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Susmita Aryal,1 Sanghyo Park,1 Hyungkyu Park,1 Chaewon Park,1 Woo Cheol Kim,1 Deepika Thakur,1 Young-Joo Won,2 Jaehong Key1 1Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon Province, 26493, Korea; 2Division of Health Administration, College of Software Digital Healthcare Convergence, Yonsei University, Wonju, Gangwon State, 26493, KoreaCorrespondence: Jaehong Key, Department of Biomedical Engineering, Yonsei University, 1 Yonseidae-Gil, Wonju, Gangwon State, 26493, Korea, Tel +82-33-760-2857, Fax +82-33-760-2919, Email jkey@yonsei.ac.krAbstract: Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.Keywords: lung cancer, clinical trials, nanomedicine, oral, intravenous, inhalation

After days of intense solar activity, active region AR3664 launched seven CMEs toward Earth producing an extreme G5 geomagnetic storm commencing at 17:05 UT on 10 May 2024. The storm impacted power grids, disrupted precision navigational systems used by farming equipment, and generated aurora seen around the globe. The storm produced remarkable effects on composition, temperature, and dynamics in the Earth's thermosphere that were observed by NASA's Global‐scale Observations of the Limb and Disk (GOLD) mission and are reported here for the first time. We use synoptic disk images of ΣO/N2 and neutral temperature (at ∼160 km) measured by GOLD to directly link dynamics resulting from the storm with dramatic changes in thermospheric composition and temperature. We observe a heretofore unseen spatial morphology simultaneously in ΣO/N2, neutral temperature, and total electron content. Equator‐to‐pole temperature differences reach 400 K with high latitude peak neutral temperatures near 160 km exceeding 1400 K. Plain Language Summary: On Saturday 10 May 2024, the sun launched a wave of energized plasma toward the Earth. A large disturbance in the Earth's magnetic field associated with the solar wind resulted in an extreme geomagnetic storm. The storm impacted power grids, disrupted navigational systems used by farming equipment, and produced aurora seen around the globe. The storm produced remarkable effects in the Earth's upper atmosphere that were observed by NASA's Global‐scale Observations of the Limb and Disk (GOLD) mission. In this letter, we use images measured by GOLD to directly link atmospheric dynamics resulting from the May 10–12 superstorm with dramatic changes in composition, temperature, and global circulation in the Earth's upper atmosphere. We observe previously unseen structure in the upper atmosphere associated with equator‐to‐pole temperature differences exceeding 400 K. Peak neutral temperatures near 160 km exceed 1400 K at high latitudes. Key Points: GOLD disk images of ΣO/N2 and neutral temperature link storm time dynamics with changes in thermospheric composition and temperatureWe observe a previously unseen spatial morphology in ΣO/N2, neutral temperature, and total electron contentPeak equator‐to‐pole temperature differences exceed 400 K but relax to pre‐storm conditions well before ΣO/N2 [ABSTRACT FROM AUTHOR]

Observations of far‐ultraviolet (FUV) dayglow by the Global‐scale Observations of Limb and Disk (GOLD) mission provide an opportunity for quantifying the global‐scale response of the thermosphere to solar extreme‐ultraviolet variability and geomagnetic activity. Relative temperature changes can be measured by monitoring changes in the rotational structure observed in molecular nitrogen Lyman‐Birge‐Hopfield (LBH) band emissions. We present a new technique for deriving effective neutral temperatures from GOLD FUV observations using optimal estimation fits to spectra containing LBH band emissions. We provide an overview of the theoretical basis for the GOLD Level 2 TDISK algorithm. Effects on derived effective neutral temperatures from instrument artifacts and particle background are reviewed. We also discuss GOLD Level 1C DAY and Level 2 TDISK data products and present representative examples of each. We show that effective neutral temperatures vary with local time, exhibit a strong dependence on season and solar zenith angle, and correlate strongly with geomagnetic and solar activity. Finally, we present results from a preliminary data product validation that show good agreement with coincident GOLD exospheric temperatures and predictions from a global reference atmospheric model. Plain Language Summary: Observations of the Earth's daytime ultraviolet emission by the Global‐scale Observations of Limb and Disk (GOLD) mission provide an opportunity to determine how geomagnetic activity alters the temperature of Earth's upper atmosphere and enable us to quantify the global‐scale response of the middle thermosphere to solar variability. We provide an overview of the GOLD upper atmosphere neutral temperature data product and present representative measurement examples. We show that derived temperatures vary with local time, exhibit a strong seasonal dependence, correlate strongly with geomagnetic and solar activity, and show good agreement with coincident GOLD exospheric temperatures and atmospheric model predictions. Key Points: Neutral temperatures derived from binned spectra of far ultraviolet emission observed by the Global‐scale Observations of the Limb and Disk (GOLD) instrument are presentedNeutral temperatures vary with local time, show a strong seasonal dependence, and correlate strongly with geomagnetic and solar activityA preliminary validation shows good agreement with coincident GOLD exospheric temperatures and a global reference atmospheric model [ABSTRACT FROM AUTHOR]

