Miracle-dz/UniFAR-FTUs huggingface dataset:
8-Hydroxylation and Glucuronidation of Mirtazapine in Japanese Psychiatric Patients: Significance of the Glucuronidation Pathway of 8-Hydroxy-Mirtazapine

Abstract Introduction To investigate the metabolism of mirtazapine (MIR) in Japanese psychiatric patients, we determined the plasma levels of MIR, N-desmethylmirtazapine (DMIR), 8-hydroxy-mirtazapine (8-OH-MIR), mirtazapine glucuronide (MIR-G), and 8-hydroxy-mirtazapine glucuronide (8-OH-MIR-G). Methods Seventy-nine Japanese psychiatric patients were treated with MIR for 1–8 weeks to achieve a steady-state concentration. Plasma levels of MIR, DMIR, and 8-OH-MIR were determined using high-performance liquid chromatography. Plasma concentrations of MIR-G and 8-OH-MIR-G were determined by total MIR and total 8-OH-MIR (i. e., concentrations after hydrolysis) minus unconjugated MIR and unconjugated 8-OH-MIR, respectively. Polymerase chain reaction was used to determine CYP2D6 genotypes. Results Plasma levels of 8-OH-MIR were lower than those of MIR and DMIR (median 1.42 nmol/L vs. 92.71 nmol/L and 44.96 nmol/L, respectively). The plasma levels (median) of MIR-G and 8-OH-MIR-G were 75.00 nmol/L and 111.60 nmol/L, giving MIR-G/MIR and 8-OH-MIR-G/8-OH-MIR ratios of 0.92 and 59.50, respectively. Multiple regression analysis revealed that smoking was correlated with the plasma MIR concentration (dose- and body weight–corrected, p=0.040) and that age (years) was significantly correlated with the plasma DMIR concentration (dose- and body weight–corrected, p=0.018). The steady-state plasma concentrations of MIR and its metabolites were unaffected by the number of CYP2D6*5 and CYP2D6*10 alleles. Discussion The plasma concentration of 8-OH-MIR was as low as 1.42 nmol/L, whereas 8-OH-MIR-G had an approximate 59.50 times higher concentration than 8-OH-MIR, suggesting a significant role for hydroxylation of MIR and its glucuronidation in the Japanese population.
Activated Carbons: In Vitro Affinity for Aflatoxin B1 and Relation of Adsorption Ability to Physicochemical Parameters.

Affinity in vitro tests were conducted of the efficacy of 17 activated carbons (ACs) in binding aflatoxin B1 from solution. Relationships between adsorption ability and physicochemical parameters of the ACs (surface area, iodine number, methylene blue index, and surface acidity) were tested. Using 5 ml of a 4 μg/ml aqueous solution of aflatoxin B1 and 2 mg of an AC, adsorption abilities ranged from 44.47% to 99.82%. Four ACs showed very high adsorption abilities, binding more than 99% of the available aflatoxin B1. In comparative testing five ACs showed a greater ability to bind aflatoxin B1 than hydrated sodium calcium aluminosilicate (HSCAS). Three ACs also showed high adsorption abilities (ca. 99%) at increasing aflatoxin B1 concentrations (50 and 250 μg/ml) whereas HSCAS adsorption ability greatly declined. With the exception of three ACs, aflatoxin B1 adsorption was significantly correlated with all the physicochemical parameters, confirming a close relationship between molecule trapping and the surface physicochemical adsorption process. The methylene blue index was more reliable than iodine number and surface area in predicting AC adsorptive ability. The results suggested that ACs with a high methylene blue index and low surface acidity have a very high in vitro affinity for aflatoxin B1; however, their efficacy in protecting against aflatoxicosis should be verified further by in vivo tests.
Interpersonal Relationships and Suicidal Ideation in Youth with Bipolar Disorder

