Powassan Virus Encephalitis: A Tertiary Center Experience.

BACKGROUND: Powassan virus (POWV) is an emerging arthropod-borne flavivirus, transmitted by Ixodes spp. ticks, which has been associated with neuroinvasive disease and poor outcomes. METHODS: A retrospective study was conducted at Mayo Clinic from 2013 to 2022. We included clinical and epidemiologic data of probable and confirmed neuroinvasive POWV cases. RESULTS: Sixteen patients with neuroinvasive POWV were identified; their median age was 63.2 years, and 62.5% were male. Six patients presented with rhombencephalitis, 4 with isolated meningitis, 3 with meningoencephalitis, 2 with meningoencephalomyelitis, and 1 with opsoclonus myoclonus syndrome. A median time of 18 days was observed between symptom onset and diagnosis. Cerebrospinal fluid analysis showed lymphocytic pleocytosis with elevated protein and normal glucose in the majority of patients. Death occurred within 90 days in 3 patients (18.8%), and residual neurologic deficits were seen in 8 survivors (72.7%). CONCLUSIONS: To our knowledge, this is the largest case series of patients with neuroinvasive POWV infection. We highlight the importance of a high clinical suspicion among patients who live in or travel to high-risk areas during the spring to fall months. Our data show high morbidity and mortality rates among patients with neuroinvasive disease.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor ligands: version 1.0.

PURPOSE: To provide practice guideline/procedure standards for diagnostics and therapy (theranostics) of meningiomas using radiolabeled somatostatin receptor (SSTR) ligands. METHODS: This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neurooncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). RESULTS: Positron emission tomography (PET) using somatostatin receptor (SSTR) ligands can detect meningioma tissue with high sensitivity and specificity and may provide clinically relevant information beyond that obtained from structural magnetic resonance imaging (MRI) or computed tomography (CT) imaging alone. SSTR-directed PET imaging can be particularly useful for differential diagnosis, delineation of meningioma extent, detection of osseous involvement, and the differentiation between posttherapeutic scar tissue and tumour recurrence. Moreover, SSTR-peptide receptor radionuclide therapy (PRRT) is an emerging investigational treatment approach for meningioma. CONCLUSION: These practice guidelines will define procedure standards for the application of PET imaging in patients with meningiomas and related SSTR-targeted PRRTs in routine practice and clinical trials and will help to harmonize data acquisition and interpretation across centers, facilitate comparability of studies, and to collect larger databases. The current document provides additional information to the evidence-based recommendations from the PET/RANO Working Group regarding the utilization of PET imaging in meningiomas Galldiks (Neuro Oncol. 2017;19(12):1576-87). The information provided should be considered in the context of local conditions and regulations.

A Radiologist's Guide to the 2021 WHO Central Nervous System Tumor Classification: Part 2-Newly Described and Revised Tumor Types.

The fifth edition of the World Health Organization classification of tumors of the central nervous system (CNS), published in 2021, introduces major shifts in the classification of brain and spine tumors. These changes were necessitated by rapidly increasing knowledge of CNS tumor biology and therapies, much of which is based on molecular methods in tumor diagnosis. The growing complexity of CNS tumor genetics has required reorganization of tumor groups and acknowledgment of new tumor entities. For radiologists interpreting neuroimaging studies, proficiency with these updates is critical in providing excellent patient care. This review will focus on new or revised CNS tumor types and subtypes, beyond infiltrating glioma (described in part 1 of this series), with an emphasis on imaging features.

