bluuebunny/crossref_metadata_2025_split huggingface dataset:
Australian clinicians’ perceptions of patients with very high risk of fracture
Authors: Girgis Christian M. , Choi Yoonah , Ebeling Peter R. 
Published: March 2022

Abstract

Background: International osteoporosis guidelines have recommended treatment approaches based on fracture risk stratification, in particular anabolic therapy for patients with very high risk (VHR) of fragility fracture. The aim of this study was to summarize Australian clinicians’ perceptions of patients at VHR of fracture. Methods: Australian clinicians invited to educational webinars on anabolic treatments for osteoporosis were surveyed in March and April 2021. The survey included 23 questions on patient characteristics and treatment approaches for a patient that the survey participant had most recently seen and identified to be at VHR of fracture. Results: Of the 268 clinician attendees who were invited to complete the post-webinar surveys, 67 (25%) responded and permitted publication of aggregated data. A typical patient perceived to have a VHR of fracture was a woman in her 80s, living at home, who had been diagnosed with osteoporosis between 5 and 10 years ago, and received treatment for 1 to 5 years’ duration, most commonly denosumab. The patient frequently had a T-score below –3.0 SD (standard deviation), multiple fragility fractures and most commonly ­suffered a vertebral fracture in the past 12 months, whilst on an adequate regimen of osteoporosis medication. There was a mismatch between the patient being eligible for anabolic therapy (64.2%) and actually having been prescribed an anabolic treatment in the past (20.9%).Conclusions: This study provided a snapshot of Australian clinicians’ perceptions of patients with a VHR of fracture. Local reimbursement criteria heavily influenced perceptions of Australian clinicians on VHR and the use of anabolic agents. The mismatch between patients deemed eligible for reimbursed anabolic therapy and those prescribed an anabolic agent, suggest treatment inertia. Further qualitative exploration of the reasons for the clinicians’ perceptions are needed. Differing definitions for VHR need inclusion in local osteoporosis guidelines.
CRELD2 is a novel modulator of calcium mobilisation and calcineurin- NFAT signalling during osteoclast differentiation
Authors: Duxfield Adam , Munkley Jennifer , Briggs Michael D. , Dennis Ella P. 
Published: March 2022

Abstract
Cysteine rich with epidermal growth factor (EGF)-like domains 2 (CRELD2) is an endoplasmic reticulum (ER) resident chaperone protein with calcium binding properties. CRELD2 is an ER-stress regulated gene that has been implicated in the pathogenesis of skeletal dysplasias and has been shown to play an important role in the differentiation of chondrocytes and osteoblasts. Despite CRELD2 having an established role in skeletal development and bone formation, its role in osteoclasts is currently unknown. Here we show for the first time that CRELD2 plays a novel role in trafficking transforming growth factor beta 1 (TGF-β1), which is linked to an upregulation in the expression of Nfat2, the master regulator of osteoclast differentiation in early osteoclastogenesis. Despite this finding, we show that CRELD2 is dispensable for osteoclastogenesis. Indeed, the overexpression of Creld2 impaired osteoclast differentiation due to a reduction in the activity of the calcium-dependant phosphatase calcineurin. This in turn led to a subsequent block in the dephosphorylation of nuclear factor of activated T cells 1 (NFATc1) dephosphorylation preventing its nuclear localisation and activation as a pro-osteoclastogenic transcription factor. Our exciting results show that the overexpression of Creld2 in osteoclasts impaired calcium mobilisation which is essential for activating calcineurin and promoting osteoclastogenesis. Therefore, our data proposes a novel inhibitory role for this calcium-binding ER-resident chaperone in modulating calcium flux during osteoclast differentiation which has important implications in our understanding of bone remodelling and the pathogenesis of skeletal diseases.
Glycosylated clusterin species facilitate Aβ toxicity in human neurons
Authors: Foster Evangeline M , Fernandes Marco , Dangla-Valls Adra , Hublitz Philip , Pangalos Menelaos Nicolas , Lovestone Simon , Ribe Elena , Buckley Noel John 
Published: March 2022

