Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol.

Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Methods: Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Discussion: Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. Trial Registration: ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.

Chemoreactive 2,5-Diketopiperazines from a Penicillium sp., Structure Revision of Reported Analogues and Proposed Facile Transformation Pathways.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous cancer. Two new prenylated indole 2,5-diketopiperazine alkaloids, brevianamides E1 (1) and E2 (2), were isolated from a Penicillium fungus. Both compounds showed moderate cytotoxic activity against select MCC cell lines (i.e., MCC13, MKL-1, UISO, and WaGa) in the low micromolar range. The relative and absolute configurations of 1 and 2 were determined by combined approaches, including NOESY spectroscopy, DFT ECD and DP4 plus calculations, and Marfey's reaction. Literature research and the comparison of NMR and ECD data led to the structure revision of three previously reported natural analogues, notoamides K and P and asperversiamide L. The structurally unstable 1 and 2 underwent steady interconversion under neutral aqueous conditions. Investigation of the degradation of 2 in acidic methanol solutions led to the identification of a new methoxylated derivative (6) and two new ring-opened products (7 and 8) with the rearranged, elongated, 4-methylpent-3-ene side chain. The facile transformation of 2 to 7 and 8 was promoted by the intrinsic impurity (i.e., formaldehyde) of HPLC-grade methanol through the aza-Cope rearrangement.

The Effects of Vitamin D Supplementation During Pregnancy on Maternal, Neonatal, and Infant Health: A Systematic Review and Meta-analysis.

CONTEXT: Previous research linked vitamin D deficiency in pregnancy to adverse pregnancy outcomes. OBJECTIVE: Update a 2017 systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of vitamin D supplementation during pregnancy, identify sources of heterogeneity between trials, and describe evidence gaps precluding a clinical recommendation. DATA SOURCES: The MEDLINE, PubMed, Europe PMC, Scopus, Cochrane Database of Systematic Reviews, Web of Science, and CINAHL databases were searched. Articles were included that reported on RCTs that included pregnant women given vitamin D supplements as compared with placebo, no intervention, or active control (≤600 IU d-1). Risk ratios (RRs) and mean differences were pooled for 38 maternal, birth, and infant outcomes, using random effects models. Subgroup analyses examined effect heterogeneity. The Cochrane risk of bias tool was used. DATA EXTRACTION: Included articles reported on a total of 66 trials (n = 17 276 participants). DATA ANALYSIS: The median vitamin D supplementation dose was 2000 IU d-1 (range: 400-60 000); 37 trials used placebo. Antenatal vitamin D supplementation had no effect on the risk of preeclampsia (RR, 0.81 [95% CI, 0.43-1.53]; n = 6 trials and 1483 participants), potentially protected against gestational diabetes mellitus (RR, 0.65 [95% CI, 0.49-0.86; n = 12 trials and 1992 participants), and increased infant birth weight by 53 g (95% CI, 16-90; n = 40 trials and 9954 participants). No effect of vitamin D on the risk of preterm birth, small-for-gestational age, or low birth weight infants was found. A total of 25 trials had at least 1 domain at high risk of bias. CONCLUSION: Additional studies among the general pregnant population are not needed, given the many existing trials. Instead, high-quality RCTs among populations with low vitamin D status or at greater risk of key outcomes are needed. Benefits of supplementation in pregnancy remain uncertain because current evidence has high heterogeneity, including variation in study context, baseline and achieved end-line 25-hydroxyvitamin D level, and studies with high risk of bias. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022350057.

Biomimetic laser-induced graphene fern leaf and enzymatic biosensor for pesticide spray collection and monitoring.

