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The existing reservoirs of neutral atomic hydrogen gas (H I) in galaxies are insufficient to have maintained the observed levels of star formation without some kind of replenishment. This refuelling of the H I reservoirs is likely to occur at column densities an order of magnitude lower than previous observational limits (NH I, limit ∼ 1019 cm−2 at a 30″ resolution over a linewidth of 20 km s−1). In this paper, we present recent deep H I observations of NGC 5068, a nearby isolated star-forming galaxy observed by MeerKAT as part of the MHONGOOSE survey. With these new data, we were able to detect low column density H I around NGC 5068 with a 3σ detection limit of NH I = 6.4 × 1017 cm−2 at a 90″ resolution over a 20 km s−1 linewidth. The high sensitivity and resolution of the MeerKAT data reveal a complex morphology of the H I in this galaxy – a regularly rotating inner disk coincident with the main star-forming disk of the galaxy, a warped outer disk of low column density gas (NH I < 9 × 1019 cm−2), in addition to clumps of gas on the north-western side of the galaxy. We employed a simple two disk model that described the inner and outer disks, which enabled us to identify anomalous gas that deviates from the rotation of the main galaxy. The morphology and the kinematics of the anomalous gas suggest a possible extra-galactic origin. We explore a number of possible origin scenarios that may explain the anomalous gas, and conclude that fresh accretion is the most likely scenario. [ABSTRACT FROM AUTHOR]

Global surface temperatures are projected to increase in the future; this will modify regional precipitation regimes and increase global atmospheric drying. Despite many drought studies examining the consequences of reduced precipitation, there are few experimental studies exploring plant responses to atmospheric drying via relative humidity and vapor pressure deficit (VPD). We examined eight native California perennial grass species grown in pots in a greenhouse in Los Angeles, California for 34 weeks. All pots were well‐watered for 21 weeks, at which point we reduced watering to zero and recorded daily growth and dormancy for 3 weeks. We used this information to better understand the drought tolerance of our species in a larger soil drying × atmospheric drying experiment. In this larger experiment, we grew all eight species together in outdoor mesocosms and measured changes in community composition after 4 years of growth. Soil drying in our small pot experiment mirrored compositional shifts in the larger experiment. Namely, our most drought‐tolerant species in our pot experiment was Poa secunda, due to a summer dormancy strategy. Similarly, the grass community shifted toward P. secunda in the driest soils as P. secunda was mostly unaffected by either soil drying or atmospheric drying. We found that some species responded strongly to soil drying (Elymus glaucus, Festuca idahoensis, and Hordeum b. californicum), while others responded strongly to atmospheric drying (Bromus carinatus and Stipa cernua). As result, community composition shifted in different and interacting ways in response to soil drying, atmospheric drying, and their combination. Further study of community responses to increasing atmospheric aridity is an essential next step to predicting the future consequences of climate change. [ABSTRACT FROM AUTHOR]

Advanced Quantitative Precipitation Information (AQPI) is a synergistic project that combines observations and models to improve monitoring and forecasts of precipitation, streamflow, and coastal flooding in the San Francisco Bay Area. As an experimental system, AQPI leverages more than a decade of research, innovation, and implementation of a statewide, state-of-the-art network of observations, and development of the next generation of weather and coastal forecast models. AQPI was developed as a prototype in response to requests from the water management community for improved information on precipitation, riverine, and coastal conditions to inform their decision-making processes. Observation of precipitation in the complex Bay Area landscape of California's coastal mountain ranges is known to be a challenging problem. But, with new advanced radar network techniques, AQPI is helping fill an important observational gap for this highly populated and vulnerable metropolitan area. The prototype AQPI system consists of improved weather radar data for precipitation estimation; additional surface measurements of precipitation, streamflow, and soil moisture; and a suite of integrated forecast modeling systems to improve situational awareness about current and future water conditions from sky to sea. Together these tools will help improve emergency preparedness and public response to prevent loss of life and destruction of property during extreme storms accompanied by heavy precipitation and high coastal water levels—especially high-moisture laden atmospheric rivers. The Bay Area AQPI system could potentially be replicated in other urban regions in California, the United States, and worldwide. [ABSTRACT FROM AUTHOR]

Radiation-induced lung injury (RILI) initiates radiation pneumonitis and progresses to fibrosis as the main side effect experienced by patients with lung cancer treated with radiotherapy. There is no effective drug for RILI. Sustained vascular activation is a major contributor to the establishment of chronic disease. Here, using a whole thoracic irradiation (WTI) mouse model, we investigated the mechanisms and effectiveness of thrombopoietin mimetic (TPOm) for preventing RILI. We demonstrated that administering TPOm 24 hours before irradiation decreased histologic lung injury score, apoptosis, vascular permeability, expression of proinflammatory cytokines, and neutrophil infiltration in the lungs of mice 2 weeks after WTI. We described the expression of c-MPL, a TPO receptor, in mouse primary pulmonary microvascular endothelial cells, showing that TPOm reduced endothelial cell-neutrophil adhesion by inhibiting ICAM-1 expression. Seven months after WTI, TPOm-treated lung exhibited less collagen deposition and expression of MMP-9, TIMP-1, IL-6, TGF-β, and p21. Moreover, TPOm improved lung vascular structure, lung density, and respiration rate, leading to a prolonged survival time after WTI. Single-cell RNA sequencing analysis of lungs 2 weeks after WTI revealed that TPOm shifted populations of capillary endothelial cells toward a less activated and more homeostatic phenotype. Taken together, TPOm is protective for RILI by inhibiting endothelial cell activation.

