bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental factors associated with juvenile idiopathic inflammatory myopathy clinical and serologic phenotypes
Authors: Scalabrini Jonathan C. , Schiffenbauer Adam I. , Farhadi Payam Noroozi , Volochayev Rita , Bayat Nastaran , Jansen Anna , Targoff Ira N. , Miller Frederick W. , Rider Lisa G. 
Published: April 2022

Abstract
Background
Environmental exposures have been associated with the juvenile idiopathic inflammatory myopathies (JIIM). We undertook a questionnaire-based study to evaluate patient-reported exposures as possible risk factors for JIIM.

Findings
One-hundred-seven patients with JIIM were enrolled in a myositis natural history protocol and completed environmental questionnaires. Frequencies of exposures in clinical and myositis-specific autoantibody (MSA) groups were examined. Patients with juvenile dermatomyositis (JDM) and juvenile connective tissue myositis (JCTM) more frequently received an immunization within 1 year of diagnosis compared to juvenile polymyositis (57.5 and 71.4% vs 0.0%, p ≤ 0.017). JCTM patients were more often underweight at diagnosis relative to JDM patients (42.9% vs 7.0%, p = 0.002). MSA-negative patients more frequently had gastroenteritis within a year of diagnosis compared to patients with anti-MDA5 autoantibodies (28.6% vs 0.0%, p = 0.032). Heavy exercise was more frequent in MSA-negative and anti-MDA5 groups compared to the anti-TIF-1 autoantibody group (42.9 and 35.3% vs. 9.0%, p ≤ 0.047). Medications received within 1 year of diagnosis were more frequent in MSA-negative patients relative to those with anti-MDA5 autoantibodies (92.9% vs. 52.8% p = 0.045). Being breastfed > 6 months was more frequent in MSA-negative patients (88.9%) compared to anti-TIF-1 and anti-MDA5 autoantibody groups (41.2 and 28.6%, p ≤ 0.036).

Conclusions
Certain environmental exposures prior to diagnosis differed among clinical and serologic subgroups of JIIM, suggesting additional exposures to be explored as possible risk factors for JIIM phenotypes.
Soluble TREM2 is associated with death and cardiovascular events after acute ischemic stroke: an observational study from CATIS
Authors: Lu Yaling , Zhao Yu , Zhang Qi , Fang Chongquan , Bao Anran , Dong Wenjing , Peng Yanbo , Peng Hao , Ju Zhong , He Jiang , Zhang Yonghong , Xu Tan , Zhong Chongke 
Published: April 2022

Abstract
Background
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2), which reflects microglia activation, has been reported closely associated with neuronal injury and neuroinflammation. We aimed to prospectively investigate the associations between plasma sTREM2 and clinical outcomes in acute ischemic stroke (AIS) patients.

Methods
Study participants were from the China Antihypertensive Trial in Acute Ischemic Stroke, plasma sTREM2 levels in the acute phase of AIS were measured in 3285 participants. The study outcomes were death, cardiovascular events and severe disability at 1 year after AIS. Cox proportional hazards models or logistic regression models were performed to examine the associations of plasma sTREM2 and clinical outcomes.

Results
After 1-year follow-up, 288 participants (8.8%) experienced cardiovascular events or died. Multivariable-adjusted hazard ratios or odds ratios (95% confidence intervals) for the highest quartile of sTREM2 were 1.57 (1.11–2.21) for the composite outcome of death and cardiovascular events, 1.68 (1.09–2.60) for death, and 1.53 (1.08–2.18) for death or severe disability compared to the lowest quartile. Moreover, incorporation sTREM2 into traditional risk factors model significantly improved risk prediction of the composite outcome of death and cardiovascular events as evidenced by net reclassification index and integrated discrimination improvement (all p values < 0.05). There were joint effects of sTREM2 and galectin-3 on death and cardiovascular events. Participants with simultaneous elevation of sTREM2 and galectin-3 levels had the highest risk of the composite outcome of death and cardiovascular events.

Conclusions
Elevated sTREM2 levels were independently associated with increased risks of death and cardiovascular events after AIS.
Microglial cell response in α7 nicotinic acetylcholine receptor-deficient mice after systemic infection with Escherichia coli
Authors: Hoogland Inge C. M. , Yik Jutka , Westhoff Dunja , Engelen-Lee Joo-Yeon , Valls Seron Merche , Man Wing Kit , Houben-Weerts Judith H. P. M. , Tanck Michael W. T. , van Westerloo David J. , van der Poll Tom , van Gool Willem A. , van de Beek Diederik 
Published: April 2022

Abstract
Background
Development of neurodegeneration in older people has been associated with microglial cell activation triggered by systemic infection. We hypothesize that α7 nicotinic acetylcholine receptor (α7nAChR) plays an important role in regulation of this process.

