St. Louis Enhancing Engagement and Retention in HIV/AIDS Care (STEER): a participatory intersectional needs assessment for intervention and implementation planning.

Background Missouri is one of seven priority states identified by the Ending the HIV Epidemic Initiative, and St. Louis contains almost half of the people living with HIV (PLWH) in Missouri. As St. Louis has a marked history of structural racism and economic inequities, we utilized the Intersectionality Based Policy Analysis (IBPA) framework to guide a participatory needs assessment for planning and program development. Methods The planning team included researchers, the lead implementer from our community partner, and two community representatives, and had biweekly 60-90 minute meetings for 18 months. The planning team discussed and approved all research materials, reviewed and interpreted results, and made decisions about outreach, recruitment, conduct of the needs assessment and development of the planned intervention. The needs assessment integrated information from existing data, (1) interviews with (a) PLWH (n=12), (b) community leaders (n=5), (c) clinical leaders (n=4), and (d) community health workers (CHWs) (n=3) and (e) CHW supervisors (n=3) who participated in a Boston University-led demonstration project on CHWs in the context of HIV and (2) focus groups (2 FG, 12 participants) with front line health workers such as peer specialists, health coaches and outreach workers. A rapid qualitative analysis approach was used for all interviews and focus groups. Results The IBPA was used to guide team discussions of team values, definition and framing of the problem, questions and topics in the key informant interviews, and implementation strategies. Applying the IBPA framework contributed to a focus on intersectional drivers of inequities in HIV services. The effective management of HIV faces significant challenges from high provider turnover, insufficient integration of CHWs into care teams, and organizational limitations in tailoring treatment plans. Increasing use of CHWs for HIV treatment and prevention also faces challenges. People living with HIV (PLWH) encounter multiple barriers such as stigma, lack of social support, co-morbidities, medication side effects and difficulties in meeting basic needs. Conclusions Addressing intersectional drivers of health inequities may require multi-level, structural approaches. We see the IBPA as a valuable tool for participatory planning while integrating community engagement principles in program and implementation design for improving HIV outcomes.

Integrated pain care models and the importance of aligning stakeholder values.

Sustained widespread deployment of clinically and cost-effective models of integrated pain care could be bolstered by optimally aligning shared stakeholder values.

Ambiphilicity of ring-expanded N-heterocyclic carbenes.

N-heterocyclic carbenes, such as imidazole-2-ylidenes and imidazolin-2-ylidenes, the popular class of singlet carbenes introduced by Arduengo in 1991 have not been shown to be ambiphilic owing to the two σ-withdrawing, π-donating amino groups flanking the carbene centre. However, our experimental data suggest that ring-expanded N-heterocyclic carbenes (RE-NHCs), especially the seven and eight membered rings, are significantly ambiphilic. Our results also show that the steric environment in RE-NHCs can become a determining factor for controlling the E-H bond activation.

Combining multimodal magnetic resonance brain imaging and machine learning to unravel neurocognitive function in non-neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. METHODS: SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning-based model (i.e. glmnet) was constructed to predict TTS. RESULTS: Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory bulb volume (OBV), olfactory function and TTS. While after correction for multiple comparisons the uncorrected increase in the blood-brain barrier (BBB) permeability parameters compared with HCs did not remain evident in SLE patients, DCE-MRI perfusion parameters, notably an increase in right amygdala perfusion, was positively correlated with TTS in SLE patients (r = 0.636, false discovery rate P < 0.05). A machine learning-trained multimodal MRI model comprising alterations of VBM, MTR, OBV and DCE-MRI parameters mainly in the limbic system regions predicted TTS in SLE patients (r = 0.644, P < 0.0005). CONCLUSION: Multimodal brain MRI demonstrated increased right amygdala perfusion that was associated with better neurocognitive performance in young SLE patients without statistically significant BBB leakage and microstructural abnormalities. A machine learning-constructed multimodal model comprising microstructural, perfusion and permeability parameters accurately predicted neurocognitive performance in SLE patients.

Low-k SiOx/AlOx Nanolaminate Dielectric on Dielectric Achieved by Hybrid Pulsed Chemical Vapor Deposition.