Change in Morphological Features of Enlarged Subarachnoid Spaces Following Treatment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Focally enlarged sulci (FES) are areas of proposed extraventricular fluid entrapment that may occur within idiopathic normal pressure hydrocephalus (iNPH) with radiographic evidence of disproportionately enlarged subarachnoid-space hydrocephalus (DESH), and should be differentiated from atrophy. PURPOSE: To evaluate for change in FES size and pituitary height after shunt placement in iNPH. STUDY TYPE: Retrospective. SUBJECTS: A total of 125 iNPH patients who underwent shunt surgery and 40 age-matched controls. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T. Axial T2w FLAIR, 3D T1w MPRAGE, 2D sagittal T1w. ASSESSMENT: FES were measured in three dimensions and volume was estimated by assuming an ellipsoid shape. Pituitary gland height was measured in the mid third of the gland in iNPH patients and controls. STATISTICAL TESTS: Wilcoxon signed-rank test for comparisons between MRI measurements; Wilcoxon rank sum test for comparison of cases/controls. Significance level was P < 0.05. RESULTS: Fifty percent of the patients had FES. FES volume significantly decreased between the pre and first postshunt MRI by a median of 303 mm3 or 30.0%. Pituitary gland size significantly increased by 0.48 mm or 14.4%. FES decreased significantly by 190 mm3 or 23.1% and pituitary gland size increased significantly by 0.25 mm or 6% between the first and last postshunt MRI. DATA CONCLUSION: Decrease in size of FES after shunt placement provides further evidence that these regions are due to disordered cerebrospinal fluid (CSF) dynamics and should not be misinterpreted as atrophy. A relatively smaller pituitary gland in iNPH patients that normalizes after shunt is a less-well recognized feature of altered CSF dynamics. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Spontaneous intracranial hypotension: updates from diagnosis to treatment.

Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leaks, which result in continued loss of CSF volume and multiple debilitating clinical manifestations. The estimated annual incidence of SIH is 5/100,000. Diagnostic methods have evolved in recent years due to improved understanding of pathophysiology and implementation of advanced myelographic techniques. Here, we synthesize recent updates and contextualize them in an algorithm for diagnosis and treatment of SIH, highlighting basic principles and points of practice variability or continued debate. This discussion includes finer points of SIH diagnosis, CSF leak classification systems, less common types and variants of CSF leaks, brain MRI Bern scoring, potential SIH complications, key technical considerations, and positioning strategies for different types of dynamic myelography. The roles of conservative measures, non-targeted or targeted blood patches, surgery, and recently developed endovascular techniques are presented.

The utility of PET for detecting corticotropinomas in Cushing disease: a scoping review.

While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.

A Radiologist's Guide to the 2021 WHO Central Nervous System Tumor Classification: Part I-Key Concepts and the Spectrum of Diffuse Gliomas.

The fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system, published in 2021, contains substantial updates in the classification of tumor types. Many of these changes are relevant to radiologists, including "big picture" changes to tumor diagnosis methods, nomenclature, and grading, which apply broadly to many or all central nervous system tumor types, as well as the addition, elimination, and renaming of multiple specific tumor types. Radiologists are integral in interpreting brain tumor imaging studies and have a considerable impact on patient care. Thus, radiologists must be aware of pertinent changes in the field. Staying updated with the most current guidelines allows radiologists to be informed and effective at multidisciplinary tumor boards and in interactions with colleagues in neuro-oncology, neurosurgery, radiation oncology, and neuropathology. This review represents the first of a two-installment review series on the most recent changes to the WHO brain tumor classification system. This first installment focuses on the changes to the classification of adult and pediatric gliomas of greatest relevance for radiologists.

Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.

The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of imaging in the management of progressive glioblastoma in adults.

