Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes of selective laser trabeculoplasty in corticosteroid-induced ocular hypertension and glaucoma

Purpose: To report the outcomes of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in patients with steroid-induced ocular hypertension and glaucoma. Methods: A retrospective chart review of patients who underwent SLT for steroid-induced ocular hypertension or glaucoma between January 2014 and October 2018. Success of SLT was defined as ⩾20% IOP reduction from baseline without further medical or surgical intervention and/or a reduction in the number of glaucoma medications by ⩾1 from baseline while maintaining the target IOP. Main outcome measures were change in IOP from baseline and reduction in the number of medications post-laser. Results: A total of 25 eyes of 17 patients were included in the study. The mean duration of follow-up was 18.8 ± 4.5 months. IOP decreased from 23.7 ± 6.7 mmHg pre-laser to 14.4 ± 3.2 mmHg post-laser, at the last follow-up visit (p < 0.001). The mean number of medications was 1.8 ± 1.6 medications pre-laser and 1.4 ± 1.3 medications post-laser (p = 0.262). The overall success rate at 12 months was 72%. No visually significant complications were encountered during the whole duration of follow-up. Conclusion: SLT is a safe and effective procedure that can result in well-controlled IOP in patients with steroid-induced ocular hypertension and glaucoma.
Topics of Nicotine-Related Discussions on Twitter: Infoveillance Study

Background Cultural trends in the United States, the nicotine consumer marketplace, and tobacco policies are changing. Objective The goal of this study was to identify and describe nicotine-related topics of conversation authored by the public and social bots on Twitter, including any misinformation or misconceptions that health education campaigns could potentially correct. Methods Twitter posts containing the term “nicotine” were obtained from September 30, 2018 to October 1, 2019. Methods were used to distinguish between posts from social bots and nonbots. Text classifiers were used to identify topics in posts (n=300,360). Results Prevalent topics of posts included vaping, smoking, addiction, withdrawal, nicotine health risks, and quit nicotine, with mentions of going “cold turkey” and needing help in quitting. Cessation was a common topic, with mentions of quitting and stopping smoking. Social bots discussed unsubstantiated health claims including how hypnotherapy, acupuncture, magnets worn on the ears, and time spent in the sauna can help in smoking cessation. Conclusions Health education efforts are needed to correct unsubstantiated health claims on Twitter and ultimately direct individuals who want to quit smoking to evidence-based cessation strategies. Future interventions could be designed to follow these topics of discussions on Twitter and engage with members of the public about evidence-based cessation methods in near real time when people are contemplating cessation.
Smartphone “Selfies”—A reliable and accurate tool for measuring elbow range of motion

Background To determine if self-taken photographs (“selfies”), performed independently after instruction by video or illustrated handout, would be an accurate and reliable tool for capturing elbow range of motion in patients with elbow contractures. Methods Fifty patients presenting with elbow contractures participated in the study. After completion of the selfie, the senior author clinically measured flexion and extension with a goniometer. The angles from the photographs were measured and analyzed. Results The agreement between goniometer and “selfie” measurements correlated closely (R2 = 0.98) and agreement was excellent in both extension and in flexion with intra-class correlation coefficients of 0.95 (95% CI 0.92 to 0.97) in extension with a mean difference of 2° (95% CI −3° to 7°), and 0.93 (95% CI 0.89 to 0.96) in flexion with a mean difference of 4° (95% CI 0° to 8°). Systematic errors were low in extension, 0° (95% CI, ±11°) and in flexion −3° (95% CI, ±10°). Six patients demonstrated ≥10° difference between clinical and selfie measurements. Ability to take a usable selfie was inversely correlated with age (R2 = 0.97). Discussion Self-taken flexion–extension photographs are a reliable and accurate tool for measuring elbow range of motion. Errors in the selfie technique are well tolerated and appear to have a negligible effect upon measurements of motion. This important parameter of elbow function can therefore be obtained outside a normal clinic visit, thereby improving frequency of follow-up assessments (and minimizing loss to follow-up) necessary for quality control and research.
Three Approaches to Restoration and Their Implications for Social Inclusion