Selective and smooth low-k SiOx/AlOx nanolaminate dielectric on dielectric (DOD) was achieved by a hybrid water-free pulsed CVD process consisting of 50 pulses of ATSB (tris(2-butoxy)aluminum) at 330 °C and a 60 s TBS (tris(tert-butoxy)silanol) exposure at 200 °C. Aniline selective passivation was demonstrated on W surfaces in preference to Si3N4 and SiO2 at 300 °C. At 200 °C, TBS pulsed CVD exhibited no growth on W or SiO2, but its growth was catalyzed by AlOx. Using a two-temperature pulsed CVD process, ∼2.7 nm selective SiOx/AlOx nanolaminate was deposited on Si3N4 in preference to aniline passivated W. Nanoselectivity was confirmed and demonstrated on nanoscale W/SiO2 patterned samples by TEM analysis. For a 1:1 Si:Al ratio, a dielectric constant (k) value of 3.3 was measured. For a 2:1 Si:Al ratio, a dielectric constant (k) value of 2.5 was measured. The k value well below that of Al2O3 and SiO2 is consistent with the formation of a low-density, low-k SiO2/Al2O3 nanolaminate in a purely thermal process. This is the first report of a further thermal CVD process for deposition of a low-k dielectric and the first report for a selective low-k process on the nanoscale.

Safety, tolerability, and effectiveness of repetitive intravenous dihydroergotamine for refractory chronic migraine with cardiovascular risk factors: A retrospective study.

BACKGROUND: Dihydroergotamine (DHE), like triptans, is contraindicated in patients with ischemic heart disease or coronary vasospasm. Its true safety, tolerability, and efficacy in patients with cardiovascular risk without ischemic heart disease or coronary vasospasm remain unclear. OBJECTIVES: To assess the safety, tolerability, and effectiveness of repetitive intravenous DHE in patients with cardiovascular risk factors. METHODS: A single-center, retrospective cohort study was conducted at the Jefferson Headache Center inpatient unit for refractory chronic migraine patients treated with our intravenous DHE protocol between January 1, 2019, and October 15, 2019. We evaluated tolerability and effectiveness outcomes based on atherosclerotic cardiovascular disease 10-year calculated risk scores, stratified into low (<5.0%) and elevated (≥5.0%) risk. Data were presented in mean ± standard deviation or median (25th percentile, 75th percentile) if non-normally distributed. RESULTS: Among 347 patients (median age of 46 [36, 57], female n = 278 [80.1%]), who received inpatient intravenous DHE, 227 patients (age 53 [45, 60], female 81.1%) had calculable risk scores, 64 (28.2%) had elevated risk, and 38 (16.7%) had cardiology consultations. There were no clinically significant electrocardiogram abnormalities or cardiovascular adverse events. The median hospital length of stay was 6 (5, 7) days. Compared to the low-risk group, those with elevated risk had higher nausea (31.3% vs. 14.1%, p = 0.008), but similar initial DHE dose (0.5 [0.25, 0.5] vs. 0.5 [0.25, 0.5], p = 0.009), lower final DHE dose (0.75 [0.5, 1] vs. 1 [0.75, 1] p < 0.001), and lower pain reduction after admission (-3.8 [2.1, 6] vs. -5 [3, 7] p = 0.037). CONCLUSION: Patients receiving intravenous DHE by the Jefferson Headache Center inpatient headache protocol had significantly reduced pain severity at discharge. No clinically significant cardiac or electrocardiogram abnormalities were detected in patients with elevated (or low) atherosclerotic cardiovascular disease risk. Repetitive intravenous DHE used by our protocol was safe in refractory chronic migraine patients.

Computational immune synapse analysis reveals T-cell interactions in distinct tumor microenvironments.

The tumor microenvironment (TME) and the cellular interactions within it can be critical to tumor progression and treatment response. Although technologies to generate multiplex images of the TME are advancing, the many ways in which TME imaging data can be mined to elucidate cellular interactions are only beginning to be realized. Here, we present a novel approach for multipronged computational immune synapse analysis (CISA) that reveals T-cell synaptic interactions from multiplex images. CISA enables automated discovery and quantification of immune synapse interactions based on the localization of proteins on cell membranes. We first demonstrate the ability of CISA to detect T-cell:APC (antigen presenting cell) synaptic interactions in two independent human melanoma imaging mass cytometry (IMC) tissue microarray datasets. We then generate melanoma histocytometry whole slide images and verify that CISA can detect similar interactions across data modalities. Interestingly, CISA histoctyometry analysis also reveals that T-cell:macrophage synapse formation is associated with T-cell proliferation. We next show the generality of CISA by extending it to breast cancer IMC images, finding that CISA quantifications of T-cell:B-cell synapses are predictive of improved patient survival. Our work demonstrates the biological and clinical significance of spatially resolving cell-cell synaptic interactions in the TME and provides a robust method to do so across imaging modalities and cancer types.

