Low-grade mucoepidermoid carcinoma mimicking benign cystic lesions in the salivary gland: A diagnostic dilemma.

Mucoepidermoid carcinoma (MEC) is a common malignancy arising in the parotid gland. The diagnosis of MEC is typically based on its morphological features alone, characteristically containing mucocytes, intermediate cells and epidermoid cells. However, when cystic degeneration is diffuse, it is challenging to distinguish MEC from other benign cystic tumors. This is a case report of a 58-year-old Caucasian man who presented with a parotid mass. H&E sections of the mass reveal multiloculated cysts lined by bland-looking epithelium with only rare papillary architectures. The papillary proliferation contains mucocytes, and epidermoid cells highlighted by the p63 immunohistochemistry study. The diagnosis was confirmed by FISH result of positive MAML2 (11q21) rearrangement. Patient underwent parotidectomy and is disease-free 6 months post-surgery. MEC with cystic degeneration is a common diagnostic pitfall which can mimic many benign lesions in the salivary gland. We present a rare case with MEC with extensive cystic change, its molecular and pathologic findings and review the diagnostic features of MEC, its benign mimickers and useful tools for distinguishing these entities.

Artificial intelligence-assisted full-mouth radiograph mounting in dental education.

OBJECTIVES: With the increasing prevalence of artificial intelligence (AI) and the significant research gap in the application of AI within dentistry, this study aimed to (1) evaluate the efficiency and accuracy of dental students in full-mouth radiograph series (FMS) mounting with and without AI assistance, and (2) assess dental students' perceptions of AI in clinical education to address the impact of AI in dental education. METHODS: An AI-based interface for mounting radiographs on FMS templates was designed and implemented in the study. Forty third-year dental students were randomly assigned to control and test groups. The control group manually mounted FMS radiographs, while the test group reviewed AI-pre-mounted radiographs for adjustments. Students' performance in efficiency and accuracy was evaluated. Pre- and post-study surveys were conducted to gauge students' confidence levels and opinions regarding the usefulness of the AI-assisted program. RESULTS: The test group (using AI) demonstrated significantly faster radiograph mounting times than the control group (manual) (p < 0.05). Accuracy was lower in the test groups, when comparing AI-assisted and manual mounting of FMS (p < 0.01). Self-confidence and confidence in AI were consistent between the control and test groups, both before and after the study. CONCLUSION: Students with AI presented with a decreased accuracy in FMS radiograph mounting. Therefore, AI automation could potentially have negative impacts in a learning environment with inexperienced clinicians.

Correlation between epidural space depth measured with ultrasound and MRI compared to clinical loss of resistance when performing lumbar epidural steroid injection.

BACKGROUND: This prospective study assessed the accuracy of MRI and ultrasound (US) measurements as a preprocedural assessment tool for predicting clinical loss of resistance depth (CLORD) during fluoroscopy-guided lumbar epidural steroid injections (ESIs). MATERIALS AND METHODS: Sixty patients enrolled received lumbar ESIs at an academic chronic pain clinic. The MRI measurement calculated the distance between the skin and the posterior epidural space, while US measurements included transverse and parasagittal oblique views of the interlaminar space. The epidural space measurements were compared with the CLORD during the performance of the prone epidural injections. The differences in measurements were analyzed using two one-sided tests for equivalency with a 0.5 equivalency margin. The intraclass correlation coefficients between CLORD and the imaging modalities were estimated using mixed effects models. RESULTS: MRI was equivalent to CLORD with a mean difference of -0.2 cm (95% CI -0.39 to -0.11). US transverse and US parasagittal oblique measurements were not equivalent to and underestimated CLORD with mean differences of -0.98 cm (90% CI -1.8 to -0.77) and -0.79 cm (90% CI -1.0 to -5.9), respectively. The intraclass correlation coefficients between MRI and CLORD were the highest at 0.85, compared with 0.65 and 0.73 for transverse and parasagittal oblique US views, respectively. CONCLUSIONS: MRI measurements are preferable over US for preprocedural assessment of patients receiving lumbar ESIs for predicting CLORD.

Region-Specific Homeostatic Identity of Astrocytes Is Essential for Defining Their Response to Pathological Insults.

