Miracle-dz/UniFAR-FTUs huggingface dataset:
Environmental Toxicology and Chemistry

Recent regulatory testing programs have been designed to evaluate whether a chemical has the potential to interact with the endocrine system and could cause adverse effects. Some endocrine pathways are highly conserved among vertebrates, providing a potential to extrapolate data generated for one vertebrate taxonomic group to others (i.e., biological read‐across). To assess the potential for biological read‐across, we reviewed tools and approaches that support species extrapolation for fish, amphibians, birds, and reptiles. For each of the estrogen, androgen, thyroid, and steroidogenesis (EATS) pathways, we considered the pathway conservation across species and the responses of endocrine‐sensitive endpoints. The available data show a high degree of confidence in the conservation of the hypothalamus–pituitary–gonadal axis between fish and mammals and the hypothalamus–pituitary–thyroid axis between amphibians and mammals. Comparatively, there is less empirical evidence for the conservation of other EATS pathways between other taxonomic groups, but this may be due to limited data. Although more information on sensitive pathways and endpoints would be useful, current developments in the use of molecular target sequencing similarity tools and thoughtful application of the adverse outcome pathway concept show promise for further advancement of read‐across approaches for testing EATS pathways in vertebrate ecological receptors. Environ Toxicol Chem 2020;39:739–753. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
Biochemical control of Alternaria tenuissima infecting post-harvest fig fruit by chickpea vicillin.

BACKGROUN Alternaria tenuissima was isolated from infected fig fruit and molecularly identified by rRNA gene sequencing. The objective of the current work was to test the inhibitory effect of vicillin as a glycoprotein isolated from chickpea against the fungus Alternaria tenuissima isolated from fig fruit in vitro and in situ to estimate its potential action in controlling the growth of Alternaria tenuissima in postharvest fig fruit. RESULTS Chickpea vicillin is a glycoprotein composed of 3 subunits of 135, 210 and 230 KDa. The linear growth of Alternaria tenuissima on the solid agar medium and in liquid media (at 25 °C) was markedly reduced by 44, 66, 77 & 83% and 20. 24, 42 & 62%, respectively in response to vicillin applications of 0.1, 0.2, 0.3 and 0.4 g/L. Chickpea vicillin (at 0.4 g/L) prevented totally fungal conidia germination during 24 h of incubation at 25 °C. electron microscope scanning of Alternaria tenuissima subjected to chickpea vicillin showed hyphae swelling and conidia deformation. Treating post-harvest fig fruit, artificially infected with Alternaria tenuissima, with chickpea vicillin (0.1-0.4 g/L) has restricted the disease severity to 15% against 55% in the positive control after 7 d keeping. CONCLUSION Vicillin can be considered a potent antifungal agent that can be used in preserving fig fruit for 7-14 d with minimum disease severity. This article is protected by copyright. All rights reserved.
Climate change contributes to widespread declines among bumble bees across continents

Increasing temperatures and declines One aspect of climate change is an increasing number of days with extreme heat. Soroye et al. analyzed a large dataset of bumble bee occurrences across North America and Europe and found that an increasing frequency of unusually hot days is increasing local extinction rates, reducing colonization and site occupancy, and decreasing species richness within a region, independent of land-use change or condition (see the Perspective by Bridle and van Rensburg). As average temperatures continue to rise, bumble bees may be faced with an untenable increase in frequency of extreme temperatures. Science, this issue p. 685; see also p. 626 An increasing frequency of hot days results in bumble bee decline. Climate change could increase species’ extinction risk as temperatures and precipitation begin to exceed species’ historically observed tolerances. Using long-term data for 66 bumble bee species across North America and Europe, we tested whether this mechanism altered likelihoods of bumble bee species’ extinction or colonization. Increasing frequency of hotter temperatures predicts species’ local extinction risk, chances of colonizing a new area, and changing species richness. Effects are independent of changing land uses. The method developed in this study permits spatially explicit predictions of climate change–related population extinction-colonization dynamics within species that explains observed patterns of geographical range loss and expansion across continents. Increasing frequencies of temperatures that exceed historically observed tolerances help explain widespread bumble bee species decline. This mechanism may also contribute to biodiversity loss more generally.
Metabolomic tools used in marine natural product drug discovery

