Miracle-dz/UniFAR-FTUs huggingface dataset:
The economic impact of drying off cows with a dry-off facilitator (cabergoline) compared with 2 methods of gradual cessation of lactation for European dairy farms.

An abrupt method to dry off cows has disadvantages and is considered inappropriate for current dairy cows due to welfare issues and risks for intramammary infections (IMI). A gradual cessation of lactation (by feeding or milking frequency reduction) has been the generally recommended method for drying off cows to prevent these adverse effects. However, a new alternative to the gradual approach is to abruptly stop milking at the same time as using cabergoline (CAB), a prolactin inhibitor. The aim of the study was to compare the net costs of 3 different methods of drying off cows [gradual reduction in feed (gradual-feeding), gradual reduction in milking frequency (gradual-milking), and abrupt cessation of milking with CAB (abrupt-CAB)]. A stochastic Monte Carlo simulation model, at cow level, was developed to calculate the net costs of applying these methods. All inputs for the model were based on literature information, authors' expertise, and expert knowledge. The net costs were determined by only including costs and benefits, which varied between the 3 methods. The model simulated a cow from 7 d before the day of drying off until the end of the next lactation. The likelihood of whether a cow was leaking milk early in the dry period was determined. Subsequently, it was determined whether or not the cow will get an IMI during the dry period, where the probability of getting an IMI was higher for cows leaking milk than for cows not leaking milk. If the IMI was not cured during the dry period, the cow had an IMI at calving. Also, milk production and feed requirements were modeled, and labor for applying the drying off method was included. For all methods, the net costs were calculated as the sum of costs for feed during the gradual feed reduction period, costs for applying the gradual-milking method, and the IMI costs during the dry period and lactation, minus the milk revenues during the transition from lactation to the dry period. Under default conditions, the average net cost of abrupt-CAB was €49.6/cow. The data showed that 90% of the net costs ranged from -€13.7 to €307.8/cow. The average net costs for gradual-feed and gradual-milking were €99.1 and €71.5/cow, respectively. In conclusion, abrupt-CAB saved €49.5 and €21.9/cow on average compared with gradual-feeding and gradual-milking, respectively. This difference was mainly due to more milk returns and lower labor and IMI costs during lactation.
Conditional Effects of Lifetime Alcohol Consumption on Methamphetamine-Associated Neurocognitive Performance

Abstract Objectives: Methamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons. Methods: Eighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA−) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression. Results: MA+ displayed moderately higher rates of impairment and lower T scores compared to MA−. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA−, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA− (b = −0.44, p = .030) but not MA+ (b = 0.08, p = .586). Conclusions: Contrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.
The dual‐functional memantine nitrate MN‐08 alleviates cerebral vasospasm and brain injury in experimental subarachnoid haemorrhage models

Cerebral vasospasm and neuronal apoptosis after subarachnoid haemorrhage (SAH) is the major cause of morbidity and mortality in SAH patients. So far, single‐target agents have not prevented its occurrence. Memantine, a non‐competitive NMDA re3ceptor antagonist, is known to alleviate brain injury and vasospasm in experimental models of SAH. Impairment of NO availability also contributes to vasospasm. Recently, we designed and synthesized a memantine nitrate MN‐08, which has potent dual functions: neuroprotection and vasodilation. Here, we have tested the therapeutic effects of MN‐08 in animal models of SAH.
Robo2 regulates synaptic oxytocin content by affecting actin dynamics

The regulation of neuropeptide level at the site of release is essential for proper neurophysiological functions. We focused on a prominent neuropeptide, oxytocin (OXT) in the zebrafish as an in vivo model to visualize and quantify OXT content at the resolution of a single synapse. We found that OXT-loaded synapses were enriched with polymerized actin. Perturbation of actin filaments by either cytochalasin-D or conditional Cofilin expression resulted in decreased synaptic OXT levels. Genetic loss of robo2 or slit3 displayed decreased synaptic OXT content and robo2 mutants displayed reduced mobility of the actin probe Lifeact-EGFP in OXT synapses. Using a novel transgenic reporter allowing real-time monitoring of OXT-loaded vesicles, we show that robo2 mutants display slower rate of vesicles accumulation. OXT-specific expression of dominant-negative Cdc42, which is a key regulator of actin dynamics and a downstream effector of Robo2, led to a dose-dependent increase in OXT content in WT, and a dampened effect in robo2 mutants. Our results link Slit3-Robo2-Cdc42, which controls local actin dynamics, with the maintenance of synaptic neuropeptide levels.
The effects of electroporation on viability and quality of in vivo-derived bovine blastocysts

