bluuebunny/crossref_metadata_2025_split huggingface dataset:
I don’t want to think about it: a qualitative study of children (6–18 years) with rheumatic diseases and parents’ experiences with regular needle injections at home
Authors: Sørensen Kari , Skirbekk Helge , Kvarstein Gunnvald , Wøien Hilde 
Published: January 2021

Abstract
Background
Overall outcomes of pediatric rheumatic diseases (RD) have improved due to treatment with biologic agents and methotrexate. For many children, this treatment often entails regular needle injections. Pain and fear of needle injections are common in childhood, but how children and parents handle long-term needle injections at home has not been fully explored. This study aimed to explore how regular needle injections affect children with RD and their parents in their daily living.

Methods
This explorative qualitative study used individual interviews and focus groups to ensure a comprehensive investigation of the topic. Children aged 6 to 16 years (n = 7) and their parents (n = 8) were interviewed individually 4 to 6 months after the onset of needle injection treatment. The focus groups included children aged 11 to 17 years (n = 9) and parents (n = 8) with a minimum of 6 months of experience with injection treatment. Data were analyzed using thematic analysis.

Results
The main themes; “challenges,” “motivational factors,” and “routines” captured experiences and strategies that influenced the continuation of needle injections at home. Many children feared the moment immediately before the needle stick, although they had become accustomed to the pain. Most parents felt insecure about handling needle injections and lacked follow-up from healthcare providers. The children’s experience of treatment effects and self-confidence were essential to maintain motivation for further injections. A number of coping strategies helped children focus away from injection related discomfort, often discovered by chance. Facilitating firm routines and shared responsibility within families helped children develop self-confidence during the procedure. Children and parents struggled to find suitable information on the Internet.

Conclusions
Children and parents experienced long-term needle injections challenging. They used their own limited resources and cooperated within the families to create routines and to introduce coping strategies necessary to manage and keep up with the procedure. Although the injection itself was not experienced very painful, the discomfort, worries and impact on daily life represented far more than a little needle stick, and thus needs more attention from healthcare providers.
Systemic inflammation and chronic kidney disease in a patient due to the RNASEH2B defect
Authors: He Tingyan , Xia Yu , Yang Jun 
Published: January 2021

Abstract
Introduction
Aicardi-Goutières (AGS) is a rare immune dysregulated disease due to mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or IFIH1. Clinical features include basal ganglia calcifications, white matter abnormalities, and cerebral atrophy. Severe systemic inflammation and chronic kidney disease (CKD) are extremely rare in AGS. Herein, we report a patient presenting with systemic inflammation and CKD to broaden the clinical phenotype spectrum of the RNASEH2B defect.

Methods
All testing and molecular genetic analysis were performed after obtaining the informed consent of the parents. Demographic, clinical, and laboratory findings were abstracted from outpatient and inpatient encounters. Cerebral magnetic resonance imaging (MRI), computed tomography (CT) scans, and renal biopsy histopathology reports were reviewed and summarized. Whole exome sequencing (WES) was performed on peripheral blood cells. After exposure to cGAMP in vitro for 24 h, mRNA expression of 12 IFN-stimulated cytokine genes in PBMCs was assessed. Serum cytokine levels were detected by Milliplex.

Results
A 11-year-old girl presented with recurrent aseptic fever, arthritis, chilblains, failure to thrive, mild hearing loss, and neurological manifestations. Laboratory and immunologic findings demonstrated lymphopenia, low complement levels, positive autoantibodies, elevated levels of acute-phase reactants and inflammatory cytokines. Cerebral imaging showed cerebral atrophy, white matter abnormalities, and intracranial calcification. Renal biopsy showed glomerular sclerosis in 3 of 14 glomeruli, infiltration of lymphocytes and other mononuclear cells. WES revealed a homozygous and heterozygous mutations in RNASEH2B. Over-expression of IFN-stimulated cytokine genes was observed, including IFI44, IFI27, IFIT1, IFIT2, IFIT3, ISG15, OAS1, and SIGLEC1.

