bluuebunny/crossref_metadata_2025_split huggingface dataset:
PKCζ activation promotes maturation of cord blood T cells towards a Th1 IFN‐γ propensity
Authors: Perveen Khalida , Quach Alex , Stark Michael J. , Prescott Susan , Barry Simon C. , Hii Charles S. , Ferrante Antonio 
Published: June 2023

AbstractA significant number of babies present transiently with low protein kinase C zeta (PKCζ) levels in cord blood T cells (CBTC), associated with reduced ability to transition from a neonatal Th2 to a mature Th1 cytokine bias, leading to a higher risk of developing allergic sensitisation, compared to neonates whose T cells have ‘normal’ PKCζ levels. However, the importance of PKCζ signalling in regulating their differentiation from a Th2 to a Th1 cytokine phenotype propensity remains undefined. To define the role of PKCζ signalling in the regulation of CBTC differentiation from a Th2 to a Th1cytokine phenotype we have developed a neonatal T cell maturation model which enables the cells to develop to CD45RA−/CD45RO+ T cells while maintaining the Th2 immature cytokine bias, despite having normal levels of PKCζ. The immature cells were treated with phytohaemagglutinin, but in addition with phorbol 12‐myristate 13‐acetate (PMA), an agonist which does not activate PKCζ. This was compared to development in CBTC in which the cells were transfected to express constitutively active PKCζ. The lack of PKCζ activation by PMA was monitored by western blot for phospho‐PKCζ and translocation from cell cytosol to the membrane by confocal microscopy. The findings demonstrate that PMA fails to activate PKCζ in CBTC. The data show that CBTC matured under the influence of the PKC stimulator, PMA, maintain a Th2 cytokine bias, characterised by robust IL‐4 and minimal interferon gamma production (IFN‐γ), and lack of expression of transcriptional factor, T‐bet. This was also reflected in the production of a range of other Th2/Th1 cytokines. Interestingly, introduction of a constitutively active PKCζ mutant into CBTC promoted development towards a Th1 profile with high IFN‐γ production. The findings demonstrate that PKCζ signalling is essential for the immature neonatal T cells to transition from a Th2 to a Th1 cytokine production bias.
‘It just stops me from living’: A qualitative study of losses experienced by women with self‐reported endometriosis
Authors: Peterson Brianna , Mikocka‐Walus Antonina , Evans Subhadra 
Published: June 2023

AbstractAimsTo understand the experience of loss in Australian women with endometriosis.DesignA total of 532 participants completed an online survey containing three open‐ended questions relating to pelvic pain and activity loss due to endometriosis. Participants were Australian women aged between 18 and 50 years (M = 30.8, SD = 7.1) with a self‐reported diagnosis of endometriosis. An inductive, qualitative approach, with template analysis was used to identify and organize themes. A pragmatic feminist perspective was used to interpret the findings.ResultsThree main themes were identified: the loss of liberty: ‘I'm trapped in the house’; the loss of bodily autonomy: ‘I can barely move/breathe/talk’ and loss of connection: ‘It stops me from being social’. Pain emerged as the greatest concern for participants, preventing them from the physical functioning required to participate in many of life's activities.ConclusionsThe losses women with endometriosis experience are wide‐reaching, restricting control and choice across multiple life domains. Losses were often unacknowledged by loved ones and healthcare providers, further impacting the physical, emotional and mental health of participants.Patient or Public ContributionPeople with endometriosis were involved in the design of the study, including identifying topics of interest.
The treatment of plantar warts using microwave—A review of 85 consecutive cases in the United States
Authors: Gupta Aditya K. , Wang Tong , Cooper Elizabeth A. , Conenello Robert M. , Bristow Ivan R. 
Published: June 2023

