Miracle-dz/UniFAR-FTUs huggingface dataset:
18 Org 25969 causes selective reversal of neuromuscular block induced by steroidal NMBs in anaesthetized guinea pigs

R. Mason and A. Bom Department of Pharmacology, Organon Laboratories, Newhouse, ML1 5SH, Scotland, UK Introduction: Complex formation between steroidal neuromuscular blocking agents (NMBs) and the novel reversal agent Org 25969 results in rapid reversal of block in the isolated mouse hemi-diaphragm preparation. In this study, we have studied this in the anaesthetized guinea pig. Method: Male Dunkin–Hartley guinea pigs (body weight: 610–870 g) were anaesthetized with pentobarbital 30 mg kg 1 and urethane 900 mg kg 1 i.p. After tracheotomy, the animals were artificially ventilated. Catheters were placed in both jugular veins and a catheter was placed in the carotid artery for continuous monitoring of arterial blood pressure and for taking blood samples for blood gas analysis. The sciatic nerve was stimulated (supramaximal rectangular pulses of 0.5 ms duration at 0.1 Hz using a Grass S88 Stimulator. The force of gastrocnemius contractions was measured using a force displacement transducer (Grass FT03). Body temperature was maintained at 37–388C by using an electrical heating pad. Muscle contractions, blood pressure and heart rate were recorded on a multi-channel recorder (Grass, model D7) After a bolus injection, an infusion of the NMB was started to obtain a steady state 90% neuromuscular block. The infusion was stopped and spontaneous recovery allowed to occur. After complete recovery, the procedure was repeated, and, after the infusion of muscle relaxant was stopped, an intravenous bolus injection of 1 mg kg 1 Org 25969 was given. The results are summarized in Table 1. Results:
Role of Chemokines and Chemokine Receptors in Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases and a prototypic inflammatory disease, affecting the small joints of the hands and feet. Chemokines and chemokine receptors play a critical role in RA pathogenesis via immune cells recruitment. Several chemokines and chemokine receptors are abundant in the peripheral blood and in the local inflamed joints of RA. Furthermore, synthetic and biologics disease modifying anti rheumatic drugs have been reported to affect chemokines expression. Thus, many studies have focused on targeting chemokines and chemokine receptors, where some have shown positive promising results. However, most of the chemokine blockers in human trials of RA treatment displayed some failures that can be attributed to several reasons in their structures and binding affinities. Nevertheless, targeting chemokines will continue to be under development, in order to improve their therapeutic potentials in RA and other autoimmune diseases. In this review we provide an up-to-date knowledge regarding the role of chemokines and chemokine receptors in RA with an emphasis on their activities on immune cells. We also discussed the effects of drugs targeting those molecules in RA. This knowledge might provide impetus for developing new therapeutic modalities to treat this chronic disease.
Identification of slit3 as a locus affecting nicotine preference in zebrafish and human smoking behaviour

To facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. From 30 screened F3 sibling groups, where each was derived from an individual ethyl-nitrosurea mutagenized F0 fish, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations carried by the F3 fish, one in the slit3 gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the human SLIT3 locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants associated with cigarette consumption and likelihood of cessation. Characterisation of slit3 mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increased htr1aa mRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.
Microscopic Theory of Plasmons in Substrate-supported Borophene.

We compute the dielectric properties of freestanding and metal-supported borophene from first-principles time-dependent density functional theory. We find that both the low- and high-energy plasmons of borophene are fully quenched by the presence of a metallic substrate at borophene-metal distances smaller than $\simeq$ 9 \AA. Based on these findings, we derive an electrodynamic model of the interacting, momentum-dependent polarizability for a two-dimensional metal on a model metallic substrate, which quantitatively captures the evolution of the dielectric properties of borophene as a function of metal-borophene distance. Applying this model to a series of metallic substrates, we show that maximizing the plasmon energy detuning between borophene and substrate is the key material descriptor for plasmonic performance.
Surgical Management of a Firearm Injury in the Infraorbital Area

