Predicting the Utility of Scientific Articles for Emerging Pandemics Using their Titles and Natural Language Processing.

Not all scientific publications are equally useful to policymakers tasked with mitigating the spread and impact of diseases, especially at the start of novel epidemics and pandemics. The urgent need for actionable, evidence-based information is paramount, but the nature of preprint and peer-reviewed articles published during these times is often at odds with such goals. For example, a lack of novel results and a focus on opinions rather than evidence were common in COVID-19 publications at the start of the pandemic in 2019. This work demonstrates that it is possible to judge the utility of these articles, from a public health policy-making perspective, based on their title and/or abstracts alone, using deep Natural Language Processing (NLP) models. These models were evaluated against expert-curated COVID-19 evidence to measure their real-world feasibility at screening these scientific publications in an automated manner. Such models can be used by public health experts to triage and filter the hundreds of new daily publications on novel diseases such as COVID-19 at the start of pandemics.

Molecular characterization of Leucoanthocyanidin reductase and Flavonol synthase gene in Arachis hypogaea.

Arachis hypogaea (peanut) is a potential source of bioactive compounds including flavonols and proanthocyanidins, which have gained particular interest of metabolic engineering owing to their significance in the growth, development and defense responses in plants. To gain insight of proanthocyanidins and flavonols production in A. hypogaea, Leucoanthocyanidin reductase (AhLAR) and Flavonol synthase (AhFLS) enzymes responsible for their production, have been structurally, transcriptionally and functionally characterized. Structural and functional analysis of putative protein sequence of AhFLS indicated two functional motifs 2OG-FeII_Oxy and DIOX_N, while six functional motifs belonging to the families of NAD-dependent dehydratase, 3, ß hydroxysteroid dehydrogenase and NmrA-like family were observed in case of AhLAR. Promoter sequence analysis unraveled several promoter elements related to the development regulation, environmental stress responses and hormonal signaling. Furthermore, the expression analysis of AhFLS and AhLAR and accumulation pattern analysis of proanthocyanidins and flavonols in three selected cultivars of A. hypogaea under saline environment confirmed their role against salinity in genotype-dependent and stress level-dependent manner. Correlation studies revealed that AhFLS and AhLAR expression is not directly dependent on the antioxidant enzymes activity, biochemical and growth parameters but higher Pearson r value depicted some level of dependency. This detailed study of AhLAR and AhFLS can assist in the metabolic engineering of flavonoid biosynthetic pathway to produce stress tolerant varieties and production of proanthocyanidins and flavonols at an industrial scale.

Diagnostic accuracy of simplified ultrasound hand examination protocols for detection of inflammation and disease burden in patients with rheumatoid arthritis.

BACKGROUND: There is no consensus regarding the minimum number of joints that should be included in an ultrasound (US) scoring system to reliably assess for disease activity in rheumatoid arthritis (RA). PURPOSE: To assess whether simplified US protocols for hand examination are as informative as the examination of 22 joints in patients with RA, and to correlate the US parameters with disease activity (DAS-28). MATERIAL AND METHODS: This is a cross-sectional study of 224 RA patients stratified based on their DAS-28 scores and assessed using eight preselected US examination protocols, including 22, 18, 16, 14, ten, eight, and two different combinations of four joints, respectively. RESULTS: We found a significant difference between US hand scores regarding their ability to detect active inflammation and erosions. DAS-28 scores correlated very well with the power Doppler (PD) scores generated by all eight US examination protocols (r = 0.89-1, P < 0.05), irrespective of patients' disease activity. Simplified US scores missed information on presence of PD in 20.6-40.2% patients ( P < 0.05) and misdiagnosed non-erosive hand RA in 12-38.4% patients ( P < 0.05), depending on the number of joints excluded from US hand examination. CONCLUSION: Preselected simplified US scores are less reliable in appreciating the disease burden when compared with an extended protocol for 22 joint US examination, raising clinicians' awareness regarding the need to comprehensively assess multiple hand joints to reliably rule out subclinical inflammation.

Renal toxicity of heavy metals (cadmium and mercury) and their amelioration with ascorbic acid in rabbits.

