Miracle-dz/UniFAR-FTUs huggingface dataset:
Vasopressin V 2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats

Sampey, Donella B. , Louise M. Burrell, and Robert E. Widdop. Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R872–R879, 1999. —The aim of the present study was to determine the receptor subtype involved in arginine vasopressin (AVP)induced modulation of baroreflex function in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel nonpeptide AVP V1and V2-receptor antagonists. Baroreceptor heart rate (HR) reflex was investigated in both SHR and WKY rats which were intravenously administered the selective V1and V2-receptor antagonists OPC-21268 and OPC-31260, respectively. Baroreflex function was assessed by obtaining alternate pressor and depressor responses to phenylephrine and sodium nitroprusside, respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex activity was tested before and after intravenous administration of vehicle (20% DMSO), OPC-21268 (10 mg/ kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not significantly alter basal mean arterial pressure (MAP) and HR values or baroreflex function in SHR or WKY rats. The V1-receptor antagonist had no significant effect on resting MAP or HR values or on baroreflex parameters in both groups of rats, although this dose was shown to significantly inhibit the pressor response to AVP (5 ng iv; ANOVA, P , 0.05). In SHR but not WKY rats the V2-receptor antagonist significantly attenuated the gain (or slope) of the baroreflex curve (to 73 6 3 and 79 6 7% of control for 1 and 10 mg/kg, respectively), although AVP-induced pressor responses were also attenuated with the higher dose of the V2-receptor antagonist. These findings suggest that AVP tonically enhances baroreflex function through a V2 receptor in the SHR.
Redefining preeclampsia using placenta-derived biomarkers.

Preeclampsia affects 3% to 8% of all pregnancies.1 Acute maternal complications include eclampsia, stroke, placental abruption, disseminated intravascular coagulation, HELLP (hemolysis, elevated liver enzymes, low platelets), liver hemorrhage or rupture, pulmonary edema, adult respiratory distress syndrome, acute renal failure, and death.2 Preeclampsia complications account for more than 50 000 maternal deaths annually.2,3 In developing countries, where lack of access to appropriate maternal care is a major problem, maternal death rates are as high as 15% as compared with 0% to 1.8% in industrialized countries.2 Perinatal consequences include stillbirth, preterm delivery, fetal growth restriction (FGR), neonatal complications, and later sequelae.4 Long-term maternal risks include chronic hypertension, diabetes mellitus, coronary artery disease,5 neurological deficit, and premature death.2 Here, we argue that the classic definitions of preeclampsia, based on concepts that are now more than 50 years old, have become outdated and that the definition could be modernized to take account of our current understanding of disease pathophysiology. We propose a first step that incorporates the placental biomarker placenta growth factor (PlGF), but we allow for the possibility that the definition may need to be expanded to include other factors, such as the antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) or soluble endoglin (sENG),6 in due course. This is intended as an exploratory rather than a final development. Diseases may be defined and classified by cause, pathogenesis, or by clinical findings. Clear definitions and classification are difficult when pathogenesis is unknown. As a result, diagnostic labels may reflect only a set of symptoms and signs, defining a syndrome. Syndromes are never precise, because the features are multiple, nonspecific, and therefore may have diverse causes. Preeclampsia is a syndrome of new onset hypertension and proteinuria in the second half of pregnancy, that was defined …
Hypotheses and Assumptions in Mendelian Randomization: Proceed With Caution.

We read with interest the paper by Wang et al(1) regarding gallstone disease (GSD) and type 2 diabetes (DM2) risk. Below, we discuss three issues regarding the study's design. First, when conducting a Mendelian randomization (MR) study, a strong hypothesis regarding a causal mechanism is needed to test the underlying assumption that a genetic risk score is associated with a given outcome only through its relationship with the exposure. We are unaware of any mechanisms by which gallstones would cause DM2, without which it is difficult to select appropriate genes that meet the assumptions underlying MR study design. This article is protected by copyright. All rights reserved.
A Trusted Routing Scheme Using Blockchain and Reinforcement Learning for Wireless Sensor Networks

A trusted routing scheme is very important to ensure the routing security and efficiency of wireless sensor networks (WSNs). There are a lot of studies on improving the trustworthiness between routing nodes, using cryptographic systems, trust management, or centralized routing decisions, etc. However, most of the routing schemes are difficult to achieve in actual situations as it is difficult to dynamically identify the untrusted behaviors of routing nodes. Meanwhile, there is still no effective way to prevent malicious node attacks. In view of these problems, this paper proposes a trusted routing scheme using blockchain and reinforcement learning to improve the routing security and efficiency for WSNs. The feasible routing scheme is given for obtaining routing information of routing nodes on the blockchain, which makes the routing information traceable and impossible to tamper with. The reinforcement learning model is used to help routing nodes dynamically select more trusted and efficient routing links. From the experimental results, we can find that even in the routing environment with 50% malicious nodes, our routing scheme still has a good delay performance compared with other routing algorithms. The performance indicators such as energy consumption and throughput also show that our scheme is feasible and effective.
Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?

