Higher unemployment benefits are associated with reduced drug overdose mortality in the United States before and during the COVID-19 pandemic.

OBJECTIVES: Overdose mortality rates in the United States remain critical to population health. Economic , such as unemployment, are noted risk factors for drug overdoses. The COVID-19 pandemic exacerbated economic hardship; as a result, the US government enacted income protection programs in conjunction with existing unemployment insurance (UI) to dampen COVID-19-related economic consequences. We investigate whether UI, operationalized as the weekly benefit allowance (WBA) replacement rate, is negatively associated with drug-related overdoses. METHODS: Data from the pooled 2014-2020 Detailed Restricted Mortality files for all counties from the Centers for Disease Control and Prevention, restricted to people ≥18 years of age, aggregated at the county-quarter level (n = 89,914). We included any fatal drug, opioid, and stimulant overdose. We modeled the association between WBA replacement rate (e.g., a greater proportion of weekly earnings replaced by UI) on each county-level age-adjusted mortality outcome using separate linear regression models during 2014-2020, pre-COVID (2014-2018), and post-COVID (2019-2020). We conducted sensitivity analyses using multi-level linear regression models. RESULTS: Results indicated that a more robust WBA replacement rate any drug (Risk Difference [RD]: -0.06, 95 % Confidence Interval [CI]: -0.08, -0.05), opioid (RD: -0.04, 95 % CI: -0.06, -0.03), and stimulant (RD: -0.03, 95 % CI: -0.04, -0.02) across the entire study period (2014-2020). A more robust WBA replacement rate was associated with fewer fatal drug, opioid and stimulant overdoses in the pre-COVID-19 period and on fatal any drug and stimulant overdoses in the COVID-19 period. CONCLUSIONS: Findings support the notion that income protection policies, such as robust UI, can have a supportive role in preventing fatal drug overdoses, calling for a broader discussion onthe role of the safety net programs to buffer drug-related harms.

Future perspective of targeted treatments in pediatric low-grade glioma (pLGG): the evolution of standard-of-care and challenges of a new era.

While surgery, when possible, remains the mainstay of pediatric low-grade glioma (pLGG) management, adjuvant therapy has significantly evolved over time. Radiation therapy was commonly used in the late 1990s for tumors that could not be resected or recurred. This resulted in significant late morbidity in this population and mortality related to secondary malignancies and chronic health conditions. Chemotherapy became the mainstay of adjuvant therapy but children still experienced late morbidity secondary to exposure to multiple lines of treatment over time. Targeted therapies emerged after the identification of frequent genetic alterations in the mitogen activated protein kinase (MAPK) pathway including KIAA1549-BRAF fusions and BRAF-V600 mutations and the near universal upregulation of the MAPK pathway in these tumors. Both BRAF and MEK inhibitors have shown efficacy in the treatment of pLGG and have led to prolonged stability in some cases. Multiple phase III clinical trials are now comparing targeted therapy to standard-of-care chemotherapy regimens setting the stage for targeted therapy to replace chemotherapy as the first-line treatment in some cases. Targeted therapy, however, is not without its challenges. There are clear examples of resistance and mechanisms of resistance have not been fully elucidated. There is also no clear duration for these therapies and rebound growth is a well-known phenomenon especially in BRAF-V600 mutant tumors. Targeted therapies are also fairly recent developments and long-term toxicities and functional outcomes are still being monitored. Very young and adolescent/young adult LGGs also carry molecular features that may not be addressed by inhibition of the MAPK pathway. Adjuvant therapy for pLGG has evolved from radiation for all unresectable or residual tumors to molecularly driven targeted therapies with improved quality of life, late effects, and less off-target toxicities. While there is still much to learn in regard to newer targeted therapies for pLGG, the era of targeted therapies for pediatric LGG is upon us.

Predictive Nomogram and Propensity Score Matching in Neuroendocrine Carcinoma of the Tubular Gastrointestinal Tract: A US Population-Based Clinical Outcome Study.

Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were >40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0-74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4-10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6-60.5%). On multivariate analysis, age > 65 (HR 2.49, 95% CI 2.36-2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52-2.62%, p ≤ 0.001), tumor size > 4 mm (HR 1.98, 95%, CI 1.70-2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86-2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15-3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools.

Is Redistribution Good for Our Health? Examining the Macrocorrelation between Welfare Generosity and Health across EU Nations over the Last 40 Years.