Papillary thyroid cancer immune phenotypes via tumor-infiltrating lymphocyte spatial analysis.

Standard-of-care treatment options provide an excellent prognosis for papillary thyroid cancers (PTCs); however, approximately 10% of cases are advanced PTCs, resulting in less than 50% 5-year survival rates. Understanding the tumor microenvironment is essential for understanding cancer progression and investigating potential biomarkers for treatment, such as immunotherapy. Our study focused on tumor-infiltrating lymphocytes (TILs), which are the main effectors of antitumor immunity and related to the mechanism of immunotherapy. Using an artificial intelligence model, we analyzed the density of intratumoral and peritumoral TILs in the pathologic slides of The Cancer Genome Atlas PTC cohort. Tumors were classified into three immune phenotypes (IPs) based on the spatial distribution of TILs: immune-desert (48%), immune-excluded (34%), and inflamed (18%). Immune-desert IP was mostly characterized by RAS mutations, high thyroid differentiation score, and low antitumor immune response. Immune-excluded IP predominantly consisted of BRAF V600E-mutated tumors and had a higher rate of lymph node metastasis. Inflamed IP was characterized by a high antitumor immune response, as demonstrated by a high cytolytic score, immune-related cell infiltrations, expression of immunomodulatory molecules (including immunotherapy target molecules), and enrichment of immune-related pathways. This study is the first to investigate IP classification using TILs in PTC through a tissue-based approach. Each IP had unique immune and genomic profiles. Further studies are warranted to assess the predictive value of IP classification in advanced PTC patients treated with immunotherapy.

Healthcare professionals' knowledge, confidence and perceptions of pharmacogenomics in primary care and pain management.

Aim: To assess knowledge, confidence and perceptions of healthcare professionals specializing in primary care and pain management at Brigham and Women's Hospital, related to clinical pharmacogenomics (PGx). Methods: A 25-question online survey was distributed to 328 Brigham and Women's Hospital clinicians for analysis. Results: Thirty-four clinicians completed the survey. Respondents had minimal experience with PGx and limited awareness of PGx resources. Although respondents expressed belief that PGx has utility to improve medication-related patient outcomes, many lack confidence to apply PGx results to their practice. For clinical drug-gene questions relevant to primary care and/or pain management, respondents scored poorly. Conclusion: More clinician education is needed for appropriate utilization of PGx in clinical practice as it pertains to primary care and pain management.

Dielectric-on-Dielectric Achieved on SiO2 in Preference to W by Water-free Chemical Vapor Depositions with Aniline Passivation.

Selective and smooth dielectric-on-dielectric was achieved by water-free single-precursor chemical vapor deposition (CVD) processes with the help of aniline passivation. Aniline selective passivation was demonstrated on W surfaces in preference to SiO2 at 250, 300, and 330 °C. After aniline passivation, selective HfO2, Al2O3, and TiO2 were deposited only on the HF-cleaned SiO2 surface by water-free single-precursor CVD using hafnium tert-butoxide Hf(OtBu)4, aluminum-tri-sec-butoxide (ATSB), and titanium isopropoxide Ti(OiPr)4 as the precursor reactants, respectively. Hf(OtBu)4 and Ti(OiPr)4 single-precursor CVD was carried out at 300 °C, while the ATSB CVD process was conducted at 330 °C. HfO2 and Al2O3 nanoselectivity tests were performed on W/SiO2 patterned samples. Transmission electron microscopy images of the W/SiO2 patterned samples after deposition demonstrated nanoselectivity and low surface roughness of HfO2 and Al2O3 deposition on the SiO2 regions only.

Syllable-PBWT for space-efficient haplotype long-match query.