Monitoring of pesticide concentration distribution across farm fields is crucial to ensure precise and efficient application while preventing overuse or untreated areas. Inspired by nature's wettability patterns, we developed a biomimetic fern leaf pesticide collection patch using laser-induced graphene (LIG) alongside an external electrochemical LIG biosensor. This "collect-and-sense" system allows for rapid pesticide spray monitoring in the farm field. The LIG is synthesized and patterned on polyimide through a high-throughput gantry-based CO2 laser process, making it amenable to scalable manufacturing. The resulting LIG-based leaf exhibits a remarkable water collection capacity, harvesting spray mist/fog at a rate approximately 11 times greater than a natural ostrich fern leaf when the collection is normalized to surface area. The developed three-electrode LIG pesticide biosensor, featuring a working electrode functionalized with electrodeposited platinum nanoparticles (PtNPs) and the enzyme glycine oxidase, displayed a linear range of 10-260 µM, a detection limit of 1.15 µM, and a sensitivity of 5.64 nA µM-1 for the widely used herbicide glyphosate. Also, a portable potentiostat with a user-friendly interface was developed for remote operation, achieving an accuracy of up to 97%, when compared to a standard commercial benchtop potentiostat. The LIG "collect-and-sense" system can consistently collect and monitor glyphosate spray after 24-48 hours of spraying, a time that corresponds to the restricted-entry interval required to enter most farm fields after pesticide spraying. Hence, this innovative "collect-and-sense" system not only advances precision agriculture by enabling monitoring and mapping of pesticide distribution but also holds the potential to significantly reduce environmental impact, enhance crop management practices, and contribute to the sustainable and efficient use of agrochemicals in modern agriculture.

A retrospective cohort study of genetic referral and diagnosis of Birt-Hogg-Dubé Syndrome in patients with Trichodiscoma and Fibrofolliculoma skin lesions.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a genetic condition caused by pathogenic variants in the FLCN gene resulting in benign skin lesions, spontaneous pneumothorax, and increased risk for a variety of renal tumors. Skin manifestations of BHD include trichodiscoma (TD) and fibrofolliculoma (FF), which may represent the same pathologic entity. These lesions can identify BHD patients, who upon positive genetic testing can be considered for life-long surveillance for renal neoplasms. OBJECTIVE: To characterize patients diagnosed with TD and FF including rates and outcomes of genetics referral. METHODS: Retrospective chart reviews of patients with confirmed or possible diagnosis of TD or FF at the University of Michigan from September 2002 through October 2020 to assess pathologic findings, personal and family history of BHD manifestations, referral for genetic evaluation, and genetic testing results. RESULTS: 64 patients had a pathologic diagnosis of TD or FF, 16 of whom (25%) were referred to cancer genetics. Fourteen patients completed genetic evaluation, 9 of whom were diagnosed with BHD (64%), with 6 unique pathogenic variants in FLCN. CONCLUSION: Providers should consider referral for genetic evaluation for patients with biopsy-proven TD or FF, as early diagnosis of BHD provides the opportunity for early detection and treatment of other BHD-associated conditions.

GAPS phase II: development and pilot results of the global assessment in pediatric surgery, an evidence-based pediatric surgical capacity assessment tool for low-resource settings.

PURPOSE: Pediatric surgical care in low- and middle-income countries is often hindered by systemic gaps in healthcare resources, infrastructure, training, and organization. This study aims to develop and validate the Global Assessment of Pediatric Surgery (GAPS) to appraise pediatric surgical capacity and discriminate between levels of care across diverse healthcare settings. METHODS: The GAPS Version 1 was constructed through a synthesis of existing assessment tools and expert panel consultation. The resultant GAPS Version 2 underwent international pilot testing. Construct validation categorized institutions into providing basic or advanced surgical care. GAPS was further refined to Version 3 to include only questions with a > 75% response rate and those that significantly discriminated between basic or advanced surgical settings. RESULTS: GAPS Version 1 included 139 items, which, after expert panel feedback, was expanded to 168 items in Version 2. Pilot testing, in 65 institutions, yielded a high response rate. Of the 168 questions in GAPS Version 2, 64 significantly discriminated between basic and advanced surgical care. The refined GAPS Version 3 tool comprises 64 questions on: human resources (9), material resources (39), outcomes (3), accessibility (3), and education (10). CONCLUSION: The GAPS Version 3 tool presents a validated instrument for evaluating pediatric surgical capabilities in low-resource settings.