Abstract
Background: Clusterin (CLU) is one of the most significant genetic risk factors for late onset Alzheimer’s disease. However, the mechanisms by which CLU contributes to AD development and pathogenesis remain unclear. Numerous studies have demonstrated that CLU-AD mutations and amyloid-β (Aβ) treatment alter the trafficking and localisation of glycosylated CLU proteins, which may contribute to AD pathogenesis. However, the roles of non-glycosylated and glycosylated CLU proteins in mediating Aβ toxicity have not been studied in human neurons. Methods: iPSCs with altered CLU trafficking were generated following the removal of CLU exon 2 by CRISPR/Cas9 gene editing. Neurons were generated from unedited wildtype, control unedited and exon 2 -/- edited iPSCs and were incubated with aggregated Aβ peptides. Changes in cell death and neurite length were quantified to determine if altered CLU protein trafficking influenced neuronal sensitivity to Aβ. Finally, RNA-Seq analysis was performed to identify key transcriptomic differences between CLU exon 2 -/- and CTR neurons.Results: The removal of CLU exon 2, and the ER-signal peptide located within, abolished the presence of glycosylated CLU and increased the abundance of intracellular, non-glycosylated CLU. Aβ25-35 treatment was demonstrated to alter glycosylated CLU trafficking in control neurons, while non-glycosylated CLU levels were unaltered in both, control and exon 2 -/- neurons. Partial protection against Aβ-induced cell death and neurite retraction was demonstrated in exon 2 -/- neurons. Transcriptome analysis identified downregulation of multiple extracellular matrix (ECM) related genes in exon 2 -/- neurons, potentially contributing to their reduced sensitivity to Aβ toxicity. Conclusions: This study identifies a crucial role of glycosylated CLU in facilitating Aβ toxicity in human neurons. The loss of these proteins reduced both, cell death and neurite damage, two key consequences of Aβ toxicity identified in the AD brain. Strikingly, transcriptomic differences between exon 2 -/- and CTR neurons were small, but a significant and consistent downregulation of ECM genes and pathways was identified in exon 2 -/- neurons. This may contribute to the reduced sensitivity of these neurons to Aβ, providing new mechanistic insights into Aβ pathologies and therapeutic targets for AD.
Calcipotriol/betamethasone dipropionate fixed combination for the treatment of psoriasis vulgaris: a systematic review and meta-analysis.
Authors: Abdel-Aziz Walid , Elnaiem Walaa , Hassan Manar Ashraf , Alsiouty Asmaa Khaled , Mahmoud Ahmed Abdelrahman , Ali Abdelrahman Ahmed , Abd-elkader Mostafa Mahmod , Ahmed Youssef , Badran Mostafa , Ragab Khaled Mohamed , Nourelden Anas Zakarya , Zaazouee Mohamed Sayed 
Published: March 2022

Abstract
Psoriasis vulgaris has serious co-morbidities and impairs the quality of life. Vitamin D analogues and corticosteroids are widely used for treating psoriasis, but they have numerous effects. This review aims to assess the efficacy and safety of calcipotriol/betamethasone dipropionate (Cal/BD) as an alternative that may enhance patients' adherence. We searched PubMed, Cochrane, Web of science, and Scopus for reliable trials. The analysis was conducted by comprehensive meta-analysis (CMA) software using the Inverse-Variance method. The analysis showed that the fixed Cal/BD combination improves the psoriasis area and severity index score in body lesions (P<0.0001 at weeks one, two, four, and eight). It improves the total sign score (TSS) and achieves TSS-based response in scalp lesions (P<0.01 at eight weeks). Treatment success was achieved according to physician’s global assessment/investigator’s global assessment in scalp lesions (P<0.001 at weeks four, and eight), and according to patient’s global assessment in body (P=0.001 at week four) and scalp lesions (P<0.05 at weekss two, four, and eight). Adverse events were low for body (P<0.05 at weeks four, eight, and twelve) and scalp lesions (P<0.0001 at week eight). Our conclusion is that Cal/BD is effective and well-tolerated alternative therapy for psoriasis vulgaris.
Clinical features and short- and mid-term follow-up of refractory Kawasaki disease in children
Authors: Yuan Jia , Li Wei , Wang Zhouping , Wang Yanfei , Xie Xiaofei , Zhang Xu , Zhang Li , Huang Ping 
Published: March 2022

