bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal Air Medical Accidents in the United States (2000-2020)
Authors: Shekhar Aditya C. , Blumen Ira J. 
Published: February 2023

AbstractIntroduction:Currently, many airplanes and helicopters are used as air ambulances to transport high-acuity patients. Unfortunately, civilian air medical transport in the United States has experienced a significant number of serious and fatal accidents. At the moment, additional research is needed to identify what factors affect air medical safety.Methods:Accident reports from the National Transportation Safety Board (NTSB) were queried. Accident reports were analyzed if the accident occurred from 2000 through 2020, involved a helicopter or airplane on an air medical flight (as identified by the NTSB), and had at least one fatality. The date of the accident, the model of aircraft involved, and NTSB-determined probable causes of the accident were examined.Results:Eighty-seven (87) accidents and 239 fatalities took place from January 2000 through December 2020. Nearly three-fourths (72.4%) of fatalities occurred on helicopters, while just 27.6% occurred on airplanes. Interpreting the NTSB findings, various human factors probably contributed to 87.4% of fatalities. These include pilot disorientation, pilot errors, maintenance errors, impairment, fatigue, or weather misestimation. Nighttime-related factors probably contributed to 38.9% of fatalities, followed by weather-related factors (35.6%), and various mechanical failures (17.2%).Conclusion:These data show that the probable causes of fatal air medical accidents are primarily human factors and are, therefore, likely preventable. Developing a safety-first culture with a focus on human factors training has been shown to improve outcomes across a wide range of medical specialties (eg, anesthesia, surgery, and resuscitation). While there have been fewer fatal accidents in recent years, a continued emphasis on various training modalities seems warranted.
Placental nanoparticle gene therapy normalizes gene expression changes in the fetal liver associated with fetal growth restriction in a fetal sex-specific manner
Authors: Wilson Rebecca L. , Stephens Kendal K. , Jones Helen N. 
Published: February 2023

AbstractFetal growth restriction (FGR) is associated with increased risk of developing non-communicable diseases. We have a placenta-specific nanoparticle gene therapy protocol that increases placental expression of human insulin-like growth factor 1 (hIGF1), for the treatment of FGR in utero. We aimed to characterize the effects of FGR on hepatic gluconeogenesis pathways during early stages of FGR establishment, and determine whether placental nanoparticle-mediated hIGF1 therapy treatment could resolve differences in the FGR fetus. Female Hartley guinea pigs (dams) were fed either a Control or Maternal Nutrient Restriction (MNR) diet using established protocols. At GD30-33, dams underwent ultrasound guided, transcutaneous, intraplacental injection of hIGF1 nanoparticle or PBS (sham) and were sacrificed 5 days post-injection. Fetal liver tissue was fixed and snap frozen for morphology and gene expression analysis. In female and male fetuses, liver weight as a percentage of body weight was reduced by MNR, and not changed with hIGF1 nanoparticle treatment. In female fetal livers, expression of hypoxia inducible factor 1 (Hif1α) and tumor necrosis factor (Tnfα) were increased in MNR compared to Control, but reduced in MNR + hIGF1 compared to MNR. In male fetal liver, MNR increased expression of Igf1 and decreased expression of Igf2 compared to Control. Igf1 and Igf2 expression was restored to Control levels in the MNR + hIGF1 group. This data provides further insight into the sex-specific mechanistic adaptations seen in FGR fetuses and demonstrates that disruption to fetal developmental mechanisms may be returned to normal by treatment of the placenta.
Glyphosate-resistant horseweed control in glyphosate/glufosinate/2,4-D-resistant soybean with one- and two-pass herbicide programs
Authors: Duenk Emily , Soltani Nader , Miller Robert T. , Hooker David C. , Robinson Darren E. , Sikkema Peter H. 
Published: February 2023