The transformation of astrocytes into reactive states constitutes a biological response of the central nervous system under a variety of pathological insults. Astrocytes display diverse homeostatic identities that are developmentally predetermined and regionally specified. Upon transformation into reactive states associated with neurodegenerative diseases and other neurological disorders, astrocytes acquire diverse reactive phenotypes. However, it is not clear whether their reactive phenotypes are dictated by region-specific homeostatic identity or by the nature of an insult. To address this question, region-specific gene expression profiling was performed for four brain regions (cortex, hippocampus, thalamus, and hypothalamus) in mice using a custom NanoString panel consisting of selected sets of genes associated with astrocyte functions and their reactivity for five conditions: prion disease, traumatic brain injury, brain ischemia, 5XFAD Alzheimer's disease model and normal aging. Upon transformation into reactive states, genes that are predominantly associated with astrocytes were found to respond to insults in a region-specific manner. Regardless of the nature of the insult or the insult-specificity of astrocyte response, strong correlations between undirected GSA (gene set analysis) scores reporting on astrocyte reactivity and on their homeostatic functions were observed within each individual brain region. The insult-specific gene expression signatures did not separate well from each other and instead partially overlapped, forming continuums. The current study demonstrates that region-specific homeostatic identities of astrocytes are important for defining their response to pathological insults. Within region-specific populations, reactive astrocytes show continuums of gene expression signatures, partially overlapping between individual insults.

Peripheral calcifying odontogenic cyst: a case report and comprehensive review of 60 years of literature.

Peripheral Calcifying Odontogenic Cyst (PCOC) is the extraosseous form of calcifying odontogenic cyst that is limited to peripheral soft tissue without bony involvement. This case report presents a case of PCOC manifested as a progressive growth of gingival mass in a young male treated with excisional biopsy. Histological examination confirmed diagnosis of PCOC with presence of characteristic ghost cells and sporadic calcifications. No recurrence of the lesion and no complication were noted at three-year follow-up. Review of available literature on PCOC noted a predilection of occurrence in the mandible (61%) and in the anterior area of the jaws (58%). Mean age of patients was 41.7 ± SD25.43 (7-83) and 95% CI [33.6, 49.8] yrs. Mean size of the lesions was 1.38 ± SD1.1 (0.5-4.3) and 95% CI [0.93, 1.83] cm. Gender distribution was noted to be 51.3% male and 48.7% female.

Managing Menopausal Symptoms: Common Questions and Answers.

Menopausal symptoms are widespread and significantly impact quality of life. Common symptoms of menopause are vasomotor (i.e., hot flashes and night sweats) and genitourinary (e.g., vulvovaginal irritation and dryness, dyspareunia, urinary problems), although women may also experience changes in sexual function, mood, and sleep. Estrogen-containing hormone therapy is effective treatment for vasomotor symptoms. Nonhormonal medications for vasomotor symptoms include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and gabapentin. Selective serotonin reuptake inhibitors should not be administered to women taking tamoxifen. Cognitive behavior therapy and clinical hypnosis are effective for short-term reduction of vasomotor symptoms and associated sleep disturbances, but data are lacking to support the effectiveness of other nonpharmacologic treatments such as herbal or botanicalsupplements, exercise, and acupuncture. Hormone-free vaginal moisturizers are noninferior to estrogen-based therapies for treating genitourinary syndrome of menopause. Other treatment options for vaginal dryness and dyspareunia associated with menopause include ospemifene and intravaginal dehydroepiandrosterone. Management of menopausal symptoms should involve shared decision-making that is informed by the best available evidence and individual risks and preferences.

Changes in serum-neutralizing antibody potency and breadth post-SARS-CoV-2 mRNA vaccine boost.