ABSTRACT Introduction: The marine environment is a very promising resource for natural product research, with many of these reaching the market as new drugs, especially in the field of cancer therapy as well as the drug discovery pipeline for new antimicrobials. Exploitation for bioactive marine compounds with unique structures and novel bioactivity such as the isoquinoline alkaloid; trabectedin, the polyether macrolide; halichondrin B, and the peptide; dolastatin 10, requires the use of analytical techniques, which can generate unbiased, quantitative, and qualitative data to benefit the biodiscovery process. Metabolomics has shown to bridge this understanding and facilitate the development of new potential drugs from marine sources and particularly their microbial symbionts. Areas covered: In this review, articles on applied secondary metabolomics ranging from 1990–2018 as well as to the last quarter of 2019 were probed to investigate the impact of metabolomics on drug discovery for new antibiotics and cancer treatment. Expert opinion: The current literature review highlighted the effectiveness of metabolomics in the study of targeting biologically active secondary metabolites from marine sources for optimized discovery of potential new natural products to be made accessible to a R&D pipeline.
Surface Stiffness and Footwear Affect the Loading Stimulus for Lower Extremity Muscles When Running

Supplemental Digital Content is Available in the Text. Abstract Willwacher, S, Fischer, KM, Rohr, E, Trudeau, MB, Hamill, J, and Brüggemann, G-P. Surface stiffness and footwear affect the loading stimulus for lower extremity muscles when running. J Strength Cond Res 36(1): 82–89, 2022—Running in minimal footwear or barefoot can improve foot muscle strength. Muscles spanning the foot and ankle joints have the potential to improve performance and to reduce overuse injury risk. Surface stiffness or footwear use could modify the intensity of training stimuli acting on lower extremity joints during running. The purpose of this study was to systematically investigate external ankle, knee, and hip joint moments during shod and barefoot running while considering the stiffness of the running surface. Two footwear conditions (barefoot and neutral running shoe) and 4 surface conditions (Tartan, Tartan + Ethylene Vinyl Acetate [EVA] foam, Tartan + artificial turf, Tartan + EVA foam + artificial turf) were tested at 3.5 m·s−1. Repeated measures analysis of variance revealed that barefoot running in general and running barefoot on harder surfaces increased and decreased ankle (between +5 and +26%) and knee (between 0 and −11%) joint moments, respectively. Averaged over all surfaces, running barefoot was characterized by a 6.8° more plantarflexed foot strike pattern compared with running shod. Foot strike patterns were more plantarflexed on harder surfaces; the effects, however, were less than 3°. Most surface effects were stronger in barefoot compared with shod running. Surface stiffness may be used to modulate the loading intensity of lower extremity muscles (in particular extrinsic and intrinsic foot muscles) during running. These results need to be considered when coaches advise barefoot running as a method to improve the strength of extrinsic and intrinsic foot muscles or when trying to reduce knee joint loading.
Outcome and factors of patients with nosocomial meningitis by multi-drug-resistant Gram-negative bacteria in a tertiary hospital in China: a retrospective study

Abstract Background: Few data are available on the risk factors involved in nosocomial meningitis from multi-drug-resistant Gram-negative bacteria (MDR-GNB). Our aim was to identify the risk factors of prognosis for MDR-GNB nosocomial meningitis. Methods: Retrospective study of patients undergoing neurosurgery and with positive cerebrospinal fluid culture results post operation between January 2012 and January 2017 in a tertiary hospital in China. Results: In total, 3533 patients were screened. Forty patients with meningitis and completed data were included and divided into two groups, 29 who survived in the successful group (SG) and 11 who died in the failed group (FG). Statistically significant different factors involved in treating successful and failed were pathogen types, highest body temperature in the first 24h of symptoms, CSF glucose content and meropenem susceptibility (for Acinetobacter baumannii). The most common pathogen in the failed ones is Acinetobacter baumannii with meropenem MIC ≥ 16mg/L. Conclusions: Treatment of MDR-GNB nosocomial meningitis is more likely to fail in patients with severe condition when symptoms occur and infected by Acinetobacter baumannii. Researches with larger population are needed to find more factors to improve patient outcome.
Substrate-Specific Activation of α-Secretase by 7-Deoxy-Trans-Dihydronarciclasine Increases Non-Amyloidogenic Processing of β-Amyloid Protein Precursor

Accumulation of β-amyloid (Aβ) in the brain has been implicated in the pathology of Alzheimer’s disease (AD). Aβ is produced from the Aβ precursor protein (APP) through the amyloidogenic pathway by β-, and γ-secretase. Alternatively, APP can be cleaved by α-, and γ-secretase, precluding the production of Aβ. Thus, stimulating α-secretase mediated APP processing is considered a therapeutic option not only for decreasing Aβ production but for increasing neuroprotective sAPPα. We have previously reported that 7-deoxy-trans-dihydronarciclasine (E144), the active component of Lycoris chejuensis, decreases Aβ production by attenuating APP level, and retarding APP maturation. It can also improve cognitive function in the AD model mouse. In this study, we further analyzed the activating effect of E144 on α-secretase. Treatment of E144 increased sAPPα, but decreased β-secretase products from HeLa cells stably transfected with APP. E144 directly activated ADAM10 and ADAM17 in a substrate-specific manner both in cell-based and in cell-free assays. The Lineweaver–Burk plot analysis revealed that E144 enhanced the affinities of A Disintegrin and Metalloproteinases (ADAMs) towards the substrate. Consistent with this result, immunoprecipitation analysis showed that interactions of APP with ADAM10 and ADAM17 were increased by E144. Our results indicate that E144 might be a novel agent for AD treatment as a substrate-specific activator of α-secretase.
The effect of mindfulness training on burnout syndrome in nursing: a systematic review and meta-analysis.

