bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells
Authors: Sato Masako , Matsuo Kazuhiko , Susami Yoko , Yamashita Ayaka , Hayasaka Haruko , Hara Yuta , Nishiwaki Keiji , Oiso Naoki , Kawada Akira , Otsuka Atsushi , Nakayama Takashi 
Published: June 2023

Abstract
CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in AD skin lesions. Here, we investigated the role of CCR4 in an AD mouse model induced by MC903, a TSLP inducer. Topical application of MC903 to ear skin increased the expression of not only TSLP but also CCL17, CCL22, the Th2 cytokine IL-4, and the Th17 cytokine IL-17A. Consistently, MC903 induced AD-like skin lesions as shown by increased epidermal thickness; increased infiltration of eosinophils, mast cells, type 2 innate lymphoid cells, Th2 cells, and Th17 cells; and elevated serum levels of total IgE. We also found increased expansion of Th2 cells and Th17 cells in the regional lymph nodes (LNs) of AD mice. Compound 22, a CCR4 inhibitor, ameliorated AD-like skin lesions with reduction of Th2 cells and Th17 cells in the skin lesions and regional LNs. We further confirmed that compound 22 diminished the expansion of Th2 cells and Th17 cells in the coculture of CD11c+ dendritic cells (DCs) and CD4+ T cells derived from the regional LNs of AD mice. Collectively, CCR4 antagonists may exhibit anti-allergic effects by inhibiting both the recruitment and expansion of Th2 cells and Th17 cells in AD.
High satisfaction among patients at HIV clinics in Harare, Zimbabwe: a time and motion evaluation and patient satisfaction study
Authors: Link Abigail , Tshimanga Mufuta , Cochrane Barbara , Kasprzyk Danuta 
Published: June 2023

Abstract
Patient satisfaction is an important component of health and healthcare utilization, which measures the perceived needs and expectations for healthcare services. Patient satisfaction surveys are effective in improving health outcomes by informing health facilities on service and provider gaps and guiding the development of effective action plans and policies for quality improvement within a healthcare organization. Although patient satisfaction and patient flow analyses have been conducted in Zimbabwe, the combination of these two quality improvement measures in the context of Human Immunodeficiency Virus (HIV) clinics has not previously been evaluated. This study assessed and evaluated patient flow and patient satisfaction to enhance care quality and improve HIV service delivery to optimize patient health. We collected time and motion data from HIV patients who attended three purposively selected City of Harare Polyclinics in Harare, Zimbabwe. All patients who sought care at the clinic were given time and motion forms to track their movement and the time spent at each service area. After services were completed, patients were invited to participate in a satisfaction survey regarding their services and care. The average waiting time from clinic arrival to see the provider was 2 hr and 14 min. The areas with the longest waiting time and bottlenecks occurred at registration (49 min) and the HIV clinic waiting area (44 min). Despite these extended times, the overall patient satisfaction for HIV services was high at 72%, with over half (59%) reporting that there was nothing they did not like about their services. Patients were most satisfied with services provided (34%), timely service (27%), and antiretroviral medications (19%). The areas of least satisfaction were related to time delays (24%) and cashier delays (6%). Despite prolonged waiting times, patients’ overall satisfaction with their clinic experience remains high. Perceptions of satisfaction are influenced by experience, culture, and context. However, there are still several areas of recommendations to improve service, care, and quality. Specifically, reducing or eliminating service fees, increasing clinic hour times, and having available medication were most cited. Support from the Zimbabwe Ministry of Health and Child Care, City of Harare, and other decision-makers is needed to improve patient satisfaction and address patients’ recommendations within the City of Harare Polyclinic organization in accordance with the 2016–20 National Health Strategies for Zimbabwe.
From Satanic Minister to Holy Model: The Sacralization of the Medieval Jongleur
Authors: Dickason Kathryn 
Published: June 2023

