A Nonlinear Peptide Topology for Synthetic Virions.

a nonlinear de novo peptide topology for the assembly of synthetic virions is reported. The topology is a backbone cyclized amino-acid sequence in which polar l- and hydrophobic d-amino acid residues of the same-type alternate. This arrangement introduces pseudo C4 symmetries of side chains within the same cyclopeptide ring, allowing for the lateral propagation of cyclopeptides into networks with a [3/6, 4]-fold rotational symmetry closing into virus-like shells. A combination of computational and experimental approaches was used to establish that the topology forms morphologically uniform, nonaggregating and nontoxic nanoscale shells. These effectively encapsulate genetic cargo and promote its intracellular delivery and a target genetic response. The design introduces a nanotechnology inspired solution for engineering virus-like systems thereby expanding traditional molecular biology approaches used to create artificial biology to chemical space.

Rapid profiling of transcription factor-cofactor interaction networks reveals principles of epigenetic regulation.

Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here, we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced histone 3 lysine 27 acetylation (H3K27ac). Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data support clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.

Smartphone Applications for Remote Monitoring of Patients After Transsphenoidal Pituitary Surgery: A Narrative Review of Emerging Technologies.

OBJECTIVE: Almost all postoperative assessments for pituitary patients are performed in clinical settings under the supervision of medical providers. With the emergence of telemedicine, however, there are opportunities to monitor these patients remotely. The potential for use of such technologies is inconsistently described in the brain tumor literature, especially for patients with pituitary adenomas. METHODS: In this comprehensive narrative review, we present the literature for the use of mobile applications (apps) for monitoring of postoperative symptomatology that is specific to patients undergoing pituitary surgery. Our primary research question was: "Which smartphone apps exist in the literature to monitor parameters associated with common complications of pituitary surgery?" Specifically, we search for apps in the literature that facilitate the measurement of parameters associated with adrenal insufficiency, disorders of water imbalance, and visual changes-3 common complications of pituitary surgery. RESULTS: Twenty-six apps were identified. Fourteen apps pertained to monitoring of visual changes, followed by 9 apps for monitoring water and electrolyte imbalances and 3 apps for monitoring adrenal dysfunction. Novel technologies that were integrated into these apps included digital image-based colorimetry, sonouroflowmetry, visual contrast sensitivity, and lateral flow immunoassays, among others. CONCLUSIONS: Due to advancing capabilities of smartphone apps, the potential of telemedicine may extend beyond patient appointments. We show that by integrating novel advances in medical technologies from a variety of specialties, it is possible to develop smartphone-based protocols for remote monitoring of patients after pituitary surgery.

The Impact of Social Determinants on Receipt of Adjuvant Radiation Nationally Following Atypical Meningioma Surgery.

OBJECTIVE: We aimed to identify socioeconomic gaps in the administration of adjuvant radiotherapy (RT) for patients with atypical meningioma (AM) and secondarily to determine differences in survival between patients receiving radiation and those not receiving radiation at 12 and 60 months. METHODS: The National Cancer Database was queried for patients receiving AM surgery between 2004 and 2019. Statistical analyses were performed to assess the association between receipt of adjuvant radiation and social determinants. Secondarily, Kaplan-Meir curves were used to compare overall patient survival between those that received radiation and those that did not. RESULTS: Adjuvant radiation was less likely to be administered to patients over 65 (95% confidence interval [CI] = 0.53-22 0.77) and more likely to be administered to males (95% CI = 1.07-1.38). Compared to the Southern USA, patients were more likely to receive RT in the Northeastern (95% CI 24 = 1.40-2.05), Midwestern (95% CI = 1.06-1.54), and Western parts of the USA (95% 25 CI = 1.31-2.00). Patients residing furthest from their facility were less likely to receive radiation (95% CI = 0.65-0.98). Insured patients were more likely to receive radiation (P = 0.048) than uninsured patients. On multivariate analysis, no differences were found between racial groups regarding adjuvant radiation. For patients unstratified, radiation was shown to improve survival at 12 and 60 months. CONCLUSIONS: Disparities exist in the administration of adjuvant RT for AM. Patients over 65, women, those residing in the Southern USA, those living further from their facilities and uninsured patients are less likely to receive radiation than their counterparts.