AbstractGlyphosate-resistant (GR) biotypes of horseweed were first confirmed in southern Ontario in 2010 and have spread across southern Ontario. A total of four field experiments were conducted between 2021 and 2022 to determine GR horseweed control with one- and two-pass herbicide programs in glyphosate/glufosinate/2,4-D-resistant (GG2R) soybean. 2,4-D choline/glyphosate DMA, halauxifen-methyl, and saflufenacil applied preplant (PP) controlled GR horseweed by 59%, 72%, and 78% 8 wk after postemergence (POST) application (WAA-POST); there was no improvement of GR horseweed control when 2,4-D choline/glyphosate DMA was added to saflufenacil; in contrast, there was improved GR horseweed control when saflufenacil was added to 2,4-D choline/glyphosate DMA. Glufosinate and 2,4-D choline/glyphosate DMA applied POST controlled glyphosate-resistant horseweed by 71% and 86%, respectively, 8 WAA-POST. Two-pass herbicide programs of a PP followed by POST application provided greater GR horseweed control than a PP or POST herbicide applied alone. Glufosinate or 2,4-D choline/glyphosate DMA applied POST following 2,4-D choline/glyphosate DMA or halauxifen-methyl applied PP improved GR horseweed control by 29% to 38% and 24%, respectively at 8 WAA-POST. The application of 2,4-D choline/glyphosate DMA applied POST following saflufenacil applied PP improved control by 20% 8 WAA-POST; there was no improvement of GR horseweed control when glufosinate was applied POST following saflufenacil applied PP or when either POST herbicide was applied following saflufenacil + 2,4-D choline/glyphosate DMA applied PP. When used in a two-pass program, 2,4-D choline/glyphosate DMA POST provided 2% to 3% greater control of GR horseweed than glufosinate.
Mechanisms and Impacts of Earth System Tipping Elements
Authors: Wang Seaver , Foster Adrianna , Lenz Elizabeth A. , Kessler John D. , Stroeve Julienne C. , Anderson Liana O. , Turetsky Merritt , Betts Richard , Zou Sijia , Liu Wei , Boos William R. , Hausfather Zeke 
Published: February 2023

AbstractTipping elements are components of the Earth system which may respond nonlinearly to anthropogenic climate change by transitioning toward substantially different long‐term states upon passing key thresholds or “tipping points.” In some cases, such changes could produce additional greenhouse gas emissions or radiative forcing that could compound global warming. Improved understanding of tipping elements is important for predicting future climate risks and their impacts. Here we review mechanisms, predictions, impacts, and knowledge gaps associated with 10 notable Earth system components proposed to be tipping elements. We evaluate which tipping elements are approaching critical thresholds and whether shifts may manifest rapidly or over longer timescales. Some tipping elements have a higher risk of crossing tipping points under middle‐of‐the‐road emissions pathways and will possibly affect major ecosystems, climate patterns, and/or carbon cycling within the 21st century. However, literature assessing different emissions scenarios indicates a strong potential to reduce impacts associated with many tipping elements through climate change mitigation. The studies synthesized in our review suggest most tipping elements do not possess the potential for abrupt future change within years, and some proposed tipping elements may not exhibit tipping behavior, rather responding more predictably and directly to the magnitude of forcing. Nevertheless, uncertainties remain associated with many tipping elements, highlighting an acute need for further research and modeling to better constrain risks.
Gravity Wave Modulations at the Lower Altitudes of Venus Ionosphere
Authors: Tripathi Keshav R. , Choudhary R. K. , Jose Jeslin S. , Ambili K. M. , Imamura T. 
Published: February 2023

AbstractUsing measurements from radio science experiments onboard Venus Express and Akatsuki orbiter, we explore factors that control the occurrence and spatial structure of the electron density enhancement at lower altitudes (V0 layer) in the Venus ionosphere. Results suggest that the Gravity Waves (GWs) play a crucial role in determining the shape of the V0 layer. For solar zenith angle (SZA) less than 40°, when the average gravity wave potential energy (AGPE) is less than 4.7 J/kg, V0 has a single well‐defined peak. For higher AGPE, the V0 peak height gets perturbed and exhibits a wave‐like structure. For SZA >40°, and AGPE >4.7 J/kg, mostly wave‐like feature at the base of the V0 layer emerges. We surmise that although GW do not control the formation of a V0 layer, they likely control its shape and occurrence altitude.
Subseasonal Predictability of the July 2021 Extreme Rainfall Event Over Henan China in S2S Operational Models
Authors: Yan Yuhan , Zhu Congwen , Liu Boqi 
Published: February 2023