AbstractFew figures in the medieval West were as religiously ambivalent as the medieval jongleur, a broad French term for a popular entertainer. Ecclesiastical authorities typically critiqued jongleurs, aligning them with avarice, folly, and prostitution. However, by the thirteenth century, the jongleur emerged as a more complex figure. Far from being a disciple of the devil, the jongleur could imitate the humility of King David and, by extension, the Passion of Christ. In religious texts and imagery, the jongleur’s embodied performance could exemplify a sacred rite. Showcasing the medieval European jongleur, this article argues that the divide between the sacred and the profane is not as rigid as much scholarship assumes. Ultimately, this study shows the importance of bodily performance in Western medieval religion and therefore complicates the presumed binary between written/Western and embodied/Eastern religiosity.
Antimicrobial susceptibility of Clostridioides difficile to omadacycline and comparator antimicrobials
Authors: Skinner Andrew M , Petrella Laurica A , Cheknis Adam , Johnson Stuart 
Published: June 2023

Abstract

Background
Omadacycline is a novel aminomethylcycline tetracycline antimicrobial that was approved for the treatment of community-associated bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Omadacycline has demonstrated a high degree of in vitro activity towards Clostridioides difficile and previous data have hypothesized that use of omadacycline for CABP or ABSSSI may decrease the risk of C. difficile infections.

Objectives
To compare the in vitro antimicrobial activity of omadacycline versus commonly used antimicrobials for the approved indications of use.

Methods
We compared the antimicrobial activity of eight antimicrobials approved for CABP and ABSSSI against omadacycline by agar dilution on 200 clinically relevant contemporary C. difficile isolates representing local and national prevalent strain types.

Results
The in vitro omadacycline geometric mean MIC was 0.07 mg/L. Ceftriaxone resistance was noted in &gt;50% of all isolates tested. The epidemic strain group, identified as restriction endonuclease analysis (REA) group BI, was commonly resistant to azithromycin (92%), moxifloxacin (86%) and clindamycin (78%). REA group DH strains had an elevated trimethoprim/sulfamethoxazole geometric mean MIC of 17.30 mg/L compared with the geometric mean MIC of 8.14 mg/L noted in all other isolates. In the REA group BK isolates that had a doxycycline MIC of ≥2 mg/L, the omadacycline MIC was &lt;0.5 mg/L.

Conclusions
Among 200 contemporary C. difficile isolates, there were no notable elevations in the in vitro omadacycline MIC, indicating a high level of activity towards C. difficile in comparison with commonly used antimicrobials for CABP and ABSSSI.
In vitro and in vivo susceptibility to cefalexin and amoxicillin/clavulanate in canine low-level methicillin-resistant Staphylococcus pseudintermedius
Authors: Pirolo Mattia , Menezes Mareliza , Damborg Peter , Wegener Alice , Duim Birgitta , Broens Els , Jessen Lisbeth Rem , Schjærff Mette , Guardabassi Luca 
Published: June 2023

Abstract

Background
Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually display low oxacillin MICs (0.5–2 mg/L).

Objectives
To evaluate how oxacillin MICs correlate with PBP mutations and susceptibility to β-lactams approved for veterinary use.

Methods
Associations between MICs and PBP mutations were investigated by broth microdilution, time–kill and genome sequence analyses in 117 canine MRSP strains harbouring these SCCmec types. Clinical outcome was retrospectively evaluated in 11 MRSP-infected dogs treated with β-lactams.

Results
Low-level MRSP was defined by an oxacillin MIC &lt;4 mg/L. Regardless of strain genotype, all low-level MRSP isolates (n = 89) were cefalexin susceptible, whereas no strains were amoxicillin/clavulanate susceptible according to clinical breakpoints. Exposure to 2× MIC of cefalexin resulted in complete killing within 8 h. High (≥4 mg/L) oxacillin MICs were associated with substitutions in native PBP2, PBP3, PBP4 and acquired PBP2a, one of which (V390M in PBP3) was statistically significant by multivariable modelling. Eight of 11 dogs responded to systemic therapy with first-generation cephalosporins (n = 4) or amoxicillin/clavulanate (n = 4) alone or with concurrent topical treatment, including 6 of 7 dogs infected with low-level MRSP.

