Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic Administration of the AMPA Receptor Antagonist, NBQX, Reduces Alcohol Drinking in Male C57BL/6J, but not Female C57BL/6J or High Alcohol Preferring (HAP) Mice.

BACKGROUND AMPA receptors are ionotropic glutamate receptors that have been investigated for their role in modulating alcohol consumption. However, little is known about the role of AMPA receptors in the control of binge-like or free-access alcohol drinking in C57BL/6J or in selectively bred high alcohol preferring (HAP) mice. The purpose of this experiment was to assess the role of systemic administration of the AMPA receptor antagonist, NBQX, on alcohol consumption using a model of binge-like drinking, Drinking-in-the-Dark (DID) and free-access two-bottle choice (2BC) in male and female C57BL/6J and HAP mice METHODS: C57BL/6J mice were allowed free access to 20% (v/v) alcohol for two hours each day beginning three hours into the dark cycle for four days. On day five mice were intraperitoneally injected with one of four doses of NBQX (0, 3, 10, or 30 mg/kg; n=10) 15-minutes before alcohol presentation and were given four-hour alcohol access (extended DID). HAP mice were given 24-hour free access to 10% (v/v) alcohol and water for 19 days. On day 20 mice were intraperitoneally injected with one of four doses of NBQX (0, 3, 10, 30 mg/kg; n=9) 15-minutes before alcohol and water presentation. RESULTS In the first two-hours of DID, at 30 mg/kg, male, but not female C57BL/6J or HAP, mice drank significantly less alcohol compared to controls and 30 mg/kg NBQX did not alter saccharin intake in the males. Although male HAP mice drank significantly less alcohol than female mice following 10 mg/kg NBQX, neither sex exhibited drinking that differed significantly from controls. NBQX did not reduce locomotor behavior at any dose, sex, or genotype. CONCLUSIONS These data suggest that AMPA receptors play a key role in modulating binge-like alcohol consumption without altering saccharin consumption or general locomotion, and that this effect is specific to sex and genotype.
Artificial intelligence in the diagnosis, treatment and prevention of urinary stones

Purpose of review There has a been rapid progress in the use of artificial intelligence in all aspects of healthcare, and in urology, this is particularly astute in the overall management of urolithiasis. This article reviews advances in the use of artificial intelligence for the diagnosis, treatment and prevention of urinary stone disease over the last 2 years. Pertinent studies were identified via a nonsystematic review of the literature performed using MEDLINE and the Cochrane database. Recent findings Twelve articles have been published, which met the inclusion criteria. This included three articles in the detection and diagnosis of stones, six in the prediction of postprocedural outcomes including percutaneous nephrolithotomy and shock wave lithotripsy, and three in the use of artificial intelligence in prevention of stone disease by predicting patients at risk of stones, detecting the stone type via digital photographs and detecting risk factors in patients most at risk of not attending outpatient appointments. Summary Our knowledge of artificial intelligence in urology has greatly advanced in the last 2 years. Its role currently is to aid the endourologist as opposed to replacing them. However, the ability of artificial intelligence to efficiently process vast quantities of data, in combination with the shift towards electronic patient records provides increasingly more ‘big data’ sets. This will allow artificial intelligence to analyse and detect novel diagnostic and treatment patterns in the future.
Lack of Superiority of Epidural Injections with Lidocaine with Steroids Compared to Without Steroids in Spinal Pain: A Systematic Review and Meta-Analysis.

