Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of linalool on extinction of mouse operant behaviour

Linalool is an enanitomer monoterpene compound identified as the pharmacologically active constituent in a number of essential oils and has been reported to display anxiolytic properties in humans and in animal models and to exert both GABAergic and glutamatergic effects. In Experiment 1 linalool (100, 200, and 300, i.p.) had no significant effects compared with saline in an activity tracker with C57BL/6j mice. Experiment 2 assessed the effects on operant extinction with mice of chlordiazepoxide at a dose (15 mg/kg, i.p.) previously shown to facilitate extinction, and the same doses of linalool, compared with saline. Linalool had a dose-related facilitatory effect on extinction. While the effects of the highest dose of linalool most closely resembled the effects of chlordiazepoxide, the pattern of results suggested that linalool may affect both the acquisition of extinction learning, which is influenced by glutamatergic processes, and the expression of extinction, known to be affected by GABAergic agents such as chlordiazepoxide.
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy

Significance The development of novel, effective treatments for patients with advanced/recurrent cervical cancer remains an unmet medical need. Using whole-exome sequencing, we identified multiple genes with recurrent alterations in cervical cancer, including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle pathways. Using fully sequenced cell lines and xenografts, we found pan-HER (afatinib/neratinib) and PIK3CA (copanlisib) inhibitors to be active, but only transiently effective in controlling the in vivo growth of PIK3CA-mutated cervical tumor xenografts. In contrast, the combination of irreversible pan-HER kinase and PIK3CA inhibitors was highly synergistic and able to induce durable regression of xenografts harboring derangements in the ERBB2/PI3K/AKT/mTOR pathway in vivo. These findings suggest a large subset of cervical tumors (>70%) might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs. The prognosis of advanced/recurrent cervical cancer patients remains poor. We analyzed 54 fresh-frozen and 15 primary cervical cancer cell lines, along with matched-normal DNA, by whole-exome sequencing (WES), most of which harboring Human-Papillomavirus-type-16/18. We found recurrent somatic missense mutations in 22 genes (including PIK3CA, ERBB2, and GNAS) and a widespread APOBEC cytidine deaminase mutagenesis pattern (TCW motif) in both adenocarcinoma (ACC) and squamous cell carcinomas (SCCs). Somatic copy number variants (CNVs) identified 12 copy number gains and 40 losses, occurring more often than expected by chance, with the most frequent events in pathways similar to those found from analysis of single nucleotide variants (SNVs), including the ERBB2/PI3K/AKT/mTOR, apoptosis, chromatin remodeling, and cell cycle. To validate specific SNVs as targets, we took advantage of primary cervical tumor cell lines and xenografts to preclinically evaluate the activity of pan-HER (afatinib and neratinib) and PIK3CA (copanlisib) inhibitors, alone and in combination, against tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway (71%). Tumors harboring ERBB2 (5.8%) domain mutations were significantly more sensitive to single agents afatinib or neratinib when compared to wild-type tumors in preclinical in vitro and in vivo models (P = 0.001). In contrast, pan-HER and PIK3CA inhibitors demonstrated limited in vitro activity and were only transiently effective in controlling in vivo growth of PIK3CA-mutated cervical cancer xenografts. Importantly, combinations of copanlisib and neratinib were highly synergistic, inducing long-lasting regression of tumors harboring alterations in the ERBB2/PI3K/AKT/mTOR pathway. These findings define the genetic landscape of cervical cancer, suggesting that a large subset of cervical tumors might benefit from existing ERBB2/PIK3CA/AKT/mTOR-targeted drugs.
Comparison of Interstitial Fluid Glucose Levels Obtained by Continuous Glucose Monitoring and Flash Glucose Monitoring in Patients With Type 2 Diabetes Mellitus Undergoing Hemodialysis

