Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurotransmitter System-Targeting Drugs Antagonize Growth of the Q Fever Agent, Coxiella burnetii, in Human Cells

Coxiella burnetii causes the debilitating disease Q fever in humans. This infection is difficult to treat with current antibiotics and can progress to long-term, potentially fatal infection in immunocompromised individuals or when treatment is delayed. ABSTRACT Coxiella burnetii is a highly infectious, intracellular, Gram-negative bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis. C. burnetii is transmitted to humans via aerosols and has long been considered a potential biological warfare agent. Although antibiotics, such as doxycycline, effectively treat acute Q fever, a recently identified antibiotic-resistant strain demonstrates the ability of C. burnetii to resist traditional antimicrobials, and chronic disease is extremely difficult to treat with current options. These findings highlight the need for new Q fever therapeutics, and repurposed drugs that target eukaryotic functions to prevent bacterial replication are of increasing interest in infectious disease. To identify this class of anti-C. burnetii therapeutics, we screened a library of 727 FDA-approved or late-stage clinical trial compounds using a human macrophage-like cell model of infection. Eighty-eight compounds inhibited bacterial replication, including known antibiotics, antipsychotic or antidepressant treatments, antihistamines, and several additional compounds used to treat a variety of conditions. The majority of identified anti-C. burnetii compounds target host neurotransmitter system components. Serotoninergic, dopaminergic, and adrenergic components are among the most highly represented targets and potentially regulate macrophage activation, cytokine production, and autophagy. Overall, our screen identified multiple host-directed compounds that can be pursued for potential use as anti-C. burnetii drugs. IMPORTANCE Coxiella burnetii causes the debilitating disease Q fever in humans. This infection is difficult to treat with current antibiotics and can progress to long-term, potentially fatal infection in immunocompromised individuals or when treatment is delayed. Here, we identified many new potential treatment options in the form of drugs that are either FDA approved or have been used in late-stage clinical trials and target human neurotransmitter systems. These compounds are poised for future characterization as nontraditional anti-C. burnetii therapies.
A Retrospective Review of Four-Factor Prothrombin Complex Concentrate for Factor Xa Inhibitor-Related Bleedings

Background: The use of factor Xa inhibitors has grown in popularity; however, the risk of major bleeding events requires for the appropriate reversal agent. The recent approved agent for factor Xa inhibitor reversal, andexanet alfa, has limited clinical efficacy and safety data, and it can be a financial burden on healthcare systems due to its high cost. Four-factor prothrombin complex concentrate (4F-PCC) has been utilized off label in patients with factor Xa inhibitor-related bleedings. Objective: The aim of this study was to assess the safety and efficacy of 4F-PCC in managing factor Xa inhibitor-related bleedings. Methods: This is an observational, retrospective review of 4F-PCC usage in treating factor Xa inhibitor-related bleeds from May 2014 to December 2018 at a single health system. Efficacy was evaluated using the assessment criteria described by Sarode et al. Secondary outcomes analyzed included thromboembolic events, length of stay, mortality, and discharge disposition. Results: Fifty-nine patient charts were reviewed, and 48 patients were included in the study analysis. The administration of 4F-PCC achieved effective hemostasis in 33 patients (68%), and effective hemostasis was achieved in 12 patients (86%) who had intracranial hemorrhage and did not receive any surgical intervention. Thromboembolic events occurred in 4 patients within 30 days from 4F-PCC use. A majority of patients (85.4%) were discharged from the hospital to home or long-term care; 7 patients (14.6%) expired in the hospital. Conclusion: Efficacy was achieved in over half of the patient population in this cohort who received 4F-PCC for factor Xa inhibitor-related bleeding events.
The vulnerability of bananas to globally emerging disease threats.

Banana cultivation has increased significantly over the last century to meet the growing demand for this popular fruit. Originating in Southeast Asia, bananas are now produced in over 135 different countries in tropical and subtropical regions of the world. The vast majority of this expansion of production is based on a single banana variety "Cavendish" which makes up almost all the export trade grown in large scale monocultures as well as a large part of the local trade and represents over 40% of all bananas grown globally. Over the last century several major diseases of the banana have emerged, and widely expanded their geographic ranges. Cultivars within the "Cavendish" variety are highly susceptible to these diseases including: Yellow Sigatoka, Black leaf streak, Eumusae leaf spot, Freckle, Fusarium wilt Tropical race 4, Banana bunchy top and the bacterial wilts Moko, Xanthomonas wilt and Banana blood disease. This review graphically illustrates the emergence and rapid intercontinental spread of these diseases and discusses several major disease epidemics in bananas. Evidently, the large-scale monoculture based on the single variety "Cavendish" has resulted in an extreme level of genetic vulnerability. The resistance to diversification in the Cavendish production chain and the lack of investment in genetics and plant breeding in the recent past means that currently limited genetic solutions are available to replace the Cavendish banana with a set of market acceptable resistant varieties utilising a range of different genetic backgrounds.
Automatic extraction and measurement of individual trees from mobile laser scanning point clouds of forests