Sex differences in the presentation and outcomes of patients with acute myocardial infarction complicated by cardiogenic shock: a critical review of contemporary data and a look towards future directions.

PURPOSE OF REVIEW: Cardiogenic shock (CS) is a devasting complicating of acute myocardial infarction (AMI), associated with significant mortality. Prior studies have reported sex differences in the presentation, management and outcomes of patients with AMI and CS. These differences are likely due to a variety of factors influencing therapeutic decision-making and impacting survival. This review highlights the more contemporary studies exploring differences in women and men with AMI-CS, providing a critical perspective towards understanding the factors that might lead to these differences and outlining potential opportunities to reduce disparities in treatment and improve survival for women with AMI-CS. RECENT FINDINGS: Recent reports demonstrate that women with AMI-CS are older than men and have more cardiovascular comorbidities. When examining an unselected population of patients with AMI-CS, women receive less aggressive treatment compared to men and have poorer outcomes. However, when examining a selected population of patients with AMI-CS treated with mechanical circulatory support (MCS) and/or admitted to centers that implement CS protocols to manage AMI-CS, these sex-based differences in outcomes are largely mitigated. SUMMARY: Standardizing protocols for the diagnosis and treatment of patients with AMI-CS, with an emphasis on early revascularization and appropriate invasive therapies, can improve outcomes in women and narrow the gender gap.

Comparison of Three Deep Learning Models in Accurate Classification of 770 Dermoscopy Skin Lesion Images.

Accurately determining and classifying different types of skin cancers is critical for early diagnosis. In this work, we propose a novel use of deep learning for classification of benign and malignant skin lesions using dermoscopy images. We obtained 770 de-identified dermoscopy images from the University of Missouri (MU) Healthcare. We created three unique image datasets that contained the original images and images obtained after applying a hair removal algorithm. We trained three popular deep learning models, namely, ResNet50, DenseNet121, and Inception-V3. We evaluated the accuracy and the area under the curve (AUC) receiver operating characteristic (ROC) for each model and dataset. DenseNet121 achieved the best accuracy (80.52%) and AUC ROC score (0.81) on the third dataset. For this dataset, the sensitivity and specificity were 0.80 and 0.81, respectively. We also present the SHAP (SHapley Additive exPlanations) values for the predictions made by different models to understand their interpretability.

Understanding family-level decision-making when seeking access to acute surgical care for children: Protocol for a cross-sectional mixed methods study.

BACKGROUND: There is limited understanding of how social determinants of health (SDOH) impact family decision-making when seeking surgical care for children. Our objectives of this study are to identify key family experiences that contribute to decision-making when accessing surgical care for children, to confirm if family experiences impact delays in care, and to describe differences in family experiences across populations (race, ethnicity, socioeconomic status, rurality). METHODS: We will use a prospective, cross-sectional, mixed methods design to examine family experiences during access to care for children with appendicitis. Participants will include 242 parents of consecutive children (0-17 years) with acute appendicitis over a 15-month period at two academic health systems in North Carolina and Virginia. We will collect demographic and clinical data. Parents will be administered the Adult Responses to Children's Symptoms survey (ARCS), the child and parental forms of the Adverse Childhood Experiences (ACE) survey, the Accountable Health Communities Health-Related Social Needs Screening Tool, and Single Item Literacy Screener. Parallel ARCS data will be collected from child participants (8-17 years). We will use nested concurrent, purposive sampling to select a subset of families for semi-structured interviews. Qualitative data will be analyzed using thematic analysis and integrated with quantitative data to identify emerging themes that inform a conceptual model of family-level decision-making during access to surgical care. Multivariate linear regression will be used to determine association between the appendicitis perforation rate and ARCS responses (primary outcome). Secondary outcomes include comparison of health literacy, ACEs, and SDOH, clinical outcomes, and family experiences across populations. DISCUSSION: We expect to identify key family experiences when accessing care for appendicitis which may impact outcomes and differ across populations. Increased understanding of how SDOH and family experiences influence family decision-making may inform novel strategies to mitigate surgical disparities in children.

