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Objective: To evaluate oocyte retrieval experiences and side effects under minimally controlled ovarian stimulation (COS) treatment for in vitro maturation (IVM) of oocytes compared with conventional COS treatment., Design: A retrospective survey study., Setting: Clinical in vitro fertilization treatment center., Patient(s): Data were collected from subjects undergoing minimal COS treatment (n = 110; 600-800 IU follicle-stimulating hormone) for IVM of oocytes and conventional COS treatment for egg donation (n = 48; 1,800-2,600 IU follicle-stimulating hormone) from April 2022 to November 2023., Intervention(s): Minimal and conventional COS treatments., Main Outcome Measure(s): The most common side effects experienced during ovarian stimulation and after oocyte pick-up, satisfaction level, and the likelihood of recommending or repeating minimal or conventional COS. Statistical analysis included Mann-Whitney U test and χ 2 tests, with a significance level., Result(s): During minimal COS treatment, most subjects did not experience breast swelling (86%), pelvic or abdominal pain (76%), nausea or vomiting (96%), and bleeding (96%). After oocyte pick-up, the majority (75%) reported no pelvic or abdominal pain. The most common side effect was abdominal swelling (52%). Compared with conventional COS cycles, minimal COS subjects reported significantly less postretrieval pain, with 33% experiencing no pain (vs. 6%) and with a reduced severe level of pain (5% vs. 19%), leading to fewer subjects requiring pain medication (25% vs. 54%). Additionally, 85% of women were very satisfied with minimal stimulation treatment and would recommend or repeat the treatment., Conclusion(s): Reducing the hormonal dose for ovarian stimulation has a beneficial effect on subjects, suggesting the combination of minimal COS treatment with IVM techniques is a well-tolerated alternative for women who cannot or do not wish to undergo conventionally controlled ovarian hyperstimulation treatment., Competing Interests: Declaration of interests M.M. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. M.M. is listed on a patent covering the use of ovarian support cells (OSCs) for in vitro maturation (IVM): US Provisional Patent Application No. 63/492,210. F.B. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.P. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.P. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. M.F.G. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. A.G. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. A.G. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. T.S. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. S.K. has nothing to disclose. B.P. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. B.P. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. E.G. has nothing to disclose. V.C. has nothing to disclose. A.S. has nothing to disclose. B.A. has nothing to disclose. J.K. has nothing to disclose. P.K. has nothing to disclose. D.O. has nothing to disclose. C.C.K. reported being a shareholder in Gameto Inc., a for-profit biotechnology company. C.C.K. is listed on a patent covering the use of OSCs for IVM: US Provisional Patent Application No. 63/492,210. C.C.K. is listed on three patents covering the use of OSCs for IVM: US Patent Application No. 17/846,725, US Patent Application No. 17/846,845, and International Patent Application No.: PCT/US2023/026012. C.C.K. is additionally listed on three patents for the transcription factor-directed production of granulosa-like cells from stem cells: International Patent Application No.: PCT/US2023/065140, US Provisional Application No. 63/326,640, and US. Provisional Application No. 63/444,108., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Convalescent sera, rich in pathogen-specific antibodies, offers passive immunity to patients with infectious diseases. Screening assays using convalescent sera are crucial for evaluating therapeutic efficacy, selecting suitable serum donors, and standardizing assays. They measure antibody levels, neutralizing potential, and specificity against viruses like SARS-CoV-2, ensuring therapeutic serum contains potent antibodies. Standardized procedures enable reliable results and wider adoption of serum therapy for COVID-19. We have developed a high-content image-based assay for screening convalescent sera against SARS-CoV-2 variants. Using various cell lines, we identified optimal candidates, employed immunofluorescence to visualize infected cells, and assessed neutralizing antibody efficacy. Screening convalescent sera for therapeutic potential identified neutralizing activity against SARS-CoV-2 variants. Dose-response analysis showed variable neutralizing activity, with some sera exhibiting broad neutralization. Additionally, we explored the synergy between neutralizing sera and β-d-N4-hydroxycytidine (NHC), an initial metabolite of molnupiravir. These assays enhance serum therapy's benefits for COVID-19 treatment and aid in understanding neutralizing activity against SARS-CoV-2 variants, addressing viral challenges.

To investigate watershed remediation within a Total Maximum Daily Load program, this study examined the field-scale filtration performance of two specialty absorbents. The goal was to simultaneously remove nutrients and biological pollutants along Canal 23 (C-23) in the St. Lucie River Basin, Florida. The filtration system installed in the C-23 river corridor was equipped with either clay-perlite with sand sorption media (CPS) or zero-valent iron and perlite green environmental media (ZIPGEM). Both media were formulated with varying combinations of sand, clay, perlite, and/or recycled iron based on distinct recipes. In comparison with CPS, ZIPGEM exhibited higher average removal percentages for nutrients. Findings indicated that ZIPGEM could remove total nitrogen up to 49.3%, total Kjeldahl nitrogen up to 67.1%, dissolved organic nitrogen (DON) up to 72.9%, total phosphorus up to 79.6%, and orthophosphate up to 73.2%. Both ZIPGEM and CPS demonstrated similar efficiency in eliminating biological pollutants, such as E. coli (both media exhibiting an 80% removal percentage) and chlorophyll a (both media achieving approximately 95% removal). Seasonality effects were also evident in nutrient removal efficiencies, particularly in the case of ammonia nitrogen; the negative removal efficiency of ammonia nitrogen from the fifth sampling event could be attributed to processes such as photochemical ammonification, microbial transformation, and mineralization of DON in wet seasons. Overall, ZIPGEM demonstrated a more stable nutrient removal efficiency than CPS in the phase of seasonal changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Although smallpox has been eradicated, other orthopoxviruses continue to be a public health concern as exemplified by the ongoing Mpox (formerly monkeypox) global outbreak. While medical countermeasures (MCMs) previously approved by the Food and Drug Administration for the treatment of smallpox have been adopted for Mpox, previously described vulnerabilities coupled with the questionable benefit of at least one of the therapeutics during the 2022 Mpox outbreak reinforce the need for identifying and developing other MCMs against orthopoxviruses. Here, we screened a panel of Merck proprietary small molecules and identified a novel nucleoside inhibitor with potent broad-spectrum antiviral activity against multiple orthopoxviruses. Efficacy testing of a 7-day dosing regimen of the orally administered nucleoside in a murine model of severe orthopoxvirus infection yielded a dose-dependent increase in survival. Treated animals had greatly reduced lesions in the lung and nasal cavity, particularly in the 10 µg/mL dosing group. Viral levels were also markedly lower in the UMM-766-treated animals. This work demonstrates that this nucleoside analog has anti-orthopoxvirus efficacy and can protect against severe disease in a murine orthopox model.IMPORTANCEThe recent monkeypox virus pandemic demonstrates that members of the orthopoxvirus, which also includes variola virus, which causes smallpox, remain a public health issue. While currently FDA-approved treatment options exist, risks that resistant strains of orthopoxviruses may arise are a great concern. Thus, continued exploration of anti-poxvirus treatments is warranted. Here, we developed a template for a high-throughput screening assay to identify anti-poxvirus small-molecule drugs. By screening available drug libraries, we identified a compound that inhibited orthopoxvirus replication in cell culture. We then showed that this drug can protect animals against severe disease. Our findings here support the use of existing drug libraries to identify orthopoxvirus-targeting drugs that may serve as human-safe products to thwart future outbreaks., Competing Interests: K.P.K., D.O., C.R.Q., J.P.T., and C.C. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Rahway, NJ, USA, and may own stock or hold stock options in Merck & Co. Inc., Rahway, NJ, USA.