OBJECT The authors undertook this study to investigate whether the physiological mechanism of cerebral blood flow (CBF) regulation by alteration of the arterial partial pressure of carbon dioxide (PaCO₂) can be used to increase CBF after aneurysmal subarachnoid hemorrhage (aSAH). METHODS In 6 mechanically ventilated patients with poor-grade aSAH, the PaCO₂ was first decreased to 30 mm Hg by modification of the respiratory rate, then gradually increased to 40, 50 and 60 mm Hg for 15 minutes each setting. Thereafter, the respirator settings were returned to baseline parameters. Intracerebral CBF measurement and brain tissue oxygen saturation (StiO₂), measured by near-infrared spectroscopy (NIRS), were the primary and secondary end points. Intracranial pressure (ICP) was controlled by external ventricular drainage. RESULTS A total of 60 interventions were performed in 6 patients. CBF decreased to 77% of baseline at a PaCO₂ of 30 mm Hg and increased to 98%, 124%, and 143% at PaCO₂ values of 40, 50, and 60 mm Hg, respectively. Simultaneously, StiO₂ decreased to 94%, then increased to 99%, 105%, and 111% of baseline. A slightly elevated delivery rate of cerebrospinal fluid was noticed under continuous drainage. ICP remained constant. After returning to baseline respirator settings, both CBF and StiO₂ remained elevated and only gradually returned to pre-hypercapnia values without a rebound effect. None of the patients developed secondary cerebral infarction. CONCLUSIONS Gradual hypercapnia was well tolerated by poor-grade SAH patients. Both CBF and StiO₂ reacted with a sustained elevation upon hypercapnia; this elevation outlasted the period of hypercapnia and only slowly returned to normal without a rebound effect. Elevations of ICP were well compensated by continuous CSF drainage. Hypercapnia may yield a therapeutic potential in this state of critical brain perfusion. Clinical trial registration no.: NCT01799525 ( ClinicalTrials.gov ).
Current Information and Asian Perspectives on Long-Chain Polyunsaturated Fatty Acids in Pregnancy, Lactation, and Infancy: Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop

The Early Nutrition Academy supported a systematic review of human studies on the roles of pre- and postnatal long-chain polyunsaturated fatty acids (LC-PUFA) published from 2008 to 2013 and an expert workshop that reviewed the information and developed recommendations, considering particularly Asian populations. An increased supply of n-3 LC-PUFA during pregnancy reduces the risk of preterm birth before 34 weeks of gestation. Pregnant women should achieve an additional supply ≥200 mg docosahexaenic acid (DHA)/day, usually achieving a total intake ≥300 mg DHA/day. Higher intakes (600-800 mg DHA/day) may provide greater protection against early preterm birth. Some studies indicate beneficial effects of pre- and postnatal DHA supply on child neurodevelopment and allergy risk. Breast-feeding is the best choice for infants. Breast-feeding women should get ≥200 mg DHA/day to achieve a human milk DHA content of ∼0.3% fatty acids. Infant formula for term infants should contain DHA and arachidonic acid (AA) to provide 100 mg DHA/day and 140 mg AA/day. A supply of 100 mg DHA/day should continue during the second half of infancy. We do not provide quantitative advice on AA levels in follow-on formula fed after the introduction of complimentary feeding due to a lack of sufficient data and considerable variation in the AA amounts provided by complimentary foods. Reasonable intakes for very-low-birth weight infants are 18-60 mg/kg/day DHA and 18-45 mg/kg/day AA, while higher intakes (55-60 mg/kg/day DHA, ∼1% fatty acids; 35-45 mg/kg/day AA, ∼0.6-0.75%) appear preferable. Research on the requirements and effects of LC-PUFA during pregnancy, lactation, and early childhood should continue.
Multidisciplinary Pain Management for Pediatric Patients with Acute and Chronic Pain: A Foundational Treatment Approach When Prescribing Opioids

