Miracle-dz/UniFAR-FTUs huggingface dataset:
PARP Inhibition Increases the Reliance on ATR/CHK1 Checkpoint Signaling Leading to Synthetic Lethality—An Alternative Treatment Strategy for Epithelial Ovarian Cancer Cells Independent from HR Effectiveness

Poly (ADP-ribose) polymerase inhibitor (PARPi, olaparib) impairs the repair of DNA single-strand breaks (SSBs), resulting in double-strand breaks (DSBs) that cannot be repaired efficiently in homologous recombination repair (HRR)-deficient cancers such as BRCA1/2-mutant cancers, leading to synthetic lethality. Despite the efficacy of olaparib in the treatment of BRCA1/2 deficient tumors, PARPi resistance is common. We hypothesized that the combination of olaparib with anticancer agents that disrupt HRR by targeting ataxia telangiectasia and Rad3-related protein (ATR) or checkpoint kinase 1 (CHK1) may be an effective strategy to reverse ovarian cancer resistance to olaparib. Here, we evaluated the effect of olaparib, the ATR inhibitor AZD6738, and the CHK1 inhibitor MK8776 alone and in combination on cell survival, colony formation, replication stress response (RSR) protein expression, DNA damage, and apoptotic changes in BRCA2 mutated (PEO-1) and HRR-proficient BRCA wild-type (SKOV-3 and OV-90) cells. Combined treatment caused the accumulation of DNA DSBs. PARP expression was associated with sensitivity to olaparib or inhibitors of RSR. Synergistic effects were weaker when olaparib was combined with CHK1i and occurred regardless of the BRCA2 status of tumor cells. Because PARPi increases the reliance on ATR/CHK1 for genome stability, the combination of PARPi with ATR inhibition suppressed ovarian cancer cell growth independently of the efficacy of HRR. The present results were obtained at sub-lethal doses, suggesting the potential of these inhibitors as monotherapy as well as in combination with olaparib.
Role of Thermodynamics and Kinetics in the Composition of Ternary III-V Nanowires

We explain the composition of ternary nanowires nucleating from a quaternary liquid melt. The model we derive describes the evolution of the solid composition from the nucleated-limited composition to the kinetic one. The effect of the growth temperature, group V concentration and Au/III concentration ratio on the solid-liquid dependence is studied. It has been shown that the solid composition increases with increasing temperature and Au concentration in the droplet at the fixed In/Ga concentration ratio. The model does not depend on the site of nucleation and the geometry of monolayer growth and is applicable for nucleation and growth on a facet with finite radius. The case of a steady-state (or final) solid composition is considered and discussed separately. While the nucleation-limited liquid-solid composition dependence contains the miscibility gap at relevant temperatures for growth of InxGa1−xAs NWs, the miscibility gap may be suppressed completely in the steady-state growth regime at high supersaturation. The theoretical results are compared with available experimental data via the combination of the here described solid-liquid and a simple kinetic liquid-vapor model.
Animal Welfare and Meat Quality Assessment in Gas Stunning during Commercial Slaughter of Pigs Using Hypercapnic-Hypoxia (20% CO2 2% O2) Compared to Acute Hypercapnia (90% CO2 in Air)