Representation of aided AAC in contemporary young adult fiction.

The current study explored both the extent to which representation of augmentative and alternative communication (AAC) exists in young adult literature, as well as qualitative characteristics of that representation. A systematic search of multiple databases was conducted using standardized keywords and inclusion criteria. Descriptive statistics and literary content analysis were employed in order to analyze quantitative and qualitative information about each of the 32 novels that fit inclusion criteria. Results indicated that, while representation of AAC in young adult fiction largely aligned with existing statistics regarding types of AAC devices used, stories often differed from current information about the most common etiologies of AAC users. Analyses of character development revealed most featured AAC-using characters were multidimensional and expressed positive attitudes regarding their devices, although some characters also expressed frustration. These results indicated that representation of AAC in young adult literature was sparse. However, the representation that did exist at least partially reflected reality and may represent a positive portrayal of AAC use and users.

Impact of the COVID-19 pandemic on perinatal care and outcomes: A retrospective study in a tertiary hospital in Northern Ghana.

BACKGROUND: Perinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health. OBJECTIVES: Examine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana. METHODS: A hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH. RESULTS: A total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time. CONCLUSION: The COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.

Glucagon-like-peptide 1 receptor agonism and attempted suicide: A Mendelian randomisation study to assess a potential causal association.

Glucagon-like-peptide 1 receptor agonists (GLP-1RA) have transformed type 2 diabetes (T2D) and obesity management. Multiple regulatory agencies are investigating reported associations between GLP1-RA and increased suicide attempts (SA), but observational data may be prone to confounding. Randomised control trials (RCT) of GLP-1RA were largely undertaken in people at lower risk of SA. Real-world data suggest semaglutide use associates with reduced suicidal ideation and depression but was under-powered to statistically assess risk of SA. Mendelian randomisation (MR) leverages genetic instrument(s) to infer potential causal association between an exposure and an outcome. We undertook MR using missense variants in the gene encoding GLP1R that improve glycemia, lower T2D risk and/or lower BMI, to investigate potential causal association between GLP-1RA and SA. In people of European ancestry, MR did not find evidence genetically proxied GLP1RA increased SA in a general population cohort: (rs10305492, exposure: HbA1c, odds ratio [OR] and 95% confidence interval [CI]: 1.38, 0.41-4.62, p = .60), (rs10305492, exposure: FG, OR 1.27, 0.52-3.13, p = .60) and (rs1042044, exposure BMI, OR 0.30, 0.06-1.48) with concordant results in a multi-ancestry SA case-control cohort. In conclusion, we did not find MR evidence that increased GLP-1RA impacts SA. This awaits confirmation with RCT and real-world data.

Hyperexcitability and translational phenotypes in a preclinical mouse model of SYNGAP1-Related Intellectual Disability.

Disruption of SYNGAP1 directly causes a genetically identifiable neurodevelopmental disorder (NDD) called SYNGAP1-related intellectual disability (SRID). Without functional SynGAP1 protein, individuals are developmentally delayed and have prominent features of intellectual disability, motor impairments, and epilepsy. Over the past two decades, there have been numerous discoveries indicting the critical role of Syngap1. Several rodent models with a loss of Syngap1 have been engineered identifying precise roles in neuronal structure and function, as well as key biochemical pathways key for synapse integrity. Homozygous loss of SYNGAP1/Syngap1 is lethal. Heterozygous mutations of Syngap1 result in a broad range of behavioral phenotypes. Our in vivo functional data, using the original mouse model from the Huganir laboratory, corroborated behaviors including robust hyperactivity and deficits in learning and memory in young adults. Furthermore, we described impairments in the domain of sleep, characterized using neurophysiological data collected with wireless, telemetric electroencephalography (EEG). Syngap1+/- mice exhibited elevated spiking events and spike trains, in addition to elevated power, most notably in the delta power frequency. For the first time, we illustrated primary neurons from Syngap1+/- mice displayed increased network firing activity, greater bursts, and shorter inter-burst intervals between peaks by employing high density microelectrode arrays (HD-MEA). Our work bridges in-vitro electrophysiological neuronal activity and function with in vivo neurophysiological brain activity and function. These data elucidate quantitative, translational biomarkers in vivo and in vitro that can be utilized for the development and efficacy assessment of targeted treatments for SRID.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus. We also characterize immune responses elicited following administration of the phage cocktail. While minimal innate responses are observed after phage administration, two rounds of treatment induces phage-specific neutralizing antibodies and accelerate phage clearance from tissues. Interestingly, the myophages in our cocktail induce a more robust neutralizing antibody response than the siphophages. This anti-phage immunity reduces the effectiveness of the phage cocktail in our murine model. Collectively, this study shows phage-specific immune responses may be an important consideration in the development of phage cocktails for therapeutic use.