Methods
8- to 10-week-old male wild-type (WT) and α7nAChR knock-out (α7nAChR−/−) mice were intraperitoneally inoculated with live Escherichia (E.) coli or saline. After inoculation, all mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h and killed at 2 or 3 days. The microglial response was characterized by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry. To quantify inflammatory response, mRNA expression of pro- and anti-inflammatory mediators was measured in brain and spleen.

Results
We observed no differences in Iba-1 positive cell number or morphology and flow cytometry (CD11b, CD45 and CD14) of microglial cells between WT and α7nAChR−/− mice after systemic infection. Infected α7nAChR−/− mice showed significantly higher mRNA expression in brain for tumor necrosis factor alpha (TNF-α) at day 2 and 3, interleukin 6 (IL-6) at day 2 and monocyte chemotactic protein 1 (MCP-1) and suppressor of cytokine signaling 1 (SOCS1) at day 3, there was significantly lower mRNA expression in brain for mitogen-activated protein kinase 1 (MAPK1) at day 2 and 3, high-mobility group 1 (HMGB-1) and CD11b at day 2, and deubiquitinase protein A20 (A20) at day 3 compared to infected WT mice.

Interpretation
Loss of function of α7nAChR during systemic infection led to an increased expression of TNF-α and IL-6 in brain after systemic infection with E. coli, but not to distinct differences in microglial cell number or morphological activation of microglia.
A subterminal growth zone at arm tip likely underlies life-long indeterminate growth in brittle stars
Authors: Mashanov Vladimir , Whaley Lauren , Davis Kenneth , Heinzeller Thomas , Machado Denis Jacob , Reid Robert W. , Kofsky Janice , Janies Daniel 
Published: April 2022

AbstractBackgroundEchinoderms are a phylum of marine invertebrates with close phylogenetic relationships to chordates. Many members of the phylum Echinodermata are capable of extensive post-traumatic regeneration and life-long indeterminate growth. Different from regeneration, the life-long elongation of the main body axis in adult echinoderms has received little attention. The anatomical location and the nature of the dividing progenitor cells contributing to adults’ growth is unknown.ResultsWe show that the proliferating cells that drive the life-long growth of adult brittle star arms are mostly localized to the subterminal (second from the tip) arm segment. Each of the major anatomical structures contains dividing progenitors. These structures include: the radial nerve, water-vascular canal, and arm coelomic wall. Some of those proliferating progenitor cells are capable of multiple rounds of cell division. Within the nervous system, the progenitor cells were identified as a subset of radial glial cells that do not express Brn1/2/4, a transcription factor with a conserved role in the neuronal fate specification. In addition to characterizing the growth zone and the nature of the precursor cells, we provide a description of the microanatomy of the four distal-most arm segments contrasting the distal with the proximal segments, which are more mature.ConclusionsThe growth of the adult brittle star arms occurs via proliferation of progenitor cells in the distal segments, which are most abundant in the second segment from the tip. At least some of the progenitors are capable of multiple rounds of cell division. Within the nervous system the dividing cells were identified as Brn1/2/4-negative radial glial cells.
Correlation between quality and geographical origins of Leonuri Herba revealed by the qualitative fingerprint profiling and quantitative determination of chemical components
Authors: Lam Kelly Yinching , Wang Yinghao , Lam Tszking , Ku Chuenfai , Yeung Wingping , Zhao Zhongzhen 
Published: April 2022

Abstract
Background
Leonuri Herba (Yimucao) is a very common Chinese herbs for treating menstrual and maternal diseases for thousands of years in China. However, the herb collected in different origins was easily found in the markets which induce the unstable quality for clinic use. In this study, a comprehensive strategy of using multiple chromatographic analysis and chemometric analysis was firstly investigated for chemical discrimination of Leonuri Herba from different geographical origins.

Methods
UHPLC-QTOF-MS/MS was applied to identify the peaks of Leonuri Herba and chemical fingerprints were established in 30 batches from different geographical origins. Meanwhile, dissimilarities of chemical compositions among different origins were further investigated by principal component analysis and cluster analysis. And a quantitative UHPLC-QTOF-MS/MS approach were established to investigate the potential marker for quality control of Leonuri Herba.

Results
A total of 49 chromatographic peaks of Leonuri Herba were identified by UHPLC-QTOF-MS/MS. Leonuri Herba were classified into four categories, and eight major compounds detected could be used as chemical markers for discrimination. Also, the eight components, including leonurine, 4',5-dihydroxy-7-methoxyflavone, rutin, hyperoside, apigenin, quercetin, kaempferol and salicylic acid, were simultaneously quantified using the extracting ion mode of UHPLC-QTOF-MS/MS.