Simple Summary Animals must be stunned before slaughter to avoid fear, pain, and distress. In pigs, the most extensively used method is exposure to hypercapnia (high (>80%) concentrations of carbon dioxide (CO2)). However, it produces irritation of the mucosa and a sense of breathlessness, reducing the welfare before slaughter. We investigated whether using hypercapnic-hypoxia (20% CO2 and less than 2% O2) reduced aversion and discomfort compared to hypercapnia, and whether the quality of the stunning was adequate, meaning that no animals regain conscious after stunning. Moreover, we compared the impact of both stunning gases for meat and carcass quality. Our results suggest that both gases provoked aversion and discomfort, but these were lower in pigs stunned with the N2 mixture compared to high CO2. On the other hand, the stun quality of the N2 mixture was poorer than high CO2 stunning, given that more animals regained consciousness before sticking with the N2 gas mixture. The stunning quality of the N2 mixture, however, was improved when oxygen concentration was below 2%. Meat quality was slightly poorer in N2 stunning compared to high CO2, with a higher percentage of carcasses showing pale, soft, and exudative pork. Abstract This study assessed aversion, stunning effectiveness, and product quality of nitrogen and carbon dioxide (CO2) mixtures used for stunning pigs. A total of 1852 slaughter pigs divided into two similar batches was assessed during routine slaughter in a Swedish commercial abattoir using either hypercapnic-hypoxia (20% CO2 and less than 2% O2; 20C2O) or hypercapnia (90% CO2; 90C) gas mixtures. Behavioral indicators of aversion and discomfort were recorded. After exposure, the stunning quality was assessed through brainstem reflexes. After slaughter, the pH and electric conductivity of carcasses were assessed to estimate the incidence of pale, soft, and exudative (PSE) pork, and the presence of ecchymosis were inspected. Compared to 90C, pigs exposed to 20C2O showed a later (p < 0.05) onset of behaviors indicative of aversion, and a lower (p < 0.01) incidence of breathlessness. However, unconsciousness (i.e., losing posture) appeared earlier (p < 0.01) in 90C compared to 20C2O. In 90C, all (100%) pigs were adequately stunned, whereas in 20C2O a 7.4% of pigs showed signs of poor stunning, especially when oxygen concentrations were >2% (p < 0.001). The percentage of PSE carcasses was higher (p < 0.01) in 20C2O than 90C. In conclusion, compared to 90C, 20C2O reduced aversion and discomfort but showed lower stun effectiveness, especially when O2 was above 2%, and a slightly poorer pork quality.
Identification and Physicochemical Characterization of a New Allergen from Ascaris lumbricoides

To analyze the impact of Ascaris lumbricoides infection on the pathogenesis and diagnosis of allergic diseases, new allergens should be identified. We report the identification of a new Ascaris lumbricoides allergen, Asc l 5. The aim of this study was to evaluate the physicochemical and immunological features of the Asc l 5 allergen. We constructed an A. lumbricoides cDNA library and Asc l 5 was identified by immunoscreening. After purification, rAsc l 5 was physicochemically characterized. Evaluation of its allergenic activity included determination of Immunoglobulin E (IgE) binding frequency (in two populations: 254 children and 298 all-age subjects), CD203c based-basophil activation tests (BAT) and a passive cutaneous anaphylaxis (PCA) mouse model. We found by amino acid sequence analysis that Asc l 5 belongs to the SXP/RAL-2 protein family of nematodes. rAsc l 5 is a monomeric protein with an alpha-helical folding. IgE sensitization to rAsc l 5 was around 52% in general population; positive BAT rate was 60%. rAsc l 5 induced specific IgE production in mice and a positive PCA reaction. These results show that Asc l 5 has structural and immunological characteristics to be considered as a new allergen from A. lumbricoides.
Rumen and Hindgut Bacteria Are Potential Indicators for Mastitis of Mid-Lactating Holstein Dairy Cows

Mastitis is one of the major problems for the productivity of dairy cows and its classifications have usually been based on milk somatic cell counts (SCCs). In this study, we investigated the differences in milk production, rumen fermentation parameters, and diversity and composition of rumen and hindgut bacteria in cows with similar SCCs with the aim to identify whether they can be potential microbial biomarkers to improve the diagnostics of mastitis. A total of 20 dairy cows with SCCs over 500 × 103 cells/mL in milk but without clinical symptoms of mastitis were selected in this study. Random forest modeling revealed that Erysipelotrichaceae UCG 004 and the [Eubacterium] xylanophilum group in the rumen, as well as the Family XIII AD3011 group and Bacteroides in the hindgut, were the most influential candidates as key bacterial markers for differentiating “true” mastitis from cows with high SCCs. Mastitis statuses of 334 dairy cows were evaluated, and 96 in 101 cows with high SCCs were defined as healthy rather than mastitis according to the rumen bacteria. Our findings suggested that bacteria in the rumen and hindgut can be a new approach and provide an opportunity to reduce common errors in the detection of mastitis.
Statistical mechanics of isomerization dynamics in liquids and the transition state approximation

In this article, time correlation function methods are used to discuss classical isomerization reactions of small nonrigid molecules in liquid solvents. Molecular expressions are derived for a macroscopic phenomenological rate constant. The form of several of these equations depend upon what ensemble is used when performing averages over initial conditions. All of these formulas, however, reduce to one final physical expression whose value is manifestly independent of ensemble. The validity of the physical expression hinges on a separation of time scales and the plateau value problem. The approximations needed to obtain transition state theory are described and the errors involved are estimated. The coupling of the reaction coordinate to the liquid medium provides the dissipation necessary for the existence of a plateau value for the rate constant, but it also leads to failures of Wigner’s fundamental assumption for transition state theory. We predict that for many isomerization reactions, the transmissio.
Extraction of organic pollutants from environmental solids with sub- and supercritical water

