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Rangelands cover ~23 million hectares and support a $3.4 billion annual cattle industry in California. Large variations in forage production from year to year and across the landscape make grazing management difficult. We here developed optimized methods to map high-resolution forage production using multispectral remote sensing imagery. We conducted monthly flights using a Small Unmanned Aerial System (sUAS) in 2017 and 2018 over a 10-ha deferred grazing rangeland. Daily maps of NDVI at 30-cm resolution were first derived by fusing monthly 30-cm sUAS imagery and more frequent 3-m PlanetScope satellite observations. We estimated aboveground net primary production as a product of absorbed photosynthetically active radiation (APAR) derived from NDVI and light use efficiency (LUE), optimized as a function of topography and climate stressors. The estimated forage production agreed well with field measurements having a R2 of 0.80 and RMSE of 542 kg/ha. Cumulative NDVI and APAR were less correlated with measured biomass (R2 = 0.68). Daily forage production maps captured similar seasonal and spatial patterns compared to field-based biomass measurements. Our study demonstrated the utility of aerial and satellite remote sensing technology in supporting adaptive rangeland management, especially during an era of climatic extremes, by providing spatially explicit and near-real-time forage production estimates.

Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.

Nucleic acid therapeutics have demonstrated an impressive acceleration in recent years. They work through multiple mechanisms of action, including the downregulation of gene expression and the modulation of RNA splicing. While several drugs based on the former mechanism have been approved, few target the latter, despite the promise of RNA splicing modulation. To improve our ability to discover novel RNA splicing-modulating therapies, we developed HCS-Splice, a robust cell-based High-Content Screening (HCS) assay. By implementing the use of a two-colour (GFP/RFP) fluorescent splicing reporter plasmid, we developed a versatile, effective, rapid, and robust high-throughput strategy for the identification of potent splicing-modulating molecules. The HCS-Splice strategy can also be used to functionally confirm splicing mutations in human genetic disorders or to screen drug candidates. As a proof-of-concept, we introduced a dementia-related splice-switching mutation in the Microtubule-Associated Protein Tau (MAPT) exon 10 splicing reporter. We applied HCS-Splice to the wild-type and mutant reporters and measured the functional change in exon 10 inclusion. To demonstrate the applicability of the method in cell-based drug discovery, HCS-Splice was used to evaluate the efficacy of an exon 10-targeting siRNA, which was able to restore the correct alternative splicing balance.

Faunal remains from Ḥorvat Tevet, a site located in the rural hinterlands of the Jezreel Valley, reveal patterns of a complex redistributive apparatus during the Late Iron IIA. This paper assesses a large assemblage of animal bones within inter- and intra-site comparative analyses. Inter-site comparisons to contemporary sites in the northern valleys of Israel demonstrate that the agricultural production of grain and animal by-products at Ḥorvat Tevet is unprecedented and went far beyond the site's local needs. Further, an intra-site comparison reveals a hierarchical distinction in the consumption patterns between elites and the labour force. These results further reinforce the conclusion that the late Iron IIA Ḥorvat Tevet was an administrative centre of a royal Israelite estate in the Jezreel Valley. [ABSTRACT FROM AUTHOR]

Background: The purpose of this multicenter study was to retrospectively investigate the prognostic significance of the tumor microenvironment, in relation to survival in a large cohort of patients with laryngeal squamous cell carcinoma (LSCC), using the method proposed by the International TILs Working Group in breast cancer. Methods: All consecutive patients with biopsy‐proven LSCC who underwent total laryngectomy (TL) between January 2014 and January 2023 were retrospectively included in the study. A retrospective review of medical records including surgical, pathological and follow‐up reports was performed. The density of TILs was determined according to the recommendations of the International TILs Working Group. Results: The study group included 186 patients with LSCC. High TILs were statistically correlated with reduced size and extension of primary tumor (pT stage) with a statistically significant value (S: p = 0.01; P: p = 0.0003) and without needs of salvage therapy (S: p = 0.03; P: p = 0.004). Low TILs were indicative of worse prognosis. Conclusions: Our study confirmed the protective value of TILs and the prognostic role of the tumor microenvironment in LSCC; furthermore, our results showed that the score proposed by the International TILs Working Group for breast cancer can be applied to LSCC. [ABSTRACT FROM AUTHOR]