Background and Objectives: Dysphagia and vocal cord palsy (VCP) are common otolaryngological complications after revision anterior cervical discectomy and fusion (rACDF) procedures. Our objective was to determine the early incidence and risk factors of VCP and dysphagia after rACDF using a 2-team approach., Methods: Single-institution, retrospective analysis of a prospectively collected database of patients undergoing rACDF was enrolled from September 2010 to July 2021. Of 222 patients enrolled, 109 patients were included in the final analysis. All patients had prior ACDF surgery with planned revision using a single otolaryngologist and single neurosurgeon. MD Anderson Dysphagia Inventory and fiberoptic endoscopic evaluation of swallowing (FEES) were used to assess dysphagia. VCP was assessed using videolaryngostroboscopy., Results: Seven patients (6.7%) developed new postoperative VCP after rACDF. Most cases of VCP resolved by 3 months postoperatively (mean time-to-resolution 79 ± 17.6 days). One patient maintained a permanent deficit. Forty-one patients (37.6%) reached minimum clinically important difference (MCID) in their MD Anderson Dysphagia Inventory composite scores at the 2-week follow-up (MCID decline of ≥6), indicating new clinically relevant swallowing disturbance. Forty-nine patients (45.0%) had functional FEES Performance Score decline. On univariate analysis, there was an association between new VCPs and the number of cervical levels treated at revision ( P = .020) with long-segment rACDF (≥4 levels) being an independent risk factor ( P = .010). On linear regression, there was an association between the number of levels treated previously and at revision for FEES Performance Score decline ( P = .045 and P = .002, respectively). However, on univariate analysis, sex, age, body mass index, operative time, alcohol use, smoking, and individual levels revised were not risk factors for reaching FEES Performance Score decline nor MCID at 2 weeks postoperatively., Conclusion: VCP is more likely to occur in long-segment rACDF but is often temporary. Clinically relevant and functional rates of dysphagia approach 37% and 45%, respectively, at 2 weeks postoperatively after rACDF., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Postoperative pseudomeningocele (PMC) and cerebrospinal fluid (CSF) leak are common complications following posterior fossa and posterolateral skull base surgeries. We sought to 1) determine the rate of CSF-related complications and 2) develop a perioperative model and risk score to identify the highest risk patients for these events., Methods: We performed a retrospective cohort of 450 patients undergoing posterior fossa and posterolateral skull base procedures from 2016 to 2020. Logistic regressions were performed for predictor selection for 3 prespecified models: 1) a priori variables, 2) predictors selected by large effect sizes, and 3) predictors with P ≤ 0.100 on univariable analysis. A final model was created by elimination of nonsignificant predictors, and the integer-based postoperative CSF-related complications (POCC) clinical risk score was derived. Internal validation was done using 10-fold cross-validation and bootstrapping with uniform shrinkage., Results: A total of 115 patients (25.6%) developed PMC and/or CSF leakage. Age >55 years (odds ratio [OR], 0.560; 95% confidence interval [CI], 0.328-0.954), body mass index >30 kg/m 2 (OR, 1.88; 95% CI, 1.14-3.10), and postoperative CSF diversion (OR, 2.85; 95% CI, 1.64-5.00) were associated with CSF leak and PMC. Model 2 was the most predictive (cross-validated area under the receiver operating characteristic curve, 0.690). The final risk score was devised using age, body mass index class, dural repair technique, use of bone substitute, and duration of postoperative CSF diversion. The POCC score performed well (cross-validated area under the receiver operating characteristic curve, 0.761) and was highly specific (96.1%)., Conclusions: We created the first generalizable and predictive risk score to identify patients at risk of CSF-related complications. The POCC score could improve surveillance, inform doctor-patient discussions regarding the risks of surgery, and assist in perioperative management., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: There remains a paucity of literature examining the decision algorithm for use of nasoseptal flap (NSF) after endoscopic endonasal approaches (EEA) to pituitary adenoma resection. In 2018, we published the first ever flap risk score (FRS) to predict the use of NSF. We present here a validity study examining the FRS as applied to our center., Methods: A retrospective review was completed of consecutive patients undergoing EEA from January 2015 to March 2021. The sensitivity, specificity, and predictive value of the FRS were calculated. A multivariate logistic model was used to determine the relative weight imaging characteristics in predicting need for NSF. The relative weighting of the FRS was then re-optimized., Results: A total of 376 patients underwent EEA for pituitary adenoma resection, with 113 (30.1%) requiring NSF. The FRS had a sensitivity and specificity of 43.4% and 94.7%, respectively. Sphenoid sinus extension increased the odds of needing a NSF equivalent to 19 mm of tumor height, as opposed to 6 mm in the original 2018 cohort. The re-optimized model had sensitivity and specificity of 79.6% and 76.4%, respectively., Conclusion: We present a validity study examining the utility of FRS in predicting the use of NSF after EEA for pituitary adenoma resection. Our results show that while FRS is still predictive of the need for NSF after EEA, it is not as predictive now as it was for its original cohort. Therefore, a more comprehensive model is necessary to more accurately stratify patients' preoperative risk for NSF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: The COVID-19 pandemic has had a severe impact on the Latin American subcontinent, particularly in areas with limited hospital resources and a restricted Intensive Care Unit (ICU) capacity. This study aimed to provide a comprehensive description of the clinical characteristics, outcomes, and factors associated with survival of COVID-19 hospitalized patients in Honduras., Research Question: What were the characteristics and outcomes of COVID-19 patients in a large referral center in Honduras?, Study Design and Methods: This study employed a retrospective cohort design conducted in a single center in San Pedro Sula, Honduras, between October 2020 to March 2021. All hospitalized cases of confirmed COVID-19 during this timeframe were included in the analysis. Univariable and multivariable survival analysis were performed using Kaplan-Meier curves and Cox proportional hazards model aiming to identify factors associated with decreased 30 day in-hospital survival, using a priori-selected factors., Results: A total of 929 confirmed cases were identified in this cohort, with males accounting for 55.4 % of cases. The case fatality rate among the hospitalized patients was found to be 50.1 % corresponding to 466 deaths. Patients with comorbidities such as hypertension, diabetes, obesity, chronic kidney disease, chronic obstructive pulmonary disease and cardiovascular disease had a higher likelihood of mortality. Additionally, non-survivors had a significantly longer time from illness onset to hospital admission compared to survivors (8.2 days vs 4.7 days). Among the cohort, 306 patients (32.9 %) met criteria for ICU admission. However, due to limited capacity, only 60 patients (19·6 %) were admitted to the ICU. Importantly, patients that were unable to receive level-appropriate care had lower likelihood of survival compared to those who received level-appropriate care (hazard ratio: 1.84)., Interpretation: This study represents, the largest investigation of in-hospital COVID-19 cases in Honduras and Central America. The findings highlight a substantial case fatality rate among hospitalized patients. In this study, patients who couldn't receive level-appropriate care (ICU admission) had a significantly lower likelihood of survival when compared to those who did. These results underscore the significant impact of healthcare access during the pandemic, particularly in low- and middle-income countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Objectives: To evaluate and describe neurosurgery applicant perceptions of the postinterview communication (PIC) process during the US residency match., Methods: A voluntary and anonymous postmatch web-based survey was developed and sent to 209 candidates who applied to 1 academic neurosurgery practice during the 2022-2023 recruitment cycle, approximately 1 week following match day. Survey questions focused on their perceptions of and participation behaviors with PIC and how this impacted their final rank list., Results: Seventy-eight (37.3%) of the 209 candidates responded to the survey. Sixty-four (84.2%) respondents reported submitting a letter of intent (LOI) to their number 1 ranked program. Sixty-one (82%) felt pressured to send a LOI to improve their rank status, fearing that it may harm them if they did not. Fifty-four (73.0%) respondents felt pressured to send an early LOI despite not seeing the program in person to communicate interest before programs certified their rank lists. Fourteen (18.9%) respondents agreed that a second look experience impacted their rank list enough to where they regretted an early LOI. Fifty-five (76.4%) respondents disagreed that second-look attendance had no impact on their rank status with a program. Fifty (71.4%) respondents agreed that PIC causes undue stress during the match process. Sixty-one (84.7%) respondents agreed that aspects of PIC require universal guidelines., Conclusions: This is the first study to describe the perceptions of PIC and behaviors of neurosurgery applicants during the US residency match process. Standardized PIC practices may help to ensure transparency and relieve stress for applicants during the match process., (Published by Elsevier Inc.)