Opioid therapy is the cornerstone of treatment for acute procedural and postoperative pain and is regularly prescribed for severe and debilitating chronic pain conditions. Although beneficial for many patients, opioid therapy may have side effects, limited efficacy, and potential negative outcomes. Multidisciplinary pain management treatments incorporating pharmacological and integrative non-pharmacological therapies have been shown to be effective in acute and chronic pain management for pediatric populations. A multidisciplinary approach can also benefit psychological functioning and quality of life, and may have the potential to reduce reliance on opioids. The aims of this paper are to: (1) provide a brief overview of a multidisciplinary pain management approach for pediatric patients with acute and chronic pain, (2) highlight the mechanisms of action and evidence base of commonly utilized integrative non-pharmacological therapies in pediatric multidisciplinary pain management, and (3) explore the opioid sparing effects of multidisciplinary treatment for pediatric pain.
Partial thickness cornea tissue from small incision lenticule extraction

Objective: The aim of the present study was to observe the feasibility and effect of cornea slice acquired from femtosecond laser surgery, small incision lenticule extraction (SMILE) as patch graft for the prevention of drainage tube exposure and to compare with the sclera. Methods: The research is a prospective comparative randomized study. Patients who received Ahmed glaucoma valve implantation surgery from August 2015 to January 2017 at the Xiamen Eye Center were randomly divided into 2 groups. Group A (corneal group) included 131 cases (135 eyes), receiving the 3 layers of allogeneic cornea slices as graft. Group B (scleral group) included 124 cases (127 eyes), using the sclera as allograft. The appearance, graft, conjunctiva melting, and tube exposure were the primary observation points. Results: After followed up for 6 to 20 months, a thinner appearance was seen in 3 eyes (2.2%) in the corneal graft group and 7 eyes (5.5%) in the scleral group. Conjunctiva melted and drainage tube exposed in 0 eyes (0%) in the corneal graft group and 2 eyes (1.6%) in the scleral group. One eye needed repair surgery. There was no statistical difference between the 2 groups (P > .05). After surgery, the intraocular pressure was reduced significantly in both groups (P < .05). The white sclera slice could be seen under the conjunctiva, thereby affecting the cosmetic appearance. Conclusion: The cornea slice acquired from SMILE surgery can effectively prevent drainage tube exposure. Moreover, it is easy to acquire, safe, and cheaper, giving the patient a better cosmetic appearance.
Rods contribute to the light-induced phase shift of the retinal clock in mammals

While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a “rod-only” mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals.
Humanization of Murine Neutralizing Antibodies against Human Herpesvirus 6B

Human herpesvirus 6B (HHV-6B) establishes lifelong latent infection in most individuals after the primary infection. Encephalitis is the most severe complication caused by both the primary infection and the reactivation of HHV-6B and is the cause of considerable mortality in patients, without any established treatments to date. The humanization of the murine neutralizing antibodies described in this research provided a feasible way to reduce the inherent immunogenicity of the antibodies without changing their neutralizing activities. These newly designed chimeric antibodies against HHV-6B have the potential to be candidates for antivirals for future use. ABSTRACT Exanthem subitum is a common childhood illness caused by primary infection with human herpesvirus 6B (HHV-6B). It is occasionally complicated by febrile seizures and even encephalitis. HHV-6B reactivation also causes encephalitis, especially after allogeneic hematopoietic stem cell transplantation. However, no adequate antiviral treatment for HHV-6B has yet been established. Mouse-derived monoclonal antibodies (MAbs) against the HHV-6B envelope glycoprotein complex gH/gL/gQ1/gQ2 have been shown to neutralize the viral infection. These antibodies have the potential to become antiviral agents against HHV-6B despite their inherent immunogenicity to the human immune system. Humanization of MAbs derived from other species is one of the proven solutions to such a dilemma. In this study, we constructed chimeric forms of two neutralizing MAbs against HHV-6B to make humanized antibodies. Both showed neutralizing activities equivalent to those of their original forms. This is the first report of humanized antibodies against HHV-6B and provides a basis for the further development of HHV-6B-specific antivirals. IMPORTANCE Human herpesvirus 6B (HHV-6B) establishes lifelong latent infection in most individuals after the primary infection. Encephalitis is the most severe complication caused by both the primary infection and the reactivation of HHV-6B and is the cause of considerable mortality in patients, without any established treatments to date. The humanization of the murine neutralizing antibodies described in this research provided a feasible way to reduce the inherent immunogenicity of the antibodies without changing their neutralizing activities. These newly designed chimeric antibodies against HHV-6B have the potential to be candidates for antivirals for future use.
Back to Bayesian: A strategy to enhance prognostication of metastatic spine disease