A better understanding of the durability and breadth of serum-neutralizing antibody responses against multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants elicited by COVID-19 vaccines is crucial in addressing the current pandemic. In this study, we quantified the decay of serum neutralization antibodies (nAbs) after second and third doses of the original COVID-19 mRNA vaccine. Using an authentic virus-neutralization assay, we found that decay half-lives of WA1- and Delta-nAbs were both ∼60 days after second and third vaccine dose. Unexpectedly, the durability of serum antibodies that neutralize three different Omicron subvariants (BA.1.1, BA.5, BA.2.12.1) was substantially better, with half-lives of ≥6 months. A booster dose of the original COVID-19 vaccine was also found to broaden antibody responses against SARS-CoV and four other sarbecoviruses, in addition to multiple SARS-CoV-2 strains. These findings suggest that repeated vaccinations with the COVID-19 vaccine may confer a degree of protection against future spillover of sarbecoviruses from animal reservoirs.

polishCLR: A Nextflow Workflow for Polishing PacBio CLR Genome Assemblies.

Long-read sequencing has revolutionized genome assembly, yielding highly contiguous, chromosome-level contigs. However, assemblies from some third generation long read technologies, such as Pacific Biosciences (PacBio) continuous long reads (CLR), have a high error rate. Such errors can be corrected with short reads through a process called polishing. Although best practices for polishing non-model de novo genome assemblies were recently described by the Vertebrate Genome Project (VGP) Assembly community, there is a need for a publicly available, reproducible workflow that can be easily implemented and run on a conventional high performance computing environment. Here, we describe polishCLR (https://github.com/isugifNF/polishCLR), a reproducible Nextflow workflow that implements best practices for polishing assemblies made from CLR data. PolishCLR can be initiated from several input options that extend best practices to suboptimal cases. It also provides re-entry points throughout several key processes, including identifying duplicate haplotypes in purge_dups, allowing a break for scaffolding if data are available, and throughout multiple rounds of polishing and evaluation with Arrow and FreeBayes. PolishCLR is containerized and publicly available for the greater assembly community as a tool to complete assemblies from existing, error-prone long-read data.

Chromosome-scale genome assembly of the pink bollworm, Pectinophora gossypiella, a global pest of cotton.

The pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), is a major global pest of cotton. Current management practices include chemical insecticides, cultural strategies, sterile insect releases, and transgenic cotton producing crystalline (Cry) protein toxins of the bacterium Bacillus thuringiensis (Bt). These strategies have contributed to the eradication of P. gossypiella from the cotton-growing areas of the United States and northern Mexico. However, this pest has evolved resistance to Bt cotton in Asia, where it remains a critical pest, and the benefits of using transgenic Bt crops have been lost. A complete annotated reference genome is needed to improve global Bt resistance management of the pink bollworm. We generated the first chromosome-level genome assembly for pink bollworm from a Bt-susceptible laboratory strain (APHIS-S) using PacBio continuous long reads for contig generation, Illumina Hi-C for scaffolding, and Illumina whole-genome re-sequencing for error correction. The pseudo-haploid assembly consists of 29 autosomes and the Z sex chromosome. The assembly exceeds the minimum Earth BioGenome Project quality standards, has a low error rate, is highly contiguous at both the contig and scaffold levels (L/N50 of 18/8.26 MB and 14/16.44 MB, respectively), and is complete, with 98.6% of lepidopteran single-copy orthologs represented without duplication. The genome was annotated with 50% repeat content and 14,107 protein-coding genes, further assigned to 41,666 functional annotations. This assembly represents the first publicly available complete annotated genome of pink bollworm and will serve as the foundation for advancing molecular genetics of this important pest species.

Analysis of perceptual errors in skull-base pathology.

PURPOSE: Medical errors result in significant mortality and morbidity. The purpose of this study is to analyze skull-base errors at a single tertiary institution, identify common anatomic sites of errors, and offer strategies to reduce errors in this region. METHODS: A Neuroradiology Quality Assurance Database of radiologic errors was searched for attending physician computer tomography and magnetic resonance imaging errors in skull-base pathology from 2014 to 2020. Data were limited to CT and MRI reports. Errors were separated into four subcategories (tumor, trauma, vascular, and congenital) and further divided by relevant anatomic site. RESULTS: A total of 90 skull-based errors were identified. Most errors were perceptual (87%), with common study types including MRI Brain (39%) and CT Head (24%). Most common errors were tumors (55%), followed by trauma (24%), vascular (10%), and congenital (7%). Six anatomic sites were identified and encompassed over half of errors (58%): sella, occipital bone, cerebellopontine angle/internal auditory canal (CPA/IAC), foramen magnum and clivus, cavernous sinus, and dural venous sinus. SUMMARY: Most of the skull-base errors were perceptual. Placing a strong emphasis on both the pathology and closely examining its critical anatomic site (sella, occipital bone, CPA/IAC, foramen magnum and clivus, cavernous sinus, and dural venous sinus) could potentially reduce up to 60% of errors in these regions.