Background: The accuracy of flash glucose monitoring (FGM, FreeStyle Libre Pro [FSL-Pro]) remains unclear in patients with type 2 diabetes mellitus (T2DM) undergoing hemodialysis. Methods: We assessed 13 patients with T2DM undergoing hemodialysis. They simultaneously underwent FGM, continuous glucose monitoring (CGM, iPro2), and self-monitoring blood glucose (SMBG). Results: Parkes error grid analysis against SMBG showed that 49.0% and 51.0% of interstitial fluid glucose (ISFG) levels measured using FGM and 93.3% and 6.7% of those measured using CGM fell into zones A and B, respectively. Mean absolute relative difference (MARD) against SMBG for FGM was significantly higher than that for CGM (19.5% ± 13.2% vs 8.1% ± 7.6%, P < .0001). Parkes error grid analysis of 2496 paired ISFG levels between FGM and CGM showed that 53.6%, 46.2%, and 0.2% of the plots fell into zones A, B, and C, respectively. Mean ISFG levels were lower with FGM than with CGM (143.7 ± 67.2 mg/dL vs 164.6 ± 58.5 mg/dL; P < .0001). Mean absolute relative difference of ISFG levels between FGM and CGM was 19.2% ± 13.8%. Among three groups classified according to CGM ISFG levels (hypoglycemia, <70 mg/dL; euglycemia, 70-180 mg/dL; and hyperglycemia, >180 mg/dL), the MARDs for hypoglycemia (31.9% ± 25.0%) and euglycemia (22.8% ± 14.6%) were significantly higher than MARD for hyperglycemia (13.0% ± 8.5%) (P < .0001 in both). Conclusions: Flash glucose monitoring may be clinically acceptable. Average ISFG levels were lower with FGM than with CGM, and MARDs were higher for hypoglycemia and euglycemia in patients with T2DM undergoing hemodialysis.
Clinical Reasoning and Diagnostic Error: A Call to Merge Two Worlds to Improve Patient Care.

Numerous and substantial challenges exist in the provision of safe, cost-effective, and efficient health care. The prevalence and consequences of diagnostic error, one of these challenges, have been established by the literature; however, these errors persist, and the pace of improvement has been slow. One potential reason for the lack of needed progress is that addressing delayed and wrong diagnoses will require contributions from two currently distinct worlds: clinical reasoning and diagnostic error. In this Invited Commentary, the authors argue for merging the diagnostic error and clinical reasoning fields as the perspectives, frameworks, and methodologies of these two fields could be leveraged to yield a more aligned approach to understanding and subsequently to mitigating diagnostic error. The authors focus on the problem of diagnostic labeling (a categorization task where one has to choose the correct label or diagnosis). The authors also elaborate on why this alignment could also help guide health care improvement efforts, using the vexing problem of context specificity that leads to unwanted variance in health care as an example.
By word of mouse: using animal models in venous thrombosis research

Abstract Deep vein thrombosis (DVT) is a disease with high prevalence and morbidity. It can lead to pulmonary embolism with severe respiratory insufficiency and risk of death. Mechanisms behind all stages of DVT, such as thrombosis commencement, propagation, and resolution, remain incompletely understood. Animal models represent an invaluable tool to explore these problems and identify new targets for DVT prevention and treatment. In this review, we discuss existing models of venous thrombosis, their advantages and disadvantages, and applicability to studying different aspects of DVT pathophysiology. We also speculate about requirements for an “ideal model” that would best recapitulate features of human DVT and discuss readouts of various models.
The role of mental health variables and coping strategies in premenstrual syndrome

Abstract In this study we aimed to examine the relationship between PMS and some mental health variables (anxiety, depression, neuroticism) and coping strategies. We analyzed their predictive value by assessing 55 women’s symptoms. We found that all the studied health variables and coping strategies were significantly correlated with reported PMS’s Negative Symptomatology scores in the premenstrual phase. Interdisciplinary training programs on instrumental coping strategies might be carried out. In future studies researchers might examine how severe Depression would impact on PMS, and which specific intervention strategies would diminish PMS’s distressing effects on women’s quality of life worldwide.
Bone and Soft‐Tissue Sarcoma Risk in Long‐Term Survivors of Hereditary Retinoblastoma Treated With Radiation