Conclusion
The current strategy not only clearly expounded the correlation between quality and geographical origins of Leonuri Herba, but also provided a fast, accurate and comprehensive qualitative and quantitative method for assessing the quality of Leonuri Herba.
The national economic burden of rare disease in the United States in 2019
Authors: Yang Grace , Cintina Inna , Pariser Anne , Oehrlein Elisabeth , Sullivan Jamie , Kennedy Annie 
Published: April 2022

Abstract
Background
To provide a comprehensive assessment of the total economic burden of rare diseases (RD) in the United States (U.S.) in 2019. We followed a prevalence-based approach that combined the prevalence of 379 RDs with the per-person direct medical and indirect costs, to derive the national economic burden by patient age and type of RD. To estimate the prevalence and the direct medical cost of RD, we used claims data from three sources: Medicare 5% Standard Analytical File, Transformed Medicaid Statistical Information System, and Optum claims data for the privately insured. To estimate indirect and non-medical cost components, we worked with the rare disease community to design and implement a primary survey.

Results
There were an estimated 15.5 million U.S. children (N = 1,322,886) and adults (N = 14,222,299) with any of the 379 RDs in 2019 with a total economic burden of $997 billion, including a direct medical cost of $449 billion (45%), $437 billion (44%) in indirect costs, $73 billion in non-medical costs (7%), and $38 billion (4%) in healthcare costs not covered by insurance. The top drivers for excess medical costs associated with RD are hospital inpatient care and prescription medication; the top indirect cost categories are labor market productivity losses due to absenteeism, presenteeism, and early retirement.

Conclusions
Our findings highlight the scale of the RD economic burden and call for immediate attention from the scientific communities, policy leaders, and other key stakeholders such as health care providers and employers, to think innovatively and collectively, to identify new ways to help improve the care, management, and treatment of these often-devastating diseases.
Increased COVID-19 mortality rate in rare disease patients: a retrospective cohort study in participants of the Genomics England 100,000 Genomes project
Authors: Zhang Huayu , Thygesen Johan H. , Shi Ting , Gkoutos Georgios V. , Hemingway Harry , Guthrie Bruce , Wu Honghan ,   Genomics England Research Consortium
Published: April 2022

Abstract
Background
Several common conditions have been widely recognised as risk factors for COVID-19 related death, but risks borne by people with rare diseases are largely unknown. Therefore, we aim to estimate the difference of risk for people with rare diseases comparing to the unaffected.

Method
To estimate the correlation between rare diseases and COVID-19 related death, we performed a retrospective cohort study in Genomics England 100k Genomes participants, who tested positive for Sars-Cov-2 during the first wave (16-03-2020 until 31-July-2020) of COVID-19 pandemic in the UK (n = 283). COVID-19 related mortality rates were calculated in two groups: rare disease patients (n = 158) and unaffected relatives (n = 125). Fisher’s exact test and logistic regression was used for univariable and multivariable analysis, respectively.

Results
People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21– 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65–5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61–10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60–11.08]).

Conclusions
Our results showed that rare disease patients, especially ones affected by neurology and neurodevelopmental disorders, in the Genomics England cohort had increased risk of COVID-19 related death during the first wave of the pandemic in UK. The high risk is likely associated with rare diseases themselves, while we cannot rule out possible mediators due to the small sample size. We would like to raise the awareness that rare disease patients may face increased risk for COVID-19 related death. Proper considerations for rare disease patients should be taken when relevant policies (e.g., returning to workplace) are made.
Multidisciplinary care for patients with epidermolysis bullosa from birth to adolescence: experience of one Italian reference center
Authors: Retrosi Chiara , Diociaiuti Andrea , De Ranieri Cristiana , Corbeddu Marialuisa , Carnevale Claudia , Giancristoforo Simona , Marchili Maria Rosaria , Salvatori Guglielmo , Atti Marta Luisa Ciofi degli , El Hachem Maya , Raponi Massimiliano 
Published: April 2022

Abstract
Background
Epidermolysis bullosa (EB) is a disabling and chronic genodermatosis characterized by mucocutaneous fragility with blister formation after minimal trauma. Severity ranges between very mild forms to extremely severe or lethal subtypes. Depending on disease subtypes, blisters may be localized also in larynx, bladder, esophagus, and most frequent disease complications are malnutrition, chronic anemia, osteoporosis, limb contracture and early development of squamous cell carcinomas. EB is classified into four major groups: EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler EB (KEB). No specific treatment is available; however, a multidisciplinary management is mandatory in order to treat the lesions, to prevent complication, and to give a psychological support to the patient and family members.