Abstract Background and Aims In addition to terrestrial laser scanning (TLS), mobile laser scanning (MLS) is increasingly arousing interest as a technique which provides valuable 3-D data for various applications in forest research. Using mobile platforms, the 3-D recording of large forest areas is carried out within a short space of time. Vegetation structure is described by millions of 3-D points which show an accuracy in the millimetre range and offer a powerful basis for automated vegetation modelling. The successful extraction of single trees from the point cloud is essential for further evaluations and modelling at the individual-tree level, such as volume determination, quantitative structure modelling or local neighbourhood analyses. However, high-precision automated tree segmentation is challenging, and has so far mostly been performed using elaborate interactive segmentation methods. Methods Here, we present a novel segmentation algorithm to automatically segment trees in MLS point clouds, applying distance adaptivity as a function of trajectory. In addition, tree parameters are determined simultaneously. In our validation study, we used a total of 825 trees from ten sample plots to compare the data of trees segmented from MLS data with manual inventory parameters and parameters derived from semi-automatic TLS segmentation. Key Results The tree detection rate reached 96 % on average for trees with distances up to 45 m from the trajectory. Trees were almost completely segmented up to a distance of about 30 m from the MLS trajectory. The accuracy of tree parameters was similar for MLS-segmented and TLS-segmented trees. Conclusions Besides plot characteristics, the detection rate of trees in MLS data strongly depends on the distance to the travelled track. The algorithm presented here facilitates the acquisition of important tree parameters from MLS data, as an area-wide automated derivation can be accomplished in a very short time.
Immunotherapy in rare ovarian cancer

Purpose of review Ovarian cancer (OC) is a heterogeneous disease and a mounting body of evidence shows that a ‘one-size-fits-all’ approach is obsolete. Differences in epidemiology, tumor biology, genetic profiles and treatment responses of these different types necessitate a tumor and patient-specific approach. Ninety percentage consists of epithelial OC with 70% being high-grade serous OC. The other rarer subtypes are low-grade serous (5%), clear cell (12%), endometrioid (11%) and mucinous carcinoma (3%). The remaining 10% are nonepithelial rare OCs: germ cell (3%) and sex-cord stromal tumors (7%). Recent findings Over the past few decades, the 5-year survival rates have only improved modestly, therefore novel therapies are urgently needed. Recently, immunotherapy has been introduced into clinical practice in a number of solid tumors. Although preclinical data confirm the presence of an immunogenic microenvironment in a number of ovarian tumor types, no single-agent immune checkpoint inhibitor has been approved hitherto. Identifying suitable treatment combinations, adequate patient selection and thus correct implementation of immunotherapy remain major challenges. Summary In this review, we focus on the rationale of incorporating immune therapy in rare OC, we summarize the recent developments with preclinical data and results of clinical trials, with particular focus on rare ovarian histological subtypes.
Antiparasitic Properties of Propolis Extracts and Their Compounds

Propolis is a bee product that has been used in medicine since ancient times. Although its anti‐inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti‐parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa, studies carried out with the protozoa Trypanosoma spp. and Leishmania spp. have demonstrated promising results in vitro and in vivo. However, there are fewer studies for Plasmodium spp. , the etiological agent of malaria and less so for helminths, particularly for Fasciola spp. and Schistosoma spp. Despite the favorable in vitro results with propolis, helminth assays need to be further investigated. However, propolis has shown itself to be an excellent natural product for parasitology, thus opening new paths and approaches in its activity against protozoa and helminths.
COVID-19 in fully vaccinated Everest trekkers in Nepal

COVID-19 in a fully mRNA-1273 vaccinated aspiring Everest summiteer and an Everest trekker who had two doses of ChAdOx1nCoV-19 are presented. Delta B.1. 617.2 variant was sequenced in one of the cases. Travellers should be wary of starting up travel to under-vaccinated regions, particularly if they are at high risk for severe disease.
Sexual Re-Assault among College Women Differs Based on Sexual Refusal Assertiveness and Assertive Resistance Strategy Intentions