Background and Purpose: Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post-thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups., Methods: We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post-thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis., Results: A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations., Conclusions: In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics., (© 2024 American Society of Neuroimaging.)

Purpose: Ultrahigh dose-rate FLASH radiation therapy has emerged as a modality that promises to reduce normal tissue toxicity while maintaining tumor control. Previous studies of gastrointestinal toxicity using passively scattered FLASH proton therapy (PRT) have, however, yielded mixed results, suggesting that the requirements for gastrointestinal sparing by FLASH are an open question. Furthermore, the more clinically relevant pencil beam scanned (PBS) FLASH PRT has not yet been assessed in this context, despite differences in the spatiotemporal dose-rate distributions compared with passively scattered PRT. Here, to our knowledge, we provide the first report on the effects of PBS FLASH PRT on acute gastrointestinal injury in mice after whole abdominal irradiation., Methods and Materials: Whole abdominal irradiation was performed on C57BL/6J mice using the entrance channel of the Bragg curve of a 250 MeV PBS proton beam at field-averaged dose rates of 0.6 Gy/s for conventional (CONV) and 80 to 100 Gy/s for FLASH PRT. A 2D strip ionization chamber array was used to measure the dose and dose rate for each mouse. Survival was assessed at 14 Gy. Intestines were harvested and processed as Swiss rolls for analysis using a novel artificial intelligence-based crypt assay to quantify crypt regeneration 4 days after irradiation., Results: Survival was significantly reduced after 14 Gy FLASH PRT compared with CONV (P < .001). Our artificial intelligence-based crypt assays demonstrated no significant difference in intestinal crypts/cm or crypt depth between groups 4 days after irradiation. Furthermore, we found no significant difference in 5-ethynyl-2'-deoxyuridine + cells/crypt or Olfactomedin4 + intestinal stem cells with FLASH relative to CONV PRT., Conclusions: Overall, our data demonstrate significantly impaired survival after abdominal PBS FLASH PRT without apparent differences in intestinal histology 4 days after irradiation., (Copyright © 2024. Published by Elsevier Inc.)

G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Identification of driver mutations and development of targeted therapies has considerably improved outcomes for lung cancer patients. However, significant limitations remain with the lack of identified drivers in a large subset of patients. Here, we aimed to assess the genomic landscape of lung adenocarcinomas (LUADs) from individuals without a history of tobacco use to reveal new genetic drivers of lung cancer., Methods: Integrative genomic analyses combining whole-exome sequencing, copy number, and mutational information for 83 LUAD tumors was performed and validated using external datasets to identify genetic variants with a predicted functional consequence and assess association with clinical outcomes. LUAD cell lines with alteration of identified candidates were used to functionally characterize tumor suppressive potential using a conditional expression system both in vitro and in vivo., Results: We identified 21 genes with evidence of positive selection, including 12 novel candidates that have yet to be characterized in LUAD. In particular, SNF2 Histone Linker PHD RING Helicase (SHPRH) was identified due to its frequency of biallelic disruption and location within the familial susceptibility locus on chromosome arm 6q. We found that low SHPRH mRNA expression is associated with poor survival outcomes in LUAD patients. Furthermore, we showed that re-expression of SHPRH in LUAD cell lines with inactivating alterations for SHPRH reduces their in vitro colony formation and tumor burden in vivo. Finally, we explored the biological pathways associated SHPRH inactivation and found an association with the tolerance of LUAD cells to DNA damage., Conclusions: These data suggest that SHPRH is a tumor suppressor gene in LUAD, whereby its expression is associated with more favorable patient outcomes, reduced tumor and mutational burden, and may serve as a predictor of response to DNA damage. Thus, further exploration into the role of SHPRH in LUAD development may make it a valuable biomarker for predicting LUAD risk and prognosis., (© 2024. The Author(s).)

Background: Ulnar collateral ligament (UCL) injuries are a source of significant injury among baseball players, and are increasingly evaluated under ultrasound. The purpose of this study is to determine the effect of a single session of pitching upon UCL thickness and laxity via a cross sectional, controlled ultrasonographic study. We hypothesize that a single session of pitching will cause the ulnar collateral ligament to thicken and become more lax., Methods: This was a cross sectional comparative study of collegiate and high school pitchers. Pitchers underwent an ultrasonographic assessment of the UCL before and after a thirty-pitch bullpen warm-up. Laxity was measured as the change in the distance between the ulna and the trochlea with and without a 5-pound weight held in hand with the elbow at 30° of flexion. Pre- and post-throwing UCL thickness and medial laxity were statistically compared with paired tests., Results: Our study included 15 pitchers, 8 collegiate and 7 high school level athletes. All played baseball at least 6 days a week, and nearly all played for at least 10 months a year. Pitchers reported a peak velocity of 89 ± 6 (77 to 98) miles per hour. In the prior season, these pitchers pitched 56 ± 33 (10 to 120) games, throwing 62 ± 34 (25-140) pitches per game on average. After throwing, there was significantly less UCL laxity (P = .013). Post-throwing laxity was significantly positively correlated with both peak pitch velocity (P = .009) and an average number of pitches thrown per game (P = .10)., Conclusion: Throwing 30 pitches significantly decreases medial elbow laxity with stress, possibly due to flexor-pronator activation. Post-throwing medial laxity is correlated with both peak pitch velocity and average number of pitches thrown per game. Future studies should be conducted to determine the number of throws at which laxity begins to increase, as this may provide a workload management guideline for injury prevention., (Copyright © 2023 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Objective: This study was undertaken to examine averted stroke in optimized stroke systems., Methods: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis., Results: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution., Interpretation: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361., (© 2023 American Neurological Association.)