TARGET POPULATION: These recommendations apply to adults with glioblastoma who have been previously treated with first-line radiation or chemoradiotherapy and who are suspected of experiencing tumor progression. QUESTION: In patients with previously treated glioblastoma, is standard contrast-enhanced magnetic resonance imaging including diffusion weighted imaging useful for diagnosing tumor progression and differentiating progression from treatment-related changes? LEVEL II: Magnetic resonance imaging with and without gadolinium enhancement including diffusion weighted imaging is recommended as the imaging surveillance method to detect the progression of previously diagnosed glioblastoma. QUESTION: In patients with previously treated glioblastoma, does magnetic resonance spectroscopy add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? LEVEL II: Magnetic resonance spectroscopy is recommended as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. QUESTION: In patients with previously treated glioblastoma, does magnetic resonance perfusion add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? LEVEL III: Magnetic resonance perfusion is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. QUESTION: In patients with previously treated glioblastoma, does the addition of single-photon emission computed tomography (SPECT) provide additional useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? LEVEL III: Single-photon emission computed tomography imaging is suggested as a diagnostic method to differentiate true tumor progression from treatment-related imaging changes or pseudo-progression in patients with suspected progressive glioblastoma. QUESTION: In patients with previously treated glioblastoma, does 18F-fluorodeoxyglucose positron emission tomography add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? LEVEL III: The routine use of 18F-fluorodeoxyglucose positron emission tomography to identify progression of glioblastoma is not recommended. QUESTION: In patients with previously treated glioblastoma, does positron emission tomography with amino acid agents add useful information for diagnosing tumor progression and differentiating progression from treatment-related changes beyond that derived from standard magnetic resonance imaging with and without gadolinium enhancement? LEVEL III: It is suggested that amino acid positron emission tomography be considered to assist in the differentiation of progressive glioblastoma from treatment related changes.

Clinical experience and outcomes in patients with pineal parenchymal tumor of intermediate differentiation (PPTID): a single-institution analysis.

PURPOSE: Pineal parenchymal tumor of intermediate differentiation (PPTID) is a neoplasm of pinealocyte origin and of intermediate differentiation (WHO grade 2 or 3). Treatment selection and prognostication is challenging for this rare, recently characterized tumor. In this single study, we review our clinical experience in patients with PPTID as well as pooled data from two other institutions. METHODS: This is a retrospective analysis of patients seen at Mayo Clinic, with additional data pooled from two similar studies at outside institutions for comparison and further analysis. RESULTS: Ten adult patients (6 male) were identified. Median age at diagnosis was 36 years (range 13-73 years). Patients were followed between 3 and 88 months with no reported deaths. The most common presenting symptom was headache, followed by nausea. Nine patients had local disease without neuroaxial dissemination at diagnosis, one of which had tumor recurrence at 36 months. Two patients underwent gross total resection (GTR) without adjuvant radiation without recurrence (PFS 4 and 46 months). In our combined analysis, we reviewed 36 patients from three different institutions. Four patients presented with disseminated disease. GTR was achieved for 16 patients. Twenty-eight patients received adjuvant radiation therapy and 16 patients experienced disease recurrence. Median overall survival was 44 months. CONCLUSION: Our single institution experience and combined multi-institution analysis suggest GTR is associated with improved outcomes. The role of adjuvant radiation therapy and utility of CSI compared to focal RT is less unclear. Prospective study is required to identify optimal adjuvant therapy selection.

Assessing drivers of localized invasive spread to inform large-scale management of a highly damaging insect pest.

Studies of biological invasions at the macroscale or across multiple scales can provide important insights for management, particularly when localized information about invasion dynamics or environmental contexts is unavailable. In this study, we performed a macroscale analysis of the roles of invasion drivers on the local scale dynamics of a high-profile pest, Lymantria dispar dispar L., with the purpose of improving the prioritization of vulnerable areas for treatment. Specifically, we assessed the relative effects of various anthropogenic and environmental variables on the establishment rate of 8010 quadrats at a localized scale (5 × 5 km) across the entire L. dispar transition zone (the area encompassing the leading population edge, currently from Minnesota to North Carolina). We calculated the number of years from first detection of L. dispar in a quadrat to the year when probability of establishment of L. dispar was greater than 99% (i.e., waiting time to establishment after first detection). To assess the effects of environmental and anthropogenic variables on each quadrat's waiting time to establishment, we performed linear mixed-effects regression models for the full transition zone and three subregions within the zone. Seasonal temperatures were found to be the primary drivers of local establishment rates. Winter temperatures had the strongest effects, especially in the northern parts of the transition zone. Furthermore, the effects of some factors on waiting times to establishment varied across subregions. Our findings contribute to identifying especially vulnerable areas to further L. dispar spread and informing region-specific criteria by invasion managers for the prioritization of areas for treatment.