The introduction of exogenous molecules into embryos is required for analyses of molecular dynamics and specific gene functions during early embryonic development. Electroporation is an effective method to transport exogenous molecules into cells, but is rarely used in bovine embryos. First, we evaluated the viability of in vivo-derived bovine blastocysts after electroporation with fluorescein (FAM) labeled-oligonucleotides with varying pulse numbers (3, 5, 7, and 10), while keeping the pulse duration at 1 msec and the electric field of 20 V/mm. Next, we examined the effects of zona pellucida status on blastocyst quality after electroporation, by comparing the average diameter of blastocysts before and after electroporation using blastocysts with intact zona pellucida and hatching/hatched blastocysts. Electroporation successfully introduced exogenous molecules into in vivo-derived bovine blastocysts without loss of viability. Moreover, the status of the zona pellucida may be associated with the quality of blastocysts after electroporation.
The use of indwelling pleural catheters for the treatment of malignant pleural effusions

ABSTRACT Introduction: The presence of a malignant pleural effusion (MPE) is a marker of advanced disease and associated with a poor prognosis. Patients are in a palliative stage of their disease and often suffer distressing symptoms including breathlessness and pain. Indwelling pleural catheters (IPCs) are effective in managing pleural effusions and allow ambulatory drainage of the pleural space, reducing symptoms associated with effusions and lowering overall hospital stay. The role of IPCs as a first line option in managing MPEs is expanding with a multitude of recent studies into the optimal application of IPCs, necessitating a review of the current literature. Areas covered: This article will provide an overview of IPCs in MPE; how they’re inserted, their indications, continuing management, complications and possible future applications. Expert opinion: IPCs should be considered first-line management of MPEs, alongside standard talc pleurodesis. Recognition of the advantages and disadvantages of each approach allows a more informed patient choice. It is recognized that the use of IPCs can provoke pleurodesis, leading to removal of the catheter. For patients in whom prompt removal of the catheter is a priority, then a more aggressive drainage regime or instillation of talc via the IPC is a reasonable option.
Polyethyleneimine and quaternized ammonium polyethyleneimine: the versatile materials for combating bacteria and biofilms

Abstract Bacterial infection has become a serious clinical concern due to the emergence of drug-resistance and biofilm formation. Therefore, it is in great demand to develop efficient antimicrobial agents to treat bacterial infection without using antibiotics. Herein, we successfully prepared four quaternized ammonium PEI (QPEI: PEI1200-C2, PEI1200-C4, PEI1200-C6 and PEI1200-C8) using the commercial available PEI1200. Both PEI and four QPEI presented broad-spectrum antimicrobial activity against Gram-negative bacteria (E. coli, and P. aeruginosa) and Gram-positive bacteria (B. amyloliquefaciens and S. aureus), especially PEI1200-C6 showed the strongest antimicrobial activity with good biocompatibility at the MIC concentrations. Besides, PEI1200-C6 showed 4-16-fold better antibacterial effect than PEI1200, and fluorescent microscope imaging demonstrated that both of them could efficiently eradicate biofilms formed by four bacterial strains in vitro. As the accessible broad-spectrum antibacterial agents, PEI1200 and PEI1200-C6 are significant candidates to treat bacterial infections or eradicate biofilms on indwelling medical devices.
Exploiting knowledge on pharmacodynamics-pharmacokinetics for accelerated anti-leishmanial drug discovery/development

ABSTRACT Introduction: Being on the top list of neglected tropical diseases, leishmaniasis has been marked for elimination by 2020. In the light of small armamentarium of drugs and their associated drawbacks, the understanding of pharmacodynamics and/or pharmacokinetics becomes a priority to achieve and sustain disease elimination. Areas covered: The authors have looked into pharmacological aspects of existing and emerging drugs for treatment of leishmaniasis. An in-depth understanding of pharmacodynamics and pharmacokinetics (PKPD) provides a rationale for drug designing and optimizing the treatment strategies. It forms a key to prevent drug resistance and avoid drug-associated adverse effects. The authors have compiled the researches on the PKPD of different anti-leishmanial formulations that have the potential for improved and/or effective disease intervention. Expert opinion: Understanding the pharmacological aspects of drugs forms the basis for the clinical application of novel drugs. Tailoring drug dosage and individualized treatment can avoid the adverse events and bridge gap between the in vitro models and their clinical application. An integrated approach, with pragmatic use of technological advances can improve phenotypic screening and physiochemical properties of novel drugs. Concomitantly, this can serve to improve clinical efficacies, reduce the incidence of relapse and accelerate the drug discovery/development process for leishmaniasis elimination.
Interactive effects of casein micelle size and calcium and citrate content on rennet-induced coagulation in bovine milk.