AbstractA record‐breaking flooding event occurred in Zhengzhou, Henan Province of China during 17–23 July 2021, causing hundreds of deaths and vast economic losses. Here, we evaluated the predictability of this extreme rainfall event and the impacts of tropical cyclones (TCs) using subseasonal‐to‐seasonal (S2S) operational models. On the monthly timescale, most models initialized in late June reasonably predicted the wet‐in‐north and dry‐in‐south patterns of anomalous rainfall over China in July, accompanied by the well‐predicted westward extension of the western North Pacific subtropical high (WNPSH) and eastward stretching of the South Asian High. On the weekly timescale, only four models captured the location, probability, and sudden intensification of the rainfall extremes in advance of 1 week, largely due to their reasonable prediction of WNPSH variability in mid‐latitudes. However, the S2S models still underestimated the super extremeness of this event. The prediction discrepancies came from the poor predictability of Typhoon IN‐FA and its impact on the daily evolution of the extreme rainfall event, even within a few days forecast lead. Compared with the observation, the prediction bias of tropical disturbance changed the environmental monsoon airflow to induce the earlier warning of rainfall extremes prior to the formation of IN‐FA. After the formation of IN‐FA, the prediction bias of the typhoon's moving speed distorted the typhoon location, which incorrectly predicted the moisture convergence center and underestimated their remote impacts on this heavy rainfall event.
The Sensitivity of Tidal Channel Systems to Initial Bed Conditions, Vegetation, and Tidal Asymmetry
Authors: Geng L. , Lanzoni S. , D'Alpaos A. , Sgarabotto A. , Gong Z. 
Published: February 2023

AbstractIn tidal environments, channel networks act as essential drainage pathways. Although the complex interactions between environmental factors have been studied extensively, the effects of the initial bathymetry on tidal network ontogeny are poorly understood. In this contribution, we used a numerical model to mimic a schematic tidal basin subjected to tidal forcing. The effects of the initial bathymetry and vegetation growth are analyzed by changing the features of randomly generated bed perturbation and the intertidal platform slope. Different perturbation densities mildly affect the growth of tidal networks, which, at equilibrium, share similar values in terms of channel length, tidal prism, and cross‐sectional area. The complexity and structure of channel networks are more sensitive to variations in the perturbation distribution. Increasing the initial bathymetry slope can shorten channels and reduce the tidal prism and drainage efficiency. Vegetation growth is found to invariably promote channel lengthening and narrowing, increasing the complexity and drainage efficiency of the system. An asymmetrical tidal forcing generally leads to longer channels and smaller unchanneled lengths. Under ebb‐dominant conditions, channels get deeper, and the increased channel length ensures a higher drainage efficiency. The insights of our study provide a deeper understanding of the environmental factors controlling the equilibrium morphology of tidal channel systems and their overall resilience. Further implications concern the restoration and management of coastal areas through the informed use of topographic changes and planting arrangements. Finally, accounting for the uncertainties associated with initial conditions is relevant when modeling other earth systems and comparing them with real systems.
Expansion of Reducing Marine Environments During the Ireviken Biogeochemical Event: Evidence From the Altajme Core, Gotland, Sweden
Authors: Stolfus Brittany M. , Allman Lindsi J. , Young Seth A. , Calner Mikael , Hartke Emma R. , Oborny Stephan C. , Bancroft Alyssa M. , Cramer Bradley D. 
Published: February 2023