Sexual assault and sexual re-assault are common problems on college campuses for women, and experiencing an initial assault dramatically increases risk for experiencing sexual re-assault. Low use of sexual refusal assertiveness and assertive resistance strategy intentions has been found to predict initial victimization, yet few studies to date look collectively at the associations of sexual refusal assertiveness and assertive resistance strategy intentions to sexual re-assault. The current study examined both sexual refusal assertiveness and assertive resistance strategy intentions as potential moderators of sexual re-assault among college women. It was hypothesized that the association between sexual assault severity before college and sexual assault severity since college would be stronger among those with low sexual refusal assertiveness compared to those with high sexual refusal assertiveness (Hypothesis 1). it was also hypothesized that the association between sexual assault severity before college and sexual assault severity since college would be stronger among those who endorsed assertive resistance strategy intentions (Hypothesis 2). Participants (N = 623) included college women at a large, public university within the northwestern region of the United States, who completed a web-based survey. Results revealed that the association between sexual assault severity before college and sexual assault severity since college was significant among those with lower levels of sexual refusal assertiveness (t = 91.42, p < 0 .001). Results also revealed that the association between sexual assault severity before college and sexual assault severity since college was stronger among those who endorsed non-assertive resistance strategy intentions to a potential sexual assault scenario (t = 25.09, p < 0.001). These findings provide insight into risk for sexual re-assault, wherein risk reduction programmatic efforts may be targeted towards women entering college with a sexual assault history to increase their use of sexual refusal assertiveness and assertive resistance strategy intentions.
Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia: Practical Considerations.

The positive symptoms of schizophrenia are usually treated with oral antipsychotics despite high rates of nonadherence leading to relapse and rehospitalization. Seven long-acting injectable (LAI) antipsychotics are currently approved by the U.S. Food and Drug Administration for maintenance treatment of schizophrenia. These medications reduce the risk for nonadherence and relapse, yet relatively few clinicians prescribe them. All LAI anti-psychotics are equally effective in treating the positive symptoms of schizophrenia. Dosing requirements, dosing frequencies, and what clinicians should consider in choosing a LAI antipsychotic for a specific patient are discussed. Communication strategies that help patients and families understand what they need to know about schizophrenia and its treatment to share in the decision-making process are also provided. [Journal of Psychosocial Nursing and Mental Health Services, 59(7), 7-12. ].
Effects of extreme heat stress and continuous lighting on growth performance and blood lipid in broiler chickens

In this study, the effect of extreme heat diet on growth performance, lymphoid organ, blood immunoglobulin and cecum microflora change in broilers exposed to continuous lighting and  주저자 (E-mail : bspark@kangwon.ac.kr) 2 박상오. 황보종. 류채민. 윤재성. 박병성. 강환구. 서옥석. 채현석. 최희철. 최양호 韓國油化學會誌 79 extreme heat stress (EHS) was studied. Broilers raised under normal environment temperature (25°C or extreme heat stress temperature (33±2°C, and consumed chow diet (CD) or extreme heat stress diet (EHSD). Five hundred Ross 308 day-old commercial broilers were arranged in a completely randomized block design of 5 treatment groups with 4 repetitions (25 heads per repetition pen). The broilers were divided into: T1 (normal environment+CD), T2 (EHS+CD), T3 (EHS+EHSD in which the tallow in CD was substituted by soy oil and contained 5% molasses), T4 (EHS+EHSD in which the tallow in CD was substituted by soy oil and contained 5% molasses, and 1.5 times more methionine and lysine than CD), and T5 (EHS+EHSD in which the tallow in CD was substituted by soy oil, contained 5% molasses, 1.5 times more methionine and lysine than CD, and 300ppm of vitamin C). The EHS significantly reduced the body weight gain and feed intake. The blood immunoglobulin, bursa of Fabricius, thymus, and spleen weight were significantly reduced when broilers were exposed to EHS. Compared to the normal environment temperature group, the cecum Lactobacillus sp. was low in the EHS treatment group, while Escherichia sp. , Salmonella sp. and total aerobic bacteria in the EHS treatment group were high. A statistically significant difference was acknowledged between the treatment groups.
The Reassessed Impact of Nicotine against Neurotoxicity in Mesencephalic Dopaminergic Cell Cultures and Neuroblastoma N18TG2 Cells