A Chromosome-Scale Genome Assembly of a Helicoverpa zea Strain Resistant to Bacillus thuringiensis Cry1Ac Insecticidal Protein.

Helicoverpa zea (Lepidoptera: Noctuidae) is an insect pest of major cultivated crops in North and South America. The species has adapted to different host plants and developed resistance to several insecticidal agents, including Bacillus thuringiensis (Bt) insecticidal proteins in transgenic cotton and maize. Helicoverpa zea populations persist year-round in tropical and subtropical regions, but seasonal migrations into temperate zones increase the geographic range of associated crop damage. To better understand the genetic basis of these physiological and ecological characteristics, we generated a high-quality chromosome-level assembly for a single H. zea male from Bt-resistant strain, HzStark_Cry1AcR. Hi-C data were used to scaffold an initial 375.2 Mb contig assembly into 30 autosomes and the Z sex chromosome (scaffold N50 = 12.8 Mb and L50 = 14). The scaffolded assembly was error-corrected with a novel pipeline, polishCLR. The mitochondrial genome was assembled through an improved pipeline and annotated. Assessment of this genome assembly indicated 98.8% of the Lepidopteran Benchmark Universal Single-Copy Ortholog set were complete (98.5% as complete single copy). Repetitive elements comprised approximately 29.5% of the assembly with the plurality (11.2%) classified as retroelements. This chromosome-scale reference assembly for H. zea, ilHelZeax1.1, will facilitate future research to evaluate and enhance sustainable crop production practices.

Prevention of Neisseria gonorrhoeae With Meningococcal B Vaccine: A Matched Cohort Study in Southern California.

BACKGROUND: Neisseria gonorrhoeae is acquiring increasing resistance to available oral antibiotics, and current screening and treatment approaches have not decreased gonorrhea incidence. Although a gonorrhea-specific vaccine does not exist, N. gonorrhoeae shares much of its genome with Neisseria meningitidis, notably critical antigenic determinants including outer membrane vesicles (OMV). Prior observational studies have suggested that OMV-based meningococcal serogroup B vaccines confer protection against gonorrhea. METHODS: We conducted a matched cohort study from 2016 to 2020 to examine the association of OMV-containing recombinant meningococcal serogroup B vaccine (4CMenB) with gonorrhea infection among teens and young adults at Kaiser Permanente Southern California. Recipients of 4CMenB were matched in a ratio of 1:4 to recipients of non-OMV-containing polysaccharide-conjugate vaccine targeting serotypes A, C, W, and Y (MenACWY) who had not received 4CMenB and were followed for incident gonorrhea. We used Cox proportional hazards regression to compare gonorrhea rates among recipients of 4CMenB vs MenACWY, adjusting for potential confounders. We conducted the same analysis with chlamydia as a negative control outcome. RESULTS: The study included 6641 recipients of 4CMenB matched to 26 471 recipients of MenACWY. During follow-up, gonorrhea incidence rates per 1000 person-years (95% confidence intervals [CIs]) were 2.0 (1.3-2.8) for recipients of 4CMenB and 5.2 (4.6-5.8) for recipients of MenACWY. In adjusted analyses, gonorrhea rates were 46% lower among recipients of 4CMenB vs MenACWY (hazard ratio [HR], 0.54; 95% CI, .34-.86), but chlamydia rates were similar between vaccine groups (HR, 0.98; 95% CI, .82-1.17). CONCLUSIONS: These results suggest cross-protection of 4CMenB against gonorrhea, supporting the potential for vaccination strategies to prevent gonorrhea.

Deficiency in ST6GAL1, one of the two α2,6-sialyltransferases, has only a minor effect on the pathogenesis of prion disease.