Low-polarity organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) typically have very low solubilities (e.g., ppb) in water at ambient conditions because of water's high polarity (dielectric constant, [epsilon] = 80). However, the dielectric constant can be drastically lowered by raising the temperature of the water under moderate pressure with dramatic increases (e.g., to percent levels) in the solubility of low-polarity organics. For example, subcritical water at 250[degree]C and 50 bar has [epsilon] = 27, which allowed quantitative extractions of PAHs in 15 min from soil and urban air particulates. Decreasing the polarity of water by sequentially raising the extraction temperature from 50 to 250[degree]C (subcritical water) and finally to 400[degree]C (supercritical water if P > 221 bar) allowed class-selective extractions of polar organics (e.g., chlorinated phenols), low-polarity organics (e.g., PAHs), and nonpolar organics (alkanes) to be performed. Simple methods for using sub- and supercritical water for quantitative extraction of organics from environmental solids are presented. 30 refs., 6 figs., 5 tabs.
Comparative Study between Full-Endoscopic Discectomy and Microendoscopic Discectomy for the Treatment of Lumbar Disc Herniation

Background and objectives: Lumbar disc herniation (LDH) is a common disease in the meridian of life. Although surgical discectomy is commonly used to treat LDH, there are several different strategies. We compared the outcomes of uniportal full-endoscopic discectomy (FED) with those of microendoscopic discectomy (MED) in treating LDH. Materials and Methods: FED was performed using a 4.1-mm working channel endoscope, and MED was performed using a 16-mm diameter tubular retractor and endoscope. Data of patients with LDH treated with FED (n = 39) or MED (n = 27) by the single surgeon were retrospectively reviewed. Patient background information and operative data were collected. Pre- and postoperative low back and leg pain were evaluated using the numerical rating scale (NRS) score. Pre- and postoperative disc height index (DHI) values were calculated from plain radiographs, and the disc height loss was evaluated using the ratio (DHI ratio); Results: The median (interquartile range (IQR) Q25–75) operation times for FED and MED were 42 (33–61) and 43 (33–50) minutes, respectively. The median (IQR Q25–75) pre- and postoperative NRS scores for low back pain were 5 (2–7) and 1 (0–4), respectively, for FED and 6 (3–8) and 1 (0–2), respectively, for MED. The median (IQR Q25–75) pre- and postoperative NRS scores for leg pain were 7 (5–8) and 0 (0–2), respectively, for FED and 6 (5–8) and 0 (0–2), respectively, for MED. These data were not different between the FED and MED groups. The median (IQR Q25–75) DHI ratios of FED and MED were 0.94 (0.89–1.03) and 0.90 (0.79–0.95), respectively. The DHI ratio was significantly higher (p < 0.05) in the FED group than in the MED group, and there was less blood loss; Conclusions: The pain-relieving effect of FED in treating LDH was almost identical to that of MED. However, FED was superior to MED in preventing disc height loss, which is one of the indicators of postoperative disc degeneration.
New Insight into the Mechanism of Drug Release from Poly(d,l-lactide) Film by Electron Paramagnetic Resonance

A novel approach based on convolution of the electron paramagnetic resonance (EPR) spectra was used for quantitative study of the release kinetics of paramagnetic dopants from poly(d,l-lactide) films. A non-monotonic dependence of the release rate on time was reliably recorded. The release regularities were compared with the dynamics of polymer structure changes determined by EPR, SEM, and optic microscopy. The data obtained allow for the conclusion that the main factor governing dopant release is the formation of pores connected with the surface. In contrast, the contribution of the dopant diffusion through the polymer matrix is negligible. The dopant release can be divided into two phases: release through surface pores, which are partially closed with time, and release through pores initially formed inside the polymer matrix due to autocatalytic hydrolysis of the polymer and gradually connected to the surface of the sample. For some time, these processes co-occur. The mathematical model of the release kinetics based on pore formation is presented, describing the kinetics of release of various dopants from the polymer films of different thicknesses.
Analysis of Amino and Fatty Acid Composition in Soybean Seed, Using Near Infrared Reflectance Spectroscopy

