Starting a New Oral Oncology Agent in the Midst of the Pandemic

Abbey Kaler pictured. Breast Medical Oncology Kaler A, McClosky V, Raghavendra AS, Tripathy D. Oral Oncolytics: Using Remote Technology to Improve Access, Operational Efficiency, and Satisfaction. Clinical journal of oncology nursing. 2022;26(3):308-312. doi:10.1188/22.CJON.308-312https://openworks.mdanderson.org/aprn-week-22/1002/thumbnail.jp

Improving Diversity of Demographic Representation in Large Language Models via Collective-Critiques and Self-Voting

A crucial challenge for generative large language models (LLMs) is diversity: when a user's prompt is under-specified, models may follow implicit assumptions while generating a response, which may result in homogenization of the responses, as well as certain demographic groups being under-represented or even erased from the generated responses. In this paper, we formalize diversity of representation in generative LLMs. We present evaluation datasets and propose metrics to measure diversity in generated responses along people and culture axes. We find that LLMs understand the notion of diversity, and that they can reason and critique their own responses for that goal. This finding motivated a new prompting technique called collective-critique and self-voting (CCSV) to self-improve people diversity of LLMs by tapping into its diversity reasoning capabilities, without relying on handcrafted examples or prompt tuning. Extensive empirical experiments with both human and automated evaluations show that our proposed approach is effective at improving people and culture diversity, and outperforms all baseline methods by a large margin.Comment: To appear at EMNLP 2023 main conferenc

A Review on Computer Aided Diagnosis of Acute Brain Stroke.

Amongst the most common causes of death globally, stroke is one of top three affecting over 100 million people worldwide annually. There are two classes of stroke, namely ischemic stroke (due to impairment of blood supply, accounting for ~70% of all strokes) and hemorrhagic stroke (due to bleeding), both of which can result, if untreated, in permanently damaged brain tissue. The discovery that the affected brain tissue (i.e., 'ischemic penumbra') can be salvaged from permanent damage and the bourgeoning growth in computer aided diagnosis has led to major advances in stroke management. Abiding to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, we have surveyed a total of 177 research papers published between 2010 and 2021 to highlight the current status and challenges faced by computer aided diagnosis (CAD), machine learning (ML) and deep learning (DL) based techniques for CT and MRI as prime modalities for stroke detection and lesion region segmentation. This work concludes by showcasing the current requirement of this domain, the preferred modality, and prospective research areas

12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets

Context: The 12-lipoxygenase (12-LO) pathway produces proinflammatory metabolites, and its activation is implicated in islet inflammation associated with type 1 and type 2 diabetes (T2D). Objectives: We aimed to test the efficacy of ML355, a highly selective, small molecule inhibitor of 12-LO, for the preservation of islet function. Design: Human islets from nondiabetic donors were incubated with a mixture of tumor necrosis factor α , interluekin-1β, and interferon-γ to model islet inflammation. Cytokine-treated islets and human islets from T2D donors were incubated in the presence and absence of ML355. Setting: In vitro study. Participants: Human islets from organ donors aged >20 years of both sexes and any race were used. T2D status was defined from either medical history or most recent hemoglobin A1c value >6.5%. Intervention: Glucose stimulation. Main Outcome Measures: Static and dynamic insulin secretion and oxygen consumption rate (OCR). Results: ML355 prevented the reduction of insulin secretion and OCR in cytokine-treated human islets and improved both parameters in human islets from T2D donors. Conclusions: ML355 was efficacious in improving human islet function after cytokine treatment and in T2D islets in vitro. The study suggests that the blockade of the 12-LO pathway may serve as a target for both form of diabetes and provides the basis for further study of this small molecule inhibitor in vivo