PURPOSE Survivors of hereditary retinoblastoma have excellent survival but substantially increased risks of subsequent bone and soft-tissue sarcomas, particularly after radiotherapy. Comprehensive investigation of sarcoma risk patterns would inform clinical surveillance for survivors. PATIENTS AND METHODS In a cohort of 952 irradiated survivors of hereditary retinoblastoma who were originally diagnosed during 1914 to 2006, we quantified sarcoma risk with standardized incidence ratios (SIRs) and cumulative incidence analyses. We conducted analyses separately for bone and soft-tissue sarcomas occurring in the head and neck (in/near the radiotherapy field) versus body and extremities (out of field). RESULTS Of 105 bone and 124 soft-tissue sarcomas, more than one half occurred in the head and neck (bone, 53.3%; soft tissue, 51.6%), one quarter in the body and extremities (bone, 29.5%; soft tissue, 25.0%), and approximately one fifth in unknown/unspecified locations (bone, 17.1%; soft tissue, 23.4%). We noted substantially higher risks compared with the general population for head and neck versus body and extremity tumors for both bone (SIR, 2,213; 95% CI, 1,671 to 2,873 v SIR, 169; 95% CI, 115 to 239) and soft-tissue sarcomas (SIR, 542; 95% CI, 418 to 692 v SIR, 45.7; 95% CI, 31.1 to 64.9). Head and neck bone and soft-tissue sarcomas were diagnosed beginning in early childhood and continued well into adulthood, reaching a 60-year cumulative incidence of 6.8% (95% CI, 5.0% to 8.7%) and 9.3% (95% CI, 7.0% to 11.7%), respectively. In contrast, body and extremity bone sarcoma incidence flattened after adolescence (3.5%; 95% CI, 2.3% to 4.8%), whereas body and extremity soft-tissue sarcoma incidence was rare until age 30, when incidence rose steeply (60-year cumulative incidence, 6.6%; 95% CI, 4.1% to 9.2%), particularly for females (9.4%; 95% CI, 5.1% to 13.8%). CONCLUSION Strikingly elevated bone and soft-tissue sarcoma risks differ by age, location, and sex, highlighting important contributions of both radiotherapy and genetic susceptibility. These data provide guidance for the development of a risk-based screening protocol that focuses on the highest sarcoma risks by age, location, and sex.
Spatial-Temporal Characteristics of Agriculture Green Total Factor Productivity in China, 1998–2016: Based on More Sophisticated Calculations of Carbon Emissions

Environmental costs should be taken into account when measuring the achievements of China’s agricultural development, since the long-term extensive development of agriculture has caused huge environmental pollution. This study took agricultural carbon emissions as an undesired output to estimate the agricultural development efficiency in 31 provinces of China from 1998 to 2016, based on the green total factor productivity, as assessed by the slacks-based measure directional distance function and constructing the global Malmquist–Luenberger index. We measured agricultural carbon emissions in terms of five aspects: agricultural materials, rice planting, soil, livestock and poultry farming, and straw burning, and then compared the green total factor productivity index and the total factor productivity index. The study came to the following conclusions: (1) the green technology efficiency change was smaller than the technology efficiency change at first, but the gap between them is narrowing with time, such that the former is now larger than the latter; (2) the green technology efficiency was in a declining state and the green technology progress was increasing, promoting the green total factor productivity growth, from 1998 to 2016; and (3) China’s agricultural green total factor productivity increased by 4.2% annually in the east, 3.4% annually in the central region, and 2.5% annually in the west.
Theory and Guidelines for the Application of the Geophysical Sensor EM38

Characterization of spatial soil variability is key for a better understanding of soils. To arrive at such information geophysical techniques have been used in the last two decades. Due to its easy handling, the geophysical sensor EM38 has widely been used to characterize agricultural areas. The theoretical background and usage of the EM38 is described, and based on multifaceted applications, the interpretation of the results as well as optimized steps for using it are outlined. Common principles and models of the apparent electrical conductivity (ECa) and strengths and limitations of this technique (calibration and temperature effects) are described as well as additional applications, such as the magnetic susceptibility, a comparison of measurements in vertical and horizontal modes, the use of weighted depth information and the influence of measurement conditions are addressed. Further a comparison of EM38 with other proximal soil sensors and fusion with other devices is described. The study reveals that EM38 is useful because the readings can reflect many different soil parameters.
The relationship between levels of self-esteem and the development of depression in young adults with mild depressive symptoms