Health Disparities in the Neurosurgical Care of Patients with Trigeminal Neuralgia.

BACKGROUND: There has been limited investigation into how social determinants of health impact treatment outcomes in patients with trigeminal neuralgia (TN). We aimed to investigate how social determinants of health may alter the course of clinical care for patients with TN. METHODS: The electronic medical record was queried for patients with a diagnosis of TN comanaged by neurosurgeons and other facial pain specialists at our medical center. Area Deprivation Index served as a proxy for socioeconomic status (SES). Multivariable linear regression models were performed using RStudio to assess the impact of social determinants on the time to neurosurgical referral and surgical intervention. RESULTS: A total of 229 patients (mean age 50 years, 74% female) were included. Of these, 135 (60%) patients underwent a neurosurgical procedure after referral, the most common being microvascular decompression (n = 84, 62%) (Table 1). Most of the patients were white (76.3%) and insured by Medicare (51.8%), followed by private insurance (38.6%). Age and sex were significant predictors of time to neurosurgical referral after symptom onset, as older patients (P < 0.01, Figure 3) and females (P = 0.02) tended to have a greater delay between symptom onset and specialist referral. Race, SES, and insurance status were not significantly associated with time-to-referral or time-to-treatment. CONCLUSION: This study found that older and female patients with TN had a longer time from symptom onset to specialist referral. Based on these data, there is no association between race, SES, and insurance status with time-to-referral or time-to-treatment in patients with TN.

Frailty in patients with IDH-mutant gliomas: experience from a high-volume tumor center.

PURPOSE: Gliomas are increasingly diagnosed in an aging population, with treatment outcomes influenced by factors like tumor genetics and patient frailty. This study focused on IDH-mutant gliomas and assessed how frailty affects 30-day readmission and overall survival (OS). We aimed to address a gap in understanding the impact of frailty on this specific glioma subtype. METHODS: 136 patients with an IDH-mutant glioma between 2007 and 2021 were identified at our institution. High frailty was classified by scores ≥ 1 on the 5-factor modified frailty index (mFI-5) and ≥ 3 on the Charlson Comorbidity Index (CCI). Patient and tumor characteristics including age, sex, race, Karnofsky Performance Status (KPS), Body Mass Index (BMI), tumor type and location, type of operation, and therapy course were recorded. Outcomes measured included 30-day readmission and overall survival (OS). Analysis was conducted utilizing logistic regression and Kaplan-Meier curves. RESULTS: Of the 136 patients, 52 (38%) had high frailty: 18 with CCI ≥ 3, 34 with mFI-5 ≥ 1. High frailty correlated with increased BMI (CCI: 30.2, mFI-5: 30.1 kg/m2), more neurological deficits (CCI: 61%, mFI-5: 56%), and older age at surgery (CCI: 63, mFI-5: 48 years). Hospital readmission within 30 days occurred in 8 (5.9%) patients. Logistic regression indicated no significant difference in 30-day readmission rates (CCI: p = 0.30, mFI-5: p = 0.62) or median OS between high and low frailty groups. However, patients treated at our institution with newly diagnosed tumors with high mFI-5 had a 6.79 times higher adjusted death hazard than those with low mFI-5 (p = .049). CONCLUSION: Our analysis revealed that CCI and mFI-5 were not significantly associated with 30-day nor OS. However, in patients with non-recurrent tumors, there was a significant association of mFI-5 with OS. Further study of frailty with larger cohorts is warranted to enhance prognostication of outcome after neurosurgical treatment.

Characterizing the association between CSF biomarkers and risk for ventriculoperitoneal shunt following posterior fossa tumor resection in a case-control study.