Building on the Bonn Challenge, the UN Decade advances global restoration on an unprecedented scale. Research increasingly points to the need for greater social inclusion in restoration projects, yet the approaches that favor such inclusion remain opaque in practice. In this paper, we identify three restoration approaches that figure in the international agenda and analyze these through the lens of social inclusion. We argue that: (1) restoration aimed at bringing ecosystems back to a previous state, or “return” restoration, favors natural science at the landscape scale over social inclusion at the community scale; (2) restoration seeking to recreate functional ecosystems in locations away from where the degradation has occurred, or “reorganization” restoration, fails to adequately address historical inequities and perpetuates legacies of exploitation; and (3) “resilience” oriented restoration is promising but remains theoretical, and risks instrumentalizing marginalized communities and their lands as experimental sites for restoration. Though both “return” and “reorganize” restoration face substantial criticism, these approaches continue to play a central role in the major paradigms and practices that enliven the global restoration agenda. To improve prospects for social inclusion in the global restoration movement, we advance that the movement must evolve beyond productivity-based inclusion schemes and address the role that international initiatives play in perpetuating systems of exploitation. Finally, we argue that “resilience” restoration offers the most promising pathway towards meaningful social inclusion when it can empower community members to participate in restoration as agents of change and co-experimenters.
Assessing Social Equity in Farmer-Managed Natural Regeneration (FMNR) Interventions: Findings from Ghana

Achieving social equity in land and forest restoration is a key objective of major international frameworks and commitments, including the UN Decade on Ecosystem Restoration. Meeting this objective requires consideration of key governance questions such as who makes decisions about what is restored, where, and how? And how do factors specific to local contexts influence which decisions are made, and, in turn, the distribution of benefits? Despite the demonstrated importance of social equity on project outcomes in many natural resource-based fields, there have to date been no assessments of social equity of farmer-managed natural regeneration (FMNR), an approach used mainly for restoring degraded agricultural land. Drawing on findings from community-based fieldwork in 2019–2020 in northeastern Ghana, this paper aims to fill this void. We address the following question: How do historical, socio-ecological, and political processes condition prospects for social equity in FMNR interventions? Key findings were: 1) Preexisting hierarchies in authority, control, and access over land and trees shaped decision-making in project design and the potential distribution of benefits from FMNR 2) FMNR, when implemented on farmland, generally aligned with local agroecological practices; but, when implemented to restore communal lands, it created tensions with local perceptions of equity as well as traditional land and natural resource management practices, and 3) The FMNR project reflected the continuing salience of dominant political and environmental discourses, which carry implications for restoring landscapes with FMNR. To support practitioners, we provide several recommendations for strengthening social equity of FMNR project designs.
Nitrate Reduction Stimulates and Is Stimulated by Phenazine-1-Carboxylic Acid Oxidation by Citrobacter portucalensis MBL

Phenazines are increasingly appreciated for their roles in structuring microbial communities. These tricyclic aromatic molecules have been found to regulate gene expression, be toxic, promote antibiotic tolerance, and promote survival under oxygen starvation. ABSTRACT Phenazines are secreted metabolites that microbes use in diverse ways, from quorum sensing to antimicrobial warfare to energy conservation. Phenazines are able to contribute to these activities due to their redox activity. The physiological consequences of cellular phenazine reduction have been extensively studied, but the counterpart phenazine oxidation has been largely overlooked. Phenazine-1-carboxylic acid (PCA) is common in the environment and readily reduced by its producers. Here, we describe its anaerobic oxidation by Citrobacter portucalensis strain MBL, which was isolated from topsoil in Falmouth, MA, and which does not produce phenazines itself. This activity depends on the availability of a suitable terminal electron acceptor, specifically nitrate. When C. portucalensis MBL is provided reduced PCA and nitrate, it oxidizes the PCA at a rate that is environmentally relevant. We compared this terminal electron acceptor-dependent PCA-oxidizing activity of C. portucalensis MBL to that of several other gammaproteobacteria with various capacities to respire nitrate. We found that PCA oxidation by these strains in a nitrate-dependent manner is decoupled from growth and strain dependent. We infer that bacterial PCA oxidation is widespread and genetically determined. Notably, oxidizing PCA enhances the rate of nitrate reduction to nitrite by C. portucalensis MBL beyond the stoichiometric exchange of electrons from PCA to nitrate, which we attribute to C. portucalensis MBL’s ability to also reduce oxidized PCA, thereby catalyzing a complete PCA redox cycle. This bidirectionality highlights the versatility of PCA as a biological redox agent. IMPORTANCE Phenazines are increasingly appreciated for their roles in structuring microbial communities. These tricyclic aromatic molecules have been found to regulate gene expression, be toxic, promote antibiotic tolerance, and promote survival under oxygen starvation. In all of these contexts, however, phenazines are studied as electron acceptors. Even if their utility arises primarily from being readily reduced, they need to be oxidized in order to be recycled. While oxygen and ferric iron can oxidize phenazines abiotically, biotic oxidation of phenazines has not been studied previously. We observed bacteria that readily oxidize phenazine-1-carboxylic acid (PCA) in a nitrate-dependent fashion, concomitantly increasing the rate of nitrate reduction to nitrite. Because nitrate is a prevalent terminal electron acceptor in diverse anoxic environments, including soils, and phenazine producers are widespread, this observation of linked phenazine and nitrogen redox cycling suggests an underappreciated role for redox-active secreted metabolites in the environment.
Gene age predicts the transcriptional landscape of sexual morphogenesis in multicellular fungi