Background and Objectives: Endovascular thrombectomy has previously been reserved for patients with small to medium acute ischemic strokes. Three recent randomized control trials have demonstrated functional benefit and risk profiles for thrombectomy in large-volume ischemic strokes. The primary objective of the meta-analysis was to determine the combined benefit of endovascular thrombectomy in patients with large-volume ischemic strokes and to determine the risk of adverse events after treatment., Methods: We systematically searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Scopus, the Cochrane Central Register, and Google Scholar for randomized trials published between January 1, 2010, and February 19, 2023. We included trials specifically comparing endovascular thrombectomy with medical therapy in adults with acute ischemic stroke with large-volume infarctions (defined by Alberta Stroke Program Early Computed Tomography Score 3-5 or a calculated infarct volume of >50 mL). Data were extracted based on prespecified variables on study methods and design, participant characteristics, analysis approach, and efficacy/safety outcomes. Results were combined using a restricted maximum-likelihood estimation random-effects model. Studies were assessed for potential bias and quality of evidence. The primary outcome was an overall ordinal shift across modified Rankin scale scores toward a better outcome at 90 days after either treatment arm., Results: Three thousand forty-four studies were screened, and 29 underwent full-text review. Three randomized trials (N = 1011) were included in the analysis. The pooled random-effects model for the primary outcome favored endovascular thrombectomy over medical management, with a generalized odds ratio of 1.55 (95% CI 1.25-1.91, I 2 = 42.84%). There was a trend toward increased risk of symptomatic intracranial hemorrhage in the thrombectomy group, with a relative risk of 1.85 (95% CI 0.94-3.63, I 2 = 0.00%)., Conclusion: In patients with large-volume ischemic strokes, endovascular thrombectomy has a clear functional benefit and does not confer increased risk of significant complications compared with medical management alone., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Glioblastoma (GBM) is the most common malignant primary brain tumor. Emerging reports have suggested that racial and socioeconomic disparities influence the outcomes of patients with GBM. No studies to date have investigated these disparities controlling for isocitrate dehydrogenase (IDH) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) status., Methods: Adult patients with GBM were retrospectively reviewed at a single institution from 2008 to 2019. Univariable and multivariable complete survival analyses were performed. A Cox proportional hazards model was used to assess the effect of race and socioeconomic status controlling for a priori selected variables with known relevance to survival., Results: In total, 995 patients met inclusion criteria. Of these, 117 patients (11.7%) were African American (AA). The median overall survival for the entire cohort was 14.23 months. In the multivariable model, AA patients had better survival compared with White patients (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.2-0.69). The observed survival difference was significant in both a complete case analysis model and a multiple imputations model accounting for missing molecular data and controlling for treatment and socioeconomic status. AA patients with low income (HR, 2.17; 95% CI, 1.04-4.50), public insurance (HR, 2.25; 95% CI, 1.04-4.87), or no insurance (HR, 15.63; 95% CI, 2.72-89.67) had worse survival compared with White patients with low income, public insurance, or no insurance, respectively., Conclusions: Significant racial and socioeconomic disparities were identified after controlling for treatment, GBM genetic profile, and other variables associated with survival. Overall, AA patients demonstrated better survival. These findings may suggest the possibility of a protective genetic advantage in AA patients., Plain Language Summary: To best personalize treatment for and understand the causes of glioblastoma, racial and socioeconomic influences must be examined. The authors report their experience at the O'Neal Comprehensive Cancer Center in the deep south. In this report, contemporary molecular diagnostic data are included. The authors conclude that there are significant racial and socioeconomic disparities that influence glioblastoma outcome and that African American patients do better., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objective: The optimal extent of resection of craniopharyngiomas to minimize the long-term risks of hypothalamic and endocrine dysfunction (obesity and panhypopituitarism) in children remains uncertain. The purpose of this study was to report long-term outcomes of pediatric patients with craniopharyngioma undergoing surgical treatment and to study rates of endocrinological and hypothalamic dysfunction in association with extent of resection., Methods: This retrospective study was performed in a cohort of children who underwent resection for craniopharyngioma at Children's of Alabama between 1990 and 2020. The primary outcome was hypothalamic dysfunction defined as a 0.5 increase in body mass index (BMI) Z-score and as a BMI > 2 SDs with or without psychiatric disturbances. Univariable analysis was performed using ANOVA, Wilcoxon rank-sum test, Pearson's chi-square test, and Fisher's exact test as appropriate. Missing data on the primary outcome were handled via multiple imputations. Relative risks were estimated using a multivariable generalized linear model with a priori variables selected using a modified Poisson regression approach with robust error variance to estimate risk ratios., Results: The cohort includes 39 patients (24 girls and 15 boys; age range 1 month-16 years) who underwent resection of craniopharyngioma at the authors' center between 1990 and 2020. The preoperative goal of treatment was cyst decompression (CD) in 5, subtotal resection (STR) in 13, and gross-total resection (GTR) in 21 patients. The median long-term follow-up after surgery was 8.11 years (average 8.21, range 0.4-24.33 years). Univariate analysis demonstrated a statistically significant increase in hypothalamic dysfunction in patients undergoing GTR when compared to those undergoing STR or CD at 1 month postoperatively (p = 0.006) and 6-11 months postoperatively (p = 0.010), but with this difference not persisting beyond 1 year. Multivariable analysis showed patients older than 10 years at time of surgery to be the most affected and at highest risk of developing significant hypothalamic dysfunction. There was no significant difference in pituitary or neurological function between the STR/CD and GTR groups at 12-24 months or at most recent follow-up. There was no significant difference in BMI Z-scores between the STR/CD and GTR groups at 6-12 months or at most recent follow-up., Conclusions: Both STR and GTR of craniopharyngioma were associated with significant endocrinological sequelae after 1 year. These potential complications should be discussed with patients and their families, and postoperative protocols should include early nutritional and endocrinological interventions with endocrinologist consultation.

