Miracle-dz/UniFAR-FTUs huggingface dataset:
Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism

Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi-ventricular pressure–volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure (p < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume (p < 0.001) and improved right ventricular function and cardiac output (p < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function (p < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction.
Metabolic Profiles of Brassica juncea Roots in Response to Cadmium Stress

Brassica juncea has great application potential in phytoremediation of cadmium (Cd)-contaminated soil because of its excellent Cd accumulating and high biomass. In this study, we compared the effects of Cd under 48 h and 7 d stress in roots of Brassica juncea using metabolite profiling. The results showed that many metabolic pathways and metabolites in Brassica juncea roots were altered significantly in response to Cd stress. We found that significant differences in levels of amino acids, organic acids, carbohydrates, lipids, flavonoids, alkaloids, and indoles were induced by Cd stress at different times, which played a pivotal role in the adaptation of Brassica juncea roots to Cd stress. Meanwhile, Brassica juncea roots could resist 48 h Cd stress by regulating the biosynthesis of amino acids, linoleic acid metabolism, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, ABC transporters, arginine biosynthesis, valine, leucine and isoleucine biosynthesis, and alpha-linolenic acid metabolism; however, they regulated alpha-linolenic acid metabolism, glycerophospholipid metabolism, ABC transporters, and linoleic acid metabolism to resist 7 d Cd stress. A metabolomic expedition to the response of Brassica juncea to Cd stress will help to comprehend its tolerance and accumulation mechanisms of Cd.
Fermentation Strategies to Improve Soil Bio-Inoculant Production and Quality

The application of plant beneficial microorganisms has been widely accepted as an efficient alternative to chemical fertilizers and pesticides. Isolation and selection of efficient microorganisms, their characterization and testing in soil-plant systems are well studied. However, the production stage and formulation of the final products are not in the focus of the research, which affects the achievement of stable and consistent results in the field. Recent analysis of the field of plant beneficial microorganisms suggests a more integrated view on soil inoculants with a special emphasis on the inoculant production process, including fermentation, formulation, processes, and additives. This mini-review describes the different groups of fermentation processes and their characteristics, bearing in mind different factors, both nutritional and operational, which affect the biomass/spores yield and microbial metabolite activity. The characteristics of the final products of fermentation process optimization strategies determine further steps of development of the microbial inoculants. Submerged liquid and solid-state fermentation processes, fed-batch operations, immobilized cell systems, and production of arbuscular mycorrhiza are presented and their advantages and disadvantages are discussed. Recommendations for further development of the fermentation strategies for biofertilizer production are also considered.
FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice

Simple Summary FGFR inhibitors evolved as therapeutic options in cholangiocarcinoma and urothelial malignancies. Given the implications of FGFR pathway in various physiological functions, FGFR inhibitors are known to cause unique toxicities. In this review, we summarized the physiology of FGF/FGFR signaling and briefly discussed the possible mechanisms that could lead to FGFR inhibitor resistance and side effects. In addition, we proposed treatment guidelines for the management of FGFR-inhibitor-associated toxicities. Abstract Fibroblast Growth Factor receptor (FGFR) pathway aberrations have been implicated in approximately 7% of the malignancies. As our knowledge of FGFR aberrations in cancer continues to evolve, FGFR inhibitors emerged as potential targeted therapeutic agents. The promising results of pemigatinib and infigratinib in advanced unresectable cholangiocarcinoma harboring FGFR2 fusions or rearrangement, and erdafitinib in metastatic urothelial carcinoma with FGFR2 and FGFR3 genetic aberrations, lead to their accelerated approval by the United States (USA) FDA. Along with these agents, many phase II/III clinical trials are currently evaluating the use of derazantinib, infigratinib, and futibatinib either alone or in combination with immunotherapy. Despite the encouraging results seen with FGFR inhibitors, resistance mechanisms and side effect profile may limit their clinical utility. A better understanding of the unique FGFR-inhibitor-related toxicities would invariably help us in the prevention and effective management of FGFR-inhibitor-induced adverse events thereby enhancing their clinical benefit. Herein, we summarized the physiology of FGF/FGFR signaling and briefly discussed the possible mechanisms that could lead to FGFR inhibitor resistance and side effects. In addition, we proposed treatment guidelines for the management of FGFR-inhibitor-associated toxicities. This work would invariably help practicing oncologists to effectively manage the unique toxicities of FGFR inhibitors.
Differential Transcript Profiles in Cumulus-Oocyte Complexes Originating from Pre-Ovulatory Follicles of Varied Physiological Maturity in Beef Cows