Multicellularity has been one of the most important innovations in the history of life. The role of regulatory evolution in driving transitions to multicellularity is being increasingly recognized; however, patterns and drivers of transcriptome evolution are poorly known in many clades. We here reveal that allele-specific expression, natural antisense transcripts and developmental gene expression, but not RNA editing or a developmental hourglass act in concert to shape the transcriptome of complex multicellular fruiting bodies of fungi. We find that transcriptional patterns of genes are strongly predicted by their evolutionary age. Young genes showed more expression variation both in time and space, possibly because of weaker evolutionary constraint, calling for partially non-adaptive interpretations of evolutionary changes in the transcriptome of multicellular fungi. Gene age also correlated with function, allowing us to separate fruiting body gene expression related to simple sexual development from that potentially underlying complex morphogenesis. Our study highlighted a transcriptional complexity that provides multiple speeds for transcriptome evolution, but also that constraints associated with gene age shape transcriptomic patterns during transitions to complex multicellularity in fungi.
An Alanine Aminotransferase is Required for Polysaccharide Regulation and Resistance of Aspergillus fumigatus Biofilms to Echinocandin Treatment

Alanine metabolism has been suggested as an adaptation strategy to oxygen limitation in organisms ranging from plants to mammals. Within the pulmonary infection microenvironment A. fumigatus forms biofilms with steep oxygen gradients defined by regions of oxygen limitation. A significant increase in alanine levels was observed in A. fumigatus cultured under oxygen limiting conditions. An alanine aminotransferase, AlaA, was observed to function in alanine catabolism and is required for several aspects of A. fumigatus biofilm physiology. Loss of alaA, or its catalytic activity, results in decreased adherence of biofilms through a defect in the maturation of the extracellular matrix polysaccharide galactosaminogalactan (GAG). Additionally, exposure of cell wall polysaccharides is also impacted by loss of alaA and loss of AlaA catalytic activity confers increased biofilm susceptibility to echinocandin treatment which is correlated with enhanced fungicidal activity. The increase in echinocandin susceptibility is specific to biofilms and chemical inhibition of alaA by the alanine aminotransferase inhibitor β-chloro-L-alanine is sufficient to sensitize A. fumigatus biofilms to echinocandin treatment. Finally, loss of alaA increases susceptibility of A. fumigatus to in vivo echinocandin treatment in a murine model of invasive pulmonary aspergillosis. Our results provide insight into the interplay of metabolism, biofilm formation, and antifungal drug resistance in A. fumigatus and describes a mechanism of increasing susceptibility of A. fumigatus biofilms to the echinocandin class of antifungal drugs. eLife Digest Aspergillus fumigatus is a ubiquitous filamentous fungus that causes an array of diseases depending on the immune status of an individual, collectively termed aspergillosis. Antifungal therapy for invasive pulmonary aspergillosis (IPA) or chronic pulmonary aspergillosis (CPA) is limited and too often ineffective. This is in part due to A. fumigatus biofilm formation within the infection environment and the resulting emergent properties, particularly increased antifungal resistance. Thus, insights into biofilm formation and mechanisms driving increased antifungal drug resistance are critical for improving existing therapeutic strategies and development of novel antifungals. In this work, we describe an unexpected observation where alanine metabolism, via the alanine aminotransferase AlaA, is required for several aspects of A. fumigatus biofilm physiology including resistance of A. fumigatus biofilms to the echinocandin class of antifungal drugs. Importantly, we observed that chemical inhibition of alanine aminotransferases is sufficient to increase echinocandin susceptibility and that loss of alaA increases susceptibility to echinocandin treatment in a murine model of IPA.
Spatial cell type mapping of the oligodendrocyte lineage in the mouse juvenile and adult CNS with in situ sequencing