Interactive effects of casein micelle size and milk calcium and citrate content on rennet-induced coagulation were investigated. Milk samples containing small (SM) and large (LM) micelles, obtained from individual Holstein cows, were modified by addition of calcium and/or citrate and milk coagulation properties were evaluated in a full factorial design. The results showed that LM milk had a higher relative proportion of casein, coagulated faster, and resulted in a stronger gel than SM milk. Addition of calcium slightly decreased casein micelle size, while addition of citrate slightly increased micelle size. Calcium addition resulted in a shorter coagulation time and the strongest gels, while citrate addition increased the coagulation time and resulted in the weakest gels. Addition of calcium and citrate in combination resulted in intermediate coagulation properties. The interactive effect of micelle size and citrate was significant for gel strength. Microstructural differences between the milk gels were consistent with the rheological properties, e.g., the micrographs revealed that a more homogeneous network was formed when calcium was added, resulting in a stronger gel. A more inhomogeneous network structure was formed when citrate was added, resulting in a weaker gel. Thus, variations in casein micelle size and in calcium and citrate content influence rennet-induced coagulation in bovine milk. This article is protected by copyright. All rights reserved.
Risk-Benefit assessment of infant exposure to lithium through breast milk: a systematic review of the literature

Abstract The continuation of lithium while breastfeeding is a controversial topic, and clinical recommendations vary. A systematic review was completed of available data on lithium and breastfeeding to determine the degree of lithium exposure through breast milk and assess the potential risk to the infant. Databases, including PubMed MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL Register of Controlled Trials databases, were searched for articles on lithium and breastfeeding from the start dates of the databases through December 2018. Articles were included if the report included at least one maternal serum/plasma and/or breast milk lithium concentration and one infant serum/plasma lithium concentration. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Twelve articles, all case reports, were selected for inclusion out of 441 articles that were found and 230 that were reviewed from the search. Data are limited on the safety of lithium continuation while breastfeeding. Among the adverse effects reported, it is difficult to differentiate poor outcomes from factors affecting infant health, concomitant medications, and gestational lithium exposure. Recommendations on whether to continue lithium while breastfeeding must be personalized to the individual woman and her infant.
Nicotinamide phosphoribosyltransferase postpones rat bone marrow mesenchymal stem cell senescence by mediating NAD+–Sirt1 signaling

In vitro replicative senescence affects MSC characteristics and functionality, thus severely restricting their application in regenerative medicine and MSC-based therapies. Previously, we found that MSC natural senescence is accompanied by altered intracellular nicotinamide adenine dinucleotide (NAD+) metabolism, in which Nampt plays a key role. However, whether Nampt influences MSC replicative senescence is still unclear. Our study showed that Nampt expression is down-regulated during MSC replicative senescence. Nampt depletion via a specific Nampt inhibitor FK866 or Nampt knockdown in early passage MSCs led to enhanced senescence as indicated by senescence-like morphology, reduced proliferation, and adipogenic and osteogenic differentiation, and increased senescence-associated-β-galactosidase activity and the expression of the senescence-associated factor p16INK4a. Conversely, Nampt overexpression ameliorated senescence-associated phenotypic features in late passage MSCs. Further, Nampt inhibition resulted in reduced intracellular NAD+ content, NAD+/NADH ratio, and Sirt1 activity, whereas overexpression had the opposite effects. Exogenous intermediates involved in NAD+ biosynthesis not only rescued replicative senescent MSCs but also alleviated FK866-induced MSC senescence. Thus, Nampt suppresses MSC senescence via mediating NAD+-Sirt1 signaling. This study provides novel mechanistic insights into MSC replicative senescence and a promising strategy for the severe shortage of cells for MSC-based therapies.
Molecular level comparison of water extractives of maple and oak with negative and positive ion ESI FT-ICR mass spectrometry.