AIM To analyse the effect of mindfulness training on levels of burnout among nurses. BACKGROUND Burnout syndrome is a common occupational hazard for nursing staff. Mindfulness training has been proposed as a valid intervention for burnout. DESIGN Systematic review and meta-analysis. DATA SOURCES The CINAHL, LILACS, Medline, ProQuest, PsycINFO, Scielo and Scopus databases were consulted, using the search equation "Nurs * AND burnout AND mindfulness". There was no restriction on the year of publication. REVIEW METHODS Papers were selected for analysis in accordance with the PRISMA guidelines. The meta-analysis was carried out using Review Manager 5.3 software. RESULTS The sample was of 17 articles including 632 nurses. Mindfulness training reduces levels of burnout, producing lower scores for emotional exhaustion and depersonalization and higher for personal accomplishment. The differences in the means were 1.32 (95% CI: -9.41 - 6.78), 1.91 (95% CI: -4.50 - 0.68) and 2.12 (95% CI: -9.91 - 14.14) respectively, between the intervention and control groups. CONCLUSION Mindfulness training reduces the emotional burden and hence levels of burnout, among nurses. However, further randomised clinical trials are required. IMPACT Mindfulness intervention reduces the level of burnout among nursing staff. Mindfulness, through body-mind training, allows workers to address and overcome situations of severe emotional impact. These results may have a positive impact for well-being and quality of life in nurses and also for the quality care. Hospitals can provide mindfulness training, which has been proposed as a potential strategy to reduce nurses burnout.
A Rectangular Notch-Band UWB Antenna with Controllable Notched Bandwidth and Centre Frequency

This paper presents the design and realization of a compact ultra-wideband (UWB) antenna with a rectangular notch wireless area network (WLAN) band that has controllable notched bandwidth and center frequency. The UWB characteristics of the antenna are achieved by truncating the lower ends of the rectangular microstrip patch, and the notch characteristics are obtained by using electromagnetic bandgap (EBG) structures. EBGs consist of two rectangular metallic conductors loaded on the back of the radiator, which is connected to the patch by shorting pins. A rectangular notch at the WLAN band with high selectivity is realized by tuning the individual resonant frequencies of the EBGs and merging them. Furthermore, the results show that the bandwidth and frequency of the rectangular notch band could be controlled according to the on-demand rejection band applications. In the demonstration, the rectangular notch band was shifted to X-band satellite communication by tuning the EBG parameters. The simulated and measured results show that the proposed antenna has an operational bandwidth from 3.1–12.5 GHz for |S11| < -10 with a rectangular notch band from 5–6 GHz, thus rejecting WLAN band signals. The antenna also has additional advantages: the overall size of the compact antenna is 16 × 25 × 1.52 mm3 and it has stable gain and radiation patterns.
Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails

The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the “microbiota”) that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.
Effect of hyperglycemia and rosiglitazone on renal and urinary neprilysin in db/db diabetic mice

Alteration in renin‐angiotensin system (RAS) has been implicated in the pathophysiology of diabetic kidney disease (DKD). The deleterious actions of angiotensin II (Ang II) could be antagonized by the formation of Ang‐(1–7), generated by the actions of angiotensin‐converting enzyme 2 (ACE2) and neprilysin (NEP). NEP degrades several peptides, including natriuretic peptides, bradykinin, amyloid beta, and Ang I. Although combination of Ang II receptor and NEP inhibitor treatment benefits patients with heart failure, the role of NEP in renal pathophysiology is a matter of active research. NEP pathway is a potent enzyme in Ang I to Ang‐(1–7) conversion in the kidney of ACE2‐deficient mice, suggesting a renoprotective role of NEP. The aim of the study is to test the hypothesis that chronic hyperglycemia downregulates renal NEP protein expression and activity in db/db diabetic mice and treatment with rosiglitazone normalizes hyperglycemia, renal NEP expression, and attenuates albuminuria. Mice received rosiglitazone (20 mg kg−1 day−1) for 10 weeks. Western blot analysis, immunohistochemistry, and enzyme activity revealed a significant decrease in renal and urinary NEP expression and activity in 16‐wk db/db mice compared with lean control (p < .0001). Rosiglitazone also attenuated albuminuria and increased renal and urinary NEP expressions (p < .0001). In conclusion, data support the hypothesis that diabetes decreases intrarenal NEP, which could have a pivotal role in the pathogenesis of DKD. Urinary NEP may be used as an index of intrarenal NEP status. The renoprotective effects of rosiglitazone could be mediated by upregulation of renal NEP expression and activity in db/db diabetic mice.
Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