The surgical management of firearm injuries to the zygomaticomaxillary complex is a topic that needs to be addressed with much care. The complications that can arise during treatment, as well as the potential residual problems that can appear, lead to the need of recognizing these injuries as a maxillofacial treatment challenge. The infraorbital zone is the second most common area of injury in the face, accounting for up to 45% of midfacial fractures. The case presented is of a 54 year old man affected by the backward firing of a gun rifle that caused an oblique impaction towards the posterior lateral inferior side of the infraorbital complex. He was rapidly stabilized with an antibiotic and analgesic scheme, yet presented the following: a comminute fracture of the orbit floor with consequent communication towards the maxillary sinus, a non-displacing fracture of the frontomalar suture, a non-displacing fracture of the zygomatic arch and a lesion with loss of osseous tissue in the petrous region of the temporal bone. Rigid fixation followed stabilization, and the area was covered with a titanium mesh. Occasional tinnitus and photopsia were reported by the patient upon return, yet all other evaluated factors were in order. There have been different forms of management described in the literature, and it is recognized that each patient has different needs, therefore each case must be closely evaluated, so it is approached in the most appropriate manner.
Molecular interactions of vinclozolin metabolites with human estrogen receptors 1GWR-α and 1QKM and androgen receptor 2AM9-β: Implication for endocrine disruption

Abstract Background: Vinclozolin (VCZ) is a widely used antifungal agent with capability to enter into the human food chain. VCZ metabolizes into seven metabolites M1–M7. Several studies have shown its effects on reprotoxicity. However, there is limited information available on the interaction of VCZ metabolites with nuclear receptors. In silico studies aimed at identifying interaction of endocrine disruptor with nuclear receptors serve a prescreening framework in risk assessment. Methods: We studied interactive potential of VCZ and its metabolites with human estrogen (ER) and androgen receptor (AR) using molecular docking method. Binding potential of VCZ and its metabolites with estrogen receptors 1GWR-α, 1QKM and androgen receptor 2AM9-β was checked by using Schrodinger Maestro 10.5. Estradiol (E2), a natural ligand of ER and AR was taken as a reference. Results: VCZ and its metabolites showed higher or similar binding efficiency on interaction with target proteins when compared with E2. VCZ and its metabolites also exhibited agonistic effect against 1GWR-α, 1QKM and 2AM9-β with strong binding potential to them. Conclusion: Some VCZ metabolites such as M4 and M5 showed higher binding potencies with 1GWR-α, 1QKM and 2AM9-β than E2. Toxicity data of VCZ is well endowed. However, endocrine disrupting potential of VCZ via nuclear receptor mediated pathway is less understood. This in silico study revealing that not only VCZ but its metabolites have potential to interact with 1GWR-α, 1QKM and 2AM9-β offers a platform for further exploration of VCZ in this direction.
Attachment security in infancy predicts reduced parasympathetic reactivity in middle childhood

ABSTRACT Children with histories of secure attachments during infancy are expected to develop healthier patterns of physiological activity at rest and in response to a stressor than children with insecure attachments. The present study examined longitudinal associations between infant attachment security and children’s respiratory sinus arrhythmia (RSA) at rest and in response to a frustration task at age 9. The study focused on a sample of children referred from Child Protective Services (N = 97). RSA reflects the regulation of the parasympathetic branch of the autonomic nervous system, is sensitive to environmental influences, and is associated with emotion regulation. Children with histories of secure attachments during infancy exhibited less RSA withdrawal during a frustration task than children with histories of insecure attachments. Attachment security was not significantly associated with baseline RSA. Results suggest that mitigating parasympathetic reactivity during frustrating situations may be one avenue by which infant attachment security promotes emotion regulation.
Universal In Situ Substitutional Doping of Transition Metal Dichalcogenides by Liquid Phase Precursor-Assisted Synthesis.

Doping lies at the heart of modern semiconductor technologies. Therefore, for two-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), the significance of controlled doping is no exception. Recent studies have indicated that, by substitutionally doping 2D TMDs with a judicious selection of dopants, their electrical, optical, magnetic and catalytic properties can be effectively tuned, endowing them with great potential for various practical applications. Herein, and inspired by the sol-gel process, we report a liquid phase precursor-assisted approach for in situ substitutional doping of monolayered TMDs and their in-plane heterostructures with tunable doping concentration. This highly reproducible route is based on the high-temperature chalcogenation of spin-coated aqueous solutions containing host and dopant precursors. The precursors are mixed homogeneously at the atomic level in the liquid phase prior to the synthesis process, thus allowing for an improved doping uniformity and controllability. We further demonstrate the incorporation of various transition metal atoms, such as iron (Fe), rhenium (Re) and vanadium (V), into the lattice of TMD monolayers, so as to form Fe-doped WS2, Re-doped MoS2, and more complex material systems such as V-doped in-plane WxMo1-xS2-MoxW1-xS2 heterostructures, among others. We envisage that our developed approach is universal and could be extended to incorporate a variety of other elements into 2D TMDs and create in-plane hetero-interfaces in a single-step, which may enable applications such as electronics and spintronics at the 2D limit.
Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