BACKGROUND Multiple randomized controlled trials (RCTs) and systematic reviews have been conducted to summarize the evidence for administration of local anesthetic (lidocaine) alone or with steroids, with discordant opinions, more in favor of equal effect with local anesthetic alone or with steroids. OBJECTIVE To evaluate the comparative effectiveness of lidocaine alone and lidocaine with steroids in managing spinal pain to assess superiority or equivalency. STUDY DESIGN A systematic review of RCTs assessing the effectiveness of lidocaine alone compared with addition of steroids to lidocaine in managing spinal pain secondary to multiple causes (disc herniation, radiculitis, discogenic pain, spinal stenosis, and post-surgery syndrome). METHODS This systematic review was performed utilizing Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) for literature search, Cochrane review criteria, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) to assess the methodologic quality assessment and qualitative analysis utilizing best evidence synthesis principles, and quantitative analysis utilizing conventional and single-arm meta-analysis. PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1966 through December 2019. The evidence was summarized utilizing principles of best evidence synthesis on a scale of 1 to 5. OUTCOME MEASURES A hard endpoint for the primary outcome was defined as the proportion of patients with 50% pain relief and improvement in function. Secondary outcome measures, or soft endpoints, were pain relief and/or improvement in function. Effectiveness was determined as short-term if it was less than 6 months. Improvement that lasted longer than 6 months, was defined as long-term. RESULTS Based on search criteria, 15 manuscripts were identified and considered for inclusion for qualitative analysis, quantitative analysis with conventional meta-analysis, and single-arm meta-analysis. The results showed Level II, moderate evidence, for short-term and long-term improvement in pain and function with the application of epidural injections with local anesthetic with or without steroid in managing spinal pain of multiple origins. LIMITATIONS Despite 15 RCTs, evidence may still be considered as less than optimal and further studies are recommended. CONCLUSION Overall, the present meta-analysis shows moderate (Level II) evidence for epidural injections with lidocaine with or without steroids in managing spinal pain secondary to disc herniation, spinal stenosis, discogenic pain, and post-surgery syndrome based on relevant, high-quality RCTs. Results were similar for lidocaine, with or without steroids.
A New Approach for Detecting Sleep Apnea Using a Contactless Bed Sensor: Comparison Study

Background At present, there is an increased demand for accurate and personalized patient monitoring because of the various challenges facing health care systems. For instance, rising costs and lack of physicians are two serious problems affecting the patient’s care. Nonintrusive monitoring of vital signs is a potential solution to close current gaps in patient monitoring. As an example, bed-embedded ballistocardiogram (BCG) sensors can help physicians identify cardiac arrhythmia and obstructive sleep apnea (OSA) nonintrusively without interfering with the patient’s everyday activities. Detecting OSA using BCG sensors is gaining popularity among researchers because of its simple installation and accessibility, that is, their nonwearable nature. In the field of nonintrusive vital sign monitoring, a microbend fiber optic sensor (MFOS), among other sensors, has proven to be suitable. Nevertheless, few studies have examined apnea detection. Objective This study aims to assess the capabilities of an MFOS for nonintrusive vital signs and sleep apnea detection during an in-lab sleep study. Data were collected from patients with sleep apnea in the sleep laboratory at Khoo Teck Puat Hospital. Methods In total, 10 participants underwent full polysomnography (PSG), and the MFOS was placed under the patient’s mattress for BCG data collection. The apneic event detection algorithm was evaluated against the manually scored events obtained from the PSG study on a minute-by-minute basis. Furthermore, normalized mean absolute error (NMAE), normalized root mean square error (NRMSE), and mean absolute percentage error (MAPE) were employed to evaluate the sensor capabilities for vital sign detection, comprising heart rate (HR) and respiratory rate (RR). Vital signs were evaluated based on a 30-second time window, with an overlap of 15 seconds. In this study, electrocardiogram and thoracic effort signals were used as references to estimate the performance of the proposed vital sign detection algorithms. Results For the 10 patients recruited for the study, the proposed system achieved reasonable results compared with PSG for sleep apnea detection, such as an accuracy of 49.96% (SD 6.39), a sensitivity of 57.07% (SD 12.63), and a specificity of 45.26% (SD 9.51). In addition, the system achieved close results for HR and RR estimation, such as an NMAE of 5.42% (SD 0.57), an NRMSE of 6.54% (SD 0.56), and an MAPE of 5.41% (SD 0.58) for HR, whereas an NMAE of 11.42% (SD 2.62), an NRMSE of 13.85% (SD 2.78), and an MAPE of 11.60% (SD 2.84) for RR. Conclusions Overall, the recommended system produced reasonably good results for apneic event detection, considering the fact that we are using a single-channel BCG sensor. Conversely, satisfactory results were obtained for vital sign detection when compared with the PSG outcomes. These results provide preliminary support for the potential use of the MFOS for sleep apnea detection.
Protective Mechanism of the Selective Vasopressin V1A Receptor Agonist Selepressin against Endothelial Barrier Dysfunction