Characterizing Help-Seeking Searches for Substance Use Treatment From Google Trends and Assessing Their Use for Infoveillance: Longitudinal Descriptive and Validation Statistical Analysis.

BACKGROUND: There is no recognized gold standard method for estimating the number of individuals with substance use disorders (SUDs) seeking help within a given geographical area. This presents a challenge to policy makers in the effective deployment of resources for the treatment of SUDs. Internet search queries related to help seeking for SUDs using Google Trends may represent a low-cost, real-time, and data-driven infoveillance tool to address this shortfall in information. OBJECTIVE: This paper assesses the feasibility of using search query data related to help seeking for SUDs as an indicator of unmet treatment needs, demand for treatment, and predictor of the health harms related to unmet treatment needs. We explore a continuum of hypotheses to account for different outcomes that might be expected to occur depending on the demand for treatment relative to the system capacity and the timing of help seeking in relation to trajectories of substance use and behavior change. METHODS: We used negative binomial regression models to examine temporal trends in the annual SUD help-seeking internet search queries from Google Trends by US state for cocaine, methamphetamine, opioids, cannabis, and alcohol from 2010 to 2020. To validate the value of these data for surveillance purposes, we then used negative binomial regression models to investigate the relationship between SUD help-seeking searches and state-level outcomes across the continuum of care (including lack of care). We started by looking at associations with self-reported treatment need using data from the National Survey on Drug Use and Health, a national survey of the US general population. Next, we explored associations with treatment admission rates from the Treatment Episode Data Set, a national data system on SUD treatment facilities. Finally, we studied associations with state-level rates of people experiencing and dying from an opioid overdose, using data from the Agency for Healthcare Research and Quality and the CDC WONDER database. RESULTS: Statistically significant differences in help-seeking searches were observed over time between 2010 and 2020 (based on P<.05 for the corresponding Wald tests). We were able to identify outlier states for each drug over time (eg, West Virginia for both opioids and methamphetamine), indicating significantly higher help-seeking behaviors compared to national trends. Results from our validation analyses across different outcomes showed positive, statistically significant associations for the models relating to treatment need for alcohol use, treatment admissions for opioid and methamphetamine use, emergency department visits related to opioid use, and opioid overdose mortality data (based on regression coefficients having P≤.05). CONCLUSIONS: This study demonstrates the clear potential for using internet search queries from Google Trends as an infoveillance tool to predict the demand for substance use treatment spatially and temporally, especially for opioid use disorders.

Growth hormone deficiency in a child with branchio-oto-renal spectrum disorder: Clinical evidence of EYA1 in pituitary development and a recommendation for pituitary function surveillance.

Branchio-oto-renal spectrum disorder (BORSD) is a rare autosomal dominant condition characterized by ear abnormalities with hard of hearing/deafness, second branchial arch malformations and renal anomalies. Pathogenic variations in EYA1 gene are found in the majority of clinically diagnosed individuals with BORSD. We describe an infant with BORSD related to a paternally inherited heterozygous pathogenic variation in EYA1 gene presenting with poor growth and hypoglycemia due to growth hormone deficiency. Magnetic resonance imaging revealed a diminutive pituitary gland and morphologically abnormal sella. Upon initiation of growth hormone therapy, the hypoglycemia resolved and catch up growth ensued. Pituitary abnormalities have not been reported previously in patients with BORSD. The zebrafish ortholog of eya1 is important for the development of adenohypophysis, suggesting that this patient's growth hormone deficiency and pituitary abnormality are part of BORSD. Inclusion of screening for pituitary hormone deficiency and pituitary imaging should be considered as a part of surveillance in patients with BORSD.