Objective: Hemispherectomy is highly effective for patients with medically refractory epilepsy (MRE) arising from a single hemisphere. Recently, the Hemispherectomy Outcome Prediction Scale (HOPS) was developed as a prediction tool for seizure freedom after hemispherectomy. The authors' goal was to perform a validation study to determine the generalizability of the HOPS score., Methods: The authors present an observational, retrospective, 20-year, single-institution, two-surgeon experience using the lateral peri-insular hemispherectomy approach to validate the HOPS score. Variables used to derive the HOPS score included seizure onset age, semiology, PET hypometabolism, seizure substrate, and history of prior epilepsy resection. Multivariable logistic regression, multiple imputation, and Bayesian analyses were used to determine validity., Results: The authors' cohort comprised 60 patients; 55% of patients were male and 78% were Caucasian. The median age at first hemispherectomy surgery was 72 months. At 1 year postoperatively, 80% of patients had Engel class I outcomes, analogous to most contemporary series. All patients who experienced seizure recurrence after hemispherectomy did so within the first 2 years postoperatively. Sixteen (27%) and 10 (17%) patients had contralateral MRI findings and hypometabolism on PET, respectively. Both a multivariable logistic regression model using HOPS score variables (model p = 0.2588) and a revised model that included contralateral MRI findings (model p = 0.4715) were not statistically significant in this cohort. Bayesian analysis also did not validate the HOPS score., Conclusions: While seizure outcome prediction tools may be helpful for counseling patients about postoperative outcomes, rigorous validity and reliability testing are required. Prospective, standardized, and longitudinal evaluation of patients undergoing hemispherectomy are needed.

Introduction: Many pediatric patients with malignant tumors continue to suffer poor outcomes. The current standard of care includes maximum safe surgical resection followed by chemotherapy and radiation which may be associated with considerable long-term morbidity. The emergence of oncolytic virotherapy (OVT) may provide an alternative or adjuvant treatment for pediatric oncology patients., Areas Covered: We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). For each virus, we discuss the mechanism of tumor-specific replication and cytotoxicity as well as key findings of preclinical and clinical studies., Expert Opinion: Substantial progress has been made in the past 10 years regarding the clinical use of OVT. From our review, OVT has favorable safety profiles compared to chemotherapy and radiation treatment. However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future.

Background: As the obesity epidemic grows, the number of morbidly obese patients undergoing anterior cervical discectomy and fusion (ACDF) continues to increase. Despite the association of obesity with perioperative complications in anterior cervical surgery, the impact of morbid obesity on ACDF complications remains controversial, and studies examining morbidly obese cohorts are limited., Methods: A single-institution, retrospective analysis of patients undergoing ACDF from September 2010 to February 2022 was performed. Demographic, intraoperative, and postoperative data were collected via review of the electronic medical record. Patients were categorized as nonobese (body mass index [BMI] <30), obese (BMI 30-39.9), or morbidly obese (BMI ≥40). Associations of BMI class with discharge disposition, length of surgery, and length of stay were assessed using multivariable logistic regression, multivariable linear regression, and negative binomial regression, respectively., Results: The study included 670 patients undergoing single-level or multilevel ACDF: 413 (61.6%) nonobese, 226 (33.7%) obese, and 31 (4.6%) morbidly obese patients. BMI class was associated with prior history of deep venous thrombosis (P < 0.01), pulmonary thromboembolism (P < 0.05), and diabetes mellitus (P < 0.001). In bivariate analysis, there was no significant association between BMI class and reoperation or readmission rates at 30, 60, or 365 days postoperatively. In multivariable analysis, greater BMI class was associated with increased length of surgery (P = 0.03), but not length of stay or discharge disposition., Conclusions: For patients undergoing ACDF, greater BMI class was associated with increased length of surgery, but not reoperation rate, readmission rate, length of stay, or discharge disposition., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The optimal surgical management of Chiari malformation type I (CM-I) remains controversial and heterogeneous. The authors sought to investigate patient-specific, technical, and perioperative features that may affect the incidence of CSF-related complications including pseudomeningocele and CSF leak at their institution., Methods: The authors performed a single-center, retrospective review of all adult patients with CM-I who underwent posterior fossa decompression. Patient demographics, operative details, and perioperative factors were collected via electronic medical record review. The authors performed Fisher's exact test and independent Student t-tests for categorical and continuous variables, respectively. Univariate regression analysis was performed to determine odds ratios. A multivariable regression analysis was performed for those factors with p < 0.10 or large effect sizes (OR ≥ 2.0 or ≤ 0.50) by univariate analysis. The STROBE guidelines for observational studies were followed., Results: A total of 59 adult patients were included. Most patients were female (78.0%), and the mean body mass index was 32.2 (± 9.0). Almost one-third (30.5%) of patients had a syrinx on preoperative imaging. All patients underwent expansile duraplasty, of which 47 (79.7%) were from autologous pericranium. Arachnoid opening for fourth ventricular inspection was performed in 26 (44.1%) cases. CSF-related complications were identified in 18 (30.5%) of cases. Thirteen (22.0%) patients required readmission and 11 (18.6%) required intervention such as wound revision (n = 5), wound revision with CSF diversion (n = 4), CSF diversion alone (n = 1), or blood patch (n = 1). Three (5.1%) patients required permanent CSF diversion. Male sex (OR 3.495), diabetes mellitus (OR 0.249), tobacco use (OR 2.53), body mass index more than 30 (OR 2.45), preoperative syrinx (OR 1.733), autologous duraplasty (OR 0.331), and postoperative steroids (OR 2.825) were included in the multivariable analysis. No factors achieved significance by univariate or multivariable analysis (all p > 0.05)., Conclusions: The authors report a single-center, retrospective experience of posterior fossa decompression for 59 adults with CM-I. No perioperative or technical features were found to affect the CSF-related complication rate. More standardized practices within centers are necessary to better delineate the true risk factors and potential protective factors against CSF-related complications.