AbstractNew δ34Spy (pyrite) and δ34SCAS (carbonate‐associated sulfate) across the Llandovery‐Wenlock boundary (∼432 Ma) provide evidence for the expansion of reduced marine environments during the Ireviken Biogeochemical Event. This event consists of a major positive carbon isotope excursion, increased biotic turnover, and other major perturbations and changes within biogeochemical cycles. This interval of time has been hypothesized to coincide with an expansion of reducing marine environments that caused increased organic carbon burial and led to the Ireviken positive carbon isotope excursion (ICIE). Previous high‐resolution carbon isotope work in the Altajme core from Gotland, Sweden provides the highest resolution record of the ICIE yet documented and provides an ideal expanded stratigraphic section to study this event. Local expansion of reduced marine environments within the deeper shelf setting of the Altajme core is indicated by a positive shift in δ34Spy values and increase in pyrite sulfur concentrations at the onset of the ICIE. These data are indicative of increased microbial sulfate reduction within this portion of the Baltic Basin. Combined with new δ34SCAS data from this core, as well as additional data from distant basins, the new data presented here suggest a global expansion of reduced environments led to an increase in organic carbon burial and the ICIE.
Association of the COVID-19 pandemic with changes in objectively measured sedentary behaviour and adiposity
Authors: Kinoshita Keita , Ozato Naoki , Yamaguchi Tohru , Bushita Hiroto , Sudo Motoki , Yamashiro Yukari , Mori Kenta , Katsuragi Yoshihisa , Sasai Hiroyuki , Murashita Koichi , Takahashi Yoshiko , Ihara Kazushige 
Published: February 2023

Abstract
Background
Several studies have reported that the coronavirus disease (COVID-19) pandemic has increased sedentary behaviour and obesity; however, these analyses used self-reported data, and the association between sedentary behaviour and visceral fat and adipocytokines during the COVID-19 pandemic remains unclear. We aimed to investigate the association of the COVID-19 pandemic with objectively measured sedentary behaviour and these obesity-related factors.

Methods
Longitudinal analysis was conducted on 257 Japanese participants who underwent health check-ups in 2018 before and in 2020 during the COVID-19 pandemic. For both time points, sedentary behaviour was measured using an accelerometer for at least 7 days, visceral fat area (VFA) was measured using abdominal bioelectrical impedance analysis, and blood adiponectin level was measured using latex agglutination turbidimetric immunoassay. Multiple linear regression was performed to determine the association between sedentary behaviour and these outcomes.

Results
Compared with data in 2018, sedentary behaviour and VFA were significantly increased (P < 0.001, P = 0.006) whereas adiponectin level was significantly decreased (P < 0.001) in 2020. Increased sedentary behaviour was significantly associated with an increase in VFA (β = 3.85, 95% CI 1.22–6.49, P = 0.004) and a decrease in adiponectin level (β = −0.04, 95% CI −0.06 to −0.01, P = 0.005). However, the association of sedentary behaviour with adiponectin level was not significant after considering the effects of VFA.

Conclusions
The COVID-19 pandemic was associated with objectively measured sedentary behaviour and obesity-related factors in Japanese adults. Additionally, an increase in sedentary behaviour was associated with an increase in VFA, whereas the association of sedentary behaviour with adiponectin was partly mediated by VFA. These results suggest that avoiding increasing sedentary time is important to prevent visceral adiposity thereby ameliorating adiponectin, especially during behavioural limitations such as the COVID-19 pandemic.
RGS12 represses oral squamous cell carcinoma by driving M1 polarization of tumor-associated macrophages via controlling ciliary MYCBP2/KIF2A signaling
Authors: Yuan Gongsheng , Yang Shuting , Yang Shuying 
Published: February 2023

AbstractTumor-associated macrophages (TAMs) play crucial roles in tumor progression and immune responses. However, mechanisms of driving TAMs to antitumor function remain unknown. Here, transcriptome profiling analysis of human oral cancer tissues indicated that regulator of G protein signaling 12 (RGS12) regulates pathologic processes and immune-related pathways. Mice with RGS12 knockout in macrophages displayed decreased M1 TAMs in oral cancer tissues, and extensive proliferation and invasion of oral cancer cells. RGS12 increased the M1 macrophages with features of increased ciliated cell number and cilia length. Mechanistically, RGS12 associates with and activates MYC binding protein 2 (MYCBP2) to degrade the cilia protein kinesin family member 2A (KIF2A) in TAMs. Our results demonstrate that RGS12 is an essential oral cancer biomarker and regulator for immunosuppressive TAMs activation.
A Phase 1/2 study of the PD-L1 inhibitor, BGB-A333, alone and in combination with the PD-1 inhibitor, tislelizumab, in patients with advanced solid tumours
Authors: Desai Jayesh , Fong Peter , Moreno Victor , Frentzas Sophia , Meniawy Tarek , Markman Ben , Voskoboynik Mark , Rahman Tahmina , Budha Nageshwar , Wu John , Marlow Jin , Yang Silu , Calvo Emiliano , Martin-Liberal Juan 
Published: February 2023