Abstract
Objective To investigate the clinical manifestations, laboratory data and coronary artery lesions of refractory Kawasaki disease, and to follow up the patients in the near to medium term. Methods Patients with refractory KD admitted to Guangzhou Women and Children's Medical Center between January 1, 2016 and December 31, 2020 were collected and their clinical data were retrospectively analyzed. Results A total of 42 patients were diagnosed with refractory KD, including 31 (73.81%) and 11 (26.19%) were male and female, respectively, with a median age of 26.7±19.3 (2-99) months. The average time, from onset to diagnosis and IVIG use, was 5.8±0.9 (4-12 ) days, while the fever lasted for 14.8±4.0 (8-34) days. A total of 29 patients exhibited coronary artery disease complications. All patients exhibited persistent or recurrent fever after two doses of IVIG therapy. A total of 41 patients were given a methylprednisolone regimen for up to three consecutive days as follows, while one patient continued to receive IVIG. The diameter of coronary arteries returned to normal 10 patients during the follow-up period, patients with medium and huge tumors exhibited shrunken diameter of coronary arteries, although they were not completely normal. Follow-up observations are still ongoing. Conclusion There is no unified diagnostic criteria and treatment plan for children with refractory KD. For patients that still experience fever after two IVIG treatments, clinicians need to consider the possibility of this type of KD. Development of an effective treatment plan is imperative to shortening fever time and prevention of progressive aggravation of coronary artery disease. Longer follow-up observation is also needed for this group of patients with coronary artery outcomes.
The correlation between multiple congenital anomalies hypotonia seizures syndrome 2 and PIGA: a case of novel PIGA germline variant and literature review
Authors: Liu Xiangyu , Meng Jing , Shu Jianbo , Gu Chunyu , Chen Xiaofang , Li Dong , Cai Chun-Quan 
Published: March 2022

Abstract
Background: PIGA (PIG class A) gene codes the PIG-A protein, which is a catalytic subunit of GPI-GlcNAc transferase. GPI-anchored proteins play important roles in the metabolism of mammals. Somatic variants of PIGA genes of bone marrow hematopoietic stem cells often result in Paroxysmal Nocturnal Haemoglobinuria, and the germline PIGA variant causes multiple congenital anomalies hypotonia seizures syndrome 2 (MCAHS2) because of glycosylphosphatidylinositol metabolic abnormalities.Methods: Whole exome sequencing was performed on peripheral blood samples of the proband with MCAHS2. A novel germline PIGA variant were found, and Sanger sequencing was performed as verification for the variants. Then we used the keywords to retrieve relevant reports and provided a literature review.Results: A novel hemizygous germline PIGA variant (NM_002641.3:c.971G>A) at exon4 was identified through the outcomes of whole exome sequencing. And it is highly probable pathogenic variant. Sanger sequencing yielded consistent results. The missense variant cause change of p.(Cys324Tyr) in the transcription product according to the predicting outcomes.Conclusion: We reported a case of MCAHS2 caused by navel PIGA variant. Following a review of the literature, we suggest that MCAHS2 should be considered as a disorder spectrum consisting of core symptoms, multi-system impairment, and premature death. The core symptoms include of hypotonia, psychomotor delay, epilepsy (intractable epilepsy mostly) and early death. Core symptoms nearly happened to almost all patients. Meanwhile MCAHS2 involves a wide range of organ and system impairments with changeable form.
Establishing the Taxa with Phylogenetic Profile and in-silico Ayurvedic Remedy of Human Oropharynx Microbiome
Authors: Kumari B. Yeswanthi , IA Shylesh Murthy , Bagchi Preenon 
Published: March 2022

