Aggressive Targets Research Articles

Clinically aggressive follicular cell-derived thyroid carcinoma: A comprehensive series with histomolecular characterization and discovery of novel gene fusions

Thyroid cancer rates are increasing, mostly with a good prognosis and less than 2 % of cases are more aggressive. Recent efforts focus on understanding molecular events predicting tumor aggressiveness and treatment targets in advanced thyroid cancer. This study concerned 57 patients with aggressive metastatic, and/or radioiodine-refractory thyroid carcinomas, excluding anaplastic cases. Molecular profiling, including next-generation sequencing and RNA sequencing, was conducted to dissect the complex molecular landscape of these aggressive tumors. Histopathological analysis indicated that papillary carcinomas and high-grade thyroid carcinomas were predominant. The molecular analysis revealed a spectrum of mutations, with prevalent occurrences of BRAF V600E, TERT promoter, and RAS mutations. RNA sequencing identified ten gene fusions, such as NTRK and RET fusions. Three novel fusions were discovered: UGGT1::TERT, BTBD9::TERT, and TG::IGF1R, potentially driving aggressive behavior. UGGT1::TERT was linked to radioiodine-refractory tall cell PTC, BTBD9::TERT to high-grade follicular PTC, and TG::IGF1R to oncocytic carcinoma. These findings underscore the importance of TERT alterations in aggressive phenotypes and offer insights into molecular mechanisms guiding targeted therapies. Further research is necessary to confirm their significance as diagnostic and prognostic markers in thyroid cancer.

HIV and cardiovascular risk: should we use other targets for cholesterol control? Brazilian data compared to major studies

Abstract In daily clinical practice, cardiologists are confronted with patients with HIV/AIDS and this population needs special attention due to their higher cardiovascular risk. Studies show an increase in cardiovascular disease (CVD) among people with HIV/AIDS and one of the main causes of death in this group. HIV is associated with dyslipidaemia and endothelial damage, which have been proposed as a cause of the increased risk of events, and HIV replication is a determining factor in endothelial dysfunction. With antiretroviral therapy (ART) there has been a reduction in morbidity and mortality from HIV/AIDS, however, several studies have shown an increase risk factors for CVD in this population, both in individuals on ART and those not on it. Two high-impact studies related to cardiovascular risk in the HIV population are Start and Smart. Studies are important for understanding this occurrence and its relationship with the presence of the virus and the use of antiretroviral therapy in this population. In view of the higher cardiovascular risk of these patients and the question of whether they deserve a different cholesterol target from other populations. Methods A retrospective, observational study was carried out on a sample of HIV patients from the Brazilian STD/AIDS Reference Centre (CRT), selected by lottery using their registration number, from 1 January 2011 to February 2023, aged over 18. 148 medical records were assessed and the following were collected population characteristics. Discussion: the CRT data were compared with the Start and Smart studies. The Reprieve study showed benefits earlier than expected with patients receiving a statin. An interim analysis revealed a 35 per cent reduction in serious adverse cardiovascular events in the statin group, leading to the placebo group stopping earlier. The viral load varied between the studies, with CRT having an average of 500,000 copies/ml, Start 12,759 copies/ml and Smart less than 400 copies/ml. Studies have associated HIV infection and higher viral loads with impaired endothelial function and vasodilation. Despite the data in the literature, all the patients with heart disease had undetected viral loads and CD4+ cell counts above 500 cells/mm³. Those with a high viral load in the study were not the ones with CVD. Conclusions In CRT, the percentage of primary events attributable to serious conditions unrelated to AIDS was 1.3 per cent. Analysing biomarkers could elucidate the effects of antiretroviral therapy on arterial disease. Another fact that probably justifies the low occurrence of cardiovascular and cerebral events in CRT is the multidisciplinary care given to patients, providing intensive primary and secondary prevention through counselling and follow-up. We suggest better control of cardiovascular risk factors with multi-professional intervention and more aggressive targets for the control of comorbidities.Characteristics and Cardiovascular risk

Effect of Optimal Heart Rate on Left Ventricular Remodeling in Patients with Systolic Heart Failure Following Acute Coronary Syndrome.