This study examines how relationship quality in family and peer domains are associated with suicidal ideation (SI) in youth with bipolar disorder (BP). We assessed 404 Course and Outcome of Bipolar Youth study participants for psychiatric disorders and SI at intake and for family/peer relationships the month after intake. Multivariate logistic regression examined associations between relationships and SI, controlling for significant covariates. There were 144 youth (36%) who reported SI at intake; bivariate analyses indicated they had significantly worse family/peer relationships. Multivariate analyses showed that family/peer relationships were associated with current SI, controlling for significant covariates. Results support associations between poor relationships and SI in BP youth, regardless of current mood symptom severity. Clinicians should assess relationships when completing risk assessments with BP youth.
Classical and novel strategies to develop a Shigella glycoconjugate vaccine: from concept to efficacy in human

ABSTRACT Shigella are gram-negative bacteria that cause severe diarrhea and dysentery, with a high level of antimicrobial resistance. Disease-induced protection against reinfection in Shigella-endemic areas provides convincing evidence on the feasibility of a vaccine and on the importance of Shigella lipopolysaccharides as targets of the host humoral protective immune response against disease. This article provides an overview of the original and current strategies toward the development of a Shigella glycan-protein conjugate vaccine that would cover the most commonly detected strains. Going beyond pioneering “lattice”-type polysaccharide-protein conjugates, progress, and challenges are addressed with focus on promising alternatives, which have reached phases I and II clinical trial. Glycoengineered bioconjugates and “sun”-type conjugates featuring well-defined synthetic carbohydrate antigens are discussed with insights on the molecular parameters governing the rational design of a cost-effective glycoconjugate vaccine efficacious in preventing diseases caused by Shigella in the most at risk populations, young children living in endemic areas.
Nutrient Deprivation-Associated Changes in Green Microalga Coelastrum sp. TISTR 9501RE Enhanced Potent Antioxidant Carotenoids

The utilization of microalgae as a source of carotenoid productions has gained increasing popularity due to its advantages, such as a relatively fast turnaround time. In this study, a newly discovered Coelastrum sp. TISTR 9501RE was characterized and investigated for its taxonomical identity and carotenoid profile. To the best of our knowledge, this report was the first to fully investigate the carotenoid profiles in a microalga of the genus Coelastrum. Upon use of limited nutrients as a stress condition, the strain was able to produce astaxanthin, canthaxanthin, and lutein, as the major carotenoid components. Additionally, the carotenoid esters were found to be all astaxanthin derivatives, and β-carotene was not significantly present under this stress condition. Importantly, we also demonstrated that this practical stress condition could be combined with simple growing factors, such as ambient sunlight and temperature, to achieve even more focused carotenoid profiles, i.e., increased overall amounts of the aforementioned carotenoids with fewer minor components and chlorophylls. In addition, this green microalga was capable of tolerating a wide range of salinity. Therefore, this study paved the way for more investigations and developments on this fascinating strain, which will be reported in due course.
Intravenous Versus Oral Acetaminophen in Ambulatory Surgical Center Laparoscopic Cholecystectomies: A Retrospective Analysis.

Study Objective The primary aim was to compare postoperative pain scores in patients undergoing laparoscopic cholecystectomy and receiving intravenous (IV) or oral (PO) acetaminophen (APAP) as part of a multimodal analgesic regimen to examine whether PO APAP is non-inferior to IV APAP. Design Retrospective analysis. Setting Ambulatory surgical center (ASC) in an academic setting. Patients 579 patients (18-70 years old), American Society of Anesthesiologists physical status I-III, undergoing laparoscopic cholecystectomy. Interventions Patients received 1,000 mg IV APAP intraoperatively (n = 319) or 1,000 mg PO APAP preoperatively (n = 260). Measurements The primary outcome was the median difference in post-anesthesia care unit (PACU) end-pain scores between the groups. Median pain scores were also compared on PACU admission, and at 15, 30, 45, and 60 minutes. Additional measures include PACU rescue-analgesia consumption, time to first PACU rescue analgesia, intraoperative use of opioid and nonopioid analgesics, PACU length of stay, and PACU rescue nausea and vomiting therapy. Main Results In both groups, the PACU median end-pain score was 2. The 90% confidence interval (CI) for difference in median pain scores between groups was [0, 0]; the CI upper limit was below the non-inferior margin of 1 pain-score point, indicating PO APAP's non-inferiority to IV APAP. There were no statistically significant differences in the percentages of patients receiving PACU hydromorphone equivalents between the IV and PO groups (75% vs. 77%, P = 0.72) or in the mean dose received (0.5 mg vs. 0.5 mg, P = 0.66). Conclusion Single-dose PO APAP is non-inferior to IV APAP for postoperative analgesia in ASC laparoscopic cholecystectomy patients. The value of single-dose IV APAP in this population should be further explored.
For Massachusetts Eye and Ear Special Issue: Updates on Therapies for Multiple Sclerosis for the Ophthalmologist