Abstract Little is known about the relationship between levels of self-esteem and the development of depression in young adults. The present study investigated the relationship between self-esteem and depression to determine whether self-esteem levels are a risk factor for the development of depression in young adults. This study was conducted with 113 college students aged 19 to 35 (major depressive disorder (MDD) n = 44, Mild Depressive Symptoms (MDS) n = 37, Healthy Control n = 32). The levels of clinical symptoms, self-esteem, resilience, social support, and quality of life, as well as personality traits, were assessed (by Patient Health Questionnaire-9, generalized anxiety disease-7, State-Trait Anxiety Inventory-S, Resilience Appraisal Scale, Rosenberg Self-Esteem Scale, Quality of Life, and NEO-personality inventory (NEO-PI)). The MDS group with high self-esteem reported having the lowest levels of social support, resilience, agreeableness, and extraversion compared to those of the MDD group and control group with high self-esteem. In contrast, the MDS group with low self-esteem showed no differences in social support, resilience, agreeableness and openness according to the NEO-PI scale. Sex and age had no significant impact on the results. Levels of self-esteem are strongly associated with the development of depression. Results suggest that early intervention for depression in young adults needs to focus on improving their levels of social support, resilience, and positive domains of personality. Further studies on the effects of high self-esteem in the development of depression are warranted.
Comparison of Whole-Genome Sequences of Legionella pneumophila in Tap Water and in Clinical Strains, Flint, Michigan, USA, 2016

During the water crisis in Flint, Michigan, USA (2014–2015), 2 outbreaks of Legionnaires’ disease occurred in Genesee County, Michigan. We compared whole-genome sequences of 10 clinical Legionella pneumophila isolates submitted to a laboratory in Genesee County during the second outbreak with 103 water isolates collected the following year. We documented a genetically diverse range of L. pneumophila strains across clinical and water isolates. Isolates belonging to 1 clade (3 clinical isolates, 3 water isolates from a Flint hospital, 1 water isolate from a Flint residence, and the reference Paris strain) had a high degree of similarity (2–1,062 single-nucleotide polymorphisms), all L. pneumophila sequence type 1, serogroup 1. Serogroup 6 isolates belonging to sequence type 2518 were widespread in Flint hospital water samples but bore no resemblance to available clinical isolates. L. pneumophila strains in Flint tap water after the outbreaks were diverse and similar to some disease-causing strains.
The membrane effects of melittin on gastric and colorectal cancer

The cytotoxic effects of melittin, a bee-venom peptide, have been widely studied towards cancer cells. Typically, these studies have examined the effect of melittin over extended-time courses (6–24 hours), meaning that immediate cellular interactions have been overlooked. In this work, we demonstrate the rapid effects of melittin on both gastric and colorectal cancer, specifically AGS, COLO205 and HCT-15 cell lines, over a period of 15 minutes. Melittin exhibited a dose dependent effect at 4 hours of treatment, with complete cellular death occurring at the highest dose of 20 μg/mL. Interestingly, when observed at shorter time points, melittin induced cellular changes within seconds; membrane damage was observed as swelling, breakage or blebbing. High-resolution imaging revealed treated cells to be compromised, showing clear change in cellular morphology. After 1 minute of melittin treatment, membrane changes were observed, and intracellular material could be seen expelled from the cells. Overall, these results enhance our understanding of the fast acting anti-cancer effects of melittin.
Immunomodulating Activity of Chikusetsusaponin IVa from Alternanthera philoxeroides

Alternanthera philoxeroides has been used as antipyretic, dressing for wounds and ulcers in Thai traditional medicine. The present study aims to investigate the immunomodulating activity of this plant by using splenocyte proliferation test. The results showed that methanol (MeOH) extract, diethyl ether (Et ₂ O) and n-butanol (n-BuOH) fractions of A. philoxeroides were not cytotoxic to host cells up to the concentration tested (200 µg/ml). For immunomodulating study, MeOH extract, Et ₂ O and n-BuOH fractions suppressed splenocyte proliferation. Et ₂ O fraction at a concentration of 50 µg/ml significantly suppressed splenocyte proliferation (p < 0.05). Whereas chikusetsusaponin IVa increased splenocyte proliferation in dose-dependent manner and at a concentration of 25 µg/ml the compound significantly increased splenocyte proliferation (p < 0.05).
Rumen Inoculum Collected from Cows at Slaughter or from a Continuous Fermenter and Preserved in Warm, Refrigerated, Chilled or Freeze-Dried Environments for In Vitro Tests