The optimal therapeutic approach to facilitate reverse remodeling is desired in patients with systolic heart failure following acute coronary syndrome (ACS). The association between heart rate (HR) and reverse remodeling in this cohort has remained elusive.Patients with left ventricular ejection fraction (LVEF) < 50% who received echocardiography assessments following ACS were retrospectively included. Theoretically ideal HR was calculated using a previously established formula: 93 - 0.13 × (deceleration time [msec]). Impacts of HR on echocardiographic left ventricular (LV) reverse remodeling during the 2-year observational period were compared between 2 groups stratified by the HR difference between theoretically ideal and actual values: optimal HR group (HR difference ≤ 10 bpm) versus sub-optimal HR group (HR difference > 10 bpm).A total of 27 patients (median 72 years old, 23 males) were included. There were no significant differences in the baseline characteristics including maximum serum creatinine kinase level and the dose of beta-blocker between the 2 groups. LV ejection fraction increased significantly only in the optimal HR group at follow-up (from 42% to 54%; P = 0.001). The optimal HR group exhibited a more pronounced decrease in LV end-diastolic diameter (from 57 to 52 mm) compared to the sub-optimal HR group (from 58 to 56 mm).Optimal HR, which was calculated using a previously proposed formula, was associated with more substantial post-infarct LV reverse remodeling. The implications of aggressive HR modulation targeting theoretically ideal HR among those with systolic heart failure following ACS are the focus of our investigation here.

Public control of coal resources of the United States’ Powder River Basin for a managed decarbonization transition

Abstract The United States (US) has set aggressive targets for reaching a carbon pollution-free power sector by 2035 and a net-zero economy by 2050. Reaching these goals will require both rapid expansion of zero- and negative-carbon infrastructure and a phase-out of unabated fossil fuel infrastructure. New subsidy and regulatory actions focus on eliminating coal emissions at the point of consumption either through carbon capture and storage (CCS) or coal-fired power plant retirement. Yet, these pathways have opposite implications for coal production: CCS is coal intensive, while coal retirement is not. Despite a record of chaotic and harmful transition and significant social scientific research suggesting better outcomes from managed, coordinated decline, these mechanisms rely on uncoordinated private decision making by mine and plant owners. Coal mining has rapidly declined since peak production in 2008. Production has dropped by half; bankruptcies are the norm; and coal mine and power plant host communities have experienced highly disruptive decline as a result of this unmanaged transition. Given this history, we argue the current market-based, plant-driven governance approach could worsen transition challenges, including potentially stranding costly CCS investments. We argue that the US should complement its extensive investments in technology demonstrations with innovative governance demonstrations to facilitate a just energy transition. Specifically, we argue that the Powder River Basin, which is the US’ largest coal basin and consists primarily of federally leased coal, should be brought under public control for managed decline both to meet emissions reduction targets and advance a just energy transition.

Composite Anode for PEM Water Electrolyzers: Lowering Iridium Loadings and Reducing Material Costs with a Conductive Additive.

To enable the greater installed capacity of proton exchange membrane water electrolysis (PEMWE) for clean hydrogen production, associated costs must be lowered while achieving high current density performance and durability. Scarce and expensive iridium (Ir) required for the oxygen evolution reaction (OER) is a large contributor to the overall cost, yet high loadings of Ir (1-2 mgIr cm-2) are currently needed in commercial systems to maintain sufficient activity, conductivity, and durability. To meet the aggressive targets for low Ir loadings, we introduce a composite anode approach using a conductive additive that is less expensive than Ir to facilitate robust, high-performance operation with low Ir loading by retaining electrode thickness and in-plane electrical conductivity. In this demonstration, we use platinum (Pt) black as the conductive additive given its high electrical conductivity, acid stability, and current price one-fifth that of Ir. Using a high-activity commercial Ir oxide (IrO x ) catalyst, we present a 95% Ir loading reduction and 80% cost reduction of the anode catalyst materials while maintaining equal current density performance at a cell voltage of 1.8 V. Furthermore, we show enhanced stability of a composite anode compared to an IrO x anode with loadings of 0.10 mgIr cm-2 via accelerated stress test (AST) and postmortem imaging. With this approach, we show promising results toward lowering Ir loadings and material costs, addressing a significant barrier to the widespread adoption of PEMWE for clean hydrogen production.