Soybean [Glycine max (L.) Merr. ] is an important animal and human food source, mainly because of its high protein and oil concentrations. However, there is a need to improve the quality of soybean protein and oil. The objectives of this study were to (i) determine the potential use of near infrared reflectance spectroscopy (NIRS) for amino and fatty acid analysis in soybean seed and (ii) compare NIRS amino and fatty add equations developed with ground-seed and whole-seed soybean samples. A total of 90 NIRS calibration samples and 26 NIRS validation samples were used for NIRS equation development and validation, respectively. All 116 soybean samples were grown at St. Paul and Rosemount, MN, in 1994 and 1995. Seventeen amino acid and five fatty acid NIRS equations for both ground-seed and whole-seed soybean samples were developed using the calibration samples. Validation of these NIRS equations showed a wide range for bias (-1.7 to 3.2g kg -1 ), standard error of prediction corrected for bias [SEP(C)] (1.4 to 13.1 g kg -1 ), and coefficient of determination (R 2 ) (0.38 to 0.85) for all ground-seed NIRS equations, and a broad range for bias (-3.1 to 4.2), SEP(C) (2.6 to 17.8), and R 2 (0.06 to 0.83) for all whole-seed NIRS equations. It was concluded that NIRS could be used as a gross screening method for many amino and fatty acids contained in soybean seed. Additionally, NIRS was more accurate for amino and fatty acid analysis of ground-seed than whole-seed soybean samples.
A Survey on Daily Activity Inclination and Health Complaints among Urban Youth in Malaysia

Environmental influence is one of the attributing factors for health status. Chronic interaction with electronic display technology and lack of outdoor activities might lead to health issues. Given the concerns about the digital impact on lifestyle and health challenges, we aimed to investigate the daily activity inclination and health complaints among the Malaysian youth. A self-administered questionnaire covering lifestyle and health challenges was completed by 220 youths aged between 16 and 25. There were a total of 22 questions. Seven questions inspected the patterns of indoor and outdoor activities. Fifteen questions focused on the visual and musculoskeletal symptoms linked to both mental and physical health. The total time spent indoors (15.0 ± 5.4 hours/day) was significantly higher than that spent outdoors (2.5 ± 2.6 hours/day) (t = 39.01, p < 0.05). Total time engrossed in sedentary activities (13.0 ± 4.5 hours/day) was significantly higher than that in nonsedentary activities (4.5 ± 3.8 hours/day) comprised of indoor sports and any outdoor engagements (t = 27.10, p < 0.05). The total time spent on electronic related activities (9.5 ± 3.7 hours/day) was were higher than time spent on printed materials (3.4 ± 1.6 hours/day) (t = 26.01, p < 0.05). The association of sedentary activities was positive in relation to tired eyes (χ2 = 17.58, p < 0.05), sensitivity to bright light (χ2 = 12.10, p < 0.05), and neck pain (χ2 = 17.27, p < 0.05) but negative in relation to lower back pain (χ2 = 8.81, p < 0.05). Our youth spent more time in building and engaged in sedentary activities, predominantly electronic usage. The health-related symptoms, both visual and musculoskeletal symptoms, displayed a positive association with a sedentary lifestyle and a negative association with in-building time.
Solar Cell Module Coated with Fluorescent Coloring Agent

Coatings of fluorescent coloring agent (FCA) on the glass of a solar cell module were proposed to increase the energy conversion efficiency of the cells by preventing the layer of glass and filler from absorbing light at wavelengths below 400 nm. The FCA coating showed no reduction in reflectivity at wavelengths longer than that for excitation, because the refractive index of FCA was close to that of glass, i.e., 1.5 Yellow FCA absorbed light at wavelengths below 500 nm as the excitation light and emitted light at wavelengths longer than 420 nm, which are not absorbed in the layer of glass and filler. Thus the change in wavelength through the yellow FCA coating yielded a 6% increase in the energy conversion efficiency of the solar cell.
Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment – Old Questions, New Answers?