Conclusions
Oxacillin MIC variability in MRSP is influenced by mutations in multiple PBPs and correlates with cefalexin susceptibility. The expert rule recommending that strains with oxacillin MIC ≥0.5 mg/L are reported as resistant to all β-lactams should be reassessed based on these results, which are highly clinically relevant in light of the shortage of effective antimicrobials for systemic treatment of MRSP infections in veterinary medicine.
NT-proBNP Reference Intervals in Healthy U.S. Children, Adolescents, and Adults
Authors: Mu Scott , Echouffo-Tcheugui Justin B , Ndumele Chiadi E , Coresh Josef , Juraschek Stephen , Brady Tammy , McEvoy John William , Ozkan Bige , Tang Olive , Christenson Robert H , Selvin Elizabeth 
Published: June 2023

Abstract

Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults.

Methods
We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories.

Results
NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348).

Conclusions
Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk.
Virulence and antimicrobial resistance of Shiga toxin-producing Escherichia coli from dairy goat and sheep farms in The Netherlands
Authors: van Hoek Angela H A M , Lee Seungeun , van den Berg Redmar R , Rapallini Michel , van Overbeeke Lennert , Opsteegh Marieke , Bergval Indra , Wit Ben , van der Weijden Coen , van der Giessen Joke , van der Voort Menno 
Published: June 2023

Abstract

Aims
The aim of our study was to investigate the virulence and resistance of STEC from small ruminants farms in The Netherlands. Moreover, the potential transmission of STEC between animals and humans on farms was evaluated.

Methods and results
From 182 farms, in total, 287 unique STEC isolates were successfully recovered from animal samples. In addition, STEC was isolated from eight out of 144 human samples. The most detected serotype was O146:H21; however, among other serotypes also O26:H11, O157:H7, and O182:H25 isolates were present. Whole genome sequencing covering all human isolates and 50 of the animal isolates revealed a diversity of stx1, stx2, and eae sub-types and an additional 57 virulence factors. The assessed antimicrobial resistance phenotype, as determined by microdilution, was concordant with the genetic profiles identified by WGS. WGS also showed that three of the human isolates could be linked to an animal isolate from the same farm.

Conclusions
The obtained STEC isolates showed great diversity in serotype, virulence, and resistance factors. Further analysis by WGS allowed for an in-depth assessment of the virulence and resistance factors present and to determine the relatedness of human and animal isolates.
Validation and Standardization of Gallic Acid and Ellagic Acid in Quercus Infectoria, Terminalia Chebula, and Pistacia Integerrima
Authors: Saini Anil Kumar , Zahiruddin Sultan , Newton Kakumani Godwin , Sawant Laxman , Mitra Ranjan , Kumar Rai Rajiva , Ahmad Sayeed 
Published: June 2023

Abstract

Background
Due to its medicinal properties, Pistacia integerrima is in high demand and is extensively used as a key ingredient in various formulations. However, its popularity has led to its inclusion on the International Union for Conservation of Nature threatened category list. In Ayurvedic texts, such as Bhaishajaya Ratnavali, Quercus infectoria is recommended as a substitute for P. integerrima in different formulations. Additionally, Yogratnakar highlights that Terminalia chebula shares similar therapeutic properties with P. integerrima.

Objective
The objective of the current study was to gather scientific data on metabolite profiling and marker-based comparative analysis of Q. infectoria, T. chebula, and P. integerrima.

Methods
In present study, hydroalcoholic and aqueous extracts of all three plants were prepared and standardized for the comparative evaluation of secondary metabolites. TLC was carried out for the comparative fingerprinting of the extracts using chloroform–methanol–glacial acetic acid–water (60 + 8 + 32 + 10, by volume) as a solvent system. A fast, sensitive, selective, and robust HPLC method was developed to determine gallic acid and ellagic acid from both extracts of all three plants. The method was validated for precision, robustness, accuracy, LOD and LOQ as per the International Conference on Harmonization guidelines.