Prion diseases are a group of fatal neurodegenerative diseases caused by misfolding of the normal cellular form of the prion protein or PrPC, into a disease-associated self-replicating state or PrPSc. PrPC and PrPSc are posttranslationally modified with N-linked glycans, in which the terminal positions occupied by sialic acids residues are attached to galactose predominantly via α2-6 linkages. The sialylation status of PrPSc is an important determinant of prion disease pathogenesis, as it dictates the rate of prion replication and controls the fate of prions in an organism. The current study tests whether a knockout of ST6Gal1, one of the two mammalian sialyltransferases that catalyze the sialylation of glycans via α2-6 linkages, reduces the sialylation status of PrPSc and alters prion disease pathogenesis. We found that a global knockout of ST6Gal1 in mice significantly reduces the α2-6 sialylation of the brain parenchyma, as determined by staining with Sambucus Nigra agglutinin. However, the sialylation of PrPSc remained stable and the incubation time to disease increased only modestly in ST6Gal1 knockout mice (ST6Gal1-KO). A lack of significant changes in the PrPSc sialylation status and prion pathogenesis is attributed to the redundancy in sialylation and, in particular, the plausible involvement of a second member of the sialyltransferase family that sialylate via α2-6 linkages, ST6Gal2.

Skull base infections, their complications, and management.

OBJECTIVE: Our review aims to summarize the current literature on skull base infections (SBIs) and retrospectively analyze any such cases encountered at our institution. DESIGN: A literature search was conducted using online databases PubMed, MEDLINE, and ResearchGate with the terms "skull base osteomyelitis," "temporal bone osteomyelitis," "skull base infections," "necrotizing otitis media," and "SBO". References from the resulting manuscripts were reviewed for relevant articles. A search of our electronic health records using the same key terms was also performed to identify patients with a tissue biopsy-confirmed diagnosis of skull base infections. Patients with an indeterminate diagnosis or inaccessible/poor imaging were excluded. SETTING: A level one trauma and major tertiary academic medical center. PARTICIPANTS: All patients treated at the University of California Davis Health System with a confirmed diagnosis of skull base infections from January 2005 to November 2020. MAIN OUTCOME MEASURES: Imaging results, symptoms, treatment, morbidity, and mortality. RESULTS: Our literature search yielded 59 articles ranging from 1982 to 2021. A retrospective search of our electronic health records identified two cases of skull base infections. CONCLUSION: Skull base infections have no pathognomonic findings. A multimodal approach with computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine is necessary to characterize the disease process in addition to a biopsy for definitive diagnosis. Other diagnoses can mimic SBI on imaging, such as nasopharyngeal carcinoma and inflammatory pseudotumor. Culture-guided antimicrobial treatment and surgery are mainstay therapies. Other adjuvant strategies currently lack the robust evidence necessary to characterize their risks and benefits.

Antigenic Characterization and Pandemic Risk Assessment of North American H1 Influenza A Viruses Circulating in Swine.

The first pandemic of the 21st century was caused by an H1N1 influenza A virus (IAV) introduced from pigs into humans, highlighting the importance of swine as reservoirs for pandemic viruses. Two major lineages of swine H1 circulate in North America: the 1A classical swine lineage (including that of the 2009 H1N1 pandemic) and the 1B human seasonal-like lineage. Here, we investigated the evolution of these H1 IAV lineages in North American swine and their potential pandemic risk. We assessed the antigenic distance between the HA of representative swine H1 and human seasonal vaccine strains (1978 to 2015) in hemagglutination inhibition (HI) assays using a panel of monovalent antisera raised in pigs. Antigenic cross-reactivity varied by strain but was associated with genetic distance. Generally, the swine 1A lineage viruses that seeded the 2009 H1 pandemic were antigenically most similar to the H1 pandemic vaccine strains, with the exception of viruses in the genetic clade 1A.1.1.3, which had a two-amino acid deletion mutation near the receptor-binding site, which dramatically reduced antibody recognition. The swine 1B lineage strains, which arose from previously circulating (pre-2009 pandemic) human seasonal viruses, were more antigenically similar to pre-2009 human seasonal H1 vaccine viruses than post-2009 strains. Human population immunity was measured by cross-reactivity in HI assays to representative swine H1 strains. There was a broad range of titers against each swine strain that was not associated with age, sex, or location. However, there was almost no cross-reactivity in human sera to the 1A.1.1.3 and 1B.2.1 genetic clades of swine viruses, and the 1A.1.1.3 and 1B.2.1 clades were also the most antigenically distant to the human vaccine strains. Our data demonstrate that the antigenic distances of representative swine strains from human vaccine strains represent an important part of the rational assessment of swine IAV for zoonotic risk research and pandemic preparedness prioritization. IMPORTANCE Human H1 influenza A viruses (IAV) spread to pigs in North America, resulting in a sustained circulation of two major groups of H1 viruses in swine. We quantified the genetic diversity of H1 in swine and measured antigenic phenotypes. We demonstrated that the swine H1 lineages were significantly different from the human vaccine strains and that this antigenic dissimilarity increased over time as the viruses evolved in swine. Pandemic preparedness vaccine strains for human vaccines also demonstrated a loss in similarity with contemporary swine strains. Human sera revealed a range of responses to swine IAV, including two groups of viruses with little to no immunity. The surveillance and risk assessment of IAV diversity in pig populations are essential to detect strains with reduced immunity in humans and provide critical information for pandemic preparedness.