MOTIVATION: The positional Burrows-Wheeler transform (PBWT) has led to tremendous strides in haplotype matching on biobank-scale data. For genetic genealogical search, PBWT-based methods have optimized the asymptotic runtime of finding long matches between a query haplotype and a predefined panel of haplotypes. However, to enable fast query searches, the full-sized panel and PBWT data structures must be kept in memory, preventing existing algorithms from scaling up to modern biobank panels consisting of millions of haplotypes. In this work, we propose a space-efficient variation of PBWT named Syllable-PBWT, which divides every haplotype into syllables, builds the PBWT positional prefix arrays on the compressed syllabic panel, and leverages the polynomial rolling hash function for positional substring comparison. With the Syllable-PBWT data structures, we then present a long match query algorithm named Syllable-Query. RESULTS: Compared to the most time- and space-efficient previously published solution to the long match query problem, Syllable-Query reduced the memory use by a factor of over 100 on both the UK Biobank genotype data and the 1000 Genomes Project sequence data. Surprisingly, the smaller size of our syllabic data structures allows for more efficient iteration and CPU cache usage, granting Syllable-Query even faster runtime than existing solutions. AVAILABILITY AND IMPLEMENTATION: https://github.com/ZhiGroup/Syllable-PBWT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Using Health Care Professionals' Perspectives to Refine a Clinical Decision Support Implementation Strategy for Increasing the Prescribing of HIV Preexposure Prophylaxis (PrEP) in Alabama.

Pre-exposure prophylaxis (PrEP) is underused in the southern United States (US), a region with high HIV incidence. Clinical decision support (CDS) tools could increase PrEP prescriptions. We explored barriers to PrEP delivery and views of CDS tools to identify refinements for implementation strategies for PrEP prescribing and PrEP CDS tools. We conducted focus groups with health care providers from two federally qualified health centers in Alabama and analyzed the results using rapid qualitative methods. Barriers to PrEP included providers' lack of training in PrEP, competing priorities and time constraints during clinical visits, concerns about side effects, and intensive workload. We identified refinements to the planned implementation strategies to address the barriers, including training all clinic staff in PrEP and having CDS PrEP alerts in electronic health records sent to all staff. Development and deployment of CDS tools in collaboration with providers has potential to increase PrEP prescribing in high-priority jurisdictions.

TNF-α and NF-κB signaling play a critical role in cigarette smoke-induced epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both surfaces of the retina, resulting in recurrent retinal detachments and poor visual outcomes. Proinflammatory cytokines like tumor necrosis factor alpha (TNFα) have been associated with PVR and the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. Cigarette smoke is the only known modifiable risk factor for PVR, but the mechanisms are unclear. The purpose of this study was to examine the impact of cigarette smoke on the proinflammatory TNFα/NF-κB/Snail pathway in RPE cells to better understand the mechanisms through which cigarette smoke increases the risk of PVR. Human ARPE-19 cells were exposed to cigarette smoke extract (CSE), for 4 to 24-hours and TNFα, Snail, IL-6, IL-8, and α-SMA levels were analyzed by qPCR and/or Western blot. The severity of PVR formation was assessed in a murine model of PVR after intravitreal injection of ARPE-19 cells pre-treated with CSE or not. Fundus imaging, OCT imaging, and histologic analysis 4 weeks after injection were used to examine PVR severity. ARPE-19 cells exposed to CSE expressed higher levels of TNFα, SNAIL, IL6 and IL8 mRNA as well as SNAIL, Vimentin and α-SMA protein. Inhibition of TNFα and NF-κB pathways blocked the effect of CSE. In vivo, intravitreal injection of ARPE-19 cells treated with CSE resulted in more severe PVR compared to mice injected with untreated RPE cells. These studies suggest that the TNFα pathway is involved in the mechanism whereby cigarette smoke increases PVR. Further investigation into the role of TNFα/NF-κB/Snail in driving PVR and pharmacological targeting of these pathways in disease are warranted.

P-smoother: efficient PBWT smoothing of large haplotype panels.

Motivation: As large haplotype panels become increasingly available, efficient string matching algorithms such as positional Burrows-Wheeler transformation (PBWT) are promising for identifying shared haplotypes. However, recent mutations and genotyping errors create occasional mismatches, presenting challenges for exact haplotype matching. Previous solutions are based on probabilistic models or seed-and-extension algorithms that passively tolerate mismatches. Results: Here, we propose a PBWT-based smoothing algorithm, P-smoother, to actively 'correct' these mismatches and thus 'smooth' the panel. P-smoother runs a bidirectional PBWT-based panel scanning that flips mismatching alleles based on the overall haplotype matching context, which we call the IBD (identical-by-descent) prior. In a simulated panel with 4000 haplotypes and a 0.2% error rate, we show it can reliably correct 85% of errors. As a result, PBWT algorithms running over the smoothed panel can identify more pairwise IBD segments than that over the unsmoothed panel. Most strikingly, a PBWT-cluster algorithm running over the smoothed panel, which we call PS-cluster, achieves state-of-the-art performance for identifying multiway IBD segments, a challenging problem in the computational community for years. We also showed that PS-cluster is adequately efficient for UK Biobank data. Therefore, P-smoother opens up new possibilities for efficient error-tolerating algorithms for biobank-scale haplotype panels. Availability and implementation: Source code is available at github.com/ZhiGroup/P-smoother.