Abstract
Fusobacterium, a Gram-negative bacteria, is the cause of oropharyngeal cancer, a type of head and neck cancer. Metagenome sequence of Human Oropharynx Microbiome was taken and metagenomics pipeline of Galaxy we performed know the taxanomy and phylogenetic profile. This was viewed using Krona. Also, using the metagenomics analysis gene family information was identified. Using this gene information, the receptors involved in Oropharynx was identified. Using homology modelling, the 3d structure of the Human Oropharynx was modelled. Further, ADME studies and computer-aided drug design using the phytocompounds from the ayurvedic medicinal herbs performed to identify the best ligand for oropharyngeal cancer receptor.
A Life-cycle Digital-twin Collaboration Framework Based-on Industrial Internet
Authors: Fan Yepeng , Dai Chaoren , Huang Si , Hu Pengcheng , Wang Xiaoyu , Yan Man 
Published: March 2022

Abstract
While the new generation of smart manufacturing technology is enabling manufacturing upgrades, it is also making manufacturing systems increasingly complex. The integration of information and ontology across the full life cycle of a product involves multi-scientific and multi-disciplinary dimensions. It requires deep integration of industry chain alliance enterprises in the process of domain ontology sharing and digital asset collaboration to achieve efficient "new demand → existing ontology → innovation → new product → new ontology" agile manufacturing paradigm transfer. This paper presents a digital-twin and ontology collaboration framework based on the Industrial Internet Identification and Resolution System (I3R System). Taking flexible manufacturing systems (FMS) as an example, the four core key technologies required in this framework are described in detail: (1) A generic digital-twin modeling approach for the full life cycle of FMS; (2) Ontology for the full life cycle of FMS; (3) Real-time data collection technology for Human-cyber-physical system (HCPS) in smart manufacturing; (4) Distributed collaboration framework based on I3R. In order to illustrate in detail how the proposed methods and techniques can be applied in reality, we show different application scenarios based on the proposed methods and techniques in the various stages of the full FMS life cycle. At the same time, the implementation method of the I3R System-based digital-twin collaborative prototyping platform for industry chain alliance enterprises is discussed, as well as the idea of its derived top-level application.
Bioprospecting for Indigenous Ruderal Plants with Potentials for Phytoremediation of Soil Heavy Metals in the Southern Guinea Savanna of North Western Nigeria
Authors: Bako Sunday , EZEALOR AUGUSTINE , Tanimu Yahuza 
Published: March 2022

Abstract
In a study to evaluate the response of indigenous ruderal plants to the metal deposition regime imposed by anthropogenic modification in the Southern Guinea Savanna of north Western Nigeria during the dry and wet seasons, herbaceous plants and samples of soils were collected in three 5m by 5m quadrats laid around the environs of the Kaduna Refinery and Petrochemical Company and the banks of River Kaduna. Heavy metal concentration (Cd, Ni, Cr, Cu, Fe, Mn and Zn) in soil and plant samples was determined using Energy Dispersive X-ray Fluorescence. Concentrations of heavy metals in soils were generally observed to be higher during the wet season in both locations although the differences were not statistically significant (P > 0.05). Concentrations of Cd, Zn, Cr, Cu and Ni in all the plants observed were found to be below levels described as phytotoxic to plants. However, above ‘normal’ concentrations of Cr was observed in most of the plant species sampled. The concentrations of Cr, Cu, Ni and Zn in soils around the KRPC and RKB were found to be above the acceptable limits. Although no hyper accumulator plant species was encountered in this study, twenty (20) plant species were identified to have high bioconcentration (BCF > 1.0) of Cd and Cu, which indicated tolerance of these plants to excessive or phytotoxic concentrations of these metals. In addition, they generally produce high above ground biomass, due to rapid vegetative growth. These are likely species for phytoextraction. Elevated concentration of metals in both soil and plant materials may cause a decrease in biodiversity due to direct toxicity. There are also risks to humans and other animals due to bioaccumulation across the food chain. There are further possibilities of further evaluating and genetically improving metal tolerance traits in some of these plant species in relation to their potential use in phytoremediation programmes in metal polluted sites.
Regeneration of injured endometrium using acellularized amniotic membrane loaded with adipose- derived mesenchymal stem cells in a rat model
Authors: Li Chunbo , Guo Luopei , Hua Keqin 
Published: March 2022

