worse QoL than their counterparts who complete their chemotherapy cycles. As a result, healthcare providers must offer targeted interventions to improve quality of life, particularly for those who fall into the older age group and those receiving chemotherapy.

Modeling the Role in pH on Contaminant Sequestration by Zerovalent Metals: Chromate Reduction by Zerovalent Magnesium.

The role of pH in sequestration of Cr(VI) by zerovalent magnesium (ZVMg) was characterized by global fitting of a kinetic model to time-series data from unbuffered batch experiments with varying initial pH values. At initial pH values ranging from 2.0 to 6.8, ZVMg (0.5 g/L) completely reduced Cr(VI) (18.1 µM) within 24 h, during which time pH rapidly increased to a plateau value of ∼10. Time-series correlation analysis of the pH and aqueous Cr(VI), Cr(III), and Mg(II) concentration data suggested that these conditions are controlled by combinations of reactions (involving Mg0 oxidative dissolution and Cr(VI) sequestration) that evolve over the time course of each experiment. Since this is also likely to occur during any engineering applications of ZVMg for remediation, we developed a kinetic model for dynamic pH changes coupled with ZVMg corrosion processes. Using this model, the synchronous changes in Cr(VI) and Mg(II) concentrations were fully predicted based on the Langmuir-Hinshelwood kinetics and transition-state theory, respectively. The reactivity of ZVMg was different in two pH regimes that were pH-dependent at pH < 4 and pH-independent at the higher pH. This contrasting pH effect could be ascribed to the shift of the primary oxidant of ZVMg from H+ to H2O at the lower and higher pH regimes, respectively.

Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma.

BACKGROUND: Cell-free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES-specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma. METHODS: We previously performed an integrative analysis to identify ADRN and MES-specific genes (n = 373 and n = 159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples. RESULTS: Samples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p < .001). While ADRN and MES signature scores tracked together in serially collected samples, we identified instances of patients with increases in either MES or ADRN score at relapse. CONCLUSIONS: While it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.

Intravenous cangrelor use for neuroendovascular procedures: a two-center experience and updated systematic review.

Background: The optimal antiplatelet therapy regimen for certain neuroendovascular procedures remains unclear. This study investigates the safety and feasibility of intravenous dose-adjusted cangrelor in patients undergoing acute neuroendovascular interventions. Methods: We conducted a retrospective chart review of all consecutive patients on intravenous cangrelor for neuroendovascular procedures between September 1, 2020, and March 13, 2022. We also conducted an updated systematic review and meta-analysis using PubMed, Scopus, Web of Science, Embase and the Cochrane Library up to February 22, 2023. Results: In our cohort, a total of 76 patients were included [mean age (years): 57.2 ± 18.2, males: 39 (51.3), Black: 49 (64.5)]. Cangrelor was most used for embolization and intracranial stent placement (n = 24, 32%). Approximately 44% of our patients had a favorable outcome with a modified Rankin Scale (mRS) score of 0 to 2 at 90 days (n = 25/57); within 1 year, 8% of patients had recurrent or new strokes (n = 5/59), 6% had symptomatic intracranial hemorrhage [sICH] (4/64), 3% had major extracranial bleeding events (2/64), and 3% had a gastrointestinal bleed (2/64). In our meta-analysis, 11 studies with 298 patients were included. The pooled proportion of sICH and intraprocedural thromboembolic complication events were 0.07 [95% CI 0.04 to 1.13] and 0.08 [95% CI 0.05 to 0.15], respectively. Conclusion: Our study found that intravenous cangrelor appears to be safe and effective in neuroendovascular procedures, with low rates of bleeding and ischemic events. However, further research is needed to compare different dosing and titration protocols of cangrelor and other intravenous agents.

Mixed success for carbon payments and subsidies in support of forest restoration in the neotropics.

Restoration of forests in low- and middle-income countries (LMICs) has the potential to contribute to international carbon mitigation targets. However, high upfront costs and variable cashflows are obstacles for many landholders. Carbon payments have been promoted as a mechanism to incentivize restoration and economists have suggested cost-sharing by third parties to reduce financial burdens of restoration. Yet empirical evidence to support this theory, based on robust, dynamic field sampling is lacking. Here we use large, long-term datasets from Panama to evaluate the financial prospects of three forest restoration methods under different cost-sharing and carbon payment designs where income is generated through timber harvests. We show some, but not all options are economically viable. Further work combining growth and survival data from field trials with more sophisticated financial analyses is essential to understanding barriers and realizing the potential of forest restoration in LMICs to help meet global carbon mitigation commitments.

Left Ventricular Myxoma: A Case Report.

Cardiac myxomas are the most common primary cardiac neoplasms, with only a small percentage being found in the left ventricle. Herein, we describe a 25-year-old male who presented with a complaint of chest pain for almost three months and was found to have a 2x2 cm encapsulated tumor attached by a 2-3 mm stalk to the mid-septum, 5 cm below the aortic annulus, via echocardiography. Additionally, a chest CT angiography was performed and revealed a small defect in the left ventricle with a low attenuation density originating from the septum. The tumor was later managed surgically with a median sternotomy approach, and left ventricular myxoma was confirmed histopathologically. Even though cardiac myxomas are incredibly uncommon, they are usually located in the left and right atria and are very unlikely to present in the left ventricle. This incident highlights the importance of taking cardiac myxoma into account as a potential differential diagnosis in cases of chest pain to prevent any further complications.

Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma.

Background: Cell free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma. Methods: We previously performed an integrative analysis to identify ADRN and MES specific genes (n=373 and n=159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples. Results: Samples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p < 0.001). While ADRN and MES signature scores tracked together in serially collected samples, we identified instances of patients with increases in either MES or ADRN score at relapse. Conclusions: While it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.