ABSTRACT In the past decade, the available disease-modifying therapies for multiple sclerosis have broadened significantly, providing physicians and patients with multiple options with different mechanisms of action, administration routes, and risk-benefit profiles. Multiple sclerosis often presents with ophthalmic manifestations due to inflammatory demyelination of the afferent and efferent visual pathways, and evidence of disease can factor into the decision to initiate or substitute a particular therapy. Furthermore, some of these drugs have toxicities that can manifest with ophthalmic complications, of which ophthalmologists should be aware.
Environmental Toxicology and Chemistry

Offspring generation (F1) rice (Oryza sativa japonica Koshihikari) seed germination and seedling growth tests were conducted for 18 d to investigate intergenerational effects of arsenic (As) and copper oxide nanoparticles (nCuO), with seeds harvested from a life cycle study exposed to As (0 and 10mg/kg) and nCuO (0, 0.1, 1.0, 10, 50, and 100mg/L). Seed germination and seedling growth of F1 plants were influenced by treatments experienced by parent generation (F0) plants (p< 0.05). Seeds produced from plants in F0 treatment with nCuO 50mg/L had the lowest germination percentage and shortest seedling shoot length and root length in F1 control (F1C) and As at 10mg/kg (F1As) alone treatments (p< 0.05). The shoot length and root length were decreased, whereas the number of root branches was increased in F1As treatment compared with F1C (p< 0.001). Interaction of As and nCuO also caused differential seed germination and seedling growth at various nCuO concentrations in quasi‐F0 treatment (seeds receiving the same exposure as F0 plants; p< 0.05). Copper and As uptake in F1C seedlings were not affected by seeds’ F0 exposure; this indicated that the transgenerational effects on rice seedling growth were not dependent on total Cu or As uptake in seedlings. The enhanced effects on seedlings from quasi‐F0 treatment were influenced by additional exposure to nCuO and As that also interacted to affect Cu and As uptake in seedlings. Environ Toxicol Chem 2019;38:1978–1987. © 2019 SETAC
Knowledge, Attitudes and Practices related to standard precautions among nurses: a comparative study.

AIM AND OBJECTIVE To describe and compare the knowledge, attitudes, and practices (KAP) pertaining to standard precautions (SPs) among nurses in China and Ethiopia. BACKGROUND SPs are guidelines for reducing the risk of transmission of blood-borne and other pathogens in hospital settings. SPs have been widely promoted to protect health care workers (HCW); however, these are not fully practiced worldwide, especially in resource-constrained countries like China and Ethiopia. DESIGN A descriptive, cross-sectional, comparative study was performed between February and April 2018. The study followed the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) guideline. METHODS Self-administered questionnaire survey of a convenience sample of 357 nurses (237 Chinese and 120 Ethiopian nurses) from one teaching hospital each in China and Ethiopia. KAP pertaining to SPs were measured. RESULTS Nurses of both countries were found to have a good understanding of the concept of SPs; however, the acceptance to organization of policies for prevention of hospital acquired infections (HAI) was lower in Ethiopia. Fewer medical resources in Ethiopia resulted in poorer adherence to use of personal protective equipment (PPE). The usage rate of PPE (except apron and goggles) among Ethiopian nurses was significantly lower than that among Chinese nurses. CONCLUSION Both Ethiopian and Chinese nurses showed favorable attitudes towards SPs; however, Chinese nurses reported better knowledge and practices. The organization should strengthen formal and on-the-job training, implement targeted infection prevention strategies, and provide adequate medical supplies in order to improve infection control in Ethiopia. RELEVANCE TO CLINICAL PRACTICE Our findings highlight some of the reasons for low compliance to SPs in both countries and potentially other similar settings. The information provided here can help develop infection prevention and control strategies for resource-constrained countries. This article is protected by copyright. All rights reserved.
Comprehensive single cell mRNA profiling reveals a detailed roadmap for pancreatic endocrinogenesis