Sepsis and septic shock are among the most common causes of death in the intensive care unit; advanced therapeutic approaches are thus urgently needed. Vascular hyperpermeability represents a major manifestation of severe sepsis and is responsible for the ensuing organ dysfunction and failure. Vasopressin V1A receptor (V1AR) agonists have shown promise in the treatment of sepsis, increasing blood pressure, and reducing vascular hyperpermeability. The effects of the selective V1AR-selective agonist selepressin have been investigated in an in vitro model of thrombin-, vascular endothelial growth factor–, angiopoietin 2–, and lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial hyperpermeability. Results suggest that selepressin counteracts the effects of all four endothelial barrier disruptors in a concentration-dependent manner, as reflected in real-time measurements of vascular permeability by means of transendothelial electrical resistance. Further, selepressin protected the barrier integrity against the LPS-mediated corruption of the endothelial monolayer integrity, as captured by VE-cadherin and actin staining. The protective effects of selepressin were abolished by silencing of the vasopressin V1AR, as well as by atosiban, an antagonist of the human V1AR. p53 appears to be involved in mediating these palliative effects, since selepressin strongly induced its expression levels, suppressed the inflammatory RhoA/myosin light chain2 pathway, and triggered the barrier-protective effects of the GTPase Rac1. We conclude that V1AR-selective agonists, such as selepressin, may prove useful in the improvement of endothelial barrier function in the management of severe sepsis. SIGNIFICANCE STATEMENT A cardinal sign of sepsis, a serious disease with significant mortality and no specific treatment, is pulmonary endothelial barrier dysfunction that leads to pulmonary edema. Here, we present evidence that in cultured human lung microvascular endothelial cells, the synthetic, selective vasopressin V1A receptor agonist selepressin protects against endothelial barrier dysfunction caused by four different edemogenic agents, suggesting a potential role of selepressin in the clinical management of sepsis.
Moving Towards a Finer Way of Light-Cured Resin-Based Restorative Dental Materials: Recent Advances in Photoinitiating Systems Based on Iodonium Salts

The photoinduced polymerization of monomers is currently an essential tool in various industries. The photopolymerization process plays an increasingly important role in biomedical applications. It is especially used in the production of dental composites. It also exhibits unique properties, such as a short time of polymerization of composites (up to a few seconds), low energy consumption, and spatial resolution (polymerization only in irradiated areas). This paper describes a short overview of the history and classification of different typical monomers and photoinitiating systems such as bimolecular photoinitiator system containing camphorquinone and aromatic amine, 1-phenyl-1,2-propanedione, phosphine derivatives, germanium derivatives, hexaarylbiimidazole derivatives, silane-based derivatives and thioxanthone derivatives used in the production of dental composites with their limitations and disadvantages. Moreover, this article represents the challenges faced when using the latest inventions in the field of dental materials, with a particular focus on photoinitiating systems based on iodonium salts. The beneficial properties of dental composites cured using initiation systems based on iodonium salts have been demonstrated.
IgG-aggregates rapidly up-regulate FcgRI expression at the surface of human neutrophils in a FcgRII-dependent fashion: A crucial role for FcgRI in the generation of reactive oxygen species

Autoimmune complexes are an important feature of several autoimmune diseases such as lupus, as they contribute to tissue damage through the activation of immune cells. Neutrophils, key players in lupus, interact with immune complexes through Fc gamma receptors (FcgR). Incubation of neutrophils with aggregated-IgGs caused degranulation and increased the surface expression of FcgRI within minutes in a concentration-dependent fashion. After 30 min, IgG aggregates (1 mg/ml) up-regulated FcgRI by 4.95 ± 0.45-fold. FcgRI-positive neutrophils reached 67.24% ± 6.88% on HA-IgGs stimulated neutrophils, from 3.12% ± 1.62% in non-stimulated cells, ranking IgG-aggregates among the most potent known agonists. FcgRIIa, and possibly FcgRIIIa, appeared to mediate this up-regulation. Also, FcgRI-dependent signaling proved necessary for reactive oxygen species (ROS) production in response to IgG-aggregates. Finally, combinations of bacterial materials with aggregates dramatically boosted ROS production. This work suggests FcgRI as an essential component in the response of human neutrophils to immune complexes leading to the production of ROS, which may help explain how neutrophils contribute to tissue damage associated with immune complex-associated diseases, such as lupus.
Association between pill burden and interdialytic weight gain in patients with hemodialysis: A multi‐center cross‐sectional study