CONTEXT: Social determinants of health are finally getting much-needed policy attention, but their political origins remain underexplored. In this article, the authors advance a theory of political determinants as accruing along three pathways of welfare state effects (redistribution, poverty reduction, and status preservation), and they test these assumptions by examining impacts of policy generosity on life expectancy (LE) over the last 40 years. METHODS: The authors merge new and existing welfare policy generosity data from the Comparative Welfare Entitlement Project with data on LE spanning 1980-2018 across 21 countries in the Organization for Economic Cooperation and Development. They then examine relationships between five welfare policy generosity measures and LE using cross-sectional differencing and autoregressive lag models. FINDINGS: The authors find consistent and positive effects for total generosity (an existing measure of social insurance generosity) on LE at birth across different model specifications in the magnitude of an increase in LE at birth of 0.10-0.15 years (p < 0.05) as well as for a measure of status preservation (0.11, p < 0.05). They find less consistent support for redistribution and poverty reduction measures. CONCLUSIONS: The authors conclude that in addition to generalized effects of policy generosity on health, status-preserving social insurance may be an important, and relatively overlooked, mechanism in increasing LE over time in advanced democracies.

Preclinical assessment of MAGMAS inhibitor as a potential therapy for pediatric medulloblastoma.

Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and non-SHH group3 subtypes. MAGMAS (Mitochondrial Associated Granulocyte Macrophage colony-stimulating factor Signaling molecules) encode for mitochondrial import inner membrane translocase subunit and is responsible for translocation of matrix proteins across the inner membrane. We previously reported that a small molecule MAGMAS inhibitor, BT9, decreases cell proliferation, migration, and oxidative phosphorylation in adult glioblastoma cell lines. The aim of our study was to investigate whether the chemotherapeutic effect of BT9 can be extended to pediatric medulloblastoma. Methods: Multiple in vitro assays were performed using human DAOY (SHH activated tp53 mutant) and D425 (non-SHH group 3) cells. The impact of BT9 on cellular growth, death, migration, invasion, and metabolic activity were quantified using MTT assay, TUNEL staining, scratch wound assay, Matrigel invasion chambers, and seahorse assay, respectively. Survival following 50mg/kg BT9 treatment was assessed in vivo in immunodeficient mice intracranially implanted with D425 cells. Results: Compared to control, BT9 treatment led to a significant reduction in medulloblastoma cell growth (DAOY, 24hrs IC50: 3.6uM, 48hrs IC50: 2.3uM, 72hrs IC50: 2.1uM; D425 24hrs IC50: 3.4uM, 48hrs IC50: 2.2uM, 72hrs IC50: 2.1uM) and a significant increase in cell death (DAOY, 24hrs p=0.0004, 48hrs p<0.0001; D425, 24hrs p=0.0001, 48hrs p=0.02). In DAOY cells, 3uM BT9 delayed migration, and significantly decreased DAOY and D425 cells invasion (p < 0.0001). Our in vivo study, however, did not extend survival in xenograft mouse model of group3 medulloblastoma compared to vehicle-treated controls. Conclusions: Our in vitro data showed BT9 antitumor efficacy in DAOY and D425 cell lines suggesting that BT9 may represent a promising targeted therapeutic in pediatric medulloblastoma. These data, however, need to be further validated in animal models.

Market Failure, State Failure: The Political Economy of Supply Chain Strengthening to Ensure Equitable Access to Vaccines and Medicines in Low- and Middle-Income Countries.

CONTEXT: Much of the existing work on the political economy of vaccine access has focused on how intellectual property rights agreements contribute to inequitable COVID-19 vaccine access between high-income and low- and middle-income countries (LMICs). The two solutions that emerged to scale up access in LMICs involved either voluntary arrangements under COVAX or a waiver of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPs) to allow immediate access to intellectual property. However, an additional constraint on access is weak and ineffective supply chains within LMICs that have eroded over several decades of health-sector reform. METHODS: This article reviews the literature on the political economy of supply chain strengthening in LMICs and identifies key challenges to equitable access to emergent vaccines and other medicines emanating from market and state failures in internal supply chains. FINDINGS: Over the past century, supply chain policies in LMICs have alternated among an emphasis on addressing market failures contributing to unaffordability of vaccines/medicines, an emphasis on state failures contributing to unavailability of vaccines/medicines, and a more recent move toward public-private hybrid arrangements to strengthen supply chains. CONCLUSIONS: In addition to reshoring production capacity through a TRIPs waiver, the international community must address chronic weakness in internal supply chains in LMICs to ensure access to novel vaccines/medicines.