Abstract Neuroprotective effects of nicotine are still under debate, so further studies on its effectiveness against Parkinsonʼs disease are required. In our present study, we used primary dopaminergic cell cultures and N18TG2 neuroblastoma cells to investigate the effect of nicotine and its neuroprotective potential against rotenone toxicity. Nicotine protected dopaminergic (tyrosine hydroxylase immunoreactive) neurons against rotenone. This effect was not nAChR receptor-dependent. Moreover, the alkaloid at a concentration of 5 µM caused an increase in neurite length, and at a concentration of 500 µM, it caused an increase in neurite count in dopaminergic cells exposed to rotenone. Nicotine alone was not toxic in either cell culture model, while the highest tested concentration of nicotine (500 µM) caused growth inhibition of N18TG2 neuroblastoma cells. Nicotine alone increased the level of glutathione in both cell cultures and also in rotenone-treated neuroblastoma cells. The obtained results may be helpful to explain the potential neuroprotective action of nicotine on neural cell cultures.
Comparative immunogenicity of outer membrane protein K and whole‐cell antigens of Vibrio parahaemolyticus for diagnosis

The immunogenicity of soluble outer membrane protein K (OmpK)‐ small ubiquitin‐like modifier, OmpK inclusion bodies, formalin, and heat‐killed Vibrio parahaemolyticus cells were prepared and studied in a mouse model. The results of whole‐cell ELISA and Western blot (WB) revealed that the serum against soluble OmpK and OmpK inclusion bodies reacted only with homologous V. parahaemolyticus. Furthermore, recombinant OmpK proteins were not recognized by the serum against whole‐cell V. parahaemolyticus antigens. Unexpectedly, the serum against formalin and heat‐killed V. parahaemolyticus reacted broadly with homologous (an immunization strain) and heterologous (non‐immunization strains) V. parahaemolyticus and Vibrio species. The WB results revealed that the serum against the two V. parahaemolyticus whole‐cell antigens primarily reacted with proteins that were approximately 100, 70, 36, 28, and 22 kDa in the cell lysates from different Vibrio strains, rather than the recombinant OmpK. The 70 and 28 kDa proteins exhibited specificity to Vibrio species, while the 22 kDa protein was more specific to V. parahaemolyticus. This study showed the limitation of recombinant OmpK to prepare diagnostic antibodies and revealed several specific Omps of Vibrio sp. and V. parahaemolyticus that were promising in diagnosis and vaccine development.
How to Find Aquifer Statistics Utilizing Pumping Tests? Two Field Studies Using welltestpy

We present a workflow to estimate geostatistical aquifer parameters from pumping test data using the Python package welltestpy. The procedure of pumping test analysis is exemplified for two data sets from the Horkheimer Insel site and from the Lauswiesen site, Germany. The analysis is based on a semi‐analytical drawdown solution from the upscaling approach Radial Coarse Graining, which enables to infer log‐transmissivity variance and horizontal correlation length, beside mean transmissivity, and storativity, from pumping test data. We estimate these parameters of aquifer heterogeneity from type‐curve analysis and determine their sensitivity. This procedure, implemented in welltestpy, is a template for analyzing any pumping test. It goes beyond the possibilities of standard methods, for example, based on Theis' equation, which are limited to mean transmissivity and storativity. A sensitivity study showed the impact of observation well positions on the parameter estimation quality. The insights of this study help to optimize future test setups for geostatistical aquifer analysis and provides guidance for investigating pumping tests with regard to aquifer statistics using the open‐source software package welltestpy.
Bedside clinical data subphenotypes of critically ill COVID-19 patients: a cohort study

Objective To identify more severe COVID-19 presentations. Methods Consecutive intensive care unit-admitted patients were subjected to a stepwise clustering method. Results Data from 147 patients who were on average 56 ± 16 years old with a Simplified Acute Physiological Score 3 of 72 ± 18, of which 103 (70%) needed mechanical ventilation and 46 (31%) died in the intensive care unit, were analyzed. From the clustering algorithm, two well-defined groups were found based on maximal heart rate [Cluster A: 104 (95%CI 99 - 109) beats per minute versus Cluster B: 159 (95%CI 155 - 163) beats per minute], maximal respiratory rate [Cluster A: 33 (95%CI 31 - 35) breaths per minute versus Cluster B: 50 (95%CI 47 - 53) breaths per minute], and maximal body temperature [Cluster A: 37.4 (95%CI 37.1 - 37.7)°C versus Cluster B: 39.3 (95%CI 39.1 - 39.5)°C] during the intensive care unit stay, as well as the oxygen partial pressure in the blood over the oxygen inspiratory fraction at intensive care unit admission [Cluster A: 116 (95%CI 99 - 133) mmHg versus Cluster B: 78 (95%CI 63 - 93) mmHg]. Subphenotypes were distinct in inflammation profiles, organ dysfunction, organ support, intensive care unit length of stay, and intensive care unit mortality (with a ratio of 4.2 between the groups). Conclusion Our findings, based on common clinical data, revealed two distinct subphenotypes with different disease courses. These results could help health professionals allocate resources and select patients for testing novel therapies.