Intelligent drugs based on notch protein remodeling: a defensive targeting strategy for tumor therapy

In the process of tumor treatment, systemic drug administration is hindered by biological barriers, leading to the retention of a large number of drug molecules in healthy tissues and causing unavoidable side effects. The precise deployment of drugs at the tumor site is expected to alleviate this phenomenon. Here, we take endostatin and Her2 (+) tumors as examples and develop an intelligent drug with simple “wisdom” by endowing mesenchymal stem cells (MSCs) with an intelligent response program (iMSCEndostatin). It can autonomously perceive and distinguish tumor cells from non-tumor cells, establishing a logical connection between tumor signals and drug release. Enable it to selectively deploy drugs at the tumor site, thereby locking the toxicity of drugs at the tumor site. Unlike traditional aggressive targeting strategies that aim to increase drug concentration at the lesion, intelligent drugs are more inclined to be defensive strategies that prevent the presence of drugs in healthy tissues.

The Expansion of Incentive (Performance-Based) Regulation of Electricity Distribution and Transmission in the United States

I examine developments in the application of performance-based regulation (PBR) to electricity distribution and transmission in the United States. Applications of comprehensive PBR to electricity distribution had been slow to diffuse in the U.S. prior to roughly 2000. PBR mechanisms are now being applied more frequently to electricity distribution, which reflects the changing structure of the electric power industry and the increasing obligations that are being placed on electric distribution companies. The new obligations are a consequence primarily of aggressive targets for decarbonizing the electricity sector in nearly half the states and the goal of using “clean” electricity to electrify transportation, buildings, and other sectors. PBR should be viewed as a set of “building blocks” that can be adopted in various combinations and should recognize that PBR and traditional cost-of-service regulation (COSR) are properly viewed as complements rather than substitutes. Recent reforms in the regulation of distribution companies in Great Britain—“RIIO”—have been influential in the U.S. The main reforms contained in RIIO are discussed. There has been essentially no application of PBR by the Federal Energy Regulatory Commission (FERC) to owners of transmission assets or to independent transmission operators. FERC has applied targeted incentives to encourage investment in transmission facilities and membership in independent system operator organizations. However, the regulation of transmission rates relies primarily on COSR in the form of formula rates and has poor incentive properties. Regulation of independent system operators is a challenge because they are non-profit organizations with no equity to put at risk. Reforms here are suggested.

Headgear use in girls' lacrosse-stakeholders not ready for change.

Mandating headgear for field players in girls' lacrosse to reduce head injuries, including concussion, has been heavily debated. However, research regarding the need and effectiveness of mandated headgear use in girls' lacrosse is still developing. Therefore, this qualitative study aimed to identify the need for and barriers to the development of mandated headgear use policies in girls' lacrosse in Ohio. We conducted six virtual focus groups, three with concussion experts (clinicians and researchers) and three with girls' lacrosse stakeholders (high school players, parents, coaches, and officials). A focus group guide was developed to explore study participants' perceptions and opinions on concussion in girls' lacrosse, headgear use among players, and policies and policy development related to headgear use or a headgear mandate. We developed the codebook using an inductive and iterative approach based on focus group transcripts and used ATLAS.TI to code and analyze the transcript data. Concussion experts and stakeholders understood the potential consequences of concussion but did not perceive concussion as a pervasive problem in girls' lacrosse. The prevention of head and facial injuries was regarded as a potential benefit of headgear use. However, stakeholders expressed that the myriad of arguments discussed opposing mandated headgear use including increased aggressive play and/or targeting, concerns over changes in the game, and cost strongly outweighed the benefits. Finally, both concussion experts and stakeholders identified multiple organizations, including USA Lacrosse, who could act as facilitators and/or barriers to developing, enacting, and implementing headgear policies. Concussion experts and stakeholders identified possible reasons for headgear use related to injury prevention but also identified several important barriers to the development of a headgear mandate for girls' lacrosse in Ohio.