Results
The TLC analysis revealed the presence of several metabolites, and the pattern of metabolites in the plants exhibited a certain degree of similarity. A highly precise and reliable quantification technique was created for gallic acid and ellagic acid, operating within a linear concentration range of 81.18–288.22 µg/mL and 3.83–13.66 µg/mL, respectively. The correlation coefficients for gallic acid and ellagic acid were 0.997 and 0.996, indicating good linear relationships. The gallic acid content in all three plants ranged from 3.74 to 10.16% w/w, while the ellagic acid content ranged from 0.10 to 1.24% w/w.

Conclusion
The study contributes to the scientific understanding of the metabolite profiles and comparative analysis of Q. infectoria, T. chebula, and P. integerrima. The findings provide valuable insights into the chemical composition of these plants and can be used for various applications in herbal medicine.

Highlights
This pioneering scientific approach highlights the phytochemical similarities between Q. infectoria, T. chebula and P. integerrima.
Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry
Authors: Joseph Delphine , Lesueur Camille , Zerizer Fanny , Fenot Alexia , Alvarez Jean Claude , Larabi Islam Amine 
Published: June 2023

Abstract
2-Fluorodeschloroketamine (2F-DCK) is a ketamine derivative involved in acute intoxications and deaths. The aim of this study is to investigate its metabolism using pooled human liver microsomes (pHLMs) and to apply it to authentic samples (urine, hair and seized materials) from a drug user. 2F-DCK (100 µM) incubates with pHLMs were analyzed by liquid chromatography–high-resolution accurate mass (LC–HRAM; Q-Exactive, Thermo Fisher Scientific®) according to a previously published protocol. Spectra annotation was performed using Compound Discoverer® software and the metabolic scheme was drawn using ChemDraw software. Urine (200 µL) and hair (previously decontaminated using dichloromethane and segmented into three segments: A, 0–3 cm; B, 3–6 cm; C, 6–9 cm) were extracted with a mixture of hexane:ethyl acetate (1:1) and chloroform:isopropanol (4:1). About 10 µL of both reconstituted residues were analyzed by LC–HRAM. Hair was also analyzed by LC–MS-MS (TSQ Vantage, Thermo Fisher Scientific®) for 2F-DCK and deschloroketamine (DCK) quantification. The two presumed 2F-DCK crystals consumed by the patient were dissolved in methanol (1 mg/mL) and 10 µL were analyzed by LC–MS-MS (Quantum Access Max, Thermo Fisher Scientific®). Twenty-six putative 2F-DCK metabolites were identified, 15 being reported for the first time. Thirteen metabolites were detected in pHLMs, 10 confirmed in both the patient’s urine and hair and all were found in at least one of the two samples. Twenty-three metabolites were detected in urine and 20 in hair. Our research confirms the reliability of nor-2F-DCK as a target analyte and suggests OH-dihydro-nor-2F-DCK and dehydro-nor-2F-DCK as new target analytes in urine and hair, respectively. This is the first study to report DCK as a 2F-DCK metabolite using pHLMs and to determine its concentrations in hair (A/B/C, 885/1,500/1,850 pg/mg) following chronic use. Finally, the two seized crystals contained 2F-DCK at 67% and 96% with traces of DCK (0.4% and 0.6%) related to cross-contamination by container exchange.
Case report of a fatal 3-hydroxyphencyclidine intoxication, including blood and hair results
Authors: Ameline Alice , Baudry Morgane , Garnier Delphine , Raul Jean-Sébastien , Kintz Pascal 
Published: June 2023

Abstract
3-Hydroxyphencyclidine (3-OH-PCP) is a hydroxy derivative of phencyclidine, synthesized in 1978 to investigate the structure–activity relationship of phencyclidine derivates. In vitro studies have shown that 3-OH-PCP, like phencyclidine, acts on the N-methyl-D-aspartate receptor and has a higher affinity for this receptor than phencyclidine. The authors report the case of a 38-year-old man, known for drug addiction, found dead at home with two plastic bags of powders found near his body. Using liquid chromatography coupled to tandem mass spectrometry, peripheral blood toxicological analysis revealed consumption of 3-OH-PCP with a concentration of 3-OH-PCP being 524 ng/mL. Blood also tested positive for nordiazepam, methylphenidate, amisulpride, methadone and benzoylecgonine, all at concentrations near those observed after recreational abuse. The blood concentration of 3-OH-PCP is the highest ever reported in the literature. Hair testing also revealed 3-OH-PCP, at 174 pg/mg, which may correspond to a chronic consumption of this molecule. A nuclear magnetic resonance analysis of the two powders highlighted 3-OH-PCP and 5-methoxy-dimethyltryptamine, estimated to have a purity of 85.4 and 91.3%, respectively, using the Electronic Reference To access In vivo Concentrations method.
Identification of postmortem paliperidone metabolite in human blood by LC–Q-Orbitrap-MS
Authors: Yamagishi Yoshikazu , Inokuchi Go , Hoshioka Yumi , Nagasawa Sayaka , Iwase Hirotaro , Ogra Yasumitsu 
Published: June 2023