Importance: Endovascular thrombectomy (ET) has previously been reserved for patients with small to medium acute ischemic strokes. Three recent randomized control trials (RCTs) have demonstrated functional benefit and risk profiles for ET in large volume ischemic strokes., Objective: The primary objective of the meta-analysis was to determine the combined benefit of ET in adult patients with large volume acute ischemic strokes and to better determine the risk of adverse events following ET., Data Sources: We systematically searched MEDLINE, EMBASE, SCOPUS, the Cochrane Central Register of Controlled, and Google Scholar for all RCTs published in English language between January 1, 2010, to February 19, 2023., Study Selection: We included only RCTs specifically comparing ET to medical therapy in patients with acute ischemic stroke with large volume infarctions as defined by Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 3-5 or calculated infarct volume of > 50-70mL. Two independent reviewers screened potential studies for full text review and metaanalysis inclusion with conflicts being resolved by consensus or third reviewer., Data Extraction and Synthesis: Data was extracted based on pre-specified variables on study methods and design, participant characteristics, analysis approach, as well as efficacy and safety outcomes. Results were combined using a restricted maximum-likelihood estimation random-effects model. Studies were assessed for potential bias and quality of evidence., Main Outcomes and Measures: The prespecified primary outcome was an overall ordinal shift across the range of modified Rankin scale scores toward a better outcome at 90 days following either ET or medical management for patients with large volume ischemic strokes., Results: A total of 3044 studies were screened, and 29 underwent full text review. 3 RCTs (1011 patients) were included in the analysis. The pooled random effects model for the primary outcome of mRS improvement favored ET over medical management, generalized odds ratio 1.55 [95% CI 1.25 - 1.91, T 2 = 0.01, I 2 = 42.84%]. There was a trend toward increased risk of symptomatic ICH in the ET group, relative risk 1.85 [95% CI 0.94 - 3.63, T 2 = 0.00, I 2 = 0.00%]., Conclusions and Relevance: In patients with large volume ischemic strokes, ET has a clear functional benefit and does not confer increased risk of significant complications compared to medical management alone.

Antibody-based therapy is emerging as a critical therapeutic countermeasure to treat acute viral infections by offering rapid protection against clinical disease. The advancements in structural biology made it feasible to rationalize monoclonal antibodies (mAbs) by identifying key and, possibly, neutralizing epitopes of viral proteins for therapeutic purposes. A critical component in assessing mAbs during pandemics requires the development of rapid but detailed methods to detect and quantitate the neutralization activity. In this study, we developed and optimized two high-content image (HCI)-based assays: one to detect viral proteins by staining and the second to quantify cytopathic viral effects by a label-free phenotypic assay. These assays were employed to screen for therapeutic antibodies against the monkeypox virus (MPXV) using surrogate poxviruses such as vaccinia virus (VACV). Plaque-based neutralization results confirmed the HCI data. The phenotypic assay found pox virus-induced syncytia formation in various cells, and we were able to quantitate and use this phenotype to screen mAbs. The HCI identified several potent VACV-neutralizing antibodies that showed in vitro efficacy against both clades of MPXV. In addition, a combination study of ST-246/tecovirimat/TPOXX a single neutralizing antibody Ab-40, showed synergistic activity against VACV in an in-vitro neutralization assay. This rapid high-content method utilizing state-of-the-art technologies enabled the evaluation of hundreds of mAbs quickly to identify several potent anti-MPXV neutralizing mAbs for further development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Food and Drug Administration (FDA) approval for vagus nerve stimulator (VNS) implantation is limited to patients older than 4 years of age with medically refractory partial-onset seizures. In younger children with severe generalized epilepsy, however, VNS implantation remains off-label. In this study, the authors followed up on their previously reported cohort to review the longer-term safety and efficacy of VNS placement in children younger than 6 years with generalized medically refractory epilepsy (MRE), providing the largest cohort with > 2 years of follow-up to date in this age group., Methods: This was a retrospective observational cohort study of patients younger than 6 years of age with generalized MRE who underwent VNS implantation at a single institution between 2010 and 2020. Inclusion criteria encompassed failure of more than two antiepileptic drugs alone or in combination, neurologist referral for vagus nerve stimulation, informed consent with knowledge of the off-label status in young children, and > 1 year of follow-up. Outcome measures included seizure reduction rate ≥ 50% and postoperative morbidity defined nominally. Statistical analysis was conducted with Stata/SE., Results: Forty-five patients were included: 11 patients younger than 4 years of age and 34 between 4 and 6 years of age. There were no intraoperative complications. Perioperative complications within 1 year occurred in 11% (n = 5) of the patients and included two wound infections, a mild cough, hyperactivity, hoarseness, and 1 patient with persistent surgical site pain. A seizure reduction ≥ 50% was observed in 36.4% (n = 4) of the patients younger than 4 years of age at the 6-month and 1-, 2-, and 5-year follow-ups. In the 4- to 6-year-old cohort, this was observed in 32.4% (n = 11) of the patients at 6 months, 41.2% (n = 14) at 1 year, 38.2% (n = 13) at 2 years, and 41.2% (n = 14) at 5 years., Conclusions: VNS implantation for patients younger than 4 years of age with generalized onset MRE has not been approved by the FDA. This retrospective study establishes feasibility, illustrates an acceptable safety profile in children younger than 6 years, and demonstrates efficacy comparable to that reported in older patients.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae., Summary: There is a substantial need for the development of new therapeutic approaches, and since the introduction of immunotherapy by immune checkpoint inhibitors, there has been an exponential increase in clinical trials to adopt these and other immunotherapy approaches in children with brain tumors. In this review, we summarize the current immunotherapy landscape for various pediatric brain tumor types including choroid plexus tumors, embryonal tumors (medulloblastoma, AT/RT, PNETs), ependymoma, germ cell tumors, gliomas, glioneuronal and neuronal tumors, and mesenchymal tumors. We discuss the latest clinical trials and noteworthy preclinical studies to treat these pediatric brain tumors using checkpoint inhibitors, cellular therapies (CAR-T, NK, T cell), oncolytic virotherapy, radioimmunotherapy, tumor vaccines, immunomodulators, and other targeted therapies., Key Messages: The current landscape for immunotherapy in pediatric brain tumors is still emerging, but results in certain tumors have been promising. In the age of targeted therapy, genetic tumor profiling, and many ongoing clinical trials, immunotherapy will likely become an increasingly effective tool in the neuro-oncologist armamentarium., (The Author(s). Published by S. Karger AG, Basel.)