A Recipe for a Great Meal: A Benchtop Route from Elemental Se to Superior Thermoelectric ß-Ag2Se.

The low-temperature modification of ß-Ag2Se has proven to be useful as a near-room-temperature thermoelectric material. Over the past years, research has been devoted to interstitial, vacancy, and substitutional doping into the parent ß-Ag2Se structure, aiming at tuning the material's charge and heat transport properties to enhance thermoelectric performance. The transformation of ß-Ag2Se into α-Ag2Se at ∼134 °C and the low solubility of dopants are the main obstacles for the doping approach. Herein, we report a facile, safe, scalable, and cost-effective benchtop approach to successfully produce metal-doped ß-Ag2Se. The doped materials display a remarkable enhancement of thermoelectric performance with a record-high peak zT of 1.30 at 120 °C and an average zT of ∼1.15 in the 25-120 °C range for 0.2 at. % Zn-doped Ag2Se. The enhancement in zT is attributed to point defects created by Zn doping into Ag vacancies/interstitials, which enhances the scattering of phonons and tunes the charge carrier properties, leading to the significant suppression of thermal conductivity. The simplicity of the synthetic method developed herein and the high performance of the final products provide an avenue to produce high-quality Ag2Se-based thermoelectric materials.

Impact of the COVID-19 pandemic in childhood and adolescent cancer care in northern Tanzania: a cross-sectional study.

INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic has strained healthcare systems and presented unique challenges for children requiring cancer care, particularly in low- and middle-income countries. This study aimed to assess the impact of the COVID-19 pandemic on access to cancer care for children and adolescents in Northern Tanzania. METHODS: In this cross-sectional study, we assessed the demographic and clinical characteristics of 547 pediatric and adolescent cancer patients (ages 0-19 years old) between 2016 and 2022 using the population-based Kilimanjaro Cancer Registry (KCR). We categorized data into pre-COVID-19 (2016-2019) and COVID-19 (2020-2022) eras, and performed descriptive analyses of diagnostic, treatment, and demographic information. A secondary analysis was conducted on a subset of 167 patients with stage of diagnosis at presentation. RESULTS: Overall admissions nearly doubled during the pandemic (n = 190 versus 357). The variety of diagnoses attended at KCMC increased during the pandemic, with only five groups of diseases reported in 2016 to twelve groups of diseases in 2021. Most patients were diagnosed at a late stage (stage III or IV) across eras, with the proportion of under-five years old patients increasing late-diagnoses from 29.4% (before the pandemic), 52.8% (during the pandemic), when compared to the overall cohort. Around 95% of children in this age category reported late-stage diagnosis during the pandemic. Six out of the twelve cancer site groups also reported an increase in late-stage diagnosis. During the pandemic, the proportion of children receiving surgery increased from 15.8 to 30.8% (p < 0.001). CONCLUSION: Childhood and adolescent cancer care changed in Northern Tanzania during the COVID-19 pandemic, with increased late-stage diagnoses presentations among younger patients and the increased use of surgical therapies in the context of a growing practice. Understanding the impact of the COVID-19 pandemic on pediatric and adolescent cancer care can help us better adapt healthcare systems and interventions to the emerging needs of children and adolescents with cancer in the midst of a health crisis.