AbstractBackgroundPlantar warts (verrucae plantaris) are a common source of pain for patients and are often refractory to treatment. Previous work has shown a high clearance rate of verrucae using a surface‐based microwave device (Swift®).AimsTo assess the efficacy, defined as the complete visible clearance of warts, in patients with verrucae plantaris receiving microwave treatment.PatientsWe undertook a retrospective review and identified records of 85 patients who underwent a course of microwave treatment at a single US‐based podiatry centre. Efficacy was analyzed on the basis on intention‐to‐treat.ResultsIn patients who received ≥1 session there was a complete clearance rate of 60.0% (51/85) (intention‐to‐treat; 59 patients completed treatment, 26 lost to follow‐up) and 86.4% (51/59) per treatment completion; no significant differences in clearance rates of children and adults were observed (61.0% [25/41] vs. 59.1% [26/44]). There were 31 patients who received three sessions of microwave therapy with a clearance rate of 71.0% (22/31) as per intention‐to‐treat (27 patients completed treatment, 4 lost to follow‐up). An average of 2.3 sessions (SD: 1.1; range: 1–6) was required for the complete clearance of plantar warts. Complete clearance was also observed in some patients with recalcitrant warts following additional treatment sessions (42.9% [3/7]). A significant reduction in wart related pain was reported for all patients undergoing treatment. Some patients continued to report a reduced amount of pain post‐therapy compared with pretherapy.ConclusionsMicrowave treatment of verrucae plantaris appears to be a safe and effective procedure.
YAP/WNT5A/FZD4 axis regulates osteogenic differentiation of human periodontal ligament cells under cyclic stretch
Authors: Zhang Xiaocen , Chang Maolin , Wang Beike , Liu Xiaoyu , Zhang Zhen , Han Guangli 
Published: June 2023

AbstractObjectiveTo verify the role of YAP/WNT5A/FZD4 axis in stretch‐induced osteogenic differentiation of hPDLCs.BackgroundDuring orthodontic tooth movement, differentiation of human periodontal ligament cells (hPDLCs) at the tension side of the periodontal ligament mediates new bone formation. WNT5A promotes osteogenesis and its regulator Yes‐associated protein (YAP) is responsive to mechanical stimulation in hPDLCs. However, the mechanisms of YAP and WNT5A in alveolar bone remodeling remain unclear.MethodsCyclic stretch was applied to hPDLCs to mimic the orthodontic stretching force. Osteogenic differentiation was determined by alkaline phosphatase (ALP) activity, Alizarin Red staining, qRT‐PCR and western blotting. To detect activation of YAP and expression of WNT5A and its receptor Frizzled‐4 (FZD4), western blotting, immunofluorescence, qRT‐PCR and ELISA were performed. Verteporfin, Lats‐IN‐1, small interfering RNAs and recombinant protein were used to explore the relationship of YAP, WNT5A and FZD4, and the effect of their relationship on stretch‐induced osteogenesis of hPDLCs.ResultsWNT5A, FZD4 and nuclear localization of YAP were upregulated by cyclic stretch. YAP positively regulated WNT5A and FZD4 expression and osteogenic differentiation of hPDLCs under cyclic stretch by YAP inhibition or activation assay. Knockdown of WNT5A and FZD4 attenuated YAP‐induced and stretch‐induced osteogenic differentiation. Recombinant WNT5A rescued the suppressed osteogenic differentiation by YAP inhibitor in hPDLCs, whereas knockdown of FZD4 weakened the effect of WNT5A and amplified the suppression.ConclusionsWNT5A/FZD4 could be positively regulated by YAP and the YAP/WNT5A/FZD4 axis mediated osteogenic differentiation of hPDLCs under cyclic stretch. This study provided further insight into the biological mechanism of orthodontic tooth movement.
Quality of amoxicillin/clavulanic acid oral formulations for intended veterinary use in the UK, Malaysia, Serbia and Thailand
Authors: Pelligand L. , Baker D. , Sivagurunathan A. , Kovačević Z. , Suemanotham N. , Stair J. L. , Scott M. , Liu F. , Page S. W. , Guardabassi L. , Steagall P. V. ,   the Therapeutic Guidelines Group of the World Small Animal Veterinary Association
Published: June 2023