Abstract
Paliperidone is a widely used antipsychotic agent detected in many fatal intoxications and suicide cases. In forensic toxicology, the accurate determination of blood paliperidone concentrations is required to prove death by paliperidone poisoning. However, the lethal concentration of paliperidone in blood at autopsy differs from that at the time of death. In this study, we found that paliperidone was decomposed by hemoglobin (Hb) through the Fenton reaction in a temperature-dependent fashion. The mechanism underlying paliperidone decomposition involves the cleavage of its C–N bond linker moiety. The mass spectra obtained by liquid chromatography–quadrupole orbitrap mass spectrometry revealed the formation of 6-fluoro-3-(4-piperidinyl)benzisoxazole (PM1) in Hb/H2O2 solution incubated with paliperidone, as well as in the blood of individuals who died from intentional ingestion of paliperidone. These results suggest that PM1 is the only metabolite produced from paliperidone as a result of temperature-dependent, postmortem changes induced by Hb via the Fenton reaction and may be useful as a biomarker to correct for the concentration of paliperidone in blood at the time of death in clinical cases.
Fashion and Image as Anthropographic Elements in Nineteenth-century Colombia
Authors: Bermúdez-Castillo Jairo , Barraza Astrid Barrios , Delgado Osorio Claudia Patricia , Verastegui Maristela 
Published: June 2023

Abstract
This article is the product of a research project about the role of image in the creation of the Colombian nation during the nineteenth century. Part of that image depended on the individuals it identified, their social status, their lifestyle, and their occupation. The image of fashion as a characteristic social identifier, as an icon, was a bearer of anthropographic symbols. In nineteenth-century Colombia, those symbols were connected to a republican identity characterized by its colonial heritage, determined by race, and by garments distinctive of specific social classes: formerly subjects and, later, citizens. Thus, the image that fashion conveyed as the “skin of the skin” of the republican ancestors, the elite, and the people constitutes a legacy that encompasses everything, from the manufacture of textiles and the indigenous ruana, to a kind of textile mestizaje with aspects of European provenance. Items from collections in museums, libraries, and archives, were compared to texts composed by travelers and illustrators, in order to unveil elements of national identity in what emerges as the landscape of fashion in Colombia during the nineteenth century.
Regulators as Guardians of Trust? The Contingent and Modest Positive Effect of Targeted Transparency on Citizen Trust in Regulated Sectors
Authors: Grimmelikhuijsen Stephan , de Vries Femke , Bouwman Robin 
Published: June 2023

Abstract
Targeted transparency has become an essential tool for regulation. Through information disclosure, regulatory agencies try to get regulated companies to improve their practices and comply with regulations. In the past, regulation was associated with distrust in regulated sectors. Recent research suggests that regulation, especially targeted transparency, may also increase citizen trust in regulated sectors. However, empirical evidence on whether transparency as a regulatory tool undermines or decreases trust in a sector is lacking. We contribute to this debate by investigating the effect of targeted transparency on citizen trust through a large-scale representative survey experiment (n = 5,303). We used 12 transparency frames in three regulated domains in the Netherlands (consumer rights, healthcare safety, and nuclear plant safety). Our findings suggest that, in general, targeted transparency does not undermine trust, but has a positive effect on trust in regulated sectors. However, this effect is small and contextual, depending on the regulatory domain and type of transparency frame.