Background: This prospective study evaluated the impact of anatomical and tomographic biomarkers on clinical outcomes of intravitreal dexamethasone implants in patients with macular edema secondary to retinal vein occlusion (RVO). Methods: The study included 46 patients (28 with branch RVO (BRVO) and 18 with central RVO (CRVO)). Best corrected visual acuity (BCVA) significantly improved from a mean baseline of 0.817 ± 0.220 logMAR to 0.663 ± 0.267 logMAR at six months and 0.639 ± 0.321 logMAR at twelve months (p < 0.05). Central retinal thickness (CRT) showed a significant reduction from 666.2 ± 212.2 µm to 471.1 ± 215.6 µm at six months and 467 ± 175.7 µm at twelve months (p < 0.05). No significant differences were found in OCT biomarkers between baseline and follow-ups. Results: The study analysed improvements in visual acuity relative to baseline biomarkers. At six months, ellipsoid zone disruption (EZD) was significant for all subgroups. Disorganization of retinal inner layers (DRIL), external limiting membrane (ELM) disruption, macular ischemia (MI), CRT, and BRVO showed significance for any improvement, while DRIL and ELM were significant for changes greater than 0.3 logMAR (p < 0.05). At twelve months, EZD remained significant for all subgroups. ELM, MI, CRT, and BRVO were significant for any improvement, while MI and BRVO were significant for changes greater than 0.3 logMAR (p < 0.05). Hyperreflective foci were not statistically significant at either time point (p > 0.05). Conclusions: The regression model suggested that MI and CRVO could be negative predictive factors for visual outcomes, while ELM and EZD were associated with BCVA improvement one-year post-treatment. [ABSTRACT FROM AUTHOR]

Recent proteomic, metabolomic, and transcriptomic studies have highlighted a connection between changes in mitochondria physiology and cellular pathophysiological mechanisms. Secondary assays to assess the function of these organelles appear fundamental to validate these -omics findings. Although mitochondrial membrane potential is widely recognized as an indicator of mitochondrial activity, high-content imaging-based approaches coupled to multiparametric to measure it have not been established yet. In this paper, we describe a methodology for the unbiased high-throughput quantification of mitochondrial membrane potential in vitro, which is suitable for 2D to 3D models. We successfully used our method to analyze mitochondrial membrane potential in monolayers of human fibroblasts, neural stem cells, spheroids, and isolated muscle fibers. Moreover, by combining automated image analysis and machine learning, we were able to discriminate melanoma cells from macrophages in co-culture and to analyze the subpopulations separately. Our data demonstrated that our method is a widely applicable strategy for large-scale profiling of mitochondrial activity.

* Context.--The improved survival and better response to treatments of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) highlight the need for effective tools in evaluating HPV status on formalin-fixed, paraffin-embedded (FFPE) cancer tissues. To date, there is no agreement regarding the most appropriate method for HPV testing on FFPE materials. Objective.--We aimed to investigate the performance of the Anyplex II HPV28 (Anyplex) on FFPE OPSCC tissues and to compare it with 2 other methods for HPV-DNA detection and p16 overexpression. Design.--One hundred sixty FFPE OPSCCs were evaluated, which had already been analyzed with the INNOLiPA HPV assay, Xpert HPV assay, and p16 immunostaining. Results.--All the samples but 1 provided valid results with the Anyplex, which showed the highest HPV detection rate and a good concordance with all the other methods ([kappa] = 0.75, 95% CI, 0.65-0.85 versus INNO-LiPA; [kappa] = 0.80, 95% CI, 0.70-0.89 versus Xpert; [kappa] = 0.76, 95% CI, 0.65-0.86 versus p16). Moreover, the HPV-driven fraction, based on HPV-DNA and p16 double positivity, was higher with Anyplex (83 of 159, 52.2%) than with the other 2 assays, that is, 78 of 156 (50.0%) for INNO-LiPA and 80 of 160 (50.0%) for Xpert. Conclusions.--Anyplex II HPV28 showed a higher HPV detection rate and HPV-associated fraction than the other methods used. This assay is suitable for HPV detection in archival OPSCC tissues. (Arch Pathol Lab Med. 2020;144:620-625; doi: 10.5858/arpa.2019-0199-OA), Human papillomavirus (HPV) has been detected in a considerable fraction of oropharyngeal squamous cell carcinomas (OPSCCs) particularly in those arising at the tonsils, (1-3) and high-risk (HR)-HPVs have been recognized [...]