Central Nervous System Involvement of Multiple Myeloma Presenting as Short-lasting Unilateral Neuralgiform Headache with Conjunctival Injection and Tearing: A Case Report.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are part of the trigeminal autonomic cephalalgia (TAC) group of headache disorders. Attacks present with repeated, severe, sharp, stabbing, or throbbing pain. Patients may experience a single attack, recurrent attacks with pain-free interictal periods, or a sawtooth pattern background pain with superimposed stabs.1,2 Although SUNCT typically presents as a primary headache disorder, it may be secondary to an underlying pathology, such as pituitary tumors or posterior fossa lesions, both intra and extra-axial (vascular lesion, tumor, or bony abnormalities). Multiple Myeloma (MM) with central nervous system involvement (CNS MM) most commonly presents with visual changes (36%), radiculopathy (27%), headache (25%), confusion (21%), dizziness (7%) and seizures (6%).3,4 Secondary SUNCT cases have been sparsely described (less than 60), and CNS MM presenting as SUNCT has not been previously described in the literature.2,5 Our case describes a previously unreported clinical presentation of CNS MM. The report highlights the need for a timely and thorough diagnostic work-up of headache in patients with risk factors for a secondary etiology, which in this case included new-onset, autonomic features, older age, and history of malignancy. A misdiagnosis will preclude a potentially life-extending or saving targeted therapy for the underlying illness. We also aim to remind practitioners of the variability in the clinical symptoms of SUNCT, which are known to occur in a significant number of cases, including migrainous features and dull interictal pain.

Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function.

Modulation of immune function at the tumor site could improve patient outcomes. Here, we analyze patient samples of metastatic melanoma, a tumor responsive to T cell-based therapies, and find that tumor-infiltrating T cells are primarily juxtaposed to CD14+ monocytes/macrophages rather than melanoma cells. Using immunofluorescence-guided laser capture microdissection, we analyze transcriptomes of CD3+ T cells, CD14 + monocytes/macrophages, and melanoma cells in non-dissociated tissue. Stromal CD14+ cells display a specific transcriptional signature distinct from CD14+ cells within tumor nests. This signature contains LY75, a gene linked with antigen capture and regulation of tolerance and immunity in dendritic cells (DCs). When applied to TCGA cohorts, this gene set can distinguish patients with significantly prolonged survival in metastatic cutaneous melanoma and other cancers. Thus, the stromal CD14+ cell signature represents a candidate biomarker and suggests that reprogramming of stromal macrophages to acquire DC function may offer a therapeutic opportunity for metastatic cancers.

Sub-Nanometer Interfacial Oxides on Highly Oriented Pyrolytic Graphite and Carbon Nanotubes Enabled by Lateral Oxide Growth.

A new generation of compact and high-speed electronic devices, based on carbon, would be enabled through the development of robust gate oxides with sub-nanometer effective oxide thickness (EOT) on carbon nanotubes or graphene nanoribbons. However, to date, the lack of dangling bonds on sp2 oriented graphene sheets has limited the high precursor nucleation density enabling atomic layer deposition of sub-1 nm EOT gate oxides. It is shown here that by deploying a low-temperature AlOx (LT AlOx) process, involving atomic layer deposition (ALD) of Al2O3 at 50 °C with a chemical vapor deposition (CVD) component, a high nucleation density layer can be formed, which templates the growth of a high-k dielectric, such as HfO2. Atomic force microscopy (AFM) imaging shows that at 50 °C, the Al2O3 spontaneously forms a pinhole-free, sub-2 nm layer on graphene. Density functional theory (DFT) based simulations indicate that the spreading out of AlOx clusters on the carbon surface enables conformal oxide deposition. Device applications of the LT AlOx deposition scheme were investigated through electrical measurements on metal oxide semiconductor capacitors (MOSCAPs) with Al2O3/HfO2 bilayer gate oxides using both standard Ti/Pt metal gates as well as TiN/Ti/Pd gettering gates. In this study, LT AlOx was used to nucleate HfO2 and it was shown that bilayer gate oxide stacks of 2.85 and 3.15 nm were able to achieve continuous coverage on carbon nanotubes (CNTs). The robustness of the bilayer was tested through deployment in a CNT-based field-effect transistor (FET) configuration with a gate leakage of less than 10-8 A/µm per CNT.