ObjectivesAmoxicillin/clavulanate is the most commonly used oral antimicrobial drug in companion animals. The objective of the study was to detect types and frequency of deficits in the quality of veterinary oral formulations of amoxicillin/clavulanate in various countries.Materials and MethodsIn a prospective study with purposive sampling, amoxicillin/clavulanate tablet formulations for canine use were collected in four countries (wholesalers or veterinary practice) and shipped to a central bioanalytical laboratory. Twenty‐four samples were collected from the UK (nine), Malaysia (nine), Serbia (four) and Thailand (two), yielding 18 different formulations (10 veterinary). Packaging inspection, tablet disintegration and content assay were conducted (validated high‐performance liquid chromatography with ultra‐violet detection); content was acceptable when within the 90% to 120% pre‐specified range (US Pharmacopeia).ResultsSecondary packaging was present for 13 of 24 samples and primary packaging integrity was verified for all but one sample. Amoxicillin trihydrate/potassium clavulanate label ratio was 4:1, except for three formulations (2:1). Tablet dose strength ranged from 250 to 625 mg. All formulations contained both analytes. For amoxicillin, two of 24 samples were out of specification with 72.8% (Malaysia) and 82.3% (Thailand) of labelled content. For clavulanate, four of 24 samples were out of specification with 46.9% (Serbia), 79.0% (UK), 84.3% (Serbia) and 86.5% (Thailand) of labelled content. One formulation (Thailand) failed for both analytes.Clinical SignificanceAntimicrobial formulations of substandard quality have negative consequences for efficacy in patients and potentially promote antimicrobial resistance. There was evidence of substandard formulations in all countries, not only for amoxicillin but especially for clavulanate; this could compromise equitable access to acceptable quality essential veterinary medicines worldwide.
Phenotypic and genetic aspects of hereditary ataxia in dogs
Authors: Stee Kimberley , Van Poucke Mario , Lowrie Mark , Van Ham Luc , Peelman Luc , Olby Natasha , Bhatti Sofie F.M. 
Published: June 2023

AbstractHereditary ataxias are a large group of neurodegenerative diseases that have cerebellar or spinocerebellar dysfunction as core feature, occurring as an isolated sign or as part of a syndrome. Based on neuropathology, this group of diseases has so far been classified into cerebellar cortical degenerations, spinocerebellar degenerations, cerebellar ataxias without substantial neurodegeneration, canine multiple system degeneration, and episodic ataxia. Several new hereditary ataxia syndromes are described, but most of these diseases have similar clinical signs and unspecific diagnostic findings, wherefore achieving a definitive diagnosis in these dogs is challenging. Eighteen new genetic variants associated with these diseases have been discovered in the last decade, allowing clinicians to reach a definitive diagnosis for most of these conditions, and allowing breeding schemes to adapt to prevent breeding of affected puppies. This review summarizes the current knowledge about hereditary ataxias in dogs, and proposes to add a “multifocal degenerations with predominant (spino)cerebellar component” category regrouping canine multiple system degeneration, new hereditary ataxia syndromes that do not fit in 1 of the previous categories, as well as specific neuroaxonal dystrophies and lysosomal storage diseases that cause major (spino)cerebellar dysfunction.
Spray‐induced gene silencing to identify powdery mildew gene targets and processes for powdery mildew control
Authors: McRae Amanda G. , Taneja Jyoti , Yee Kathleen , Shi Xinyi , Haridas Sajeet , LaButti Kurt , Singan Vasanth , Grigoriev Igor V. , Wildermuth Mary C. 
Published: June 2023

AbstractSpray‐induced gene silencing (SIGS) is an emerging tool for crop pest protection. It utilizes exogenously applied double‐stranded RNA to specifically reduce pest target gene expression using endogenous RNA interference machinery. In this study, SIGS methods were developed and optimized for powdery mildew fungi, which are widespread obligate biotrophic fungi that infect agricultural crops, using the known azole‐fungicide target cytochrome P450 51 (CYP51) in the Golovinomyces orontii–Arabidopsis thaliana pathosystem. Additional screening resulted in the identification of conserved gene targets and processes important to powdery mildew proliferation: apoptosis‐antagonizing transcription factor in essential cellular metabolism and stress response; lipid catabolism genes lipase a, lipase 1, and acetyl‐CoA oxidase in energy production; and genes involved in manipulation of the plant host via abscisic acid metabolism (9‐cis‐epoxycarotenoid dioxygenase, xanthoxin dehydrogenase, and a putative abscisic acid G‐protein coupled receptor) and secretion of the effector protein, effector candidate 2. Powdery mildew is the dominant disease impacting grapes and extensive powdery mildew resistance to applied fungicides has been reported. We therefore developed SIGS for the Erysiphe necator–Vitis vinifera system and tested six successful targets identified using the G. orontii–A. thaliana system. For all targets tested, a similar reduction in powdery mildew disease was observed between systems. This indicates screening of broadly conserved targets in the G. orontii–A. thaliana pathosystem identifies targets and processes for the successful control of other powdery mildew fungi. The efficacy of SIGS on powdery mildew fungi makes SIGS an exciting prospect for commercial powdery mildew control.
Ribosomal protein SA is a common component of neuronal intranuclear inclusions in polyglutamine diseases and Marinesco bodies
Authors: Yagita Kaoru , Sadashima Shoko , Koyama Sachiko , Noguchi Hideko , Hamasaki Hideomi , Sasagasako Naokazu , Honda Hiroyuki 
Published: June 2023