ABSTRACT Deciphering mechanisms of endocrine cell induction, specification and lineage allocation in vivo will provide valuable insights into how the islets of Langerhans are generated. Currently, it is ill defined how endocrine progenitors segregate into different endocrine subtypes during development. Here, we generated a novel neurogenin 3 (Ngn3)-Venus fusion (NVF) reporter mouse line, that closely mirrors the transient endogenous Ngn3 protein expression. To define an in vivo roadmap of endocrinogenesis, we performed single cell RNA sequencing of 36,351 pancreatic epithelial and NVF+ cells during secondary transition. This allowed Ngn3low endocrine progenitors, Ngn3high endocrine precursors, Fev+ endocrine lineage and hormone+ endocrine subtypes to be distinguished and time-resolved, and molecular programs during the step-wise lineage restriction steps to be delineated. Strikingly, we identified 58 novel signature genes that show the same transient expression dynamics as Ngn3 in the 7260 profiled Ngn3-expressing cells. The differential expression of these genes in endocrine precursors associated with their cell-fate allocation towards distinct endocrine cell types. Thus, the generation of an accurately regulated NVF reporter allowed us to temporally resolve endocrine lineage development to provide a fine-grained single cell molecular profile of endocrinogenesis in vivo. Summary: Single cell mRNA profiling of pancreatic endocrine progenitor induction, specification and segregation using a novel Ngn3 reporter mouse line reveals signature genes that define lineage restriction towards specific endocrine subtypes.
Pandora's pregnancy: NIPT, CMA, and genome sequencing—A new era for prenatal genetic testing

We delineate in this article a shift from the “traditional” technologies of karyotyping in PND to the current phase of advanced genetic technologies including noninvasive prenatal testing (NIPT), chromosomal microarray analysis (CMA), and whole‐exome sequencing (WES) with their higher detection rate and related abundance of uncertain data.
The Results of Interferon-Alpha Treatment in Behçet Uveitis

ABSTRACT Purpose: To assess the efficacy and tolerability of interferon alpha (IFN-α) treatment in patients with refractory Behçet uveitis (BU). Methods: The patients with BU who were treated with subcutaneous IFN-α were divided into groups according to treatment response. Demographic features, best corrected visual acuity (BCVA), central macular thickness (CMT) value, and fluorescein angiography (FA) scores were compared between the groups. Results: Twenty-one (84%) of the 25 patients responded to IFN-α treatment. Active inflammation resolved at the first month’s visit in all patients. The improvement in mean BCVA and CMT achieved at the first month’s visit in all groups; however, the improvement in mean CMT in the non-responder group could not be maintained at the last visit. Main FA score significantly decreased in both the complete and partial remission group; however, it decreased minimally in the non-responder group. Conclusion: IFN-α seems an effective and safe treatment option in the management of refractory BU.
Sorption of Selected Heavy Metals with Different Relative Concentrations in Industrial Effluent on Biochar from Human Faecal Products and Pine-Bark