Concurrent Epstein Barr virus-associated smooth muscle tumor and myeloid sarcoma of the liver and acute myeloid leukemia in a patient post kidney transplant: a case report and review of the literature.

Background: Epstein Barr virus-associated smooth muscle tumors (EBV-SMT) are rare neoplasms that can occur in immunocompromised individuals. The native or transplanted liver is the most commonly involved site in post transplant patients. Systemic therapies have been utilized in EBV-SMT with modest activity. Case Description: We describe a 23-year-old female kidney transplant recipient who presented with acute myeloid leukemia (AML) and hepatic myeloid sarcoma (MS). Although it was not recognized initially, her liver biopsy revealing MS at diagnosis was posthumously found to have synchronous EBV-SMT. She underwent anthracycline based induction and achieved a complete remission of her AML by bone marrow biopsy. Due to a persistent hepatic mass, she was given salvage chemotherapy including fludarabine, etoposide, cytarabine, decitabine, and venetoclax for presumed refractory MS. Re-biopsy of the liver revealed the absence of MS and presence of EBV-SMT, which subsequently grew rapidly and precluded her from a liver tumor resection. The patient underwent sirolimus mammalian target of rapamycin (mTOR) therapy with palliative intent, but the patient's EBV-SMT progressed shortly after. At time of autopsy, the patient remained in complete remission from AML/MS, but was found to have multifocal progressive metastatic EBV-SMT. Conclusions: To our knowledge this is the first reported case of synchronous AML/MS and post transplant hepatic EBV-SMT that underwent treatment for AML/MS. Our report suggests that the chemotherapeutic agents utilized for AML/MS may have poor efficacy against EBV-SMT.

Human KIT+ myeloid cells facilitate visceral metastasis by melanoma.

Metastasis of melanoma significantly worsens prognosis; thus, therapeutic interventions that prevent metastasis could improve patient outcomes. Here, we show using humanized mice that colonization of distant visceral organs with melanoma is dependent upon a human CD33+CD11b+CD117+ progenitor cell subset comprising <4% of the human CD45+ leukocytes. Metastatic tumor-infiltrating CD33+ cells from patients and humanized (h)NSG-SGM3 mice showed converging transcriptional profiles. Single-cell RNA-seq analysis identified a gene signature of a KIT/CD117-expressing CD33+ subset that correlated with decreased overall survival in a TCGA melanoma cohort. Thus, human CD33+CD11b+CD117+ myeloid cells represent a novel candidate biomarker as well as a therapeutic target for metastatic melanoma.

Considerations and Strategies for Restarting Elective Spine Surgery in the Midst of a Pandemic of COVID-19.

The 2019 coronavirus disease (COVID-19) pandemic outbreak has rapidly spread to the globe, causing severe global socioeconomic disruption on an unprecedented scale. As the first wave of COVID-19 pandemic is now going to settle down, many medical organizations are in the process of reopening surgical services. This paper describes a few key factors that spine surgeons should consider prior to resuming elective spine services namely, local outbreak situations, availability of hospital resources, manpower and personal protective equipment (PPE). Spine surgeons should prioritize their operating list based on clinical indications and likely benefits from surgical intervention so as to make optimum use of hospital resources and operating room listings. International organizations have published on general principles and recommendations on how to restart elective surgery. However, with different regions at varying phases of the outbreak and unpredictable nature of the COVID-19 pandemic, a general set of practice guidelines may not be applicable. This paper also proposes, on top of peri-operative precautionary measures already in place, clearly-defined risk stratification algorithms for hospital visitors, as well as a disease-testing protocol for patients planned for elective surgery. It is of critical importance for surgeons to define key areas of concern and assimilate these principles into clearly-defined algorithms which can be applied to the field of spine surgery so as to help re-establish continuity of care for patients.