Comfort With Uncertainty in Medical Students and Their Residency Choice: A Residency Research Network of Texas Study.

BACKGROUND AND OBJECTIVES: Little is known about how comfort with uncertainty (CwU) influences career choice in medical students. The authors of this study examined the correlation between CwU and primary care career choice. METHODS: In academic years 2017-2018 and 2018-2019, the authors distributed surveys to third-year medical students from eight US medical schools, seven in Texas. The survey tool included two CwU scales and one comfort with ambiguity scale. Other questions covered career plans, family and personal background, and student debt. In the subjects' fourth year of medical school, authors obtained match data from the medical schools and the authors further communicated with the students where indicated. The primary outcome was the composite score of the three scales correlated to career choice, with a focus on primary care and family medicine. RESULTS: Among 642 participants, there was no difference in CwU scores between students who matched into primary care versus specialty fields (3.39 vs 3.37 average of three scales, P=.65, each individual scale NS) or family medicine (FM) vs all other fields (3.39 vs 3.37 average of three scales, P=.81). Other bivariate predictors of FM choice were more similar than different to previous studies, such as osteopathic more likely than allopathic, lower family income, planning to care for underserved populations, and had a primary care role model. Logistic regression found the two biggest predictors of FM were osteopathic training and the importance of educating patients about health promotion and disease prevention. CONCLUSIONS: We found no correlation between CwU and medical student career choice for primary care or FM. We discuss confounding factors that may impact results, as well as recommendations for medication education and public policy.

Change in physical activity, food choices and hemoglobin A1c among American Indians and Alaska Natives with type 2 diabetes.

The prevalence of diabetes among American Indian and Alaska Native (AI/AN) adults is the highest of all United States racial/ethnic groups. Health behaviors, including regular physical activity and healthy food choices, are important components in the management of diabetes. We estimated the cross-sectional association between physical activity and healthy food scores, separately, and combined (PAHF) with hemoglobin A1c (HbA1c) over three years of the Special Diabetes Program for Indians-Healthy Heart demonstration project (SDPI-HH) intervention. The relationship between physical activity and food choices was also examined. Among 3,039 SDPI-HH participants at baseline, those reporting being physically active and having high healthy food scores had statistically significant lower HbA1c (mean = 7.67 ± 2.01) compared to inactive participants with low healthy food scores (7.90 ± 1.92). Among the 1,150 SDPI-HH participants who attended the three-year follow-up visit, participants who increased physical activity, consumption of healthy foods, or both had a larger decrease in HbA1c (ß = -0.29, P = 0.03) over the study period compared to participants with no improvement in physical activity or increase in consuming healthy foods. This association was statistically significant among women (ß = -0.35, P = 0.04) but not among men (ß = -0.08, P = 0.70). Our findings indicated that an increase in healthier behaviors, including physical activity and healthy food choices, was associated with a small improvement in HbA1c in the subset of women who participated in the SDPI-HH through the three-year follow up. Although the decrease in HbA1c was small, physical activity and healthy food choices are important behaviors to incorporate into everyday life among AI/AN adults, particularly those with diabetes.