Birds of a feather age together: telomere dynamics and social behavior predict life span in female Japanese quail (Coturnix japonica).

Social support is vital for mental and physical health and is linked to lower rates of disease and early mortality. Conversely, anti-social behavior can increase mortality risks, both for the initiator and target of the behavior. Chronic stress, which also can increase mortality, may serve as an important link between social behavior and healthy lifespan. There is a growing body of literature in both humans, and model organisms, that chronic social stress can result in more rapid telomere shortening, a measure of biological aging. Here we examine the role of anti-social behavior and social support on physiological markers of stress and aging in the social Japanese quail, Coturnix Japonica. Birds were maintained in groups for their entire lifespan, and longitudinal measures of antisocial behavior (aggressive agonistic behavior), social support (affiliative behavior), baseline corticosterone, change in telomere length, and lifespan were measured. We found quail in affiliative relationships both committed less and were the targets of less aggression compared to birds who were not in these relationships. In addition, birds displaying affiliative behavior had longer telomeres, and longer lifespans. Our work suggests a novel pathway by which social support may buffer against damage at the cellular level resulting in telomere protection and subsequent longer lifespans.

Charging Aggression as a Crime against Humanity? Revisiting the Proposal after Russia's Invasion of Ukraine

Abstract Much discussion over Russia's 2022 invasion of Ukraine focuses on the inability to charge aggression. However, another approach might be available: charging this under the ICC crimes against humanity (CAH) residual clause. First proposed in 2010 by Benjamin Ferencz, who lamented the circumscribed reach of aggression under the ‘Kampala Compromise’, the proposal has met with scepticism, primarily given that textbook aggression targets military forces, not civilians. Yet, civilian populations disproportionately bear the brunt of the violence of modern aggression (often being its direct targets). Russia's 2022 invasion is but the most recent and compelling example. Thus, this article resuscitates Ferencz's proposal, arguing that Russian leaders could be charged with using illegal force as a CAH under the residual clause. This approach would have practical advantages: initiating aggression in the Kremlin links liability to Putin much more directly for killing Ukrainian civilians, and charging it as CAH opens human victims to ICC participation and reparations. There are theoretical advantages, too, with utilitarian/retributive objectives better satisfied. Moreover, Ferencz's approach is better than recently proposed alternatives: using aggression merely as a gravity/liability modes/sentencing enhancer or alleging breach of the right to self-determination as the residual clause gravamen (arguably creating problems with victim group identification).

A US perspective on closing the carbon cycle to defossilize difficult-to-electrify segments of our economy.

Electrification to reduce or eliminate greenhouse gas emissions is essential to mitigate climate change. However, a substantial portion of our manufacturing and transportation infrastructure will be difficult to electrify and/or will continue to use carbon as a key component, including areas in aviation, heavy-duty and marine transportation, and the chemical industry. In this Roadmap, we explore how multidisciplinary approaches will enable us to close the carbon cycle and create a circular economy by defossilizing these difficult-to-electrify areas and those that will continue to need carbon. We discuss two approaches for this: developing carbon alternatives and improving our ability to reuse carbon, enabled by separations. Furthermore, we posit that co-design and use-driven fundamental science are essential to reach aggressive greenhouse gas reduction targets.

Fast Foods Consumption Impact on Physical Health of Adolescent Girls

The fast food industry in India became the fastest growing company in the last decade as many global companies entered the market to expand their market share and region of operations. Adolescents are an aggressive target of food marketing messages (primarily for unhealthy foods) and are susceptible to these messages due to their developmental vulnerabilities and the influence of peer groups. The negative impact on adolescent weight and insulin resistance was seen in all participants who ate frequently at fast food restaurants.