A unique phenomenon--A geomagnetically quiet time merging of Equatorial Ionization Anomaly (EIA) crests, leading to an X-pattern (EIA-X) around the magnetic equator--has been observed in the night-time ionospheric measurements by the Global-scale Observations of the Limb and Disk mission. The pattern is also reproduced in an ionospheric model that assimilates slant Total Electron Content from Global Navigation Satellite System and Constellation Observing System for Meteorology, Ionosphere, and Climate 2. A free-running whole atmospheric general circulation model simulation reproduces a similar pattern. Due to the similarity between measurements and simulations, the latter is used to diagnose this heretofore unexplained phenomenon. The simulation shows that the EIA-X can occur during geomagnetically quiet conditions and in the afternoon to evening sector at a longitude where the vertical drift is downward. The downward vertical drift is a necessary but not sufficient condition. The simulation was performed under constant low-solar and quiescent-geomagnetic forcing conditions, therefore we conclude that EIA-X can be driven by lower-atmospheric forcing. [ABSTRACT FROM AUTHOR]

Susmita Aryal,1,* Hyungkyu Park,1,* James F Leary,2 Jaehong Key11Department of Biomedical Engineering, Yonsei University, Wonju, Gangwon-do 26493, South Korea; 2Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47906, USACorrespondence: Jaehong KeyDepartment of Biomedical Engineering, Yonsei University, 1 Yonseidae-gil Wonju, Gangwon-do 26493, South KoreaTel +82 33 760 2857Fax +82 33 760 2919Email jkey@yonsei.ac.kr*These authors contributed equally to this workAbstract: Recent breakthroughs in nanoparticle research have led to improved drug delivery and have overcome problems associated with normal drug delivery methods. Optimizing the design of nanoparticles in terms of controlled size, shape, and surface chemistry of nanoparticles can maximize the therapeutic efficacy. To maximize therapeutic effects, advanced formulation and fabrication methods have been developed. Biomedical applications of nanoparticles produced using the new fabrication techniques, including drug delivery and molecular imaging, have been widely explored. This review highlights the simple and versatile manufacturing techniques that can be used in the development of new types of nanoparticles that have strictly controlled physiochemical properties and their multifaceted advantages in drug delivery and molecular imaging.Keywords: fabrication, lithography, cancer, advanced manufacturing method

John C Licciardone,1 Robert J Gatchel,2 Nicole Phillips,3 Subhash Aryal4 1Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA; 2Department of Psychology, College of Science, University of Texas at Arlington, Arlington, TX, USA; 3Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA; 4Department of Biostatistics and Epidemiology, Institute for Patient Safety, University of North Texas Health Science Center, Fort Worth, TX, USA Background: Low back pain is the leading cause of disability worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as the first-line pharmacologic therapy for subacute or chronic low back pain, with opioids reserved for patients who fail on NSAIDs. CYP2D6, CYP2C9, and CYP2C19 genes have variants that place patients using analgesics at risk for adverse events. However, precision medicine based on pharmacogenetically informed prescribing is becoming more feasible as genotyping costs decline. This study aims to compare opioids vs NSAIDs in treating adults with subacute or chronic low back pain under the alternative models of usual care and precision medicine.Methods: An observational cohort study within the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION) will be used to simulate a randomized controlled trial. Patients using opioids and NSAIDs will be optimally matched at baseline using propensity scores. A saliva sample will also be collected to determine patient genotypes for drug metabolism based on CYP2D6 (single-gene model) and CYP2D6, CYP2C9, and CYP2C19 (multigene model). Prescribing that is concordant with pharmacogenetically informed care under these models will be considered “low risk”, whereas discordant prescribing will be considered “high risk”. Primary outcomes will be assessed over 6 months using a Numerical Rating Scale for pain, the Roland-Morris Disability Questionnaire, and the Drug Adverse Events Index. Secondary outcomes will be assessed using quality-of-life measures. An estimated 600 patients will be enrolled to acquire at least 400 patients after attrition and allowing for unmatched patients. This will achieve a statistical power of at least 80% in detecting the effect sizes ranging from 0.35 (small–medium effect) to 0.69 (medium–large effect).Discussion: This PRECISION Pain Research Registry study builds on the concepts espoused in the Precision Medicine Initiative and addresses long-term goals established by the National Institutes of Health by assessing how precision medicine may prevent and treat chronic pain. Keywords: PRECISION Pain Research Registry, low back pain, physical functioning, quality of life, opioids, codeine, nonsteroidal anti-inflammatory drugs, pharmacogenetics, precision medicine, biopsychosocial model