Conclusions
To date, only two cases with AGS have been reported to have renal disease. Here, we describe a patient with both homozygous and heterozygous variants in RNASEH2B, presenting with neurological manifestations, persistently systemic autoinflammation, and CKD. CKD has never been reported in patients with AGS due to the RNASEH2B defect.

Trial registration
Not applicable; this was a retrospective study.
Gender differences in externalizing and internalizing problems in Singaporean children and adolescents with attention-deficit/hyperactivity disorder
Authors: Lau Tsz Wing Ivy , Lim Choon Guan , Acharryya Sanchalika , Lim-Ashworth Nikki , Tan Yi Ren , Fung Shuen Sheng Daniel 
Published: January 2021

AbstractBackgroundStudies on gender differences in attention-deficit/hyperactivity disorder (ADHD) comorbidities in the Asian populations have been limited and previous studies have shown inconclusive findings. Singapore is a city-state country in Southeast Asia with a population of 5.7 million. This study examined gender differences in internalizing and externalizing problems in Singaporean children and adolescents with ADHD. The plausible social factors underlying the gender differences were discussed.MethodsA total of 773 participants (aged 6 to 18, 88% males) newly diagnosed with ADHD were recruited from the largest public child and adolescent psychiatric center in Singapore. Their internalizing and externalizing problems were assessed using the Child Behavioral Checklist and Teacher’s Report Form by parents and teachers respectively. Demographics and relevant social factors were collected using parent questionnaires.ResultsFemales with ADHD were reported to have less delinquent and aggressive behavior but more depressive symptoms than their male counterparts, similar to findings in the Western literature. Gender remained a significant predictor of externalizing problem after controlling for other factors. Lower socioeconomic status and parental use of physical punishment were significant predictors of both internalizing and externalizing problems.ConclusionsGender differences in ADHD comorbidities do exist in the Asian clinical population. The lack of externalizing symptoms in females with ADHD has made timely referral and diagnosis challenging. More research is needed in understanding the gender differences in ADHD and the biopsychosocial mechanism underlying the differences in order to improve the detection of ADHD in females.
Mice carrying a schizophrenia-associated mutation of the Arhgap10 gene are vulnerable to the effects of methamphetamine treatment on cognitive function: association with morphological abnormalities in striatal neurons
Authors: Hada Kazuhiro , Wulaer Bolati , Nagai Taku , Itoh Norimichi , Sawahata Masahito , Sobue Akira , Mizoguchi Hiroyuki , Mori Daisuke , Kushima Itaru , Nabeshima Toshitaka , Ozaki Norio , Yamada Kiyofumi 
Published: January 2021

AbstractWe recently found a significant association between exonic copy-number variations in the Rho GTPase activating protein 10 (Arhgap10) gene and schizophrenia in Japanese patients. Special attention was paid to one patient carrying a missense variant (p.S490P) in exon 17, which overlapped with an exonic deletion in the other allele. Accordingly, we generated a mouse model (Arhgap10 S490P/NHEJ mice) carrying a missense variant and a coexisting frameshift mutation. We examined the spatiotemporal expression of Arhgap10 mRNA in the brain and found the highest expression levels in the cerebellum, striatum, and nucleus accumbens (NAc), followed by the frontal cortex in adolescent mice. The expression levels of phosphorylated myosin phosphatase-targeting subunit 1 and phosphorylated p21-activated kinases in the striatum and NAc were significantly increased in Arhgap10 S490P/NHEJ mice compared with wild-type littermates. Arhgap10 S490P/NHEJ mice exhibited a significant increase in neuronal complexity and spine density in the striatum and NAc. There was no difference in touchscreen-based visual discrimination learning between Arhgap10 S490P/NHEJ and wild-type mice, but a significant impairment of visual discrimination was evident in Arhgap10 S490P/NHEJ mice but not wild-type mice when they were treated with methamphetamine. The number of c-Fos-positive cells was significantly increased after methamphetamine treatment in the dorsomedial striatum and NAc core of Arhgap10 S490P/NHEJ mice. Taken together, these results suggested that schizophrenia-associated Arhgap10 gene mutations result in morphological abnormality of neurons in the striatum and NAc, which may be associated with vulnerability of cognition to methamphetamine treatment.
Molecular characterization of Cryptosporidium isolates from humans in Ontario, Canada
Authors: Guy Rebecca A. , Yanta Christine A. , Muchaal Pia K. , Rankin Marisa A. , Thivierge Karine , Lau Rachel , Boggild Andrea K. 
Published: January 2021