High daily pill burden affects quality of life and mortality. High interdialytic weight gain (IDWG) is associated with increased mortality. We examined the association between pill burden and IDWG in hemodialysis patients. This cross‐sectional study was conducted in six dialysis centers in Japan in June 2017. The exposure was the number of daily tablets, and outcome was defined as 1 day of relative IDWG divided by post‐dialysis weight from the previous session. Among 188 outpatients (mean age, 68.7 [SD, 10.3] years; men, 67.0%; median dialysis vintage, 76.0 [interquartile range, 36.5, 131.5] months), the mean number of daily tablets was 19.7 ± 9.9, and mean relative weight gain was 3.5 ± 1.2%. Multiple linear regression analysis showed a regression coefficient of 0.021 (95% confidence interval: 0.004‐0.039), indicating that one additional tablet prescription increased the IDWG by 0.021%. In hemodialysis patients, the daily pill burden was a significant, independent risk for increased relative IDWG.
Electrocatalytic CO2 fixation by regenerating reduced cofactor NADH during Calvin Cycle using glassy carbon electrode

In this study, an enzymatic pathway has been developed to replicate the Calvin Cycle by creating the individual steps of the carbon cycle in a bioreactor. The technology known as “artificial photosynthesis” converts CO2 emissions into a variety of intermediates that serve as precursors to high-value products. CO2, light, water, and electricity were used as feedstock. An electrochemical reactor was also studied for the regeneration of active NADH operating at constant electrode potential. Initially, a batch electrochemical reactor containing 80 mL of 0.2 mM NAD+ in Tris-buffer (pH 7.40) was used to evaluate the electrode material operating at normal temperature and pressure. The results showed that the cathode is highly electrocatalytically efficient and selective to regenerate 97.45±0.8% of NADH from NAD+ at electrode potential of -2.3 V vs. mercury standard electrode (MSE). The NADH regeneration system was then integrated with ATP regeneration system and bioreactor containing Ribulose bisphosphate carboxylase/oxygenase (RuBisCO). NADH was regenerated successfully during the process electrochemically and then was used by the enzymatic reaction to produce triose phosphate and 3-Phosphoglycerate (3GPA).
Use of a Novel Septal Occluder Device for Left Atrial Appendage Closure in Patients With Postsurgical and Postlariat Leaks or Anatomies Unsuitable for Conventional Percutaneous Occlusion

Supplemental Digital Content is available in the text. Background: Interventional therapies aiming at excluding the left atrial appendage (LAA) from systemic circulation have been established as a valid alternative to oral anticoagulation in patients at high thromboembolic risk. However, their efficacy on stroke prophylaxis may be compromised owing to incomplete LAA closure. Additionally, the need for an alternative thromboembolic prevention may remain unmet in patients with contraindications to oral anticoagulation whose appendage anatomy is unsuitable for some conventional devices commercially available. We aimed at evaluating the feasibility of LAA closure with the novel Gore Cardioform Septal Occluder in patients with incomplete appendage ligation or anatomic features which do not meet the manufacturer’s requirements for Watchman deployment. Methods: Twenty-one consecutive patients (mean age: 72±6 years; 85.7% males; CHA2DS2-VASc: 4.5±1.4; HAS-BLED: 3.6±1.0) were included. Transesophageal echocardiography was performed within 2 months to assess for residual LAA patency. Results: Fourteen patients had incomplete LAA closure following surgical (n=6) or Lariat ligation (n=8). In 7 patients with an appendage anatomy unsuitable for Watchman deployment, the mean maximal landing zone size and LAA depth were 14.4±1.3 and 18.6±2.8 mm. Successful Cardioform Septal Occluder deployment was achieved in all patients. No peri-procedural complications were documented. Procedure and fluoroscopy times were 46±13 and 14±5 minutes. Follow-up transesophageal echocardiography after 58±9 days revealed complete LAA closure in all patients. Conclusions: Transcatheter LAA closure via a Cardioform Septal Occluder device might be a valid alternative in patients with residual leaks following failed appendage ligation or whose LAA anatomy does not meet the minimal anatomic criteria to accommodate a Watchman device.
The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review