Small dominant follicle diameter at induced ovulation, but not at spontaneous ovulation, decreased pregnancy rate, fertilization rate, and day seven embryo quality in beef cows. We hypothesized that the physiological status of the follicle at GnRH-induced ovulation has a direct effect on the transcriptome of the Cumulus-Oocyte complex, thereby affecting oocyte competence and subsequent embryo development. The objective of this study was to determine if the transcriptome of oocytes and associated cumulus cells (CC) differed among small (≤11.7 mm) and large follicles (≥12.7 mm) exposed to a GnRH-induced gonadotropin surge and follicles (11.7–14.0 mm) exposed to an endogenous gonadotropin surge (spontaneous follicles). RNA sequencing data, from pools of four oocytes or their corresponding CC, revealed 69, 94, and 83 differentially expressed gene transcripts (DEG) among oocyte pools from small versus large, small versus spontaneous, and large versus spontaneous follicle classifications, respectively. An additional 128, 98, and 80 DEG were identified among small versus large, small versus spontaneous, and large versus spontaneous follicle CC pools, respectively. The biological pathway “oxidative phosphorylation” was significantly enriched with DEG from small versus spontaneous follicle oocyte pools (FDR < 0.01); whereas the glycolytic pathway was significantly enriched with DEG from CC pools obtained from large versus small follicles (FDR < 0.01). These findings collectively suggest that altered carbohydrate metabolism within the Cumulus-Oocyte complex likely contributes to the decreased competency of oocytes from small pre-ovulatory follicles exposed to an exogenous GnRH-induced gonadotropin surge.
miR-373-3p Regulates Invasion and Migration Abilities of Trophoblast Cells via Targeted CD44 and Radixin

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients’ blood. miR-373-3p was increased in PTL patients’ blood, and was the most expressed in PTL patients’ blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients’ blood, and their expression were the lowest in PTL patients’ blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL.
Measurement of Selected Renal Biochemical Parameters in Healthy Adult Donkeys Considering the Influence of Gender, Age and Blood Freezing

Simple Summary In animal medicine, laboratory test profiles containing selected blood or urine parameters are used to diagnose diseases of a given organ. The normal values of the serum and urine biochemical parameters are well-known in horses, but they have not been studied well in donkeys. This means that their results are often compared with horses’ reference values. The interest in donkeys continues to grow, as well as increasing attention being paid to kidney damage in animals. The objective of the study was to determine the values of the selected serum and urine parameters to assess the renal function in healthy donkeys. The effects of age, sex and freezing of the material were then assessed. Sixty-five healthy adult donkeys participated in the study. The results showed different reference values for the kidney parameters such as urea, total protein, albumin, urine protein/creatinine ratio and fractional electrolyte excretion in donkeys compared to those reported for horses. The donkeys’ gender had an effect on the creatinine and urea, while age had an effect on the albumin, total protein and electrolytes. Freezing of the material also influenced most of the parameters. To the authors’ knowledge, this is the first study to analyze the selected renal biomarkers in donkeys. Abstract The reference values of the serum and urine biochemical parameters have not been well-studied in donkeys. This study aimed to assess the normal values of the selected renal biomarkers, such as: serum creatinine, blood urea nitrogen (BUN), albumin, total protein (TP), electrolytes and symmetric dimethylarginine (SDMA), urine protein concentration (UPC), urine protein/creatinine ratio (UPCR), the urine gamma-glutamyl transferase (GGTP)-to-creatinine ratio, serum creatinine-to-urine creatinine ratio (sCr/uCr), serum BUN-to-serum creatinine ratio (sBUN/sCr) and UPC-to-TP ratio, as well as the fractional electrolyte excretion of sodium (FENa) and potassium (FEK) in donkeys. The effects of age, gender and deep freezing of the serum material were investigated. Sixty-five healthy adult donkeys were involved in this study. The results showed higher BUN and TP values and lower albumin, UPCR, FENa and FEK levels in donkeys when compared to the reference values in horses. A significant gender relationship for creatinine and BUN was found. Age influenced the values of albumin, TP, potassium and chlorine. Potassium, sodium and SDMA did not show significant concentration changes after freezing. The study results demonstrated that horse reference range values for some parameters cannot be applied to donkey samples. Only a few of the serum parameters were not affected by freezing, and this should be taken into account when storing biological materials.
RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling

DDX3 is a cellular ATP-dependent RNA helicase involved in different aspects of RNA metabolism ranging from transcription to translation and therefore, DDX3 participates in the regulation of key cellular processes including cell cycle progression, apoptosis, cancer and the antiviral immune response leading to type-I interferon production. DDX3 has also been described as an essential cellular factor for the replication of different viruses, including important human threats such HIV-1 or HCV, and different small molecules targeting DDX3 activity have been developed. Indeed, increasing evidence suggests that DDX3 can be considered not only a promising but also a viable target for anticancer and antiviral treatments. In this review, we summarize distinct functional aspects of DDX3 focusing on its participation as a double-edged sword in the host immune response and in the replication cycle of different viruses.
Risk Factors of Infection, Hospitalization and Death from SARS-CoV-2: A Population-Based Cohort Study