Abstract
Background
Cryptosporidiosis is a gastrointestinal disease with global distribution. It has been a reportable disease in Canada since 2000; however, routine molecular surveillance is not conducted. Therefore, sources of contamination are unknown. The aim of this project was to identify species and subtypes of Cryptosporidium in clinical cases from Ontario, the largest province in Canada, representing one third of the Canadian population, in order to understand transmission patterns.

Methods
A total of 169 frozen, banked, unpreserved stool specimens that were microscopy positive for Cryptosporidium over the period 2008–2017 were characterized using molecular tools. A subset of the 169 specimens were replicate samples from individual cases. DNA was extracted directly from the stool and nested PCR followed by Sanger sequencing was conducted targeting the small subunit ribosomal RNA (SSU) and glycoprotein 60 (gp60) genes.

Results
Molecular typing data and limited demographic data were obtained for 129 cases of cryptosporidiosis. Of these cases, 91 (70.5 %) were due to Cryptosporidium parvum and 24 (18.6%) were due to Cryptosporidium hominis. Mixed infections of C. parvum and C. hominis occurred in four (3.1%) cases. Five other species observed were Cryptosporidium ubiquitum (n = 5), Cryptosporidium felis (n = 2), Cryptosporidium meleagridis (n = 1), Cryptosporidium cuniculus (n = 1) and Cryptosporidium muris (n = 1). Subtyping the gp60 gene revealed 5 allelic families and 17 subtypes of C. hominis and 3 allelic families and 17 subtypes of C. parvum. The most frequent subtype of C. hominis was IbA10G2 (22.3%) and of C. parvum was IIaA15G2R1 (62.4%).

Conclusions
The majority of isolates in this study were C. parvum, supporting the notion that zoonotic transmission is the main route of cryptosporidiosis transmission in Ontario. Nonetheless, the observation of C. hominis in about a quarter of cases suggests that anthroponotic transmission is also an important contributor to cryptosporidiosis pathogenesis in Ontario.

Graphical Abstract
Lipoptena fortisetosa as a vector of Bartonella bacteria in Japanese sika deer (Cervus nippon)
Authors: Sato Shingo , Kabeya Hidenori , Ishiguro Sayuri , Shibasaki Yasuhiro , Maruyama Soichi 
Published: January 2021

AbstractBackgroundTwo species of deer ked (Lipoptena cerviandL. mazamae) have been identified as vectors ofBartonellabacteria in cervids in Europe and the USA. In an earlier study we showed that Japanese sika deer (Cervus nippon) harbor threeBartonellaspecies, namelyB. capreoli(lineage A) and two novelBartonellaspecies (lineages B and C); however, there is currently no information on the vector ofBartonellabacteria in sika deer. The aim of this study was to clarify potential vectors ofBartonellain Japanese sika deer.MethodsThirty-eight wingless deer keds (L. fortisetosa) and 36 ticks (HaemaphysalisandIxodesspecies) were collected from sika deer. The prevalence ofBartonellain the arthropods was evaluated by real-time PCR targeting the 16S−23S internal transcribed spacer (ITS) and by culture of the organisms. The total number ofBartonellabacteria were quantified using real-time PCR. The distribution ofBartonellabacteria in deer ked organs was examined by immunofluorescence analysis. The relationship ofBartonellastrains isolated from sika deer and arthropods were examined by a phylogenetic analysis based on concatenated sequences of thegltA,rpoB,ftsZ, andribCgenes, followed by a BLAST search forgltAandrpoB.ResultsBartonellaprevalence in deer keds was 87.9% by real-time PCR and 51.5% in culture and that in the ticks was 8.3% by real-time PCR and 2.8% in culture. The mean number ofBartonellabacteria per ked was calculated to be 9.2 × 105cells.Bartonellaaggregates were localized in the midgut of the keds. The phylogenetic analysis and BLAST search showed that both the host deer and the keds harbored twoBartonellaspecies (lineages B and C), whileB. capreoli(lineage A) was not detected in the keds. Two novelBartonellaspecies (lineages D and E) were isolated from one ked.ConclusionsLipoptena fortisetosalikely serves as a vector of at least twoBartonellaspecies (lineages B and C), whereas ticks do not seem to play a significant role in the transmission ofBartonellabetween sika deer based on the lower detection rates ofBartonellain ticks compared to keds.Bartonellaspecies in lineages D and E appear to beL. fortisetosa-specific strains.Graphical Abstract
Proinflammatory T cell polarization is already present in patients with early knee osteoarthritis
Authors: Rosshirt Nils , Trauth Richard , Platzer Hadrian , Tripel Elena , Nees Timo A. , Lorenz Hanns-Martin , Tretter Theresa , Moradi Babak 
Published: January 2021