Abstract
Background
Many patients do not respond or eventually relapse on treatment with programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors due to secondary or acquired resistance; therefore, there is a need to investigate novel PD-1/PD-L1 inhibitors.

Methods
This open-label, non-randomised study investigated the safety and anti-tumour activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumours with progression during/after standard therapy. The primary objectives were to determine the recommended Phase 2 dose (RP2D), safety and tolerability for BGB-A333 alone and in combination with tislelizumab (Phase 1a/1b) and to determine the overall response rate (ORR) with BGB-A333 plus tislelizumab (Phase 2).

Results
Overall, 39 patients across Phase 1a (N = 15), 1b (N = 12) and 2 (N = 12) were enroled. In Phase 1a, an RP2D of 1350 mg was determined. In Phase 1a and 1b/2, serious treatment-emergent adverse events (TEAEs) were reported in five and eight patients, respectively. Two patients experienced TEAEs that led to death. In Phase 2, the ORR was 41.7% (n = 5/12; 95% confidence interval: 15.17%, 72.33%).

Conclusions
TEAEs reported with BGB-A333 were consistent with other PD-L1 inhibitors. Encouraging preliminary anti-tumour activity was observed with BGB-A333 in combination with tislelizumab.

Clinical trial registration
NCT03379259.
Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials
Authors: Loh Jerold , Wu Jiaxuan , Chieng Jenny , Chan Aurora , Yong Wei-Peng , Sundar Raghav , Lee Soo-Chin , Wong Andrea , Lim Joline S. J. , Tan David S. P. , Soo Ross , Goh Boon-Cher , Tai Bee-Choo , Chee Cheng E. 
Published: February 2023

Abstract
Background
Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil–lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population.

Methods
We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020.

Results
The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96–1.70); RMH score 2, HR 2.27 (95% CI: 1.62–3.17); RMH score 3, HR 4.14 (95% CI: 2.62–6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24–2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16–4.35, P < 0.001) were prognostic.

Conclusions
We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65–0.76]), and validated the RMH model in the largest Asian study to date.
Glutathione system enhancement for cardiac protection: pharmacological options against oxidative stress and ferroptosis
Authors: Tan Mingyue , Yin Yunfei , Ma Xiao , Zhang Jun , Pan Wanqian , Tan Minghao , Zhao Yongjian , Yang Tianke , Jiang Tingbo , Li Hongxia 
Published: February 2023

AbstractThe glutathione (GSH) system is considered to be one of the most powerful endogenous antioxidant systems in the cardiovascular system due to its key contribution to detoxifying xenobiotics and scavenging overreactive oxygen species (ROS). Numerous investigations have suggested that disruption of the GSH system is a critical element in the pathogenesis of myocardial injury. Meanwhile, a newly proposed type of cell death, ferroptosis, has been demonstrated to be closely related to the GSH system, which affects the process and outcome of myocardial injury. Moreover, in facing various pathological challenges, the mammalian heart, which possesses high levels of mitochondria and weak antioxidant capacity, is susceptible to oxidant production and oxidative damage. Therefore, targeted enhancement of the GSH system along with prevention of ferroptosis in the myocardium is a promising therapeutic strategy. In this review, we first systematically describe the physiological functions and anabolism of the GSH system, as well as its effects on cardiac injury. Then, we discuss the relationship between the GSH system and ferroptosis in myocardial injury. Moreover, a comprehensive summary of the activation strategies of the GSH system is presented, where we mainly identify several promising herbal monomers, which may provide valuable guidelines for the exploration of new therapeutic approaches.