Increasing the potential for malaria elimination by targeting zoophilic vectors

Countries in the Asia Pacific region aim to eliminate malaria by 2030. A cornerstone of malaria elimination is the effective management of Anopheles mosquito vectors. Current control tools such as insecticide treated nets or indoor residual sprays target mosquitoes in human dwellings. We find in a high transmission region in India, malaria vector populations show a high propensity to feed on livestock (cattle) and rest in outdoor structures such as cattle shelters. We also find evidence for a shift in vector species complex towards increased zoophilic behavior in recent years. Using a malaria transmission model we demonstrate that in such regions dominated by zoophilic vectors, existing vector control tactics will be insufficient to achieve elimination, even if maximized. However, by increasing mortality in the zoophilic cycle, the elimination threshold can be reached. Current national vector control policy in India restricts use of residual insecticide sprays to domestic dwellings. Our study suggests substantial benefits of extending the approach to treatment of cattle sheds, or deploying other tactics that target zoophilic behavior. Optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Structural insights into PYR/PYL/RCAR ABA receptors and PP2Cs

[EN] Abscisic acid (ABA) plays an essential function in plant physiology since it is required for biotic and abiotic stress responses as well as control of plant growth and development. A new family of soluble ABA receptors, named PYR/PYL/RCAR, has emerged as ABA sensors able to inhibit the activity of specific protein phosphatases type-2C (PP2Cs) in an ABA-dependent manner. The structural and functional mechanism by which ABA is perceived by these receptors and consequently leads to inhibition of the PP2Cs has been recently elucidated. The module PYR/PYL/RCAR-ABA-PP2C offers an elegant and unprecedented mechanism to control phosphorylation signaling cascades in a ligand-dependent manner. The knowledge of their three-dimensional structures paves the way to the design of ABA agonists able to modulate the plant stress response. (C) 2010 Elsevier Ireland Ltd. All rights reserved.We are grateful to the European Synchrotron Radiation Facility (ESRF) and the EMBL for access to macromolecular crystallography beam lines. Work in the laboratory of Dr Rodriguez is supported by grant BIO2008-00221 from Ministerio de Educación y Ciencia and Fondo Europeo de Desarrollo Regional and Consejo Superior de Investigaciones Científicas (fellowships to JS, RA and LR; Juan de la Cierva contract to MGG). Access to the high Throughput Crystallization facility of the Partnership for Structural Biology in Grenoble (PSB) (https://htxlab.embl.fr) was supported by the European Community – Research InfrastructureAction PCUBE under the FP7 “Capacities” specific program.Santiago Cuéllar, J.; Dupeux, F.; Betz, K.; Antoni-Alandes, R.; González Guzmán, M.; Rodriguez, L.; Márquez, JA.... (2012). Structural insights into PYR/PYL/RCAR ABA receptors and PP2Cs. Plant Science. 182:3-11. https://doi.org/10.1016/j.plantsci.2010.11.014S31118

ESCRT-I Component VPS23A Affects ABA Signaling by Recognizing ABA Receptors for Endosomal Degradation

[EN] Recent discovery of PYR/PYL/RCAR-type abscisic acid (ABA) receptors has become one of most significant advances in plant science in the past decade. In mammals, endosomal sorting acts as an important pathway to downregulate different types of receptors, but its role in plant hormone signaling is poorly understood. Here, we report that an ubiquitin E2-like protein, VPS23A, which is a key component of ESCRT-I, negatively regulates ABA signaling. VPS23A has epistatic relationship with PYR/PYL/RCAR-type ABA receptors and disruption of VPS23A enhanced the activity of key kinase OST1 in the ABA signaling pathway under ABA treatment. Moreover, VPS23A interacts with PYR1/PYLs and K63-linked diubiquitin, and PYL4 possesses K63-linked ubiquitinated modification in vivo. Further analysis revealed that VPS23A affects the subcellular localization of PYR1 and the stability of PYL4. Taken together, our results suggest that VPS23A affects PYR1/PYL4 via vacuole-mediated degradation, providing an advanced understanding of both the turnover of ABA receptors and ESCRTs in plant hormone signaling.This research was supported by grant 2016YFA0500500 from the National Basic Research Program of China and NSFC 31571441 from the National Science Foundation of China.Yu, F.; Lou, L.; Tian, M.; Li, Q.; Ding, Y.; Cao, X.; Wu, Y.... (2016). ESCRT-I Component VPS23A Affects ABA Signaling by Recognizing ABA Receptors for Endosomal Degradation. Molecular Plant. 9(12):1570-1582. https://doi.org/10.1016/j.molp.2016.11.002S1570158291

Seroprevalence of Bordetella pertussis antibodies in adults in Hungary: results of an epidemiological cross-sectional study.