Soluble extractives in wood function to protect living trees from destructive agents and also contribute to wood color and fragrance. Some extractive components have biological activities with medical applications. They also play important roles in wood processing and related applications. To increase the knowledge of wood chemistry, maple and oak were extracted by water. Ultraviolet/visible (UV/vis) spectroscopy indicated the presence of a phenolic compound, resorcinol, in maple extractives having higher molecular mass and more aromatic components than oak extractives. Negative and positive electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS) identified thousands of formulas in the two samples in the m/z range of 200-800. They mainly fall into the lignin-, carbohydrate- and tannin-like compound categories. The top 25 peaks (i.e., formulas) with the highest relative magnitude in negative ESI represented nearly 50% of the summed total spectral magnitude of all formulas assigned in the maple and oak extractives. Furthermore, the base peak (i.e., most abundant peak) accounted for about 14% of the total abundance in each wood sample. Literature comparisons identified 17 of 20 formulas in the top 5 peaks of the four spectra as specific bioactive compounds in trees and other plants, implying the potential to explore utilization of maple and oak extractives for functional and medicinal applications. The various profiling of the top 25 peaks from the two samples also suggested the possible application of FT-ICR-MS for detecting chemical markers useful in profiling and identification of wood types and sources.
A Comprehensive Survey of Driving Monitoring and Assistance Systems

Improving a vehicle driver’s performance decreases the damage caused by, and chances of, road accidents. In recent decades, engineers and researchers have proposed several strategies to model and improve driving monitoring and assistance systems (DMAS). This work presents a comprehensive survey of the literature related to driving processes, the main reasons for road accidents, the methods of their early detection, and state-of-the-art strategies developed to assist drivers for a safe and comfortable driving experience. The studies focused on the three main elements of the driving process, viz. driver, vehicle, and driving environment are analytically reviewed in this work, and a comprehensive framework of DMAS, major research areas, and their interaction is explored. A well-designed DMAS improves the driving experience by continuously monitoring the critical parameters associated with the driver, vehicle, and surroundings by acquiring and processing the data obtained from multiple sensors. A discussion on the challenges associated with the current and future DMAS and their potential solutions is also presented.
Geochemical-Compositional-Functional Changes in Arctic Soil Microbiomes Post Land Submergence Revealed by Metagenomics

Lakes of meltwater in the Artic have become one of the transforming landscape changes under global warming. We herein compared microbial communities between sediments and bank soils at an arctic lake post land submergence using geochemistry, 16S rRNA amplicons, and metagenomes. The results obtained showed that each sample had approximately 2,609 OTUs on average and shared 1,716 OTUs based on the 16S rRNA gene V3–V4 region. Dominant phyla in sediments and soils included Proteobacteria, Acidobacteria, Actinobacteria, Gemmatimonadetes, and Nitrospirae; sediments contained a unique phylum, Euryarchaeota, with the phylum Thaumarchaeota being primarily present in bank soils. Among the top 35 genera across all sites, 17 were more abundant in sediments, while the remaining 18 were more abundant in bank soils; seven out of the top ten genera across all sites were only from sediments. A redundancy analysis separated sediment samples from soil samples based on the components of nitrite and ammonium. Metagenome results supported the role of nitrite because most of the genes for denitrification and methane metabolic genes were more abundant in sediments than in soils, while the abundance of phosphorus-utilizing genes was similar and, thus, was not a significant explanatory factor. We identified several modules from the global networks of OTUs that were closely related to some geochemical factors, such as pH and nitrite. Collectively, the present results showing consistent changes in geochemistry, microbiome compositions, and functional genes suggest an ecological mechanism across molecular and community levels that structures microbiomes post land submergence.
Effects of latex membrane on guided regeneration of long bones

Abstract Natural latex extracted from Hevea brasiliensis is one of the materials pointed out as potential tissue regenerators. The use of latex-based membranes in bone regeneration might be an alternative to stimulate bone formation. The aim of this study was to evaluate the effects of latex membranes in guided bone regeneration of defects produced in long bones of rats. Sixty rats were equally divided into latex and control groups, and each group was subdivided into two subgroups according to treatment duration of 1 and 4 weeks. Bone defects with 2.5 mm in diameter were surgically made in the left tibia. In the animals of the latex group, a latex membrane was placed over the bone defect. The samples underwent quantitative histological analysis of bone formation and collagen matrix, immunohistochemical analysis of osteogenic protein markers, assessment of bone mechanical properties and bone densitometry, and radiological assessment. The osteocalcin immunostaining data were submitted to the generalized linear model test with two independent factors. For the other data, the multivariate ANOVA with two independent factors was performed. The use of the latex membrane significantly improved (p < 0.005) the volume of newly formed bone, collagen type I matrix, expression of osteopontin, and bone stiffness, both in the early and late stages of regeneration. In conclusion, the latex membrane was able to promote bone regeneration in long bones.