Cadmium and mercury are among the most toxic and dangerous environmental pollutants that may cause fatal implications. Vitamin C is an important chain-breaking antioxidant and enzyme co-factor against heavy metals. The objective of the present study was to evaluate the toxicological effects of cadmium chloride, mercuric chloride, and their co-administration on biochemical parameters of blood serum and metal bioaccumulation in kidneys and also to elucidate the protective effect of vitamin C in rabbits against these metals. In the current research, cadmium chloride (1.5 mg/kg), mercuric chloride(1.2 mg/kg), and vitamin C (150 mg/kg of body weight) were orally administered to eight treatment groups of the rabbits (1, control; 2, vitamin; 3, CdCl2; 4, HgCl2; 5, vitamin + CdCl2; 6, vitamin + HgCl2; 7, CdCl2 + HgCl2, and 8, vitamin + CdCl2 + HgCl2). After the biometric measurements of all experimental rabbits, biochemical parameters viz. creatinine, cystatin C, uric acid, and alkaline phosphatase (ALP) and metal bioaccumulation were determined using commercially available kits and atomic absorption spectrophotometer, respectively. The levels of creatinine (28.3 ± 1.1 µmol/l), cystatin C (1932.5 ± 38.5 ηg/ml), uric acid (4.8 ± 0.1 mg/day), and ALP (51.6 ± 1.1 IU/l) were significantly (P < 0.05) increased due to administration of mercuric chloride but in the presence of vitamin C, the effects of mercuric chloride on creatinine (21.9 ± 1.4 µmol/l), cystatin C (1676.2 ± 42.2 ηg/ml), uric acid (3.9 ± 0.1 mg/day), and ALP (43.3 ± 0.8 IU/l) were less as compared to metal-exposed specimens. Similar results were found in rabbits treated with cadmium chloride and vitamin C and also with co-administration of both metals and vitamin C. Because of the bio-accumulative nature of cadmium chloride and mercuric chloride, these metals were accumulated in kidneys of rabbits, which might lead to deleterious effects. The results of the present study provide an insight into the toxicity of the cadmium chloride, mercuric chloride, and/or their combination on biochemical parameters as well as kidneys of the rabbits and the ameliorating potential of vitamin C against these metals is also evaluated.

Comparison between Several Ultrasound Hand Joint Scores and Conventional Radiography in Diagnosing Hand Osteoarthritis.

This is the first study to investigate the usefulness of a standardized ultrasound (US) examination protocol in diagnosing hand osteoarthritis (OA). We conducted a cross-sectional study including 62 patients, ultimately diagnosed with hand OA based on imaging evidence of osteoarthritic changes with the particular distribution required for fulfilment of American College of Radiology diagnosis criteria. We compared a 32-joint US score (wrists, metacarpophalangeal [MCP], proximal interphalangeal [PIP] or distal interphalangeal [DIP] and carpometacarpal [CMC]-1 joints), with smaller, predefined joint scores, assessing 22 joints (wrists, MCPs and PIPs or PIPs, DIPs and CMC-1), 10 joints (MCP 2-3, PIP 2-3 and CMC-1 or PIP 2-3, DIP 2-3 and CMC-1) and 6 joints (DIP 2-3, CMC-1), respectively. The US findings were correlated with radiographic scores for erosions and osteophytes. Radiographic osteophyte scores correlated well with all the US scores mentioned earlier (R = 0.381 to 0.645, p < 0.05), despite low sensitivity for detection of osteophytes (43.5%) and erosions (28.9%), compared with the 32 joint US score. Both 10 joint US protocols (assessing MCP 2-3, PIP 2-3 and CMC-1 or PIP 2-3, DIP 2-3 and CMC-1 joints) performed better than conventional radiography, by identifying osteophytes in an additional 25.6% and 23.9% of patients, respectively. The conclusion of this study is that the US examination of 10 preselected hand joints is more sensitive than conventional radiography in diagnosing hand OA in patients who do not fulfill American College of Radiology clinical criteria, a finding likely to have practical implications for facilitating diagnosis of hand OA.

Ultrasonography-detected subclinical inflammation in patients with hand osteoarthritis and established rheumatoid arthritis: a comparison between two different pathologies using the same ultrasound examination protocol.