Substantial Disparities In COVID-19 Vaccine Uptake And Unmet Immunization Demand In Low- And Middle-Income Countries.

The two primary narratives that have emerged to explain low COVID-19 vaccine uptake in low- and middle-income countries are constrained accessibility and vaccine hesitancy. However, it is unclear how much each issue contributes to low uptake. This article examines these twin barriers to access. Using global survey data from 15,696 respondents across seventeen Western Pacific and African countries, collected between May 2022 and January 2023, we estimated the unmet demand for vaccines and examined its predictors. We found that among unvaccinated respondents, by the time of the survey, 50 percent had unmet demand-meaning they were still willing to get vaccinated. Rates of unmet demand were highest in African countries and lowest in Western Pacific countries. The perceived accessibility of vaccines and respondents' age and sex were identified as consistent predictors of unmet demand. These issues suggest that inequitable supply continues to play a substantial role in limiting vaccine access. Targeted efforts to increase vaccination rates are necessary, particularly in countries with low coverage and high unmet demand. Policy efforts should address barriers to vaccine access, ensure accessibility and distribution of mRNA vaccines, and aim to overcome vaccine hesitancy-all critical factors in reducing unmet immunization demand and achieving higher vaccination rates across regions.

Who gets COVID-19 booster vaccination? Trust in public health institutions and promotion strategies post-pandemic in the Republic of Korea.

INTRODUCTION: It is increasingly recognized that regular boosters will be necessary for the continued management of the COVID-19 pandemic. While vaccine hesitancy in the context of the initial COVID-19 vaccinations has been extensively studied, less is known about hesitancy around boosters in the post-pandemic era, where the immediate threat of COVID-19 has diminished. METHODS: Using 5,584 survey responses from people who had received at least one COVID-19 vaccine dose based on a four-round survey between May and November 2022, we examined various factors that affect booster vaccine uptake and the willingness to take an additional shot. Ordinary least squares regressions were conducted to confirm the statistical significance of the findings. RESULTS: Nearly 99% of vaccinated respondents reported having had two COVID-19 vaccine doses, while 69% of respondents reported having received a booster shot (three or more vaccine doses) and 48% reported being willing to get another shot. Booster uptake was strongly increased along with the degree of trust in the Korean Disease Control Agency (KDCA) and was also significantly associated with older age, gender, political propensity, and household income-level. When examining willingness to get an additional shot, the predictors were similar to booster vaccine uptake. However, the effect of trust in the KDCA became more salient. CONCLUSION: The factors associated with booster uptake and willingness to continue to boost are similar to those associated with initial vaccine acceptance in the ROK, namely trust in the public health authority and older age. Despite high initial uptake in the ROK, convincing the public of the continued necessity of routine immunization against COVID-19 may pose challenges in the post-pandemic era.

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations.

BACKGROUND: Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that warrant further evaluation of this combination as first-line therapy. METHODS: In this phase 2 trial, patients with pediatric low-grade glioma with BRAF V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine). The primary outcome was the independently assessed overall response (complete or partial response) according to the Response Assessment in Neuro-Oncology criteria. Also assessed were the clinical benefit (complete or partial response or stable disease for ≥24 weeks) and progression-free survival. RESULTS: A total of 110 patients underwent randomization (73 to receive dabrafenib plus trametinib and 37 to receive standard chemotherapy). At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P<0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy. CONCLUSIONS: Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy. (Funded by Novartis; ClinicalTrials.gov number, NCT02684058.).

Heterogeneous splicing patterns resulting from KIF5A variants associated with amyotrophic lateral sclerosis.