Neuronal intranuclear inclusions (NIIs) are common key structures in polyglutamine (polyQ) diseases such as Huntington disease (HD), spinocerebellar ataxia type 1 (SCA1), and SCA3. Marinesco bodies (MBs) of dopaminergic neurons in the substantia nigra are also intranuclear structures and are frequently seen in normal elderly people. Ribosomal dysfunction is closely related to two differential processes; therefore, we aimed to identify the pathological characteristics of ribosomal protein SA (RPSA), a ribosomal protein, in both states. To this end, we evaluated the autopsy findings in four patients with HD, two SCA3, and five normal elderly cases (NCs). Immunohistochemical studies demonstrated that both NIIs and MBs contain RPSA. In polyQ diseases, RPSA was co‐localized with polyQ aggregations, and 3D‐reconstructed images revealed their mosaic‐like distribution. Assessments of the organization of RPSA and p62 in NIIs showed that RPSA was more localized toward the center than p62 and that this unique organization was more evident in the MBs. Immunoblotting of the temporal cortices revealed that the nuclear fraction of HD patients contained more RPSA than that of NCs. In conclusion, our study revealed that RPSA is a common component of both NIIs and MBs, indicating that a similar mechanism contributes to the formation of polyQ NIIs and MBs.
TWO BRONZE AGE MINIATURE WAGON AND WHEEL BURIALS IN ENCS (NORTH‐EASTERN HUNGARY)
Authors: Mengyán Ákos , Gémes Anett , SZeniczey Tamás , Hajdu Tamás 
Published: June 2023

SummaryDuring an excavation of a Bronze Age, Füzesabony‐culture cemetery at Encs (north‐eastern Hungary), a clay wagon model with spoked wheels (grave 1290) and three miniature solid clay wheels were found (grave 1389). Miniature wagon and wheel models in burials began to appear in the Late Copper Age and lasted until the Iron Age in Central Europe. Their presence allows of several interpretations. These spoked wheels of grave 1290 provide early evidence about the appearance of such in the Carpathian Basin. Focussing on the two graves from Encs, this article reports AMS radiocarbon dates that suggest the spoked wheels belong to the early second millennium BC. The implications of these finds are interpreted though a comparative review of both wagon models from the Füzesabony culture and the evidence for early spoked wheels in the Carpathian Basin.
Pharmacokinetic pharmacodynamic modeling of analgesics and sedatives in children
Authors: Bardol Maddlie , Pan Shan , Walker Suellen M. , Standing Joseph F. , Dawes Joy M. 
Published: June 2023

AbstractPharmacokinetic pharmacodynamic modeling is an important tool which uses statistical methodology to provide a better understanding of the relationship between concentration and effect of drugs such as analgesics and sedatives. Pharmacokinetic pharmacodynamic models also describe between‐subject variability that allows identification of subgroups and dose adjustment for optimal pain management in individual patients. This approach is particularly useful in the pediatric population, where most drugs have received limited evaluation and dosing is extrapolated from adult practice. In children, the covariates of weight and age are used to describe size‐ and maturation‐related changes in pharmacokinetics. It is important to consider both size and maturation in order to develop an accurate model and determine the optimal dose for different age groups. An adequate assessment of analgesic and sedative effect using pain scales or brain activity measures is essential to build reliable pharmacokinetic pharmacodynamic models. This is often challenging in children due to the multidimensional nature of pain and the limited sensitivity and specificity of some measurement tools. This review provides a summary of the pharmacokinetic and pharmacodynamic methodology used to describe the dose–concentration–effect relationship of analgesics and sedation in children, with a focus on the different pharmacodynamic endpoints and the challenges of pharmacodynamic modeling.
The OSUMMER lines: A series of ultraviolet‐accelerated NRAS‐mutant mouse melanoma cell lines syngeneic to C57BL/6
Authors: Murphy Brandon M. , Jensen Daelin M. , Arnold Tiffany E. , Aguilar‐Valenzuela Renan , Hughes Jase , Posada Valentina , Nguyen Kimberly T. , Chu Vi T. , Tsai Kenneth Y. , Burd Craig J. , Burd Christin E. 
Published: June 2023