AbstractBackgroundInvestigating the pathophysiological mechanisms of early osteoarthritis (OA) is of utmost interest since this stage holds the strongest promise for therapeutic interventions. The aims of this study were to analyze if synovial inflammation is already present in early OA and to characterize the involved cell populations, by investigating synovial fluid (SF) and synovial membrane (SM) of early OA patients for the presence and polarization status of CD4 T cells.MethodsA quantitative analysis of CD4+T cell infiltration in SF and SM compared to peripheral blood (PB) was performed in patients with early stages of OA. We further investigated intracellular staining (ICS), surface marker, and chemokine receptor expression profiles of CD4+T cells in SF, SM, and PB, as well as cytokine expression in native SF and PB. Matched samples of SF, SM, and PB were harvested from 40 patients with early OA at the time of surgery. Early OA was confirmed by independent surgeons intraoperatively. Samples were analyzed by flow cytometry for surface markers and cytokines, which are preferentially expressed by distinct T cell subsets (Th1, Th2, Th17, regulatory T cells). Furthermore, we analyzed native SF and PB supernatants using MACSPlex for multiple cytokine expression profiles.ResultsSF and SM showed a distinct infiltration of CD4+T lymphocytes, with significantly increased expression of chemokine receptors CXCR3/CCR5, cytokine IFN-γ (preferentially expressed by Th1 cells), and CD161 (preferentially expressed by IL-17 producing Th17 cells) compared to PB. Furthermore, the percentage of CD4+T cells polarized to Treg was significantly increased in SM compared to SF and PB. No significant differences were observed for CCR3 and CCR4 (preferentially expressed by Th2 cells), although IL-4 values were significantly higher in SM and SF compared to PB. Cytokine analysis showed comparable results between PB and SF, with only IL-6 being significantly increased in SF.ConclusionsEarly OA joints show already significant inflammation through CD4+T cell infiltration, with predominant Th1 cell polarization. Inflammation seems to be driven by direct proinflammatory cell interaction. Cytokine signaling seems to be negligible at the site of inflammation in early OA, with only IL-6 being significantly increased in SF compared to PB.
The serum levels of circulating matrix metalloproteinase MMP-9, MMP-2/TIMP-2 complex and TIMP-1 do not change significantly during normal pregnancy: a pilot study
Authors: Nissi Ritva , Santala Markku , Talvensaari-Mattila Anne 
Published: January 2021

Abstract
Objective
Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. They exhibit proteolytic activity implicating the efficiency of trophoblast invasion to the uterine wall involving marked hemodynamic and uterine changes. In this pilot study sera of 13 women with normal pregnancy was analyzed to evaluate the usage of MMPs as diagnostic tool. The concentrations of circulating MMP-9, MMP-2/TIMP-2 complex and TIMP-1 in different time points during normal pregnancy has not been studied. The serum levels of MMP-9, TIMP-1, TIMP-2 and MMP-2/TIMP-2 complex were determined by enzyme-linked immunosorbent assay (ELISA). Using the same method, we have shown that serum MMPs are elevated in spontaneous early pregnancy failure as compared to normal pregnancy.