Abstract Nocardia spp. is an environmental filamentous Gram-positive bacterium that may cause infections in humans and, despite recent progress, many challenges remain regarding the management of nocardiosis. This review aims at describing most recently published data regarding the diagnosis, treatment and follow-up of patients with invasive nocardiosis. As nocardiosis mainly affects patients with cell-mediated immunity defects, a comprehensive workup is mandatory in case of invasive nocardiosis occurring in ”apparently healthy patients”. Indeed, invasive nocardiosis might reveal an unknown primary immunodeficiency or the presence of anti-GM-CSF autoantibodies. Even if the diagnosis of nocardiosis mostly relies on direct examination and bacterial culture, a genus-specific PCR may be used for the detection of Nocardia, when directly performed on a clinical sample. Brain imaging should always be performed, even in the absence of neurological symptoms. Cotrimoxazole (trimethoprim/sulfamethoxazole), linezolid, parenteral cephalosporins, carbapenems and amikacin may be used as initial antibiotics to treat nocardiosis. Cotrimoxazole or linezolid can be used as monotherapy in selected patients without brain involvement. Although treatment duration has historically been set to at least 6 months in the absence of central nervous system involvement, shorter durations (<120 days) seem to be associated with a favourable outcome.
Study on the Effect of Huanglian Jiedu Decoction on the Composition of Gut Microflora in SD Rats Based on 16S rRNA Sequencing

Objective To study the effects of Huanglian Jiedu Decoction (HJD) on gut microflora of SD rats. Method After 3 days of adaptive feeding, 36 rats were randomly divided into 4 groups, namely, the normal control group (NC, 10 mL/kg, distilled water), high_HJD dose group (H_HJD, 6.25 g/kg, weight ratio between crude drug and rat), medium_HJD dose group (M_HJD, 3.125 g/kg), and low_HJD dose group (L_HJD, 1.56 g/kg), and each group consisted of 9 mice. The HJD groups were then treated with orally administered HJD for 21 days, while the NC group was treated with distilled water. After 7 days, 14 days, and 21 days of the experiment and after 12 hours of fasting and water deprivation, 3 SD rats in each group were randomly sacrificed by cervical dislocation and sterile operation to collect stool faces. Sample DNA was extracted by Fecal total DNA extraction kit, sequenced using Illumina MiSeq platform, and analyzed. Results The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Coprobacillus, Blautia, Akkermansia, Klebsiella, Rhodococcus, Parabacteroides, Citrobacter, Enterococcus, Bacteroides, and Erysipelotrichaceae_incertae_sedis increased after using H_HJD. The abundance of Gemella, Turicibacter, Romboutsia, and Lactobacillus decreased, while that of Blautia, Akkermansia, Escherichia_Shigella, Thiobacillus, Rothia, Enterococcus, Lactobacillus, and Erysipelotrichaceae-incertae-sedis increased after using M_HJD. The abundance of Romboutsia, Turicibacter, Lactobacillus, and Gemella decreased, while that of Escherichia_Shigella, Bacteroides, Akkermansia, Enterococcus, Rhodococcus, Parabacteroides, Desulfovibrio, Blautia, Fusobacterium, Rothia, and Streptococcus increased after using L_HJD. Conclusion HJD can regulate gut microbiota, and its effect varies with different dosage and duration of medication.
Palbociclib Plus Fulvestrant or Everolimus Plus Exemestane for Pretreated Advanced Breast Cancer with Lobular Histotype in ER+/HER2− Patients: A Propensity Score-Matched Analysis of a Multicenter Retrospective Patient Series †

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) show meaningful efficacy and tolerability in patients with metastatic breast cancer (MBC), but the optimal sequence of ET has not been established. It is not clear if patients with lobular breast carcinomas (LBC) derive the same benefits when receiving second line CDK4/6i. This retrospective study compared the efficacy of palbociclib plus fulvestrant (PALBO–FUL) with everolimus plus exemestane (EVE–EXE) as second-line ET for hormone-resistant metastatic LBC. From 2013 to 2018, patients with metastatic LBC positivity for estrogen and/or progesterone receptors and HER2/neu negativity, who had relapsed during adjuvant hormonal therapy or first-line hormonal treatment, were enrolled from six centers in Italy in this retrospective study. A total of 74 out of 376 patients (48 treated with PALBO–FUL and 26 with EVE–EXE) with metastatic LBC were eligible for inclusion. Progression-free survival (PFS) was longer in patients receiving EVE–EXE compared with PALBO–FUL (6.1 vs. 4.5 months, univariate HR 0.58, 95% CI 0.35–0.96; p = 0.025). On the propensity score (PS) analysis, PFS was confirmed to be significantly longer for patients treated with EVE–EXE compared to PALBO–FUL (6.0 vs. 4.6 months, p = 0.04). This retrospective analysis suggests that EVE–EXE is more effective than PALBO–FUL for second line ET of metastatic LBC, allowing us to speculate on the optimal therapeutic sequence.