Macroeconomic impacts and co-benefits of deep-decarbonization in Thailand

The updated Nationally Determined Contributions (NDC) in 2022 of Thailand includes an aggressive GHG emission reduction target of 40% in 2030 from its baseline emissions. However, the macroeconomic impacts and co-benefits associated with reducing GHG emissions are not addressed. This study analyzes the macroeconomic implications and co-benefits of GHG emission reduction in Thailand to achieve the NDC and net zero emission (NZE) targets by 2050 using the AIM/Hub-Thailand model. This paper provides co-benefits for Thailand on ambitious long-term GHG emission reduction targets. Considering the co-benefit analysis in the policy documents will provide holistic insights on the positive impacts of GHG mitigation. Results show that Thailand would have to bear a GDP loss of 7.7% in 2050 compared to the BAU level if the net zero emissions need to be achieved. Fuel switching from fossil fuel to electricity in the demand side and improvement of technologies in the power sector also reduces air pollutant emissions. The increasing dependence on domestic energy supply in the NZE scenario will make the country less vulnerable to the fluctuating prices in the international energy market. In terms of trade-offs, the land use for sustainable biomass in both the NDC and NZE scenarios will be larger than in the BAU scenario. Results show better land use for biomass production and higher yields in agricultural production. Moreover, the achievement of NZE pathway will require effective usage of land area and better use of energy resources, thereby making the country more energy secure.

Measuring the Health Co-Benefits of Air Pollution Interventions on Premature Deaths in Canadian Cities

Background: Climate change has significant consequences on human health. Cities are especially vulnerable, where air pollution is a major environmental health risk. Premature mortality (i.e., deaths before age 75) is a robust population health outcome amenable to targeted policy and programmatic interventions. We used the Premature Mortality Population Risk Tool augmented with environmental data (PreMPoRT-ENV) to predict the 5-year incidence of premature deaths under air pollution reduction policies. Methods: PreMPoRT-ENV is a sex-specific Weibull accelerated failure time survival model that uses the Canadian Community Health Survey (CCHS) linked to the Canadian Vital Statistics Death Database and environmental data. We applied PreMPoRT-ENV to the 2016–2017 CCHS cycles and simulated Canadian Ambient Air Quality Standards targets to predict their impact on premature mortality across Canadian census metropolitan areas. We simulated capping annual mean particulate matter 2.5 microns or less in diameter (PM2.5) and nitrogen dioxide (NO2), as well as reducing air pollutants by 10% and 25% plus capping. Results: The weighted sample included 9,240,000 females and 9,260,000 males. Capping PM2.5 to 8.8 μg/m3 and NO2 to 12.0 ppb resulted in 12 per 100,000 fewer predicted premature deaths than observed exposures over 5 years (1,110 fewer absolute premature deaths). Reducing air pollutants by 10% and 25% plus capping resulted in even fewer predicted premature deaths. Conclusion: Our study highlights how to use a model that predicts premature mortality to provide estimates of the health impacts of environmental vulnerabilities. Results suggest that more aggressive targets may be needed to further realize population health benefits.

NYSolarCast: A solar power forecasting system for New York State

Solar energy generation capacity will need to be greatly increased to meet aggressive clean energy targets by New York State (NYS), which are 70% renewable energy (RE) generation by 2030, and 100% by 2040. Because solar energy is a variable, weather-driven resource, accurate forecasts of solar energy generation both in nowcast (intra-day) and day-ahead time horizons are necessary for electric utilities and independent system operators, as they maintain grid stability and maximize RE use.Meeting this need for NYS, a gridded, open-source solar power forecasting system called NYSolarCast was developed (https://github.com/ncar/NYSolarCast_delivery). NYSolarCast makes 15-min resolution predictions of global horizontal irradiance (GHI) on a 3-km grid covering all of NYS, which are then used to estimate solar power generation both for select utility-scale PV plants (15-min resolution) and for zone-aggregated distributed PV (1-h resolution). The statewide GHI forecasts are made by applying the StatCast statistical forecasting model, which is trained on over two years of GHI observations from pyranometers at all 126 NYS Mesonet stations and gridded numerical weather prediction forecasts from both the Weather Research and Forecasting model tuned for solar applications (WRF-Solar®) and NOAA’s operational High-Resolution Rapid Refresh (HRRR) model. Forecasts are made at each NYS Mesonet site and then blended outward into the rest of the grid. This paper gives an overview of NYSolarCast performance for intra-day (0–6-h) GHI and power forecasts during a one-year period.