We conducted a prospective population-based cohort study to assess risk factors for infection, hospitalization, and death from SARS-CoV-2. The study comprised the people covered by the Health Service of Navarre, Spain. Sociodemographic variables and chronic conditions were obtained from electronic healthcare databases. Confirmed infections, hospitalizations, and deaths from SARS-CoV-2 were obtained from the enhanced epidemiological surveillance during the second SARS-CoV-2 epidemic surge (July–December 2020), in which diagnostic tests were widely available. Among 643,757 people, 5497 confirmed infections, 323 hospitalizations, 38 intensive care unit admissions, and 72 deaths from SARS-CoV-2 per 100,000 inhabitants were observed. A higher incidence of confirmed infection was associated with people aged 15–29 years, nursing home residents, healthcare workers, people born in Latin America or Africa, as well as in those diagnosed with diabetes, cardiovascular disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease, dementia, severe obesity, hypertension and functional dependence. The risk of hospitalization in the population was associated with males, higher age, nursing home residents, Latin American or African origin, and those diagnosed with immunodeficiency, diabetes, cardiovascular disease, COPD, asthma, kidney disease, cerebrovascular disease, cirrhosis, dementia, severe obesity, hypertension and functional dependence. The risk of death was associated with males, higher age, nursing home residents, Latin American origin, low income level, immunodeficiency, diabetes, cardiovascular disease, COPD, kidney disease, dementia, and functional dependence. This study supports the prioritization of the older population, nursing home residents, and people with chronic conditions and functional dependence for SARS-CoV-2 prevention and vaccination, and highlights the need for additional preventive support for immigrants.
The Evoked Potential Score for SSEP and BAEP—A Prognostic Marker for the Long-Term Neurological Outcome in Patients after Poor-Grade Subarachnoid Hemorrhage

Objective: Evoked potentials are widely used in comatose patients to evaluate neurological function; however, prognostic relevance in patients after SAH is barely investigated. Therefore, we aimed to investigate the prognostic value of the proposed Evoked Potential Score (EPS) for somatosensory (SSEP) and brainstem auditory evoked potentials (BAEP) on the neurological outcome in patients after poor-grade SAH. Methods: We retrospectively analyzed patients after poor grade SAH (Hunt and Hess (HH) grade IV and V) that were admitted to the ICU at the Department of Neurosurgery, MUV, between 2014 and 2017. Measurements of SSEP and BAEP were evaluated separately as well as in a combined model, using the EPS at admission and before ventilator weaning and correlated with the grade of the modified ranking scale at the last available follow up. Results: In total, 48 patients after SAH HH IV/V were included in this study. The EPS for SSEP at admission (p = 0.007) and both the EPS for SSEP (p = <0.0001) and BAEP (p = 0.036) before ventilator weaning were significant prognostic markers for neurological improvement at a mean follow-up period of 14.1 months. In addition, the combined model of the EPS for SSEP/BAEP performed as a prognostic marker for neurological improvement (“at admission” p = 0.007; “before ventilator weaning” p < 0.001). Conclusions: In the first series to date we found a high prognostic significance for the EPS as a combined model, as well as a separate analysis for SSEP and BAEP in patients after SAH IV and V. In the future, these findings potentially support physicians in ethically challenging decision-making processes and in advice for patients’ families under consideration of an individual evaluation of each patient.
Imaging Assessment of Tumor Response in the Era of Immunotherapy

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.
Resistance in the Genus Spodoptera: Key Insect Detoxification Genes

Simple Summary The moth larvae are among the most damaging pest species on crops worldwide. In this review, we focus on the genus Spodoptera, which can feed on many crops such as rice, cotton or corn. The massive use of insecticides to control these insects has led to the development of resistance. Here, we aim to compare the resistance mechanisms of four species (Spodoptera exigua, Spodoptera frugiperda, Spodoptera littoralis and Spodoptera litura) and highlight the role of enzymes and transporters in resistance to help us understand the molecular basis of their origin. Abstract The genus Spodoptera (Lepidoptera: Noctuidae) includes species that are among the most important crop pests in the world. These polyphagous species are able to feed on many plants, including corn, rice and cotton. In addition to their ability to adapt to toxic compounds produced by plants, they have developed resistance to the chemical insecticides used for their control. One of the main mechanisms developed by insects to become resistant involves detoxification enzymes. In this review, we illustrate some examples of the role of major families of detoxification enzymes such as cytochromes P450, carboxyl/cholinesterases, glutathione S-transferases (GST) and transporters such as ATP-binding cassette (ABC) transporters in insecticide resistance. We compare available data for four species, Spodoptera exigua, S. frugiperda, S. littoralis and S. litura. Molecular mechanisms underlying the involvement of these genes in resistance will be described, including the duplication of the CYP9A cluster, over-expression of GST epsilon or point mutations in acetylcholinesterase and ABCC2. This review is not intended to be exhaustive but to highlight the key roles of certain genes.
Circadian Blood Pressure Rhythm in Cardiovascular and Renal Health and Disease

Blood pressure (BP) follows a circadian rhythm, it increases on waking in the morning and decreases during sleeping at night. Disruption of the circadian BP rhythm has been reported to be associated with worsened cardiovascular and renal outcomes, however the underlying molecular mechanisms are still not clear. In this review, we briefly summarized the current understanding of the circadian BP regulation and provided therapeutic overview of the relationship between circadian BP rhythm and cardiovascular and renal health and disease.