Abstract Purpose: To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery. Methods: Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial–mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model. Results: We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P < 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P < 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo. Conclusions: Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma.
Vasculitis of the central nervous system

: Vasculitis of the central nervous system (CNS) is a rare disease characterized inflammation and/or sclerosis of the vascular wall, usually due to an immunological mechanism. The positive diagnosis of CNS vasculitis is difficult owing to its protean clinical manifestations, to its variable course and to the nonspecificity of CT and MRI images. Angiography itself may be of no avail since the segmental narrowing images, although suggestive, are neither constant nor pathognomonic. The causes of CNS vasculitis are very numerous. The aetiological diagnosis is easy when the causal systemic disease is already known or when an inflammatory syndrome and other localizations are present, but it is difficult in those exceptional cases where the vasculitis is limited to the CNS. Biopsy of the cortex and leptomeninges may them be required. Treatment varies according to the cause; it rests essentially on corticosteroid therapy, sometimes combined with cyclophosphamide.
One versus two-handed lifting and lowering: lumbar spine loads and recommended one-handed limits protecting the lower back

Abstract The objectives of this study were to quantify loads imposed upon the lumbar spine while lifting/lowering with one versus two hands and to create guidelines for one-handed lifting/lowering that are protective of the lower back. Thirty subjects (15 male, 15 female) performed one- and two-handed exertions in a laboratory, lifting from/lowering to 18 lift origins/destinations using medicine balls of varying masses. An electromyography-assisted model predicted peak spinal loads, which were related to tissue tolerance limits to create recommended weight limits. Compared to two-handed exertions, one-handed exertions resulted in decreased spinal compression and A/P shear loading (p < 0.001) but increased lateral shear (p < 0.001). Effects were likely driven by altered moment exposures attributable to altered torso kinematics. Differences between spinal loads for one- versus two-handed exertions were influenced by asymmetry (p < 0.001) and amplified at lower lift origin/destination heights, lower object masses and larger horizontal distances between the body and the load (p < 0.001). Practitioner summary: A biomechanical model was utilised to compare spinal loading for one versus two-handed lifting/lowering. Spinal loads in compression and A/P shear were reduced for one-handed relative to two-handed exertions. As current lifting guidelines cannot appropriately be applied to one-handed scenarios, one-handed weight limits protecting the lower back are presented herein. Abbreviations: LBD: low back disorder, EMG: electromyography, A/P: anterior/posterior, MVC: maximum voluntary contraction
MULTIMODAL IMAGING IN HELLP-RELATED CHORIORETINOPATHY

We report a case of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) complicated by multifocal serous retinal detachments and papilledema, illustrated with multimodal imaging indocyanine green angiography that revealed an irregular choroidal perfusion and localized choroidal ischemia. Spectral domain optical coherence tomography provided assessment of retinal changes during the long-term follow-up, showing damages in the outer retina. Purpose: To illustrate with multimodal imaging a case of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) complicated by bilateral multifocal serous retinal detachments, subretinal exudation, and papilledema. Methods: Case report. Fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography were performed at presentation and the day after. We also present the SD-OCT follow-up at 8 days, 1 year, and 4 years. Results: A 25-year-old 5-month-pregnant Guinean woman complained about decreased visual acuity in the right eye. Eye fundus and multimodal imaging were abnormal in both eyes. Spectral domain optical coherence tomography showed the presence of multifocal serous retinal detachments, subretinal deposits, and intraretinal cysts. Indocyanin green angiography revealed an irregular choroidal perfusion and localized choroidal ischemia. Spectral domain optical coherence tomography also provided assessment of retinal changes during the long-term follow-up, showing tissue damage in the outer retina. Conclusion: Serous retinal detachments during pregnancy can be the leading sign of HELLP syndrome—a potentially life-threatening condition. Spectral domain optical coherence tomography is a noninvasive and useful tool for its diagnosis and follow-up. ICG is important to confirm the choroidal ischemia and choroidal vascular abnormalities, underlying conditions leading to main sign of HELLP syndrome in the eye.