BACKGROUND: Recalcitrant hydrocephalus necessitating permanent cerebrospinal fluid (CSF) diversion is a known complication after resection of a posterior fossa tumor (PFT). Various CSF contents, such as protein and other markers, have been variably correlated with the need for permanent CSF diversion. This study aims to evaluate which CSF laboratory values are associated with permanent CSF diversion following PFT resection in adults. METHODS: This study queried our multi-institutional database (Central Nervous System Tumor Outcome Registry at Emory; CTORE) consisting of 617 adult patients with PFT resections from 2006 to 2021. Retrospective data was collected from the 89 patients of this cohort that required EVD placement. Patients were stratified into two groups: those that required a shunt following EVD removal (n = 30) and those that did not (n = 40). CSF variables collected included glucose, protein, nucleated cell count, and presence of infection. An unadjusted logistic regression was performed to assess exposures associated with shunt requirement and unadjusted odds ratios (ORs) and their associated 95 % confidence intervals (CIs) were obtained. RESULTS: Immediately following surgery, no CSF variables were significantly associated with shunt placement. Except for post-operative CSF being not-clear (OR: 4.15 (1.47-12.56), p = 0.009) and CSF glucose (OR: 0.97 (1.03-1.07), p = 0.031) all other variables were not significantly associated with shunt at time point 2. CONCLUSION: In our retrospective analysis, most routinely collected CSF values were not associated with permanent CSF diversion via a ventriculoperitoneal shunt following PFT resection. Further research is needed to identify other potential predictive markers.

Lipid shape and packing are key for optimal design of pH-sensitive mRNA lipid nanoparticles.

The ionizable-lipid component of RNA-containing nanoparticles controls the pH-dependent behavior necessary for an efficient delivery of the cargo-the so-called endosomal escape. However, it is still an empirical exercise to identify optimally performing lipids. Here, we study two well-known ionizable lipids, DLin-MC3-DMA and DLin-DMA using a combination of experiments, multiscale computer simulations, and electrostatic theory. All-atom molecular dynamics simulations, and experimentally measured polar headgroup pKa values, are used to develop a coarse-grained representation of the lipids, which enables the investigation of the pH-dependent behavior of lipid nanoparticles (LNPs) through Monte Carlo simulations, in the absence and presence of RNA molecules. Our results show that the charge state of the lipids is determined by the interplay between lipid shape and headgroup chemistry, providing an explanation for the similar pH-dependent ionization state observed for lipids with headgroup pKa values about one-pH-unit apart. The pH dependence of lipid ionization is significantly influenced by the presence of RNA, whereby charge neutrality is achieved by imparting a finite and constant charge per lipid at intermediate pH values. The simulation results are experimentally supported by measurements of α-carbon 13C-NMR chemical shifts for eGFP mRNA LNPs of both DLin-MC3-DMA and DLin-DMA at various pH conditions. Further, we evaluate the applicability of a mean-field Poisson-Boltzmann theory to capture these phenomena.

Volumetric Analysis of Spheno-Orbital Meningiomas: Prognostic Correlation and a Compartmentalized Approach.

BACKGROUND AND OBJECTIVES: Spheno-orbital meningiomas arise from the arachnoid villi cap cells at the sphenoid ridge and have the ability to spread through soft tissue extension and cranial bone invasion. Owing to their orbital hyperostosis and intraorbital soft tissue extension, they commonly present with ophthalmologic manifestations. This study aims to investigate the correlation between tumor volume with the presenting symptoms and postoperative outcomes. METHODS: This retrospective study analyzed patients who underwent surgical resection of spheno-orbital meningiomas. Tumor volumes in different compartments were measured using preoperative and postoperative imaging. Linear and logistic regression analyses were used to identify correlations between tumor volumes and presenting symptoms preoperatively and postoperative outcomes. RESULTS: Sixty-six patients were included in this study, of whom 86.4% had proptosis, 80.3% had decreased visual acuity (VA), 30.3% had visual field defects, and 13.6% had periorbital edema. Preoperatively, proptosis linearly correlated with intraosseous tumor volume (coefficient = 0.6, P < .001), while the decrease in baseline VA correlated with the intraorbital tumor volume (coefficient = 0.3, P = .01). The odds of periorbital edema were found to increase with an increase in intraosseous tumor volume with an adjusted odds ratio of 1.4 (95% CI, 1.1-1.7, P = .003), while the odds of visual field defects were found to increase with an increase in intraorbital tumor volume with an adjusted odds ratio of 2.7 (95% CI, 1.3-5.6, P = .01). Postoperatively, the volume of intraosseous tumor resected linearly correlated with the improvement in proptosis (coefficient = 0.7, P < .001), while the volume of intraorbital tumor resected linearly correlated with improvement in VA (coefficient = 0.5, P < .001) and with a larger effect size in patients presenting with moderate-to-severe decrease in VA preoperatively (coefficient = 0.8). CONCLUSION: Underscoring the importance of each tumor compartment relative to the patient's symptomatology serves as a valuable guide in implementing a compartmentalized resection approach tailored to the surgical objectives.