The 2022 Tongan volcanic eruption released significant energy into the atmosphere. Tropospheric satellite images show that the eruption generated pressure waves that traveled globally. The Global Observation of the Limb and Disk (GOLD) mission observed significant wave‐like thermospheric temperature perturbations (>100 K) from 12 to 16 UT. These temperature perturbations' spatial curvatures and arrival times are initially similar to the tropospheric wave‐fronts but differ significantly with eastward propagation. The perturbations had a phase speed of ∼300–400 m/s and wavelengths greater than 2,400 km. Near‐concurrent Ionospheric Connection Explorer neutral wind measurements suggest that the eruption's effects reversed the direction of the prevailing thermospheric zonal winds around the perturbed regions. The eruption's global and whole atmospheric effects provide a unique opportunity to study how different atmospheric layers exchange energy and momentum during explosive events. GOLD's synoptic observations are uniquely positioned to study these effects in the middle thermosphere. Plain Language Summary: The powerful Hunga Tonga‐Hunga Ha'apai volcanic eruption on 15 January 2022, at 4:15 UT was visible from space. Satellite images in the troposphere (near 10 km altitude) show concentric pressure waves emanating from the eruption center that travel globally. Wave signatures were seen across multiple atmospheric layers. NASA's Global‐scale Observations of Limb and Disk mission observed its signatures near 150 km altitude as neutral temperature perturbations. Explosive events that affect multiple atmospheric layers allow us to observe how the different atmospheric layers exchange energy and momentum in response to an impulsive source. In this paper, we present an analysis of the eruption induced temperature perturbation in the middle thermosphere. Key Points: Global‐scale Observations of Limb and Disk mission observed global‐scale thermospheric neutral temperature perturbations (>100 K) induced by the Tongan volcanic eruptionThe phase speeds of the perturbations are around 300–400 m/s with a large wavelength (>2,400 km)The zonal winds near the peak temperature perturbation reverse from eastward to westward [ABSTRACT FROM AUTHOR]

Shambhu Aryal,1 Enrique Diaz-Guzman,2 David M Mannino3 1Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Durham, NC, 2Division of Pulmonary, Allergy and Critical Care, University of Alabama, Birmingham, AL, 3Department of Preventive Medicine and Environmental Health, University of Kentucky, Lexington, KY, USA Abstract: Chronic obstructive pulmonary disease (COPD), one of the most common chronic diseases and a leading cause of death, has historically been considered a disease of men. However, there has been a rapid increase in the prevalence, morbidity, and mortality of COPD in women over the last two decades. This has largely been attributed to historical increases in tobacco consumption among women. But the influence of sex on COPD is complex and involves several other factors, including differential susceptibility to the effects of tobacco, anatomic, hormonal, and behavioral differences, and differential response to therapy. Interestingly, nonsmokers with COPD are more likely to be women. In addition, women with COPD are more likely to have a chronic bronchitis phenotype, suffer from less cardiovascular comorbidity, have more concomitant depression and osteoporosis, and have a better outcome with acute exacerbations. Women historically have had lower mortality with COPD, but this is changing as well. There are also differences in how men and women respond to different therapies. Despite the changing face of COPD, care providers continue to harbor a sex bias, leading to underdiagnosis and delayed diagnosis of COPD in women. In this review, we present the current knowledge on the influence of sex on COPD risk factors, epidemiology, diagnosis, comorbidities, treatment, and outcomes, and how this knowledge may be applied to improve clinical practices and advance research. Keywords: chronic obstructive lung disease, sex, smoking, comorbidity, sex bias