Frequency and Characteristics of Nodal and Deltoid FDG and 11C-Choline Uptake on PET Performed After COVID-19 Vaccination.

BACKGROUND. COVID-19 vaccination may trigger reactive lymphadenopathy, confounding imaging interpretation. There has been limited systematic analysis of PET findings after COVID-19 vaccination. OBJECTIVE. The purpose of this study was to evaluate the frequency and characteristics of abnormal FDG and 11C-choline uptake on PET performed after COVID-19 vaccination. METHODS. This retrospective study included 67 patients (43 men and 24 women; mean [± SD] age, 75.6 ± 9.2 years) who underwent PET examination between December 14, 2020, and March 10, 2021, after COVID-19 vaccination and who had undergone prevaccination PET examination without visible axillary node uptake. A total of 52 patients received the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech; hereafter referred to as the Pfizer-BioNTech vaccine), and 15 received the SARS-CoV-2 mRNA-1273 vaccine (Moderna; hereafter referred to as the Moderna vaccine). Sixty-six of the patients underwent PET/CT, and one underwent PET/MRI. Fifty-four PET examinations used FDG, and 13 used 11C-choline. PET was performed a median of 13 and 10 days after vaccination for patients who had received one (n = 44) and two (n = 23) vaccine doses, respectively. Two nuclear medicine physicians independently reviewed images and were blinded to injection laterality and the number of days since vaccination. Lymph node or deltoid SUVmax greater than the blood pool SUVmax was considered positive. Interreader agreement was assessed, and the measurements made by the more experienced physician were used for subsequent analysis. RESULTS. Positive axillary lymph node uptake was observed in 10.4% (7/67) of patients (7.4% [4/54] of FDG examinations and 23.1% [3/13] of 11C-choline examinations); of the patients with positive axillary lymph nodes, four had received the Pfizer vaccine, and three had received the Moderna vaccine. Injection laterality was documented for five of seven patients with positive axillary lymph nodes and was ipsilateral to the positive node in all five patients. PET was performed within 24 days of vaccination for all patients with a positive node. One patient showed extraaxillary lymph node uptake (ipsilateral supraclavicular uptake on FDG PET). Ipsilateral deltoid uptake was present in 14.5% (8/55) of patients with documented injection laterality, including 42.9% (3/7) of patients with positive axillary lymph nodes. Interreader agreement for SUV measurements (expressed as intraclass correlation coefficients) ranged from 0.600 to 0.988. CONCLUSION. Increased axillary lymph node or ipsilateral deltoid uptake is occasionally observed on FDG or 11C-choline PET performed after COVID-19 vaccination with the Pfizer-BioNTech or Moderna vaccine. CLINICAL IMPACT. Interpreting physicians should recognize characteristics of abnormal uptake on PET after COVID-19 vaccination to guide optimal follow-up management and reduce unnecessary biopsies.

Monitoring HIV testing and pre-exposure prophylaxis information seeking by combining digital and traditional data.

BACKGROUND: Public health is increasingly turning to non-traditional digital data to inform HIV prevention and control strategies. We demonstrate a parsimonious method using both traditional survey and internet search histories to provide new insights into HIV testing and pre-exposure prophylaxis (PrEP) information seeking that can be easily extended to other settings. METHOD: We modeled how US internet search volumes from 2019 for HIV testing and PrEP compared against expected search volumes for HIV testing and PrEP using state HIV prevalence and socioeconomic characteristics as predictors. States with search volumes outside the upper and lower bound confidence interval were labeled as either over or under performing. State performance was evaluated by (a) Centers for Disease Control and Prevention designation as a hotspot for new HIV diagnoses (b) expanding Medicaid coverage. RESULTS: Ten states over-performed in models assessing information seeking for HIV testing, while eleven states under-performed. Thirteen states over-performed in models assessing internet searches for PrEP information, while thirteen states under-performed. States that expanded Medicaid coverage were more likely to over perform in PrEP models than states that did not expand Medicaid coverage. While states that were hotspots for new HIV diagnoses were more likely to over perform on HIV testing searches. CONCLUSION: Our study derived a method of measuring HIV and PrEP information seeking that is comparable across states. Several states exhibited information seeking for PrEP and HIV testing that deviated from model assessments. Statewide search volume for PrEP information was affected by a state's decision to expand Medicaid coverage. Our research provides health officials with an innovative way to monitor statewide interest in PrEP and HIV testing using a metric for information-seeking that is comparable across states.