Clinicians must consider prognosis when offering treatment to patients with spine metastases. Although several prognostic indices have been developed and validated for this purpose, they may not be applicable in the current era of targeted systemic therapies. Even before the introduction of targeted therapies, these prognostic indices should not have been directly used for individual patient decision making without contextualising with other sources of data. By contextualising, we mean that prognostic estimates should not be based on these scores alone and formally incorporate clinically relevant factors not part of prognostic indices. Contextualisation requires the use of Bayesian statistics which may be unfamiliar to many readers. In this paper we show readers how to correctly apply prognostic scores to individual patients using Bayesian statistics. Through Bayesian analysis, we explore the impact of new targeted therapies on prognostic estimates obtained using the Tokuhashi score.
Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection

The phenotypic characterization of the cells in which HIV persists during antiretroviral therapy (ART) remains technically challenging. We developed a simple flow cytometry-based assay to quantify and characterize infected cells producing HIV proteins during untreated and treated HIV infection. By combining two antibodies targeting the HIV capsid in a standard intracellular staining protocol, we demonstrate that p24-producing cells can be detected with high specificity and sensitivity in the blood from people living with HIV. In untreated individuals, the frequency of productively infected cells strongly correlated with plasma viral load. Infected cells preferentially displayed a transitional memory phenotype and were enriched in Th17, peripheral Tfh and regulatory T cells subsets. These cells also preferentially expressed activation markers (CD25, HLA-DR, Ki67), immune checkpoint molecules (PD-1, LAG-3, TIGIT, Tim-3) as well as the integrins α4β7 and α4β1. In virally suppressed individuals on ART, p24-producing cells were only detected upon stimulation (median frequency of 4.3 p24+ cells/106 cells). These measures correlated with other assays assessing the size of the persistent reservoir including total and integrated HIV DNA, Tat/rev Induced Limiting Dilution Assay (TILDA) and quantitative viral outgrowth assay (QVOA). In ART-suppressed individuals, p24-producing cells preferentially displayed a transitional and effector memory phenotype, and expressed immune checkpoint molecules (PD-1, TIGIT) as well as the integrin α4β1. Remarkably, α4β1 was expressed by more than 70% of infected cells both in untreated and ART-suppressed individuals. Altogether, these results highlight a broad diversity in the phenotypes of HIV-infected cells in treated and untreated infection and suggest that strategies targeting multiple and phenotypically distinct cellular reservoirs will be needed to exert a significant impact on the size of the reservoir.
Enhancing Interfacial Bonding and Tensile Strength in CNT-Cu Composites by a Synergetic Method of Spraying Pyrolysis and Flake Powder Metallurgy

Carbon nanotube (CNT)-reinforced metal matrix composites (MMCs) face the problems of dispersion and interfacial wetting with regard to the matrix. A synergetic method of spray pyrolysis (SP) and flake powder metallurgy (FPM) is used in this paper to improve the dispersibility and interfacial bonding of CNTs in a Cu matrix. The results of the interface characterization show interface oxygen atoms (in the form of Cu2O) and a high density of dislocation areas, which is beneficial for interfacial bonding. The tensile results show that the tensile strength of the SP-CNT-Cu composites is much higher than that of the CNT-Cu composites when the mass fraction of the CNTs does not reach the critical value. This can be explained by the nanoparticles which are found on the surface of the CNTs during the SP process. These nanoparticles not only increase the tensile strength of the SP-CNT-Cu composites but also improve the dispersion of the CNTs in the Cu matrix. Thereby, uniform dispersion of CNTs, interfacial bonding between CNTs and the Cu matrix, and the enhancement of tensile strength are achieved simultaneously by the synergetic method.
Non‐invasive analysis of tumor mutation profiles and druggable mutations by sequencing of cell free DNA of Chinese metastatic breast cancer patients

Metastatic breast cancer (MBC) remains an incurable disease worldwide. Tumor gene mutations have evolved and led to drug resistance in the treatment course of MBC. However, data on the mutation profiles and druggable genomic alterations of MBC remain limited, particularly among Chinese patients. Our study aimed to depict the mutation profiles and identify druggable mutations in circulating tumor DNA (ctDNA) in Chinese MBC patients.
Severe Eosinophilic Allergic Asthma Responsive to Mepolizumab After Failure of 2 Consecutive Biologics.

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