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery., (© 2022 International League Against Epilepsy.)

Background: Neurosurgery (NS) is among the most selective specialties in the United States. As the United States Medical Licensing Examination (USMLE) Step 1 transitions to a binary pass/fail score, residency programs face unclear challenges in screening and evaluating applicants. The aim of this study is to provide insights into the perceived impact of changes to the USMLE Step 1 grading in the applicant selection process., Methods: We created a survey using questions regarding NS program demographics, the perceived predictive abilities of Step 1 and Step 2 clinical knowledge (CK), and several factors that programs consider when assessing applicants. We queried program directors (PDs), program coordinators (PCs), and assistant PDs at 117 NS residency programs. Respondents were asked to rank these factors in order of importance for selection at their respective training program. We used descriptive statistics and a Wilcoxon matched-pairs signed-rank test to evaluate the effects of these changes using STATA 17., Results: A total of 35 (30%) residency programs responded with 26 (74%) completing the factor ranking questions. 86% (95% confidence interval, 71.5%-94.3%) disagreed that the changes will better prepare students clinically. USMLE Step 2 CK scores, class rank, and away rotations saw significant increases in priority in the absence of a graded Step 1, whereas letters of recommendation and surrogates for research productivity saw notable, but not significant, changes after adjusting for multiple testing., Conclusions: Reporting binary Step 1 grades marks a significant shift in assessing applicants for NS residency by emphasizing Step 2 CK, class rank, and research productivity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The increasing needs of drinking water due to population growth requires seeking for new tap water sources. However, these large-scale tap water sources are oftentimes abundant with dissolved natural organic matter (NOM), such as tannic acid issue causing color in water. If not removed at the source locations beforehand, NOM would impact coagulation and flocculation unit, and/or become precursors to prompt the production of disinfectant by-products after chlorination in drinking water treatment. This study focuses on developing and testing a suite of cost-effective, scalable, adaptable, and sustainable sorption media that can be implemented near the source locations of tap water as a pretreatment option to remove color for a long-distance interbasin transfer. Within the five tested sorption media, a media recipe of Zero-valent-Iron and Perlite based Green Sorption Media (ZIPGEM) with ingredients of 85% sand, 5% clay, 6% zero-valent-iron (ZVI) and 4% perlite by volume stood out as the best option for color removal. Findings showed that ZIPGEM can maintain a color removal of ∼77% for about 14,080 min, maintaining the effluent concentration below 40 Pt-Co units given the influent condition of 175 ± 10 Pt-Co units. A recovery on the adsorption capacity of ZIPGEM was observed around 40,000 min due to synergetic effects among several different ingredients of recycled ZVI, clay, sand, and perlites. ZIPGEM can be applied to industrial wastewater treatment for dye removal as well., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This study investigated the removal of selected per- and polyfluoroalkyl substances (PFAS) from water via two green sorption media (IFGEM-7 and AGEM-2). Both selected green sorption media recipes contain sand (85-91%) and clay (3-4%), in addition to recycled iron (Fe) (5-7.5%) or aluminum (Al) (4.5% in AGEM-2 only). Batch and column studies were integrated and performed using the prescribed green sorption media recipes to determine their efficiencies in removing two most targeted PFAS, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). In the batch test, while the removal efficiencies of PFOS ranged from 27 to 46% and 23 to 42%, those for PFOA ranged from 6 to 16% and 5 to 18% when using IFGEM-7 and AGEM-2, respectively. The higher removal of PFOS than PFOA observed in both IFGEM-7 and AGEM-2 batch tests could be attributed to higher media affinity for sulfonate groups of PFOS when compared to the carboxylate groups of PFOA. In the column study, the initial removal (within 1 h) by IFGEM-7 was greater than 99% for PFOS and 28% for PFOA. When comparing different dynamic adsorption models, it appears that the non-linear equations could better describe the trend of experimental data compared to the linear forms of the Modified Dose Response model. Life expectancy calculations, performed for demonstration purposes of field applications, suggested that if IFGEM-7 were to be applied in a downflow filter box to treat a hypothetical volume of 60,000 L of water during an emergency response, and it may last for 1506 h (62.8 d) and 4.2 h for a target removal of 80% of PFOS and PFOA, respectively., Competing Interests: Declaration of competing interest The authors have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of the advances and current state of oncolytic virotherapy for the targeted treatment of GBM and malignant gliomas., Competing Interests: Disclosures Dr J.M. Markert holds equity (<8%) in Aettis, Inc. (a company that holds stocks of oncolytic virus); Treovir, Inc (25%), a company holding intellectual property and funding clinical trials of oncolytic virus for pediatric brain tumors. A company that Dr J.M. Markert formerly held equity in (<8%) Catherex, Inc., was purchased in a structured buyout. Dr J.M. Markert has served as a consultant for Imugene. He also holds a fraction of the IP associated with oncolytic virus C134, which is licensed by Mustang Biotech., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recycled materials were used in three types of green sorption media for nutrient removal and possible recovery in high nutrient-laden agricultural discharge and stormwater runoff. The three types of green sorption media included in this comparative study were two new aluminum-based green environmental media (AGEM) and one existing iron-filings based green environmental media (IFGEM). The corresponding adsorption isotherm, thermodynamics, and kinetics models were simulated based on isotherm studies to determine their removal efficiency and potential for recovery of nitrate, phosphate, and ammonia when used as a soil amendment in crop fields or in a filter for water treatment. AGEM-2 exhibited the shortest contact time required to achieve nutrient removal above 80% with an average of 7 h, followed by AGEM-1 and IFGEM with 10.6 and 28 h, respectively. Natural soil was included as a control and exhibited minimal nutrient removal. Ammonia, which may be recovered as fertilizer for drop fields in a soil-water-waste nexus, was generated by all three green sorption media mixes, therefore indicating their potential for use as soil amendments in agricultural and forested land after engineering filter applications. The kinetics analysis indicated that nitrate adsorption follows pseudo-first-order kinetics, while phosphate adsorption follows pseudo-second-order kinetics. The Gibbs free energy indicated that most of the adsorption reactions proceeded as exothermic. Lastly, a few equilibrium models, including the Langmuir, Freundlich, First Modified Langmuir, Temkin, Jovanovic, and Elovich models, were ranked and three were selected for use with IFGEM, AGEM-1, and AGEM-2, respectively, as below: (1) Langmuir, (2) Freundlich, and (3) First Modified Langmuir, according to three indices., Competing Interests: Declaration of competing interest The authors have no competing interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Nonpoint sources pollution from agricultural crop fields and urbanized regions oftentimes have elevated concentrations of dissolved organic nitrogen (DON) in stormwater runoff, which are difficult for microbial communities to decompose. The impact of elevated DON can be circumvented through the use of green sorption media, such as Biosorption Activated Media (BAM) and Iron-Filing Green Environmental Media (IFGEM), which, as integral parts of microbial ecology, can contribute to the decomposition of DON. To compare the fate, transport, and transformation of DON in green sorption media relative to natural soil (control), a series of fixed-bed columns, which contain natural soil, BAM, and two types of IFGEM, respectively, were constructed to compare nutrient removal efficiency under three distinct stormwater influent conditions containing nitrogen and phosphorus. The interactions among six microbial species, including ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, complete ammonia oxidation (comammox) bacteria, anaerobic ammonium oxidation (anammox) bacteria, dissimilatory nitrate reduction to ammonium bacteria, and iron-reducing bacteria, were further analyzed from microbial ecology perspectives to determine the DON impact on nutrient removal in BAM and IFGEM. Natural soil was only able to achieve adequate DON transformation at the influent condition of lower nutrient concentration. However, the two types of IFGEM showed satisfactory nutrient removals and achieved greater transformation of DON relative to BAM when treating stormwater in all three influent conditions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Removing excess nutrient from stormwater runoffs is necessary to protect the water quality of receiving water bodies such as rivers, lakes, springs, and groundwater aquifers. Silver Springs Springshed, located in the vicinity of Ocala, Florida, has received widespread attention from the local government and residents due to its long-term nutrient impact, which has resulted in eutrophication. Blanket filters containing Bio-sorption Activated Media (BAM) were implemented with different depths of the vadose zone in a stormwater retention basin. The design combined the interaction with groundwater as an innovative Best Management Practice can potentially boost the performance of nutrient removal. Selected storm runoffs were collected at multiple points that cover the runoff timeframe to determine the pollutant load. Infiltrating water samples were collected at various depths within BAM using lysimeters to validate the treatment effectiveness. Significant pollutant load reduction of nutrients was confirmed with highest 99% and 91% removal of nitrate and nitrite (NO x ) and total nitrogen (TN) at the deep blanket filter (with more groundwater intrusion impacts) due to more effective denitrification and longer contact time. Yet the highest pollutant load reduction of 93% and 84% removal of NO x and TN was also observed at the shallow blanket filter (with less groundwater intrusion impacts). On the other hand, better pollutant load reduction of ammonia in the BAM layer was found at the shallow blanket filter presumably due to more available oxygen for nitrification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