The Shift of Philippine Architectural Media toward Digitalization (2018-2023)

This research examines how Philippine architectural communication experienced a renewal after the pandemic crisis. First, through a shift from the country’s flagship architectural magazine, BluPrint, toward a personally initiated digital platform, Kanto. Since BluPrint started to become digital in 2018, the publishers aimed at more aggressive targets for new articles. When Covid hit the Philippines in the beginning of 2020, it made BluPrint suffer and confused. The publisher company focused on the business side to diminish the encountered deficit. They started reaching out to a common lifestyle market but the journalists wished to continue addressing architects and the public interested in architecture. As the company wanted to broaden the target, the journalists felt that most of their content did not fit for that expansion. As result of the tension, in December 2020, most of BluPrint’s former staff decided to leave and “migrate” for Kanto. Kanto, a digital platform was created out of the former personal blog of one the migrant journalists to be an intellectual venue for art and architecture advocacy. Upon this departure, BluPrint’s publisher noticed that not only the magazine could not be published for a whole year in 2020 but also, it lost its journalists for a new competitor. Thus after a significant interruption, the publisher decided to renew BluPrint with a fully new staff. This marks the second shift, the complete digital transition of the originally printed, then blended BluPrint. These dynamic communication aspects of architecture, construction and built environment have not yet been sufficiently investigated, unlike their physical aspects. In order to elaborate findings, after a review of literature on worldwide shifts towards digital media, this paper matches observations on the institutional history and performance of BluPrint and Kanto with a second line of premises, qualitative statements. It reviews how former BluPrint, now migrant journalists are successful on the digital platform Kanto, in a fully different organizational and financial system. It also presents how BluPrint also experienced a renewal with its fully new staff. Behind both shifts, an underlying dilemma between financial success and content success became sharper in times of the increasing and now almost obligatory digitalization. Events and festivals are strongly needed by both online publications to create a tangible and interactive basis for gathering experiences of architecture lovers among themselves and with their “star architects”. In summary, the digitalization established a wider variety of journalistic forms which appear in more spontaneous, less focused presentations. While BluPrint strives after a wider viewership with an entertaining character, Kanto tries to deliver more depth in the profession embedded in a variety of artistic and cultural forms. As conclusion, in both shifts, content curation strategies prevailed over technological skills. The described genre shifts propelled deeper changes in both the content and nature of architectural discourse in the Philippines. The shifts also drew up a new relationship pattern between practicing architects, contractors and architectural media.

New horizons in frailty identification via electronic frailty indices: early implementation lessons from experiences in England and the United States.

Frailty represents an integrative prognostic marker of risk that associates with a myriad of age-related adverse outcomes in older adults. As a concept, frailty can help to target scarce resources and identify subgroups of vulnerable older adults that may benefit from interventions or changes in medical management, such as pursing less aggressive glycaemic targets for frail older adults with diabetes. In practice, however, there are several operational challenges to implementing frailty screening outside the confines of geriatric medicine. Electronic frailty indices (eFIs) based on the theory of deficit accumulation, derived from routine data housed in the electronic health record, have emerged as a rapid, feasible and valid approach to screen for frailty at scale. The goal of this paper is to describe the early experience of three diverse groups in developing, implementing and adopting eFIs (The English National Health Service, US Department of Veterans Affairs and Atrium Health-Wake Forest Baptist). These groups span different countries and organisational complexity, using eFIs for both research and clinical care, and represent different levels of progress with clinical implementation. Using an implementation science framework, we describe common elements of successful implementation in these settings and set an agenda for future research and expansion of eFI-informed initiatives.