Intracranial long-term complications of radiation therapy: an image-based review.

BACKGROUND AND PURPOSE: Radiation therapy is commonly utilized in the majority of solid cancers and many hematologic malignancies and other disorders. While it has an undeniably major role in improving cancer survival, radiation therapy has long been recognized to have various negative effects, ranging from mild to severe. In this manuscript, we review several intracranial manifestations of therapeutic radiation, with particular attention to those that may be encountered by radiologists. METHODS: We conducted an extensive literature review of known complications of intracranial radiation therapy. Based on this review, we selected complications that had salient, recognizable imaging findings. We searched our imaging database for illustrative examples of these complications, focusing only on patients who had a history of intracranial radiation therapy. We then selected cases that best exemplified expected imaging findings in these entities. RESULTS: Based on our initial literature search and imaging database review, we selected cases of radiation-induced meningioma, radiation-induced glioma, cavernous malformation, enlarging perivascular spaces, leukoencephalopathy, stroke-like migraine after radiation therapy, Moyamoya syndrome, radiation necrosis, radiation-induced labyrinthitis, optic neuropathy, and retinopathy. Although retinopathy is not typically apparent on imaging, it has been included given its clinical overlap with optic neuropathy. CONCLUSIONS: We describe the clinical and imaging features of selected sequelae of intracranial radiation therapy, with a focus on those most relevant to practicing radiologists. Knowledge of these complications and their imaging findings is important, because radiologists play a key role in early detection of these entities.

Characterizing Self-Reports of Self-Identified Patient Experiences with Methadone Maintenance Treatment on an Online Community during COVID-19.

Background: The coronavirus disease (COVID-19) pandemic has impacted patients receiving methadone maintenance treatment (MMT) through opioid treatment programs (OTPs), especially because of the unique challenges of the care delivery model. Previously, documentation of patient experiences during emergencies often comes years after the fact, in part because there is a substantial data void in real-time. Methods: We extracted 308 posts that mention COVID-19 keywords on r/methadone, an online community for patients receiving MMT to share information, on Reddit occurring between January 31, 2020 and September 30, 2020. 215 of these posts self-report an impact to their MMT. Using qualitative content analysis, we characterized the impacts described in these posts and identified four emergent themes describing patients' experience of impacts to MMT during COVID-19. Results: The themes included (1) 54.4% of posts reporting impediments to accessing their methadone, (2) 28.4% reporting impediments to accessing physicial OTPs, (3) 19.5% reporting having to self-manage their care, and (4) 4.7% reporting impediments to accessing OTP providers and staff. Conclusions: Patients described unanticipated consequences to one-size-fits-all policies that are unevenly applied resulting in suboptimal dosing, increased perceived risk of acquiring COVID-19 at OTPs, and reduced interaction with OTP providers and staff. While preliminary, these results are formative for follow-up surveillance metrics for patients of OTPs as well as digitally-mediated resource needs for this online community. This study serves as a model of how social media can be employed during and after emergencies to hear the lived experiences of patients for informed emergency preparedness and response.

The anti-inflammatory TIPE2 is an inhibitor of the oncogenic Ras.