An Artificial Neural Network Model for Predicting Postoperative Facial Nerve Outcomes After Vestibular Schwannoma Surgery.

BACKGROUND AND OBJECTIVES: The emergence of machine learning models has significantly improved the accuracy of surgical outcome predictions. This study aims to develop and validate an artificial neural network (ANN) model for predicting facial nerve (FN) outcomes after vestibular schwannoma (VS) surgery using the proximal-to-distal amplitude ratio (P/D) along with clinical variables. METHODS: This retrospective study included 71 patients who underwent VS resection between 2018 and 2022. At the end of surgery, the FN was stimulated at the brainstem (proximal) and internal acoustic meatus (distal) and the P/D was calculated. Postoperative FN function was assessed using the House-Brackmann grading system at discharge (short-term) and after 9-12 months (long-term). House-Brackmann grades I-II were considered good outcome, whereas grades III-VI were considered fair/poor. An ANN model was constructed, and the performance of the model was evaluated using the area under the ROC curve for internal validation and accuracy, sensitivity, specificity, and positive and negative predictive values for external validation. RESULTS: The short-term FN outcome was grades I-II in 57.7% and grades III-VI in 42.3% of patients. Initially, a model using P/D had an area under the curve of 0.906 (internal validation) and an accuracy of 89.1% (95% CI: 68.3%-98.8%) (external validation) for predicting good vs fair/poor short-term FN outcomes. The model was then refined to include only muscles with a P/D with a proximal latency between 6 and 8 ms. This improved the accuracy to 100% (95% CI: 79%-100%). Integrating clinical variables (patient's age, tumor size, and preoperative HB grade) in addition to P/D into the model did not significantly improve the predative value. A model was then created to predict the long-term FN outcome using P/D with latencies between 6 and 8 ms and had an accuracy of 90.9% (95% CI: 58.7%-99.8%). CONCLUSION: ANN models incorporating P/D can be a valuable tool for predicting FN outcomes after VS surgery. Refining the model to include P/D with latencies between 6 and 8 ms further improves the model's prediction. A user-friendly interface is provided to facilitate the implementation of this model.

Examining the Effect of ALK and EGFR Mutations on Survival Outcomes in Surgical Lung Brain Metastasis Patients.

In the context of the post-genomic era, where targeted oncological therapies like monoclonal antibodies (mAbs) and tyrosine-kinase inhibitors (TKIs) are gaining prominence, this study investigates whether these therapies can enhance survival for lung carcinoma patients with specific genetic mutations-EGFR-amplified and ALK-rearranged mutations. Prior to this study, no research series had explored how these mutations influence patient survival in cases of surgical lung brain metastases (BMs). Through a multi-site retrospective analysis, the study examined patients who underwent surgical resection for BM arising from primary lung cancer at Emory University Hospital from January 2012 to May 2022. The mutational statuses were determined from brain tissue biopsies, and survival analyses were conducted. Results from 95 patients (average age: 65.8 ± 10.6) showed that while 6.3% had anaplastic lymphoma kinase (ALK)-rearranged mutations and 20.0% had epidermal growth factor receptor (EGFR)-amplified mutations-with 9.5% receiving second-line therapies-these mutations did not significantly correlate with overall survival. Although the sample size of patients receiving targeted therapies was limited, the study highlighted improved overall survival and progression-free survival rates compared to earlier trials, suggesting advancements in systemic lung metastasis treatment. The study suggests that as more targeted therapies emerge, the prospects for increased overall survival and progression-free survival in lung brain metastasis patients will likely improve.

Structure adaptation in Omicron SARS-CoV-2/hACE2: Biophysical origins of evolutionary driving forces.