Effectiveness of novel oral hygiene instruction avoiding inattentional blindness using an application for unique plaque control record calculation: A randomized clinical trial.

This study was performed to estimate the effectiveness of novel oral hygiene instruction (OHI) focusing on areas with deep periodontal pockets for reduction of periodontal inflammation. Because stained areas on the plaque chart do not always correspond to the areas with deep periodontal pockets, conventional OHI based on O'Leary's plaque control record (PCR) often provides guidance inconsistent with the target area. This randomized clinical trial involved two groups: (1) OHI based on the PCR limited in deep pocket sites (novel OHI group) and (2) OHI based on O'Leary's PCR (conventional OHI group). The unique PCR (aggressive target for PCR [agPCR]; only counting the plaque-stained areas with PD at ≥4 mm sites) for the novel OHI was calculate by dedicated expression program. The probing depth (PD), bleeding on probing (BOP), and periodontal inflamed surface area (PISA) were obtained at the baseline and 5 to 6 months later. The approximation curve with PISA before and after instruction indicated that the PISA converged to a lower value after instruction in the novel OHI group. The approximation curve with the improvement rate of the PISA and agPCR showed a positive correlation in the novel OHI group but no correlation in the conventional OHI group. Control of inflammation was more effective in the novel OHI group. These results suggest that this novel OHI technique using our developed application could be used as a strategy to improve the effectiveness of brushing instruction.

The cost of aggressive electrification targets – Who bears the burden without mitigating policies?

To reduce greenhouse gas emissions, governments worldwide have set aggressive targets for a transition from internal combustion engine vehicles (ICEVs) to electric vehicles (EVs). Considering California’s electrification goals for the light-duty vehicle sector as a case study, we estimate the economic cost of achieving aggressive electrification targets based on total cost of ownership (TCO) analysis. When TCO estimates incorporate both technology costs and relevant household factors (income, fleet size, dwelling type), EVs reach cost parity with ICEVs for most consumer segments in the next decade, around 2032 or later. However, the share of households with cost benefits or consumer surplus from the EV transition does not reach 100% even by 2035 without mitigating policies and the benefits and loss from EV adoption vary across sociodemographic groups over the transition period. Before 2030, high-income (middle-income) households bear an average of 35% (59%) of the $2.8 billion transition cost; and after 2030 out of the total 2 billion transition cost incurred in this period low-income households incur an average 41% of the loss. These findings highlight the long-term need for mitigating policies like monetary incentives to achieve aggressive electrification targets even if TCO parity is achieved at the vehicle-level and the temporal distribution of the household segments that will need these policies to transition to EVs.

GATA3 Positively Correlates with BCL2 Expression in Indolent and Aggressive Histological Types of Cutaneous Basal Cell Carcinoma.

Some histological basal cell carcinoma (BCC) types demonstrate more aggressive behavior than others. They are known as high-risk BCC and are more challenging in therapy, contrary to indolent (low-risk) BCC types. Identifying novel protein markers to predict aggressiveness and potential therapeutic targets in challenging cases is recommended. GATA3 is a transcription factor critical for epithelial and lymphocytic differentiation. This study investigated the immunohistochemical expression of GATA3 in indolent and aggressive BCC and its association with BCL2 expression. Retrospectively collected indolent and aggressive BCC groups (24 cases each) were immunohistochemically stained with anti-GATA3 and BCL2 antibodies. The mean expression score (by area percentage) and TIL counts were determined and compared using ImageJ analysis. Stromal tumor-infiltrating lymphocytes (TIL) were counted per high-power field (HPF) on hematoxylin and eosin (H&E) staining. GATA3 and BCL2 expressions were significantly higher in the indolent group than in the aggressive group. GATA3 expression significantly correlated with BCL2 score and TIL counts. Higher GATA3 expression was significantly associated with a more indolent BCC histological type, higher BCL2 expression, and higher TIL count. GATA3 is a possible target for immunomodulation experiments to improve BCC immunotherapy outcomes.