Objective
To report the experience on a therapeutic education plan of an Italian reference center for epidermolysis bullosa in the last 30 years.

Methods
In our study we included all patients with EB from 1990 to the present, dividing them into three age groups (< 5 years, > 5–12 years and > 12–18 years). The therapeutic plan involved all multidisciplinary team members, since born until adolescence. The multidisciplinary team has been progressively established; the dermatologists act as patient case manager, in collaboration with the pediatrician, endocrinologist, dietician, dentist, plastic surgeon, digestive surgeon, geneticist, psychologist and a dedicated nurse. Other dedicated specialists are involved upon patient needs.

Results
Two hundred fifteen patients have been recruited and followed in our hospital since 1990. One hundred forty patients (65%) are on follow-up, 27 patients (13%) died and only 11 (5%) were lost to follow-up. Our patients manifested the specific complications related to their EB subtype in keeping with the data reported in the literature. Eighteen (8%) patients affected with JEB severe died within the first year of life, 9 patients (5%) died for squamous cell carcinoma in adulthood and were affected with recessive DEB; only 1 patient died for squamous cell carcinoma at the age of 16.

Conclusions
An adequate management of EB patients require a multidisciplinary approach with an educational plan to guarantee an appropriate treatment and to support and accompany patients and their families since birth along life. The dynamic educational plan adopted in our hospital showed good clinical and psychological outcome in our population, allowing adherence to treatment, reducing the frequency of complications and improving life expectancy and quality of life.
Health belief model for empowering parental toothbrushing and sugar intake control in reducing early childhood caries among young children—study protocol for a cluster randomized controlled trial
Authors: Wang Ketian , Lee Gillian Hiu Man , Liu Pei , Gao Xiaoli , Wong Samuel Yeung Shan , Wong May Chun Mei 
Published: April 2022

Abstract
Background
It has been recognized that oral health education for parents is critical for preventing early childhood caries (ECC). Few parents practiced caries prevention procedures for their children in daily life, though. A novel intervention scheme using mobile messages will be developed in this study under the framework of the health belief model (HBM). The objective of the present randomized clinical trial (RCT) is to evaluate the effectiveness of the new scheme in promoting oral health of young children by reducing dental caries.

Methods
This RCT will involve 26–36 child care centers or kindergartens with nursery classes (clusters) located in Hong Kong. A total of 518–628 child-parent dyads (child age 18–30 months) will be recruited and randomly allocated at the cluster level into the test or control group with a 1:1 ratio. For parents in the test group, the intervention will consist of a set of HBM-based text messages sent regularly in 48 weeks. A standard text message will be sent to the parents in the control group in the first week. The primary outcome will be dental caries measured by dmft/dmfs of the children after 2 years (around 4 years of age). The secondary outcomes will be toothbtushing and sugar intake.

Discussion
HBM-based intervention via a low-cost text messaging vehicle may serve as a viable way to empower parents to establish proper oral health behaviors for their children and safeguard the oral health of children in Hong Kong.

Trial registration
ClinicalTrials.govNCT04665219. Registered on 11 December 2020.
Effect of novel training to normalize altered finger force direction post-stroke: study protocol for a double-blind randomized controlled trial
Authors: Seo Na Jin , Kamper Derek G. , Ramakrishnan Viswanathan , Harvey Jillian B. , Finetto Christian , Schranz Christian , Scronce Gabrielle , Coupland Kristen , Howard Keith , Blaschke Jenna , Baker Adam , Meinzer Caitlyn , Velozo Craig A. , Adams Robert J. 
Published: April 2022

Abstract
Background
Functional task performance requires proper control of both movement and force generation in three-dimensional space, especially for the hand. Control of force in three dimensions, however, is not explicitly treated in current physical rehabilitation. To address this gap in treatment, we have developed a tool to provide visual feedback on three-dimensional finger force. Our objective is to examine the effectiveness of training with this tool to restore hand function in stroke survivors.

Methods
Double-blind randomized controlled trial. All participants undergo 18 1-h training sessions to practice generating volitional finger force of various target directions and magnitudes. The experimental group receives feedback on both force direction and magnitude, while the control group receives feedback on force magnitude only. The primary outcome is hand function as measured by the Action Research Arm Test. Other outcomes include the Box and Block Test, Stroke Impact Scale, ability to direct finger force, muscle activation pattern, and qualitative interviews.

Discussion
The protocol for this clinical trial is described in detail. The results of this study will reveal whether explicit training of finger force direction in stroke survivors leads to improved motor control of the hand. This study will also improve the understanding of neuromuscular mechanisms underlying the recovery of hand function.

Trial registration
ClinicalTrials.govNCT03995069. Registered on June 21, 2019