Since its emergence, the COVID-19 threat has been sustained by a series of transmission waves initiated by new variants of the SARS-CoV-2 virus. Some of these arise with higher transmissivity and/or increased disease severity. Here, we use molecular dynamics simulations to examine the modulation of the fundamental interactions between the receptor binding domain (RBD) of the spike glycoprotein and the host cell receptor (human angiotensin-converting enzyme 2 [hACE2]) arising from Omicron variant mutations (BA.1 and BA.2) relative to the original wild-type strain. Our key findings are that glycans play a vital role at the RBD···hACE2 interface for the Omicrons, and the interplay between glycans and sequence mutations leads to enhanced binding. We find significant structural differences in the complexes, which overall bring the spike protein and its receptor into closer proximity. These are consistent with and attributed to the higher positive charge on the RBD conferred by BA.1 and BA.2 mutations relative to the wild-type. However, further differences between subvariants BA.1 and BA.2 (which have equivalent RBD charges) are also evident: mutations reduce interdomain interactions between the up chain and its clockwise neighbor chain in particular for the latter, resulting in enhanced flexibility for BA.2. Consequently, we see occurrence of additional close contacts in one replica of BA.2, which include binding to hACE2 by a second RBD in addition to the up chain. Although this motif is not seen in BA.1, we find that the Omicrons can directly/indirectly bind a down-RBD to hACE2 through glycans: the role of the glycan on N90 of hACE2 switches from inhibiting to facilitating the binding to Omicron spike protein via glycan-protein lateral interactions. These structural and electrostatic differences offer further insight into the mechanisms by which viral mutations modulate host cell binding and provide a biophysical basis for evolutionary driving forces.

Therapeutic response to pazopanib: case report and literature review on molecular abnormalities of aggressive prolactinomas.

Introduction: Aggressive prolactinomas (APRLs) pose a significant clinical challenge due to their high rate of regrowth and potentially life-threatening complications. In this study, we present a case of a patient with an APRL who had a trial of multiple therapeutic modalities with the aim to provide a review of molecular abnormalities and management of APRLs by corroborating our experience with previous literature. Methods: A total of 268 articles were reviewed and 46 were included. Case reports and series, and studies that investigated the molecular and/or genetic analysis of APRLs were included. Special care was taken to include studies describing prolactinomas that would fall under the APRL subtype according to the European Society of Endocrinology guidelines; however, the author did not label the tumor as "aggressive" or "atypical". Addiontionally, we present a case report of a 56-year-old man presented with an invasive APRL that was resistant to multiple treatment modalities. Results: Literature review revealed multiple molecular abnormalities of APRLs including mutations in and/or deregulation of ADAMTS6, MMP-9, PITX1, VEGF, POU6F2, CDKN2A, and Rb genes. Mismatch repair genes, downregulation of microRNAs, and hypermethylation of specific genes including RASSF1A, p27, and MGMT were found to be directly associated with the aggressiveness of prolactinomas. APRL receptor analysis showed that low levels of estrogen receptor (ER) and an increase in somatostatin receptors (SSTR5) and epidermal growth factor receptors (EGFR) were associated with increased invasiveness and higher proliferation activity. Our patient had positive immunohistochemistry staining for PD-L1, MSH2, and MSH6, while microarray analysis revealed mutations in the CDKN2A and POU6F2 genes. Despite undergoing two surgical resections, radiotherapy, and taking dopamine agonists, the tumor continued to progress. The patient was administered pazopanib, which resulted in a positive response and the patient remained progression-free for six months. However, subsequent observations revealed tumor progression. The patient was started on PD-L1 inhibitor pembrolizumab, yet the tumor continued to progress. Conclusion: APRLs are complex tumors that require a multidisciplinary management approach. Knowledge of the molecular underpinnings of these tumors is critical for understanding their pathogenesis and identifying potential targets for precision medical therapy.

Purely nasal floor mucosa-free graft for reconstruction after endoscopic endonasal transellar approach: an anatomical and clinical analysis.