The removal of heavy metals from effluents at source could reduce contamination of soil and water bodies. A batch sorption experiment was performed to determine the effects of feedstock of biochars pyrolysed at increasing temperature on sorption capacities of Cu, Cr and Zn from industrial effluent and aqueous solutions. Sewage sludge, latrine faecal waste and pine-bark biochars were used. The sorption data were fitted to the Langmuir isotherm. Maximum sorption capacities of latrine waste, sewage sludge and pine-bark biochar (350 °C) were, respectively, 313, 400 and 233 mg kg−1 for Zn, 102, 98.0 and 33.3 mg kg−1 for Cu, and 18.9, 13.8 and 67.1 mg kg−1 for Cr from industrial effluent. Conversely, sorption capacities from single metal solutions were 278, 227 and 104 mg Zn kg−1, 97.1, 137 and 21.3 mg Cu kg−1, 122, 106 and 147 mg Cr kg−1 on latrine waste, sewage sludge and pine-bark biochar, respectively. Step-wise regression analysis showed that the combined effects of ash, fixed C, pH influenced Zn sorption, ash and fixed C affected Cu sorption, and Cr sorption by ash and specific surface area of the biochar. The findings of the study imply that biochar from human faecal waste, particularly sewage sludge, has the potential to be utilized as sorbents of heavy metals from multiple metal effluent and that the sorption is affected by relative concentrations.
Salmonella biofilms program innate immunity for persistence in Caenorhabditis elegans

Significance Salmonella resides as an intracellular pathogen in eukaryotic hosts and causes diarrhea or typhoid fever. In a small but alarming proportion of infected humans, Salmonella exists asymptomatically as biofilms, a basis for long-term disease transmission. Although Salmonella biofilms have been observed in chronically infected mice, mechanisms underlying why and how such multicellular aggregates are formed in vivo remain poorly understood. We exposed optically transparent Caenorhabditis elegans to Salmonella and observed the progression of infection in intestines from free-living cells to static aggregates. We discovered that a secreted toxin is down-regulated when Salmonella forms biofilms, leading to an adaptive advantage in chronic infections. Hence, Salmonella biofilms enable dormancy to prolong in vivo existence. The adaptive in vivo mechanisms underlying the switch in Salmonella enterica lifestyles from the infectious form to a dormant form remain unknown. We employed Caenorhabditis elegans as a heterologous host to understand the temporal dynamics of Salmonella pathogenesis and to identify its lifestyle form in vivo. We discovered that Salmonella exists as sessile aggregates, or in vivo biofilms, in the persistently infected C. elegans gut. In the absence of in vivo biofilms, Salmonella killed the host more rapidly by actively inhibiting innate immune pathways. Regulatory cross-talk between two major Salmonella pathogenicity islands, SPI-1 and SPI-2, was responsible for biofilm-induced changes in host physiology during persistent infection. Thus, biofilm formation is a survival strategy in long-term infections, as prolonging host survival is beneficial for the parasitic lifestyle.
Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds

Abstract Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p < 0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity. Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.
The Treatment of Non-Traumatic Meniscus Lesions.

BACKGROUND Most meniscus lesions are of non-traumatic origin. The indications for partial meniscectomy are controversial. METHODS We systematically searched the literature for randomized controlled trials (RCTs) comparing partial meniscectomy with non-surgical treatment. RESULTS Of 6870 articles retrieved by the literature search, we were able to include six in this systematic review. Five trials showed no difference between the clinical outcomes of patients who underwent arthroscopic partial meniscectomy and those who underwent control treatment (arthroscopic lavage, physiotherapy, glucocorticoids). In three trials, however, symptoms improved in 21-30% of the patients in the physiotherapy group only after they underwent arthroscopic partial meniscectomy (crossover design). In two trials, the percentage of patients who crossed over from one treatment arm to the other was markedly lower; in one, the frequency of crossing over was not reported. In one RCT, the patients who underwent arthroscopic partial meniscectomy had significantly less pain and other symptoms. Five of the six trials had acceptable scores for method, but all had weaknesses. These mainly concerned the description of the surgical techniques and the failure to take account of analgesic use-in particular, the use of non-steroidal antiinflammatory drugs (NSAIDs). CONCLUSION For most patients with non-traumatic meniscus lesions, surgical and non-surgical treatments seem to be of equal value; only one of the six included trials revealed lower pain and symptom scores after arthroscopic partial meniscectomy. In multiple trials, however, the crossover analysis showed that non-surgical treatment fails for some patients. These patients may benefit from arthroscopic partial meniscectomy. Further trials are needed to better define this subgroup of patients.