OBJECTIVES: A recent review of ultrasound (US) studies in osteoarthritis (OA) showed very limited data about hand OA. Previous US studies in patients with OA described a degree of overlap between the US appearance of rheumatoid arthritis (RA) and OA joints. The present study aimed to assess the US features of subclinical inflammation in RA and hand OA, using the same US examination protocol. METHODS: A retrospective, cohort study compared patients with established RA (n = 224) and hand OA (n = 73), with respect to several demographic, clinical, laboratory and US parameters. We used a 22-hand joint US examination protocol (wrists, metacarpophalangeal and proximal interphalangeal joints bilaterally - Outcome Measures in Rheumatology Clinical Trials [OMERACT] scoring system) for all patients. RESULTS: Subclinical joint inflammation in the context of equivocal clinical examination was found in 9.6% of OA patients compared with 46.4% of RA patients (p = 0.0001), despite the fact that there was no significant difference between the degree of chronic joint swelling (synovial hypertrophy grades 2 and 3; p = 0.75 and p = 0.11, respectively). The presence of osteophytes was more common in patients with hand OA, as expected (p = 0.0001). CONCLUSIONS: Our study findings reflected differences between the incidence and characteristics of subclinical inflammation in patients with RA and OA, which could be helpful in patients with an equivocal clinical examination or history of both diseases. Almost one in 10 patients with hand OA had active synovitis, while almost one in two patients with RA had uncontrolled inflammation in at least one joint.

Stable C and N isotope analysis of hair suggest undernourishment as a factor in the death of a mummified girl from late 19th century San Francisco, CA.

The chance discovery of a 1.5-3.5 years old mummified girl presents a unique opportunity to further our understanding of health and disease among children in 19th Century San Francisco. This study focuses on carbon and nitrogen stable isotope signatures in serial samples of hair that cover the last 14 months of her life. Results suggest an initial omnivorous diet with little input from marine resources or C4 plants. Around six months before death δ15N starts a steady increase, with a noticeable acceleration just two months before she died. The magnitude of δ15N change, +1.5‰ in total, is consistent with severe undernourishment or starvation. Cemetery records from this time period in San Francisco indicate high rates of infant and child mortality, mainly due to bacterial-borne infectious diseases, about two orders of magnitude higher than today. Taken together, we hypothesize that the girl died after a prolonged battle with such an illness. Results highlight the tremendous impacts that modern sanitation and medicine have had since the 1800s on human health and lifespan in the United States.

Wilderness medicine at high altitude: recent developments in the field.

Travel to high altitude is increasingly popular. With this comes an increased incidence of high-altitude illness and therefore an increased need to improve our strategies to prevent and accurately diagnose these. In this review, we provide a summary of recent advances of relevance to practitioners who may be advising travelers to altitude. Although the Lake Louise Score is now widely used as a diagnostic tool for acute mountain sickness (AMS), increasing evidence questions the validity of doing so, and of considering AMS as a single condition. Biomarkers, such as brain natriuretic peptide, are likely correlating with pulmonary artery systolic pressure, thus potential markers of the development of altitude illness. Established drug treatments include acetazolamide, nifedipine, and dexamethasone. Drugs with a potential to reduce the risk of developing AMS include nitrate supplements, propagators of nitric oxide, and supplemental iron. The role of exercise in the development of altitude illness remains hotly debated, and it appears that the intensity of exercise is more important than the exercise itself. Finally, despite copious studies demonstrating the value of preacclimatization in reducing the risk of altitude illness and improving performance, an optimal protocol to preacclimatize an individual remains elusive.

Modeling the role of negative cooperativity in metabolic regulation and homeostasis.

A significant proportion of enzymes display cooperativity in binding ligand molecules, and such effects have an important impact on metabolic regulation. This is easiest to understand in the case of positive cooperativity. Sharp responses to changes in metabolite concentrations can allow organisms to better respond to environmental changes and maintain metabolic homeostasis. However, despite the fact that negative cooperativity is almost as common as positive, it has been harder to imagine what advantages it provides. Here we use computational models to explore the utility of negative cooperativity in one particular context: that of an inhibitor binding to an enzyme. We identify several factors which may contribute, and show that acting together they can make negative cooperativity advantageous.