BACKGROUND/OBJECTIVE: In this radioanatomical study with clinical correlate, we study a variation of the 'extended nasal floor mucosa' (ENFM) free-graft, the purely nasal floor mucosa (PuNFM) free-graft. The objectives of this study are to evaluate the coverage surface area provided by the PuNFM, study the adequacy of the PuNFM in the reconstruction of endoscopic endonasal approach (EEA) transsellar postoperative defects and compare and evaluate this reconstructive technique with current sellar region reconstruction practices. METHODS: Dissections were performed on five cadaveric specimens. PuNFM were harvested bilaterally and the area provided for reconstruction was calculated. Twenty-five consecutive cases of pituitary adenomas resected through an EEA were analyzed to estimate the sellar defect surface area (SDSA) after a transsellar EEA and calculate the area of PuNFM bilaterally. RESULTS: The median cadaveric SDSA was 4.77 cm2, with a median left and right side PuNFM area of 5.09 and 5.19 cm2, respectively. Clinically, the median SDSA was 5.36 cm2, and the total radiological PuNFM surface area was 5.46 cm2, with modified Knosp grade >2 tumors having larger SDSA than that of Knosp grade <2 tumors. The PuNFM graft proved to be most effective for covering modified Knosp <2 tumor defects. CONCLUSIONS: The PuNFM represents a variation of the ENFM free-graft sellar defect reconstruction technique that provides sufficient surface area to reconstruct the majority of the sellar defects related to transsellar EAA for pituitary adenomas. This technique may positively impact sinonasal function and quality of life. Future prospective clinical studies are needed to verify these findings.

Can Machine Learning Predict the Phase Behavior of Surfactants?

We explore the prediction of surfactant phase behavior using state-of-the-art machine learning methods, using a data set for twenty-three nonionic surfactants. Most machine learning classifiers we tested are capable of filling in missing data in a partially complete data set. However, strong data bias and a lack of chemical space information generally lead to poorer results for entire de novo phase diagram prediction. Although some machine learning classifiers perform better than others, these observations are largely robust to the particular choice of algorithm. Finally, we explore how de novo phase diagram prediction can be improved by the inclusion of observations from state points sampled by an analogy to commonly used experimental protocols. Our results indicate what factors should be considered when preparing for machine learning prediction of surfactant phase behavior in future studies.

Telemedicine for Neurosurgery Consultations at a Pituitary Center of Excellence: Patient Preference and Willingness to Proceed with Surgery.

Objective The purpose of this study was to evaluate pituitary tumor patient satisfaction with telemedicine, patient preference for telemedicine, potential socioeconomic benefit of telemedicine, and patients' willingness to proceed with surgery based on a telemedicine visit alone. Method In total, 134 patients who had pituitary surgery and a telemedicine visit during the coronavirus disease 2019 (COVID-19) pandemic (April 23, 2020-March 4, 2021) were called to participate in a 13-part questionnaire. Chi-square, ANOVA, and Wilcoxon Rank Sum tests were used to determine significance. Result Of 134 patients contacted, 90 responded (67%). Ninety-five percent were "satisfied" or "very satisfied" with their telemedicine visit, with 62% stating their visit was "the same" or "better" than previous in-person appointments. Eighty-two percent of the patients rated their telemedicine visit as "easy" or "very easy." On average, patients saved 150 minutes by using telemedicine compared with patient reported in-person visit times. Seventy-seven percent of patients reported the need to take off from work for in-person visits, compared with just 12% when using telemedicine. Forty-nine percent of patients preferred in-person visits, 34% preferred telemedicine, and 17% had no preference. Fifty percent of patients said they would feel comfortable proceeding with surgery based on a telemedicine visit alone. Patients with both initial evaluation and follow-up conducted via telemedicine were more likely to feel comfortable proceeding with surgery based on a telemedicine visit alone compared with patients who had only follow-up telemedicine visits ( p = 0.051). Conclusion Many patients are satisfied with telemedicine visits and feel comfortable proceeding with surgery based on a telemedicine visit alone. Telemedicine is an important adjunct to increase access to care at a Pituitary Center of Excellence.

Phase Behavior of Alkyl Ethoxylate Surfactants in a Dissipative Particle Dynamics Model.

We present a dissipative particle dynamics (DPD) model capable of capturing the liquid state phase behavior of nonionic surfactants from the alkyl ethoxylate (CnEm) family. The model is based upon our recent work [Anderson et al. J. Chem. Phys. 2017, 147, 094503] but adopts tighter control of the molecular structure by setting the bond angles with guidance from molecular dynamics simulations. Changes to the geometry of the surfactants were shown to have little effect on the predicted micelle properties of sampled surfactants, or the water-octanol partition coefficients of small molecules, when compared to the original work. With these modifications the model is capable of reproducing the binary water-surfactant phase behavior of nine surfactants (C8E4, C8E5, C8E6, C10E4, C10E6, C10E8, C12E6, C12E8, and C12E12) with a good degree of accuracy.