AbstractAn increasing number of cancer subtypes are treated with front‐line immunotherapy. However, approaches to overcome primary and acquired resistance remain limited. Preclinical mouse models are often used to investigate resistance mechanisms, novel drug combinations, and delivery methods; yet most of these models lack the genetic diversity and mutational patterns observed in human tumors. Here we describe a series of 13 C57BL/6J melanoma cell lines to address this gap in the field. The Ohio State University‐Moffitt Melanoma Exposed to Radiation (OSUMMER) cell lines are derived from mice expressing endogenous, melanocyte‐specific, and clinically relevant Nras driver mutations (Q61R, Q61K, or Q61L). Exposure of these animals to a single, non‐burning dose of ultraviolet B accelerates the onset of spontaneous melanomas with mutational patterns akin to human disease. Furthermore, in vivo irradiation selects against potent tumor antigens, which could prevent the outgrowth of syngeneic cell transfers. Each OSUMMER cell line possesses distinct in vitro growth properties, trametinib sensitivity, mutational signatures, and predicted antigenicity. Analysis of OSUMMER allografts shows a correlation between strong, predicted antigenicity and poor tumor outgrowth. These data suggest that the OSUMMER lines will be a valuable tool for modeling the heterogeneous responses of human melanomas to targeted and immune‐based therapies.
Assessment of the American Academy of Dermatology diagnostic criteria for pediatric atopic dermatitis and modification into a checkbox form: A cross‐sectional study
Authors: Udkoff Jeremy , Borok Jenna , Vaida Florin , Tang Bin , Matiz Catalina , Ahluwalia Jusleen , Russell Emma , Eichenfield Lawrence 
Published: June 2023

AbstractBackground/ObjectivesDiagnostic criteria for atopic dermatitis (AD) are limited in their performance and/or usability. The American Academy of Dermatology (AAD) consensus criteria include hierarchical categories of disease features to improve these metrics but have not been validated. Our objective was to create and validate a checkbox form of the AAD consensus criteria in the pediatric population.MethodsWe performed a cross‐sectional study of 100 pediatric patients with AD (n = 58) and diseases in the differential diagnosis of AD (n = 42).ResultsHaving three or more “Essential,” ≥2 “Important,” ≥1 “Associated” features of the AAD criteria was optimal for the diagnosis of AD in children. This combination was 91.4% (95% CI, 84.2%–98.6%) sensitive and 95.2% (88.8%–100%) specific. The UK working party criteria and the Hanifin–Rajka criteria had sensitivities of 96.6% (95% CI 91.9%–100%) and 98.3% (95% CI 94.9%–100%) and specificities of 83.3% (95% CI 72.1%–94.6%) and 71.4% (95% CI 57.8%–85.1%), respectively. The AAD criteria had significantly greater specificity than the Hanifin–Rajka criteria (p = .002).ConclusionsThis study represents an important step in validating the AAD consensus criteria and formulating a useable checkbox form for diagnosing AD in the pediatric population.
Narrowband ultraviolet B phototherapy for pityriasis lichenoides: A real‐life experience
Authors: Agaoglu Esra , Erdogan Hilal Kaya , Acer Ersoy , Saracoglu Zeynep Nurhan , Bilgin Muzaffer 
Published: June 2023

AbstractIntroductionPityriasis lichenoides (PL) is a papulosquamous disease affecting both children and adults, for which narrowband‐UVB (NB‐UVB) phototherapy is regarded as a commonly used treatment option. The aim of this study was to investigate the efficacy of NB‐UVB phototherapy in the management of PL and to compare response rates in pediatric and adult age groups.Materials and methodsThis observational, retrospective study included 20 PL patients (12 pityriasis lichenoides chronica; PLC, 8 pityriasis lichenoides et varioliformis acuta; PLEVA) who failed to respond to other treatment modalities. The data for this study were collected retrospectively from patient follow‐up forms in the phototherapy unit.ResultsA complete response (CR) was obtained in all pediatric patients with PL, while 53.8% of adult patients had achieved CR. The mean cumulative dose required to achieve the CR was higher in pediatric patients than adult patients with PL (p < .05). The CR was achieved in 6 (75%) of 8 PLEVA patients, while 8 (66.7%) of 12 PLC patients had reached to CR. The mean number of exposures for patients with PLC to achieve a CR was higher than patients with PLEVA (p < .05). Erythema was the most common adverse effect during phototherapy particularly in 5 (35.7%) of the patients with PL who had achieved CR.ConclusionsNB‐UVB is an effective and well‐tolerated treatment option for PL especially in diffuse types. A higher response can be obtained in children with higher cumulative dose. Patients with PLC may require more exposures for CR than patients with PLEVA.