N-Glycanase 1 (NGLY1) deficiency is an ultra-rare, complex and devastating neuromuscular disease. Patients display multi-organ symptoms including developmental delays, movement disorders, seizures, constipation and lack of tear production. NGLY1 is a deglycosylating protein involved in the degradation of misfolded proteins retrotranslocated from the endoplasmic reticulum (ER). NGLY1-deficient cells have been reported to exhibit decreased deglycosylation activity and an increased sensitivity to proteasome inhibitors. We show that the loss of NGLY1 causes substantial changes in the RNA and protein landscape of K562 cells and results in downregulation of proteasomal subunits, consistent with its processing of the transcription factor NFE2L1. We employed the CMap database to predict compounds that can modulate NGLY1 activity. Utilizing our robust K562 screening system, we demonstrate that the compound NVP-BEZ235 (Dactosilib) promotes degradation of NGLY1-dependent substrates, concurrent with increased autophagic flux, suggesting that stimulating autophagy may assist in clearing aberrant substrates during NGLY1 deficiency., (Copyright © 2020 Mueller et al.)

In this study, a rapid infiltration basin (RIB) designed as green infrastructure for co-disposal of wastewater effluent and stormwater runoff was retrofitted for sustainable groundwater recharge after nitrogen removal. For comparison of nitrogen removal efficiency via different filtration media, the RIB was divided into two sub-basins for different filtration processes. One sub-basin was filled with a native sandy soil with about 2-4% clay (Control RIB), and the other sub-basin was modified with Biosorption Activated Media (BAM) (BAM RIB), for the enhancement of microbial nitrogen removal. The two sub-basins accept an equal amount of excess reclaimed wastewater in non-storm periods, and stormwater during periodic storm events. The infiltrate in both the BAM RIB and the Control RIB eventually reaches the Upper Floridan Aquifer. The seven microbial species involved in this microbial ecology study are nitrite oxidizing bacteria (NOB), ammonia oxidizing bacteria (AOB), anaerobic oxidation of ammonium (anammox) bacteria, complete ammonia oxidizer (Comammox) bacteria, denitrifiers, dissimilatory nitrate reduction to ammonium (DNRA) and ammonia-oxidizing archaea (AOA). The population dynamics study was conducted with the aid of the quantitative polymerase chain reaction (qPCR) for the quantification of the microbial gene population in support of microbial ecology discovery. The qPCR results demonstrated the competition effect between AOA, AOB, and Comammox, the inhibition effect between NOB and DNRA with the presence of anammox, and the complementary effect due to an abundance of NOB and AOB in the microbial ecology. Although, competition between denitrifiers and DNRA was expected to impact population dynamics, both microbial species were found to be the most predominant in both control and BAM RIBs. Research findings indicate that the use of BAM RIB achieves significantly efficient nitrogen removal driven by complementary effects in the microbial ecology., (Copyright © 2020 Elsevier Inc. All rights reserved.)