Late Paleozoic oxygenation of marine environments supported by dolomite U-Pb dating.

Understanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U-Pb geochronology, to reconstruct seawater U/Pb ratios. Dolomite samples consistently give U-Pb dates and initial 207Pb/206Pb ratios lower than expected from their stratigraphic ages. These observations are explained by resetting of the U-Pb system long after deposition; the magnitude of deviations from expected initial 207Pb/206Pb are a function of the redox-sensitive U/Pb ratios during deposition. Reconstructed initial U/Pb ratios increased notably in the late-Paleozoic, reflecting an increase in oxygenation of marine environments at that time. This timeline is consistent with documented shifts in some other redox proxies and supports evolution-driven mechanisms for the oxygenation of late-Paleozoic marine environments, as well as suggestions that early animals thrived in oceans that on long time scales were oxygen-limited compared to today.

Salivary Gland Tumors: A 20 Year Review From a Single Community Practice.

Objective: Salivary gland tumors are a heterogenous group of lesions with variable pathology and clinical outcomes. Most published data are derived from studies conducted at tertiary care centers. Our study analyzed the experience from a community setting to determine significant differences, if any, in pathological distribution and clinical outcomes compared to the existing literature. Methods: We performed a retrospective analysis of all major salivary gland tumors that presented to a large community practice over a 20 year period. Retrospective chart analysis was performed for demographics, clinical presentation, imaging, cytology, histopathology, and clinical outcome data. Results: Of 806 patients, the parotid gland was the most common site in 683 patients (84.7%), followed by submandibular in 78 (9.7%) and sublingual in 45 (5.6%). A total of 203 patients were managed conservatively with observation without definitive diagnosis or lost to follow-up. A total of 495 patients underwent surgical intervention within the community practice. Twenty-six patients underwent surgical excision at an outside hospital. Eighty-two patients were determined to have a benign diagnosis based on ultrasound-guided fine needle aspiration or excisional biopsy alone. Final histopathology was benign in 505 cases (83.7%), while 98 tumors (16.3%) received a diagnosis of primary or secondary malignancy. For the parotid gland, pleomorphic adenoma (155) and Warthin's tumor (155) were the most common benign diagnoses, while mucoepidermoid carcinoma (13), adenocarcinoma (8), and acinic cell carcinoma (8) were the most common primary malignancies. Conclusions: We found a higher rate of benign tumor pathology compared to the existing literature. While the outcome data on surgical treatment of benign tumors are comparable to the existing literature, the same conclusion cannot be drawn for malignant tumors, given relatively small numbers in our series and likely disparity in the complexity of the surgical cases in tertiary care centers.

Considering a Utility-Centric Framework Based on "Minimum Orthophosphate" Criteria for Mitigation of Elevated Cuprosolvency in Drinking Water.

Gaps in the United States Environmental Protection Agency (US EPA) Lead and Copper Rule (LCR) leave some consumers and their pets vulnerable to high cuprosolvency in drinking water. This study seeks to help proactive utilities who wish to mitigate cuprosolvency problems through the addition of orthophosphate corrosion inhibitors. The minimum doses of orthophosphate necessary to achieve acceptable cuprosolvency in relatively new copper pipe were estimated as a function of alkalinity via linear regressions for the 90th, 95th, and 100th percentile copper tube segments (R2 > 0.98, n = 4). Orthophosphate was very effective at reducing cuprosolvency in the short term but, in some cases, resulted in higher long-term copper concentrations than the corresponding condition without orthophosphate. Alternatives to predicting "long-term" results for copper tubes using simpler bench tests starting with fresh Cu(OH)2 solids showed promise but would require further vetting to overcome limitations such as maintaining water chemistry and orthophosphate residuals and to ensure comparability to results using copper tube.