(1) Background: Obesity and mood disorders are considered as the most prevalent morbidities in many countries. We suppose that epigenetic mechanisms may induce higher rates of obesity in subjects who suffer from mood disorders. In this systematic review, we focused on the potential roles of DNA methylation on mood disorders and obesity development. (2) Methods: This systematic review was conducted in accordance with the PRISMA statement and registered in Prospero. A systematic search was conducted in MEDLINE, Scopus, Web of Science, Cochrane Central database, EMBASE, and CINHAL. We also conducted a Grey literature search, such as Google Scholar. (3) Results: After deduplication, we identified 198 potentially related citations. Finally, ten unique studies met our inclusion criteria. We have found three overlap genes that show significant DNA methylation changes, both in obesity and depression. Pathway analysis interaction for TAPBP, BDNF, and SORBS2 confirmed the relation of these genes in both obesity and mood disorders. (4) Conclusions: While mechanisms linking both obesity and mood disorders to epigenetic response are still unknown, we have already known chronic inflammation induces a novel epigenetic program. As the results of gene enrichment, pathways analysis showed that TAPBP, BDNF, and SORBS2 linked together by inflammatory pathways. Hypermethylation in these genes might play a crucial rule in the co-occurrence of obesity and mood disorders.
PRIOR INGESTION OF A KETONE MONOESTER SUPPLEMENT REDUCES POSTPRANDIAL GLYCEMIC RESPONSES IN YOUNG HEALTHY WEIGHT INDIVIDUALS.

The main objective of this study was to determine whether acute ingestion of a ketone monoester (KME) supplement impacted mixed meal tolerance test (MMTT) glucose area under the curve (AUC). Nineteen healthy young volunteers (10 males/9 females, 24.7 ± 4.9 years, BMI = 22.7 ± 2.4) participated in a double-blind, placebo-controlled crossover study. Following overnight fasting (≥10 h), participants consumed 0.45mL/kg of a KME supplement or taste-matched placebo followed by a MMTT 15 minutes later. Blood samples were collected every 15-30 minutes over 2.5 hours. KME supplementation acutely raised beta-hydroxybutyrate (β-OHB) AUC (590%, P < 0.0001, d = 2.4) and resulted in decreases in blood glucose AUC (-9.4%, P = 0.03, d = 0.56) and non-esterified fatty acid (NEFA) AUC (-27.3%, P = 0.023, d = 0.68) compared to placebo. No differences were found for plasma insulin AUC (P = 0.70) or gastric emptying estimated by co-ingested acetaminophen AUC (P = 0.96) between ketone and placebo. Overall, results indicate that KME supplementation attenuates postprandial glycemic and NEFA responses when taken 15 min prior to a mixed meal in young healthy individuals. Future studies are warranted to investigate whether KME supplementation may benefit individuals with impaired glycemic control. Novelty Bullets • Acute ketone monoester supplementation 15 min prior to a mixed meal decreased postprandial glucose and non-esterified fatty acid (NEFA) levels without significantly impacting postprandial insulin or estimates of gastric emptying. • Glucose and NEFA lowering effects of ketone monoester supplementation are apparently not mediated by changes in insulin release or gastric emptying.
Preclinical Research Reporting in Shock: Room for Improvement

ABSTRACT The ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines were endorsed by the Shock Society in 2012, but to date there has been no systematic evaluation of research reporting quality for Shock. We systematically assessed 100 randomly selected animal-based research articles published between 2014 and 2018 for reporting quality and statistical practice, compared with 40 pre-ARRIVE studies. More than half of surveyed papers omitted verifiable ethical oversight information and basic animal descriptive information. Few papers reported best-practice methods, such as sample size justification (10%), randomization (43%), randomization method (7%), blinding (23%). Only one paper reported effect sizes to interpret study results. Most troubling was inadequate reporting of welfare-related information (anesthesia, analgesia, humane endpoints, euthanasia). Almost a decade after ARRIVE endorsement, our findings show that reporting deficiencies have persisted with little sign of correction. There is a clear need for investigators to increase transparency of research methods reporting, and drastically improve skills in experimental design. Improvement in standards and greater attention paid to reporting will lead to improvement in reproducibility, replicability, and research quality. It is incumbent upon the research community to improve reporting practices; accurate and transparent reporting is integral to producing rigorous and ethical science.