Single-nucleotide variants (SNVs) in the gene encoding Kinesin Family Member 5A (KIF5A), a neuronal motor protein involved in anterograde transport along microtubules, have been associated with amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive and fatal neurodegenerative disease that primarily affects the motor neurons. Numerous ALS-associated KIF5A SNVs are clustered near the splice-site junctions of the penultimate exon 27 and are predicted to alter the carboxy-terminal (C-term) cargo-binding domain of KIF5A. Mis-splicing of exon 27, resulting in exon exclusion, is proposed to be the mechanism by which these SNVs cause ALS. Whether all SNVs proximal to exon 27 result in exon exclusion is unclear. To address this question, we designed an in vitro minigene splicing assay in human embryonic kidney 293 cells, which revealed heterogeneous site-specific effects on splicing: only 5' splice-site (5'ss) SNVs resulted in exon skipping. We also quantified splicing in select clustered, regularly interspaced, short palindromic repeats-edited human stem cells, differentiated to motor neurons, and in neuronal tissues from a 5'ss SNV knock-in mouse, which showed the same result. Moreover, the survival of representative 3' splice site, 5'ss, and truncated C-term variant KIF5A (v-KIF5A) motor neurons was severely reduced compared with wild-type motor neurons, and overt morphological changes were apparent. While the total KIF5A mRNA levels were comparable across the cell lines, the total KIF5A protein levels were decreased for v-KIF5A lines, suggesting an impairment of protein synthesis or stability. Thus, despite the heterogeneous effect on ribonucleic acid splicing, KIF5A SNVs similarly reduce the availability of the KIF5A protein, leading to axonal transport defects and motor neuron pathology.

Current advances in immunotherapy for atypical teratoid rhabdoid tumor (ATRT).

Atypical teratoid rhabdoid tumors (ATRT) are rare and aggressive embryonal tumors of central nervous system that typically affect children younger than 3 years of age. Given the generally poor outcomes of patients with ATRT and the significant toxicities associated with conventional multi-modal therapies, there is an urgent need for more novel approaches to treat ATRT, one such approach being immunotherapy. The recent rise of large-scale, multicenter interdisciplinary studies has delineated several molecular and genetic characteristics unique to ATRT. This review aims to describe currently available data on the tumor immune microenvironment of ATRT and its specific subtypes and to summarize the emerging clinical and preclinical results of immunotherapy-based approaches. It will also highlight the evolving knowledge of epigenetics on immunomodulation in this epigenetically influenced tumor, which may help guide the development of effective immunotherapeutic approaches in the future.

Communities at Risk for Mpox and Stigmatizing Policies: A Randomized Survey, Republic of Korea, 2022.

Objectives. To estimate the impact of communicating to the public that men who have sex with men (MSM) are most at risk for mpox on potential stigmatization and risk perception. Methods. We conducted a survey experiment randomizing exposure to messages about mpox among a sample of the South Korean public (n = 1500) in July 2022. We randomized respondents to receive an informational message about mpox that was (1) a neutral informational message about mpox that did not highlight its origins or risk groups (control group), (2) a message explaining that the virus originated in Africa, or (3) a message emphasizing that MSM are most at risk. Results. We found that emphasizing that MSM are most at risk increases support for policies that would restrict lesbian, gay, bisexual, transgender/-sexual, queer or questioning-related events by about 7 percentage points compared with the control condition. However, the message describing African origins did not affect support for restricting travel from Africa. Neither changed risk perceptions or willingness to be vaccinated against mpox. Conclusions. Messages aimed at educating the public about most at-risk groups may trigger increased stigmatization of those groups in ways that could contribute to unnecessary persecution. (Am J Public Health. 2023;113(10):1120-1127. https://doi.org/10.2105/AJPH.2023.307347).

Development and Earliest Validation of a Portable Device for Quantification of Hallux Extension Strength (QuHalEx).

Hallux strength is associated with sports performance and balance across the lifespan, and independently predicts falls in older adults. In rehabilitation, Medical Research Council (MRC) Manual Muscle Testing (MMT) is the clinical standard for hallux strength assessment, but subtle weakness and longitudinal changes in strength may go undetected. To address the need for research-grade yet clinically feasible options, we designed a new load cell device and testing protocol to Quantify Hallux Extension strength (QuHalEx). We aim to describe the device, protocol and initial validation. In benchtop testing, we used eight precision weights to apply known loads from 9.81 to 78.5 N. In healthy adults, we performed three maximal isometric tests for hallux extension and flexion on the right and left sides. We calculated the Intraclass Correlation Coefficient (ICC) with 95% confidence interval and descriptively compared our isometric force-time output to published parameters. QuHalEx benchtop absolute error ranged from 0.02 to 0.41 (mean 0.14) N. Benchtop and human intrasession output was repeatable (ICC 0.90-1.00, p < 0.001). Hallux strength in our sample (n = 38, age 33.5 ± 9.6 years, 53% female, 55% white) ranged from 23.1 to 82.0 N peak extension force and 32.0 to 142.4 N peak flexion, and differences of ~10 N (15%) between toes of the same MRC grade (5) suggest that QuHalEx is able to detect subtle weakness and interlimb asymmetries that are missed by MMT. Our results support ongoing QuHalEx validation and device refinement with a longer-term goal of widespread clinical and research application.