The final decision to accept an organ for transplantation remains a subjective one. With “poor organ quality” commonly cited as a major reason for kidney discard, accurate, objective, and reliable quality assessment is essential. In an era of increasingly higher-risk deceased donor kidneys, the catch is to accept those where the risk–benefit scale will tip in the right direction. Currently available assessment tools, such as risk-scores predicting outcome and zero-time biopsy, perform unsatisfactory, and assessment options during static cold storage are limited. Kidney perfusion technologies are finding their way into clinical practice, and they bring a new opportunity to assess kidney graft viability and quality, both in hypothermic and normothermic conditions. We give an overview of the current understanding of kidney viability assessment during ex situ kidney perfusion. A pragmatic framework to approach viability assessment is proposed as an interplay of three different compartments: the nephron, the vascular compartment, and the immune compartment. Although many interesting ways to assess kidney injury and function during perfusion have been proposed, none have reached the stage where they can reliably predict posttransplant outcome. Larger well-designed studies and validation cohorts are needed to provide better guidance.
Modern Soft-Sensing Modeling Methods for Fermentation Processes

For effective monitoring and control of the fermentation process, an accurate real-time measurement of important variables is necessary. These variables are very hard to measure in real-time due to constraints such as the time-varying, nonlinearity, strong coupling, and complex mechanism of the fermentation process. Constructing soft sensors with outstanding performance and robustness has become a core issue in industrial procedures. In this paper, a comprehensive review of existing data pre-processing approaches, variable selection methods, data-driven (black-box) soft-sensing modeling methods and optimization techniques was carried out. The data-driven methods used for the soft-sensing modeling such as support vector machine, multiple least square support vector machine, neural network, deep learning, fuzzy logic, probabilistic latent variable models are reviewed in detail. The optimization techniques used for the estimation of model parameters such as particle swarm optimization algorithm, ant colony optimization, artificial bee colony, cuckoo search algorithm, and genetic algorithm, are also discussed. A comprehensive analysis of various soft-sensing models is presented in tabular form which highlights the important methods used in the field of fermentation. More than 70 research publications on soft-sensing modeling methods for the estimation of variables have been examined and listed for quick reference. This review paper may be regarded as a useful source as a reference point for researchers to explore the opportunities for further enhancement in the field of soft-sensing modeling.
Discontinuation of prolonged dual antiplatelet therapy for a dental extraction; A nearly-fatal decision

Stent thrombosis remains one of the most feared complications in patients with multiple stents implanted. In this clinical setting, optimal upfront dual antiplatelet therapy (DAPT) duration still remains controversial. Herein, we wish to report a case of life-threatening very-late stent thrombosis after DAPT temporary discontinuation, highlighting the prolonged increased thrombotic risk of complex angioplasty, even in otherwise low-ischemic risk patients according to recent recommendations. Our data are in line with novel information and might be useful in the pre-operative management of patients with complex percutaneous coronary intervention (PCI).
Quality Indicators for the Diagnosis and Management of Acute Bacterial Rhinosinusitis

Background Acute bacterial rhinosinusitis (ABRS) is a highly prevalent disease that is treated by a variety of specialties, including but not limited to, family physicians, emergency physicians, otolaryngology—head and neck surgeons, infectious disease specialists, and allergy and immunologists. Unfortunately, despite high-quality guidelines, variable and substandard care continues to be demonstrated in the treatment of ABRS. Objective This study aimed to develop ABRS-specific quality indicators (QIs) to evaluate the diagnosis and management that reduces symptoms, improves quality of life, and prevents complications. Methods A guideline-based approach, proposed by Kötter et al., was used to develop QIs for ABRS. Candidate indicators (CIs) were extracted from 4 guiding documents and evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Each CI and its supporting evidence was summarized and reviewed by an expert panel based on validity, reliability, and feasibility of measurement. Final QIs were selected from CIs utilizing the modified RAND/University of California at Los Angeles appropriateness methodology. Results Twenty-nine CIs were identified after literature review and evaluated by our panel. Of these, 5 CIs reached consensus as being appropriate QIs, with 1 requiring additional discussion. After a second round of evaluations, the panel selected 7 QIs as appropriate measures of high-quality care. Conclusion This study proposes 7 QIs for the diagnosis and management of patients with ABRS. These QIs can serve multiple purposes, including documenting the quality of care; comparing institutions and providers; prioritizing quality improvement initiatives; supporting accountability, regulation, and accreditation; and determining pay for performance initiatives.
Deceleration of China’s human water use and its key drivers