Themospheric conditions during a minor geomagnetic event of 3 and 4 February 2022 has been investigated using disk temperature (Tdisk) observations from Global‐scale Observations of the Limb and Disk (GOLD) mission and model simulations. GOLD observed that the Tdisk increases by more than 60 K during the storm event when compared with pre‐storm quiet days. A comparison of the Tdisk with effective temperatures (Teff, i.e., a weighted average based on airglow emission layer) from Mass Spectrometer Incoherent Scatter radar version 2 (MSIS2) and Multiscale Atmosphere‐Geospace Environment (MAGE) models shows that MAGE outperforms MSIS2 during this particular event. MAGE underestimates the Teff by about 2%, whereas MSIS2 underestimates it by 7%. As temperature enhancements lead to an expansion of the thermosphere and resulting density changes, the value of the temperature enhancement observed by GOLD can be utilized to find a GOLD equivalent MSIS2 (GOLD‐MSIS) simulation—from a set of MSIS2 runs obtained by varying geomagnetic ap index values. From the MSIS‐GOLD run we found that the thermospheric density enhancement varies with altitude from 15% (at 150) to 80% (at 500 km). Independent simulations from the MAGE model also show a comparable enhancement in neutral density. These results suggest that even a modest storm could impact the thermospheric densities significantly and GOLD data can be used to improve the empirical and assimilative models of the thermosphere. Plain Language Summary: High speed plasma from the sun can bring energy, momentum, and particles into the Earth's upper atmosphere triggering a geomagnetic storm, which disturbs the thermosphere‐ionosphere (TI) system. It is observed that even minor geomagnetic events can have a significant impact on the TI system. In this work we have investigated the neutral properties of the thermosphere during a minor geomagnetic event using NASA‐Global‐scale Observations of the Limb and Disk (GOLD) mission observations. By calibrating the Mass Spectrometer Incoherent Scatter radar version 2 empirical model based on the temperature change observed by GOLD, we have found that the thermospheric density increased by 15% (at 150) to 80% (at 500 km). These results demonstrates that the GOLD data can help in improving thermospheric empirical models. Also, they can help satellite‐drag and space weather forecasters to find ways to improve their products. Key Points: Global‐scale Observations of the Limb and Disk (GOLD) observed a ∼60 K rise in lower‐to‐middle thermospheric temperature during a minor geomagnetic storm on 3–4 February 2022GOLD‐informed MSIS calculations indicate an increase in density by 15% (at 150) to 80% (500 km), which agrees with Multiscale Atmosphere‐Geospace Environment estimationGOLD Tdisk can be used in empirical and data assimilative forecasting models to improve thermospheric specifications [ABSTRACT FROM AUTHOR]

Global‐scale Observations of Limb and Disk (GOLD) disk measurements of far ultraviolet molecular nitrogen band emissions are used to retrieve temperatures (Tdisk), which are representative of lower thermospheric altitudes. The present investigation studies the response of lower thermospheric temperatures to geomagnetic activities of varying magnitudes. In this study, it has been observed that Tdisk increases over all latitudes in response to enhanced geomagnetic activity. The increase in temperature is proportional to the strength of the geomagnetic activity and is greater at higher latitudes. Temperature enhancements vary from 10s to 100s of Kelvins from low‐ to mid‐latitudes. Local time behavior shows that pre‐noon enhancements in temperatures, during relatively stronger geomagnetic activities, are greater compared to afternoon, which may be caused by the combined action of daytime dynamics and geomagnetic forcing. This study, thus, demonstrates the utility of GOLD Tdisk when investigating the effects of dynamical and external forcings in the thermosphere. Plain Language Summary: The thermosphere ionosphere system is influenced by waves from the lower atmosphere and solar and geomagnetic forcing from above. For such a coupled system it is important to decipher the relative influence of the two regimes of forcings. The recently launched Global‐scale Observations of Limb and Disk (GOLD) mission provides daytime thermospheric temperatures with unprecedented local time and spatial coverage. The thermospheric temperature over the Earth's disk visible from geostationary orbit is a first of its kind of measurement, which enables us to investigate the local time behavior over wide latitudinal coverage from 69°S to 69°N. We find that, during active geomagnetic conditions, the thermospheric temperature is enhanced across the whole visible hemisphere, with the largest temperature enhancements at higher mid‐latitudes. The local time behavior shows that the pre‐noon enhancement in temperature is greater compared to the afternoon, which demonstrates, for the first time, a systematic local time varying response of thermosphere to geomagnetic forcing. Key Points: Global‐scale Observations of Limb and Disk (GOLD) thermospheric temperature increases globally in response to geomagnetic activityThe increase in temperature is proportional to the strength of the activity and is greater at higher latitudesTemperature enhancement during active geomagnetic events is greater in the morning than that in the afternoon [ABSTRACT FROM AUTHOR]