With a motto of "Be Worthy to Serve the Suffering," Alpha Omega Alpha Honor Medical Society (AΩA) supports the importance, inclusion, and development of a culturally and ethnically diverse medical profession with equitable access for all. The underrepresentation of minorities in medical schools and medicine continues to be a challenge for the medical profession, medical education, and AΩA. AΩA has worked, and continues to work, to ensure the development of diverse leaders, fostering within them the objectivity and equity to be inclusive servant leaders who understand and embrace diversity in all its forms.Inclusion of talented individuals from different backgrounds benefits patient care, population health, education, and scientific discovery. AΩA values an inclusive, diverse, fair, and equitable work and learning environment for all and supports the medical profession in its work to achieve a welcoming, inclusive environment in teaching, learning, caring for patients, and collaboration.The diversity of medical schools is changing and will continue to change. AΩA is committed to continuing to work with its members, medical school deans, and AΩA chapters to assure that AΩA elections are unbiased and based on the values of AΩA and the profession of medicine in service to patients and the profession.Progress toward diversity, inclusion, and equity is more than simply checking off a box or responding to criticism-it is about being and developing diverse excellent physicians. AΩA and all those in the medical profession must continue to guide medicine to be unbiased, open, accepting, inclusive, and culturally aware in order to "Be Worthy to Serve the Suffering."

Nutrient removal efficiency in green sorption media such as biosorption activated media (BAM) for treating stormwater runoff can be heavily influenced either on a short- or long-term basis by varying field conditions of linear ditches due to the presence of copper in stormwater runoff. It is also noticeable that the linear ditch undergoes physical or mechanical impacts from the traffic compaction, chemical impact of carbon sources from the nearby farmland, and biological impact from potential animal activities (such as gopher tortoises, moles, and ants). In the nitrogen cycle, two denitrification pathways, the dissimilatory nitrate reduction to ammonia and common denitrification, are deemed critical for such assessment. A fixed-bed column study was set up to mimic different linear ditch field conditions for BAM applications and measure the effect of short-and long-term copper addition on microbial dynamics given the varying decomposition of dissolved organic nitrogen (DON). The findings confirm that, as the denitrifiers (in the second pathway) were the dominant species, their population continued to grow and maintain small-sized cells for extracellular sequestration under long-term copper impact. Furthermore, the study indicated that the ammonia oxidizer comammox was found in higher quantities than ammonia oxidizing bacteria or archaea. An enormous amount of DON was released during this process to bind the copper ion and reduce its toxicity as the enzymatic cascade effect appeared. In addition, the long-term copper exposure posed salient inhibitory effects on the microbial community regardless of varying field conditions in BAM. Short-term copper toxicity exerted an important but varying role in the enzymatic cascade effect over different linear ditch field conditions in BAM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism., Methods: Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry., Results: Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core., Conclusions: Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.

Roadside drainage networks can result in changes to watershed hydrology and water quality. By acting as hydrological links between urban development, agricultural fields, and natural streams, roadside ditches may be modified by filling in some green sorption media to control nitrogen pollution. Biosorption activated media (BAM), one of the green sorption media, are composed of sand, tire crumb, and clay, which can remove nitrogen from stormwater and groundwater through integrated hydrological, chemophysical, and microbial processes. The fate and transport processes of interest are complicated by internal microbial processes including ammonification, nitrification, denitrification, and dissimilatory nitrate reduction to ammonium (DNRA), each of which is controlled by different microbial species in addition to some varying field conditions. In this study, BAM was tested in a suite of columns to address site-specific physical, chemical and biological concerns driven by in situ traffic compaction, carbon availability, and animal impact (such as gopher turtles, moles, and ants) all of which impose different impacts on nitrogen fate and transport processes that may be signified by changing dissolved organic nitrogen species (DONs). The traffic compaction condition resulted in the most suitable hydraulic retention time in the hydrological process, which is beneficial for the assimilation of DONs in a long-term carbon rich environment due to biofilm expansion. Denitrifiers were the most predominant microbial population and the microbial species of DNRA were the second most predominant one in all three field conditions. However, the relationship of denitrifiers and DNRA in BAM can be shifted from commensalism to competition or even inhibition after carbon addition in microbial ecology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Despite significant recent efforts applied toward the development of efficacious therapies for glioblastoma (GBM) through exploration of GBM's genome and transcriptome, curative therapeutic strategies remain highly elusive. As such, novel and effective therapeutics are urgently required. In this study, the authors sought to explore the kinomic landscape of GBM from a previously underutilized approach (i.e., spatial heterogeneity), followed by validation of Bruton's tyrosine kinase (BTK) targeting according to this stepwise kinomic-based novel approach., Methods: Twelve GBM tumor samples were obtained and characterized histopathologically from 2 patients with GBM. PamStation peptide-array analysis of these tissues was performed to measure the kinomic activity of each sample. The Ivy GBM database was then utilized to determine the intratumoral spatial localization of BTK activity by investigating the expression of BTK-related transcription factors (TFs) within tumors. Genetic inhibition of BTK family members through lentiviral short hairpin RNA (shRNA) knockdown was performed to determine their function in the core-like and edge-like GBM neurosphere models. Finally, the small-molecule inhibitor of BTK, ONO/GS-4059, which is currently under clinical investigation in nonbrain cancers, was applied for pharmacological inhibition of regionally specified newly established GBM edge and core neurosphere models., Results: Kinomic investigation identified two major subclusters of GBM tissues from both patients exhibiting distinct profiles of kinase activity. Comparatively, in these spatially defined subgroups, BTK was the centric kinase differentially expressed. According to the Ivy GBM database, BTK-related TFs were highly expressed in the tumor core, but not in edge counterparts. Short hairpin RNA-mediated gene silencing of BTK in previously established edge- and core-like GBM neurospheres demonstrated increased apoptotic activity with predominance of the sub-G1 phase of core-like neurospheres compared to edge-like neurospheres. Lastly, pharmacological inhibition of BTK by ONO/GS-4059 resulted in growth inhibition of regionally derived GBM core cells and, to a lesser extent, their edge counterparts., Conclusions: This study identifies significant heterogeneity in kinase activity both within and across distinct GBM tumors. The study findings indicate that BTK activity is elevated in the classically therapy-resistant GBM tumor core. Given these findings, targeting GBM's resistant core through BTK may potentially provide therapeutic benefit for patients with GBM.