Simple Summary The utilization of animal donors of rumen fluid for laboratory experiments can raise ethical concerns due to invasive methods of collection (rumen cannulated or intubated animals). Societies are strongly oriented to support cruelty free experiments and alternatives to the collection of rumen fluids from live animals are urgently requested from the scientific community. Thus, in order to attenuate the dependence of laboratories on animal donors, this study compared the rumen inoculum collected at slaughter with the fermentation liquid from a rumen continuous fermenter and both rumen inoculum were used fresh or preserved (by refrigeration, chilling and freeze-drying). The results support the possibility of using continuous fermenters to generate inoculum for in vitro purposes, and short-term refrigeration is confirmed to be a valuable storage system to facilitate transfer inoculum from the collection sites. These findings should attenuate the need for laboratories’ frequent collections from animals while continuing research in ruminant nutrition. Abstract The utilization of animal donors of rumen fluid for laboratory experiments can raise ethical concerns, and alternatives to the collection of rumen fluids from live animals are urgently requested. The aim of this study was to compare the fresh rumen fluid (collected at slaughter, W) with that obtained from a continuous fermenter (RCF) and three methods of rumen fluid preservation (refrigeration, R, chilling, C, and freeze-drying, FD). The fermentability of different inoculum was evaluated by three in vitro tests (neutral detergent fiber (NDF) and crude protein (CP) degradability and gas production, NDFd, RDP and GP, respectively) using six feeds as substrates. Despite the two types of inoculum differed in terms of metabolites and microbiota concentration, the differences in vitro fermentability between the two liquids were less pronounced than expected (−15 and 20% for NDFd and GP when the liquid of fermenter was used and no differences for RDP). Within each in vitro test, the data obtained from rumen and from fermenter liquids were highly correlated for the six feeds, as well as between W and R (r: 0.837–0.985; p < 0.01). The low fermentative capacity was found for C and, particularly, FD for liquids. RCF could be used to generate inoculum for in vitro purposes and short-term refrigeration is a valuable practice to manage inoculum.
A Review of Biomechanical Gait Classification with Reference to Collected Trot, Passage and Piaffe in Dressage Horses

Simple Summary This paper reviews the biomechanical classification of diagonally coordinated gaits of dressage horses, specifically, collected trot, passage and piaffe. Each gait was classified as a walking gait or a running gait based on three criteria: limb kinematics, ground reaction forces and center of mass mechanics. The data for trot and passage were quite similar and both were classified as running gaits according to all three criteria. In piaffe, the limbs have relatively long stance durations and there are no aerial phases, so kinematically it was classified as a walking gait. However, the shape of the vertical ground reaction force curve and the strategies used to control movements of the center of mass were more similar to those of a running gait. The hind limbs act as springs with limb compression increasing progressively from collected trot to passage to piaffe, whereas the forelimbs show less compression in passage and piaffe and behave more like struts. Abstract Gaits are typically classified as walking or running based on kinematics, the shape of the vertical ground reaction force (GRF) curve, and the use of inverted pendulum or spring-mass mechanics during the stance phase. The objectives of this review were to describe the biomechanical characteristics that differentiate walking and running gaits, then apply these criteria to classify and compare the enhanced natural gait of collected trot with the artificial gaits of passage and piaffe as performed by highly trained dressage horses. Limb contact and lift off times were used to determine contact sequence, limb phase, duty factor, and aerial phase duration. Ground reaction force data were plotted to assess fore and hind limb loading patterns. The center of mass (COM) trajectory was evaluated in relation to changes in potential and kinetic energy to assess the use of inverted pendulum and spring-mass mechanics. Collected trot and passage were classified as running gaits according to all three criteria whereas piaffe appears to be a hybrid gait combining walking kinematics with running GRFs and COM mechanics. The hind limbs act as springs and show greater limb compression in passage and piaffe compared with trot, whereas the forelimbs behave more like struts showing less compression in passage and piaffe than in trot.