BACKGROUND: Pertussis (whooping cough) is well known to be underreported, particularly among adults, who can act as an infectious reservoir, potentially putting susceptible newborns at risk of serious illness. The purpose of this study was to estimate the seroprevalence of pertussis in adults in Hungary. METHODS: This epidemiological, cross-sectional study was conducted in adults in five general practitioners' practices in Hungary. Serum anti-pertussis toxin immunoglobulin G (anti-PT IgG) antibody levels were analyzed using enzyme-linked immunosorbent assay. Sera were classified following manufacturer's instructions as: strongly indicative of current/recent infection (>/=1.5 optical density [OD] units); indicative of current/recent infection (>/=1.0 OD units); seropositive (>0.3 OD units); or seronegative (/=60 years (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.39-2.80; p = .0002) or 18-29 years (OR, 1.67; 95% CI, 1.13-2.46; p = .0094) vs. 45-59 years; former smoker (OR, 1.46; 95% CI, 1.08-1.97; p = .014) or current smoker (OR, 1.38; 95% CI, 1.01-1.89; p = .045) vs. never smoker; and male (OR, 1.30; 95% CI, 1.01-1.68; p = .041) vs. female. Also, between increased rates of probable current/recent infection and current smoker (OR, 7.50; 95% CI, 2.32-24.31; p = .0008) or former smoker (OR, 4.07; 95% CI, 1.21-13.64; p = .023) vs. never smoker. CONCLUSIONS: Approximately 85% of the adults studied were seronegative and therefore susceptible to pertussis infection. Approximately 1% had anti-PT IgG levels indicative of current/recent pertussis infection, which could potentially be transmitted to susceptible young infants. Vaccination of adults is a key way to indirectly protect infants. TRIAL REGISTRATION: Clinical Trials.gov NCT02014519 . Prospectively registered 12 December 2013

Antibacterial activity of Artemisia nilagirica leaf extracts against clinical and phytopathogenic bacteria

<p>Abstract</p> <p>Background</p> <p>The six organic solvent extracts of <it>Artemisia nilagirica </it>were screened for the potential antimicrobial activity against phytopathogens and clinically important standard reference bacterial strains.</p> <p>Methods</p> <p>The agar disk diffusion method was used to study the antibacterial activity of <it>A. nilagirica </it>extracts against 15 bacterial strains. The Minimum Inhibitory Concentration (MIC) of the plant extracts were tested using two fold agar dilution method at concentrations ranging from 32 to 512 μg/ml. The phytochemical screening of extracts was carried out for major phytochemical derivatives in <it>A. nilagirica</it>.</p> <p>Results</p> <p>All the extracts showed inhibitory activity for gram-positive and gram-negative bacteria except for <it>Klebsiella pneumoniae, Enterococcus faecalis </it>and <it>Staphylococcus aureus</it>. The hexane extract was found to be effective against all phytopathogens with low MIC of 32 μg/ml and the methanol extract exhibited a higher inhibition activity against <it>Escherichia coli, Yersinia enterocolitica, Salmonella typhi</it>, <it>Enterobacter aerogenes</it>, <it>Proteus vulgaris</it>, <it>Pseudomonas aeruginosa </it>(32 μg/ml), <it>Bacillus subtilis </it>(64 μg/ml) and <it>Shigella flaxneri </it>(128 μg/ml). The phytochemical screening of extracts answered for the major derivative of alkaloids, amino acids, flavonoids, phenol, quinines, tannins and terpenoids.</p> <p>Conclusion</p> <p>All the extracts showed antibacterial activity against the tested strains. Of all, methanol and hexane extracts showed high inhibition against clinical and phytopathogens, respectively. The results also indicate the presence of major phytochemical derivatives in the <it>A. nilagirica </it>extracts. Hence, the isolation and purification of therapeutic potential compounds from <it>A. nilagirica </it>could be used as an effective source against bacterial diseases in human and plants.</p