Oligodendrocytes show transcriptional heterogeneity but the regional and functional implications of this heterogeneity are less clear. Here, we apply in situ sequencing (ISS) to simultaneously probe the expression of 124 marker genes of distinct oligodendrocyte populations, providing comprehensive maps of corpus callosum, cingulate, motor and somatosensory cortex in the brain, as well as gray (GM) and white matter (WM) regions in the spinal cord, at juvenile and adult stages. We systematically compare abundances of these populations and investigate the neighboring preference of distinct oligodendrocyte populations. As previously described, we observed that oligodendrocyte lineage progression is more advanced in the juvenile spinal cord compared to the brain. Additionally, myelination is ongoing in the adult corpus callosum while it is mostly completed in the cortex. Interestingly, we found a medial-to-lateral gradient of oligodendrocyte lineage progression in the juvenile cortex, which could be linked to arealization, as well as a deep-to-superficial gradient with mature oligodendrocytes preferentially accumulating in the deeper layers of the cortex. We observed differences in abundances and population dynamics over time between GM and WM regions in the brain and spinal cord, indicating regional differences within GM and WM. We also found that oligodendroglia populations’ neighboring preferences are altered from the juvenile to the adult CNS. Thus, our ISS dataset reveals spatial heterogeneity of the oligodendrocyte lineage progression in the brain and spinal cord, which could be relevant to further investigate functional heterogeneity of oligodendroglia.
US-Based Deep Learning Model for Differentiating Hepatocellular Carcinoma (HCC) From Other Malignancy in Cirrhotic Patients

The aim was to build a predictive model based on ultrasonography (US)-based deep learning model (US-DLM) and clinical features (Clin) for differentiating hepatocellular carcinoma (HCC) from other malignancy (OM) in cirrhotic patients. 112 patients with 120 HCCs and 60 patients with 61 OMs were included. They were randomly divided into training and test cohorts with a 4:1 ratio for developing and evaluating US-DLM model, respectively. Significant Clin predictors of OM in the training cohort were combined with US-DLM to build a nomogram predictive model (US-DLM+Clin). The diagnostic performance of US-DLM and US-DLM+Clin were compared with that of contrast enhanced magnetic resonance imaging (MRI) liver imaging and reporting system category M (MRI LR-M). US-DLM was the best independent predictor for evaluating OMs, followed by clinical information, including high cancer antigen 199 (CA199) level and female. The US-DLM achieved an AUC of 0.74 in the test cohort, which was comparable with that of MRI LR-M (AUC=0.84, p=0.232). The US-DLM+Clin for predicting OMs also had similar AUC value (0.81) compared with that of LR-M+Clin (0.83, p>0.05). US-DLM+Clin obtained a higher specificity, but a lower sensitivity, compared to that of LR-M +Clin (Specificity: 82.6% vs. 73.9%, p=0.007; Sensitivity: 78.6% vs. 92.9%, p=0.006) for evaluating OMs in the test set. The US-DLM+Clin model is valuable in differentiating HCC from OM in the setting of cirrhosis.
Cardia Gastric Cancer Is Associated With Increased PIK3CA Amplifications and HER2 Expression Than Noncardia Gastric Cancer According to Lauren Classification

Background To date, few reports have investigated genetic alterations and clinicopathological features in cardia and noncardia gastric cancer (GC). Methods In total, 435 GC patients receiving curative surgery were included. The clinicopathological features, recurrence patterns, prognoses and genetic alterations were compared between cardia and noncardia GC patients. Results Among the 435 enrolled patients, 47 (10.8%) had cardia GC. Compared with noncardia GC, cardia GC was associated with more intestinal-type tumors and similar initial recurrence patterns and 5-year overall survival (OS; 50.8% vs. 50.5%, P = 0.480) and disease-free survival (DFS; 48.6% vs. 48.9%, P = 0.392) rates. For both intestinal-type GC and diffuse-type GC, the clinicopathological features and 5-year OS and DFS rates were not significantly different between the cardia and noncardia GC patients. Multivariable analysis showed that cardia GC was not an independent prognostic factor. Compared with noncardia GC, cardia GC was associated with increased PIK3CA amplification than in patients with intestinal-type GC and was associated with increased HER2 expression in patients with diffuse-type GC. Conclusions Cardia GC is not an independent prognostic factor. In cardia GC patients with intestinal-type GC, PIK3CA amplification was more common, and in those with diffuse-type GC, HER2 expression was more common. Targeted therapy may be beneficial for these patient subgroups.
FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients

A patient’s response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.