HIV policy legacies, pandemic preparedness and policy effort to address COVID-19.

That the world was unprepared for a major infectious disease outbreak is now readily apparent to all credible observers. However, some countries were more prepared than others and we have seen a variety of responses to COVID-19 emerge across nations. While recognizing that the sources of variation in country responses to COVID-19 are many and varied, in this study we seek to examine how policy legacies from national responses to HIV have influenced countries' responses to COVID-19. The aim of this study was to examine whether countries with a more conducive HIV policy environment were better prepared for COVID-19 and have therefore had more preemptive and rights-based responses. Using data from the Oxford Covid-19 Government Response Tracker, we develop measures of country effort to respond to COVID-19 including early containment and closure policies, prevention policies, economic policies, and health system policies. We combine this with data from the HIV Policy Lab and correlate overall and disaggregated country HIV Policy scores with COVID-19 Policy scores. We find that the COVID-19 Containment and Closure Measures Index was negatively correlated with supportive social policies related to HIV in the early stages of the pandemic, but the association did not persist as time went on. The COVID-19 Economic Support Measures had prolonged positive associations with supportive social policies related to HIV and negative association with clinical and treatment policies. Countries with stronger structural responses to HIV have been less inclined towards involuntary measures and more prepared for the social and economic elements of COVID-19 pandemic response.

Left Behind: Medicaid Immigrant Exclusions and Access to Maternal Health Care Across the Reproductive-Perinatal Continuum.

Noncitizen immigrants are often excluded from accessing critical safety-net programs, such as Medicaid. Access to health care plays a central role in current policy debates on maternal health. Yet, immigrant exclusions are rarely considered in maternal health policy research. Through open-ended interviews with 31 policymakers, researchers, and program administrators, we examined state variations in approaches to providing care for pregnant, post, and intrapartum immigrant women. We found four themes: (a) a patchwork safety-net exists that provides some access to immigrants ineligible for Medicaid; (b) patchwork coverage leads to patchwork care, which can contribute to maternal health inequities; (c) immigrant Medicaid policy is assembled along a hierarchy of deservingness based on documentation status; (d) Trump-era public charge rules and political climate may have a substantial chilling effect on benefit uptake regardless of eligibility. We discuss implications for efforts to expand Medicaid postpartum and address the maternal health crisis.

Impaired motor unit recovery and maintenance in a knock-in mouse model of ALS-associated Kif5a variant.

Kinesin family member 5A (KIF5A) is an essential, neuron-specific microtubule-associated motor protein responsible for the anterograde axonal transport of various cellular cargos. Loss of function variants in the N-terminal, microtubule-binding domain are associated with hereditary spastic paraplegia and hereditary motor neuropathy. These variants result in a loss of the ability of the mutant protein to process along microtubules. Contrastingly, gain of function splice-site variants in the C-terminal, cargo-binding domain of KIF5A are associated with amyotrophic lateral sclerosis (ALS), a neurodegenerative disease involving death of upper and lower motor neurons, ultimately leading to degradation of the motor unit (MU; an alpha motor neuron and all the myofibers it innervates) and death. These ALS-associated variants result in loss of autoinhibition, increased procession of the mutant protein along microtubules, and altered cargo binding. To study the molecular and cellular consequences of ALS-associated variants in vivo, we introduced the murine homolog of an ALS-associated KIF5A variant into C57BL/6 mice using CRISPR-Cas9 gene editing which produced mutant Kif5a mRNA and protein in neuronal tissues of heterozygous (Kif5a+/c.3005+1G>A; HET) and homozygous (Kif5ac.3005+1G>A/c.3005+1G>A; HOM) mice. HET and HOM mice appeared normal in behavioral and electrophysiological (compound muscle action potential [CMAP] and MU number estimation [MUNE]) outcome measures at one year of age. When subjected to sciatic nerve injury, HET and HOM mice have delayed and incomplete recovery of the MUNE compared to wildtype (WT) mice suggesting an impairment in MU repair. Moreover, aged mutant Kif5a mice (aged two years) had reduced MUNE independent of injury, and exacerbation of the delayed and incomplete recovery after injury compared to aged WT mice. These data suggest that ALS-associated variants may result in an impairment of the MU to respond to biological challenges such as injury and aging, leading to a failure of MU repair and maintenance. In this report, we present the behavioral, electrophysiological and pathological characterization of mice harboring an ALS-associated Kif5a variant to understand the functional consequences of KIF5A C-terminal variants in vivo.