Results
The serum levels of MMP-9 and TIMP-1 were stable throughout pregnancy. The level of MMP-2/TIMP-2 complex was slightly increased after week 15 without statistical significance. For our best knowledge, this is a first study of the serum levels of MMP-9, MMP-2/TIMP-2 and TIMP-1 on different time points during normal pregnancy. Further measurements with the correlation to the outcome of the pregnancy are needed.
A pilot trial of human amniotic fluid for the treatment of COVID-19
Authors: Selzman Craig H. , Tonna Joseph E. , Pierce Jan , Vargas Camila , Skidmore Chloe , Lewis Giavonni , Hatton Nathan D. , Phillips John D. 
Published: January 2021

Abstract
Objective
Vertical transmission from SARS CoV-2-infected women is uncommon and coronavirus has not been detected in amniotic fluid. Human amniotic products have a broad immune-mediating profile. Observing that many COVID-19 patients have a profound inflammatory response to the virus, we sought to determine the influence of human amniotic fluid (hAF) on hospitalized patients with COVID-19.

Results
A 10-patient case series was IRB-approved to study the impact of hAF on hospitalized patients with documented COVID-19. Nine of the 10 patients survived to discharge, with one patient succumbing to the disease when enrolled on maximal ventilatory support and severe hypoxia. The study design was altered by the IRB such that the last 6 patients received higher dose of intravenous hAF. In this latter group, patients that had observed reductions in C-reactive protein were associated with improved clinical outcomes. No hAF-related adverse events were noted. Acknowledging some of the inherent limitations of this case series, these results inform and catalyze a larger scaled randomized prospective trial to further investigate hAF as a therapy for COVID-19.
Trial Registration ClinicalTrials.gov: NCT04319731; March 23, 2020
Application of Airy beam light sheet microscopy to examine early neurodevelopmental structures in 3D hiPSC-derived human cortical spheroids
Authors: Adhya Dwaipayan , Chennell George , Crowe James A. , Valencia-Alarcón Eva P. , Seyforth James , Hosny Neveen A. , Yasvoina Marina V. , Forster Robert , Baron-Cohen Simon , Vernon Anthony C. , Srivastava Deepak P. 
Published: January 2021

AbstractBackgroundThe inability to observe relevant biological processes in vivo significantly restricts human neurodevelopmental research. Advances in appropriate in vitro model systems, including patient-specific human brain organoids and human cortical spheroids (hCSs), offer a pragmatic solution to this issue. In particular, hCSs are an accessible method for generating homogenous organoids of dorsal telencephalic fate, which recapitulate key aspects of human corticogenesis, including the formation of neural rosettes—in vitro correlates of the neural tube. These neurogenic niches give rise to neural progenitors that subsequently differentiate into neurons. Studies differentiating induced pluripotent stem cells (hiPSCs) in 2D have linked atypical formation of neural rosettes with neurodevelopmental disorders such as autism spectrum conditions. Thus far, however, conventional methods of tissue preparation in this field limit the ability to image these structures in three-dimensions within intact hCS or other 3D preparations. To overcome this limitation, we have sought to optimise a methodological approach to process hCSs to maximise the utility of a novel Airy-beam light sheet microscope (ALSM) to acquire high resolution volumetric images of internal structures within hCS representative of early developmental time points.ResultsConventional approaches to imaging hCS by confocal microscopy were limited in their ability to image effectively into intact spheroids. Conversely, volumetric acquisition by ALSM offered superior imaging through intact, non-clarified, in vitro tissues, in both speed and resolution when compared to conventional confocal imaging systems. Furthermore, optimised immunohistochemistry and optical clearing of hCSs afforded improved imaging at depth. This permitted visualization of the morphology of the inner lumen of neural rosettes.ConclusionWe present an optimized methodology that takes advantage of an ALSM system that can rapidly image intact 3D brain organoids at high resolution while retaining a large field of view. This imaging modality can be applied to both non-cleared and cleared in vitro human brain spheroids derived from hiPSCs for precise examination of their internal 3D structures. This process represents a rapid, highly efficient method to examine and quantify in 3D the formation of key structures required for the coordination of neurodevelopmental processes in both health and disease states. We posit that this approach would facilitate investigation of human neurodevelopmental processes in vitro.