Widespread perturbation of ETS factor binding sites in cancer.

Although >90% of somatic mutations reside in non-coding regions, few have been reported as cancer drivers. To predict driver non-coding variants (NCVs), we present a transcription factor (TF)-aware burden test based on a model of coherent TF function in promoters. We apply this test to NCVs from the Pan-Cancer Analysis of Whole Genomes cohort and predict 2555 driver NCVs in the promoters of 813 genes across 20 cancer types. These genes are enriched in cancer-related gene ontologies, essential genes, and genes associated with cancer prognosis. We find that 765 candidate driver NCVs alter transcriptional activity, 510 lead to differential binding of TF-cofactor regulatory complexes, and that they primarily impact the binding of ETS factors. Finally, we show that different NCVs within a promoter often affect transcriptional activity through shared mechanisms. Our integrated computational and experimental approach shows that cancer NCVs are widespread and that ETS factors are commonly disrupted.

State of pediatric liver transplantation in the United States and achieving zero wait list mortality with ideal outcomes: A statement from the Starzl Network for Excellence in Pediatric Transplant Surgeon's Working Group.

BACKGROUND: Liver transplant is a life-saving therapy that can restore quality life for several pediatric liver diseases. However, it is not available to all children who need one. Expertise in medical and surgical management is heterogeneous, and allocation policies are not optimally serving children. Technical variant grafts from both living and deceased donors are underutilized. METHODS: Several national efforts in pediatric liver transplant to improve access to and outcomes from liver transplant for children have been instituted and include adjustments to allocation policies, UNOS-sponsored collaborative improvement projects, and the emergence of national learning networks to study ongoing challenges in the field the Surgical Working group of the Starzl Network for Excellence in Pediatric Transplantation (SNEPT) discusses key issues and proposes potential solutions to eliminate the persistent wait list mortality that pediatric patients face. RESULTS: A discussion of the factors impacting pediatric patients' access to liver transplant is undertaken, along with a proposal of several measures to ensure equitable access to life-saving liver transplant. CONCLUSIONS: Pediatric liver transplant wait list mortality can and should be eliminated. Several measures, including collaborative efforts among centers, could be leveraged to acheive this goal.

Complication rate of overlapping versus nonoverlapping functional and stereotactic surgery: a retrospective cohort study.

OBJECTIVE: Overlapping surgery, in which one attending surgeon manages two overlapping operating rooms (ORs) and is present for all the critical portions of each procedure, is an important policy that improves healthcare access for patients and case volumes for surgeons and surgical trainees. Despite several studies demonstrating the safety and efficacy of overlapping neurosurgical operations, the practice of overlapping surgery remains controversial. To date, there are no studies that have investigated long-term complication rates of overlapping functional and stereotactic neurosurgical procedures. The primary objective of this study was to investigate the 1-year complication rates and OR times for nonoverlapping versus overlapping functional procedures. The secondary objective was to gain insight into what types of complications are the most prevalent and test for differences between groups. METHODS: Seven hundred eighty-three functional neurosurgical cases were divided into two cohorts, nonoverlapping (n = 342) and overlapping (n = 441). The American Society of Anesthesiologists (ASA) scale score was used to compare the preoperative risk for both cohorts. A complication was defined as any surgically related reason that required readmission, reoperation, or an unplanned emergency department or clinic visit that required intervention. Complications were subdivided into infectious and noninfectious. Chi-square tests, independent-samples t-tests, and uni- and multivariable logistic regressions were used to determine significance. RESULTS: There were no significant differences in mean ASA scale score (2.7 ± 0.6 for both groups, p = 0.997) or overall complication rates (8.8% nonoverlapping vs 9.8% overlapping, p = 0.641) between the two cohorts. Infections accounted for the highest percentage of complications in both cohorts (46.6% vs 41.8%, p = 0.686). There were no statistically significant differences between mean in-room OR time (187.5 ± 141.7 minutes vs 197.1 ± 153.0 minutes, p = 0.373) or mean open-to-close time (112.2 ± 107.9 minutes vs 121.0 ± 123.1 minutes, p = 0.300) between nonoverlapping and overlapping cases. CONCLUSIONS: There was no increased risk of 1-year complications or increased OR time for overlapping functional and stereotactic neurosurgical procedures compared with nonoverlapping procedures.