Enhanced unemployment benefits, mental health, and substance use among low-income households during the COVID-19 pandemic.

OBJECTIVE: To buffer the economic impacts of the pandemic-induced economic downturns, the U.S. government passed major economic stimulus bills that provided cash payments to affected citizens and a large boost to unemployment benefits. We ask what impact these enhanced safety-net policies have had on mental health and stress-induced substance use among low-income Americans, especially enhanced unemployment insurance (UI) benefits, which constituted a large economic transfer to those eligible. METHODS: Using individual fixed effects analysis of a panel of nearly 900 low-income Americans since the start of the pandemic from the Understanding America Survey, we examine how receipt of enhanced unemployment benefits has impacted the mental health burden and substance use behaviors of low-income Americans. We additionally examine the buffering effect of a set of other safety-net measures (Stimulus, Medicaid, SNAP, TANF, housing assistance, EITC, WIC, and CHIP). RESULTS: We found that job loss, regardless of benefit receipt, was associated with increased stress and decreased average substance use, driven by reduced smoking when compared with those were employed. Yet, when factoring in UI receipt we see that receiving UI was associated with reduced stress, but no impact on depression or substance use. In contrast, those who did not receive UI experienced greater stress compared with those who were employed. Overall, we found that people who remained employed used substances more than people who were unemployed regardless of UI receipt with the exception of drinking. CONCLUSIONS: We conclude that enhanced unemployment offset some of the negative mental health effects of the pandemic and did not increase routine substance use among the unemployed.

Recurrent pediatric infratentorial ependymomas: a systematic review and meta-analysis on outcomes and molecular classification.

OBJECTIVE: The aim of this study was to summarize the prognosis of recurrent infratentorial ependymomas based on treatment and molecular characterization. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the authors searched the PubMed, Scopus, Embase, and Ovid databases for studies on recurrent infratentorial ependymomas in patients younger than 25 years of age. Exclusion criteria included case series of fewer than 5 patients and studies that did not provide time-dependent survival data. RESULTS: The authors' database search yielded 482 unique articles, of which 18 were included in the final analysis. There were 479 recurrent infratentorial pediatric ependymomas reported; 53.4% were WHO grade II and 46.6% were WHO grade III tumors. The overall mortality for recurrent infratentorial pediatric ependymomas was 49.1% (226/460). The pooled mean survival was 30.2 months after recurrence (95% CI 22.4-38.0 months). Gross-total resection (GTR) was achieved in 243 (59.0%) patients at initial presentation. The mean survival postrecurrence for those who received initial GTR was 42.3 months (95% CI 35.7-47.6 months) versus 26.0 months (95% CI 9.6-44.6 months) for those who received subtotal resection (STR) (p = 0.032). There was no difference in the mean survival between patients who received GTR (49.3 months, 95% CI 32.3-66.3 months) versus those who received STR (41.4 months, 95% CI 11.6-71.2 months) for their recurrent tumor (p = 0.610). In the studies that included molecular classification data, there were 169 (83.3%) posterior fossa group A (PFA) tumors and 34 (16.7%) posterior fossa group B (PFB) tumors, with 28 tumors harboring a 1q gain. PFA tumors demonstrated worse mean postprogression patient survival (24.7 months, 95% CI 15.3-34.0 months) compared with PFB tumors (48.0 months, 95% CI 32.8-63.2 months) (p = 0.0073). The average postrecurrence survival for patients with 1q+ tumors was 14.7 months. CONCLUSIONS: The overall mortality rate for recurrent infratentorial ependymomas was found to be 49.1%, with a pooled mean survival of 30.2 months in the included sample population. More than 80% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and both PFA tumors and those with 1q gain demonstrated worse prognosis after recurrence.