The connection between cancer and inflammation is widely recognized, yet the underlying molecular mechanisms are poorly understood. We report here that TIPE2 provides a molecular bridge from inflammation to cancer by targeting the Ras signaling pathway. TIPE2 binds the Ras-interacting domain of the RalGDS family of proteins, which are essential effectors of activated Ras. This binding prevented Ras from forming an active complex, thereby inhibiting the activation of the downstream signaling molecules Ral and AKT. Consequently, TIPE2 deficiency led to heightened activation of Ral and AKT, resistance to cell death, increased migration, and dysregulation of exocyst complex formation. Conversely, TIPE2 overexpression induced cell death and significantly inhibited Ras-induced tumorigenesis in mice. Importantly, TIPE2 expression was either completely lost or significantly downregulated in human hepatic cancer. Thus, TIPE2 is an inhibitor of both inflammation and cancer, and a potential drug target for inflammatory and neoplastic diseases.

Cervical Cancer and Human Papillomavirus Vaccine Awareness Among Married Bhutanese Refugee and Nepali Women in Eastern Nepal.

This study examined the sexually transmitted infections (STIs), cervical cancer, and human papillomavirus virus (HPV) vaccine-related awareness and knowledge among married Bhutanese refugee and Nepali women living in eastern Nepal. Participants were recruited from a women's health camp in Jhapa District in eastern Nepal. A demographic and health survey with questions on STIs, cervical cancer and HPV vaccine was administered to consenting participants. Women who were born in Bhutan or living in the United Nations administered refugee camps were classified as Bhutanese. Of the 630 participants, 14.3% of participants were Bhutanese and the mean age was 38.8 ± 8.2 years. A higher proportion of Bhutanese than Nepali women reported a lack of cervical cancer awareness (42.0% vs. 30.7%; p = 0.036). Only 21.5% of the participants knew HPV as the cause of cervical cancer; 13.9% were aware of an HPV vaccine; and 96% reported that they would have their children vaccinated against HPV if the vaccine was available free of cost to them. In multivariable analyses, the lack of awareness about STIs was directly associated with the lack of cervical cancer awareness [odds ratio (OR) 4.50; 95% confidence interval (CI) 2.99-6.77] and inversely associated with HPV-vaccine awareness [OR 0.53; 95% CI 0.29-0.97]. Low cervical cancer and HPV vaccine awareness and knowledge among Nepali and Bhutanese women in eastern Nepal highlight the need for increasing awareness and knowledge in the context of STIs and reproductive health education. Increasing awareness and knowledge of HPV, its role in cervical cancer, and prevention modalities is a first critical step for implementing successful targeted primary cervical cancer prevention measures focused on behavior modification and vaccine administration.

Evolutionary genomics of gypsy moth populations sampled along a latitudinal gradient.

The European gypsy moth (Lymantria dispar L.) was first introduced to Massachusetts in 1869 and within 150 years has spread throughout eastern North America. This large-scale invasion across a heterogeneous landscape allows examination of the genetic signatures of adaptation potentially associated with rapid geographical spread. We tested the hypothesis that spatially divergent natural selection has driven observed changes in three developmental traits that were measured in a common garden for 165 adult moths sampled from six populations across a latitudinal gradient covering the entirety of the range. We generated genotype data for 91,468 single nucleotide polymorphisms based on double digest restriction-site associated DNA sequencing and used these data to discover genome-wide associations for each trait, as well as to test for signatures of selection on the discovered architectures. Genetic structure across the introduced range of gypsy moth was low in magnitude (FST  = 0.069), with signatures of bottlenecks and spatial expansion apparent in the rare portion of the allele frequency spectrum. Results from applications of Bayesian sparse linear mixed models were consistent with the presumed polygenic architectures of each trait. Further analyses indicated spatially divergent natural selection acting on larval development time and pupal mass, with the linkage disequilibrium component of this test acting as the main driver of observed patterns. The populations most important for these signals were two range-edge populations established less than 30 generations ago. We discuss the importance of rapid polygenic adaptation to the ability of non-native species to invade novel environments.