Significance China’s rising food demand and fast economic growth increase water use and threaten water security. We present a spatially detailed survey-based reconstruction dataset of sectoral water use from 1965 to 2013 at the scale of small administrative units called prefectures. The data show that a widespread deceleration of water use in recent decades and the adoption of improved irrigation practices and industrial water recycling partly offset the increase driven by the rising water demand from economic growth and structural transition. These findings underscore the value of technological adoptions, including a determination of their potential, to help in designing targets and incentives for water scarcity mitigations. Increased human water use combined with climate change have aggravated water scarcity from the regional to global scales. However, the lack of spatially detailed datasets limits our understanding of the historical water use trend and its key drivers. Here, we present a survey-based reconstruction of China’s sectoral water use in 341 prefectures during 1965 to 2013. The data indicate that water use has doubled during the entire study period, yet with a widespread slowdown of the growth rates from 10.66 km3⋅y−2 before 1975 to 6.23 km3⋅y−2 in 1975 to 1992, and further down to 3.59 km3⋅y−2 afterward. These decelerations were attributed to reduced water use intensities of irrigation and industry, which partly offset the increase driven by pronounced socioeconomic development (i.e., economic growth, population growth, and structural transitions) by 55% in 1975 to 1992 and 83% after 1992. Adoptions for highly efficient irrigation and industrial water recycling technologies explained most of the observed reduction of water use intensities across China. These findings challenge conventional views about an acceleration in water use in China and highlight the opposing roles of different drivers for water use projections.
Methylenetetrahydrofolate Reductase ( MTHFR ) C677T and A1298C Variants, Folate Intake, and Susceptibility to Breast Cancer

Context: Breast cancer is the most common cancer among women, worldwide. Both genetic and environmental factors are involved in the risk of breast cancer. Folate is an essential nutrient that is involved in DNA synthesis, repair, and methylation. Single nucleotide polymorphisms (SNPs) in folate related genes, such as methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C are suitable candidates for investigation the role of these variants in susceptibility to breast cancer. Evidence Acquisition: Using the relevant English language studies from the search engines, such as MEDLINE/PubMed, EMBASE, and Scopus from 2005 to 2016, the present review looks at the role of MTHFR C677T and A1298C variants, synergism between these gene variants along with folate intake in susceptibility to breast cancer. Results: It seems the MTHFR C677T polymorphism is associated with the risk of breast cancer among Asians but not in Caucasians. However, the MTHFR A1298C polymorphism might not be a susceptibility factor for breast cancer. The MTHFR haplotypes alone or along with low dietary intake of folate were not involved in susceptibility to breast cancer. Conclusions: Association between MTHFR C677T polymorphism with the risk of breast cancer could be attributed to the lower activity of the MTHFR enzyme in the presence of 677T allele with reduced availability of folate that may result in uracil misincorporation in the DNA and cancer development. The absence of establishment of a role for MTHFR haplotypes and a synergism between low dietary intake of folate along with MTHFR polymorphisms in susceptibility to breast cancer might be due to differences in allelic frequency of MTHFR variants in various populations, stage of cancer, the familial and early onset cancer, and the influence of environmental factors. To establish the role of MTHFR haplotypes in relation to folate intake in susceptibility to breast cancer, more studies with adequate sample size that investigate the role of MTHFR gene polymorphisms along with dietary intake of folate in the risk of breast cancer are necessary.
Gonadotropin-releasing hormone agonist ovulation trigger—beyond OHSS prevention

Abstract In this review the advantages of the gonadotropin-releasing hormone agonist (GnRHa) trigger are discussed beyond those immediately associated with ovarian hyperstimulation syndrome (OHSS) prevention. The GnRHa trigger concept has sparked the development of novel protocols, enriching the assisted reproductive technology (ART) armamentarium for the benefit of present and future patients. Thus, GnRHa trigger already has a pivotal role, not only for the standard in vitro fertilisation (IVF) patient, but also for patient groups like oocyte donors, cancer patients, patients with poor ovarian reserve, and patients with immature oocyte syndrome and empty follicle syndrome. Herein, we discuss the importance of the GnRHa-elicited midcycle FSH surge and the potential improvement in oocyte yield and embryo competence.