Abstract
Background
Intrauterine adhesion (IUA) is characterized by the formation of fibrosis, which prevents the regeneration of functional endometrial tissue. Tissue engineering that uses suitable biochemical and stem cells to assemble functional constructs that restore or improve damaged tissues, has been very promising in the treatment of IUA.
Aim
The objective of this study is to investigate the effect of acellularized amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) on reducing IUA, promoting the regeneration of injured endometrium as well.
Methods
A total of 96 female Spargue-Dawley (SD) rats were randomly divided into four groups: sham operation group, IUA model group, experimental group treated with AAM, and experimental group treated with AAM loaded with ADSCs (ADSCs/AAM). At 3, 7, and 14 days after surgery, histological and immunohistochemical analysis were performed to evaluate the fibrosis rate of intrauterine cavity and the regeneration of injured endometrium. RNA sequancing and real-time polymerase chain reaction (RT-PCR) was used to detect the difference of biological functions and the expression of inflammatory cytokines, such as bFGF, IL-1β, IL-6, and TNF-α among various groups, respectively.
Results
Our findings indicated that ADSCs/AAM was associated with thicker endometria, increased gland numbers and lower fibrotic rate when compared with those in AAM group, and was similar with those in sham group. In addition, the transplantation of ADSCs significantly decreased the inflammatory response and mRNA levels of pro-inflammatory cytokines (TNF-α and IL-1β), and increased anti-inflammatory cytokines (bFGF, and IL-6), compared with those in AAM group.
Conclusion
Our results demonstrated that AAM loaded with ADSCs transplantation could promote injured endometrium regeneration and reduce the formation of fibrosis.
Imaging-detected Bone Stress Injuries at the Tokyo 2020 Summer Olympics: Epidemiology, Injury Onset, and Competition Withdrawal Rate
Authors: Adachi Takuya , Katagiri Hiroki , An Jae-Sung , Engebretsen Lars , Tateishi Ukihide , Saida Yukihisa , Koga Hideyuki , Yagishita Kazuyoshi , Onishi Kentaro , Forster Bruce B. 
Published: March 2022

Abstract
Background
Prevention and early detection of injuries are essential in optimising sport participation and performance. The aim of this study is to investigate the epidemiology, history, and competition withdrawal rate of imaging-detected bone stress injuries during the Tokyo 2020 Olympic Games.
Methods
We collected and analysed imaging and patient information data in athletes with bone stress injuries diagnosed in the Olympic Village polyclinic during the Games. Two physicians independently and retrospectively reviewed all imaging examinations.
Results
A total of 10,305 individual athletes from 206 National Olympic Committees competed at the Games, during which 567 MRIs and 352 X-rays were performed at the Olympic Village polyclinic. Radiology examinations revealed four stress fractures and 31 stress reactions in 29 athletes (median age 24 years, range 18–35 years). Of these, 72% of patients (n = 21) had symptoms before entering the Olympic Village. Bone stress injuries were more common in women (55%), the lower extremities (66%), and track and field athletes (45%). Six patients (21%) did not start or did not finish their competitions.
Conclusions
This study revealed 35 imaging-detected bone stress injuries in the polyclinic of the Tokyo 2020 Olympic Village. The high proportion of patients with symptoms before entering the village and the high proportion of competition withdrawals suggests the usefulness of an early MRI examination.
The effect of maternal exposure to air pollutants on small for gestational age among infants in Xuzhou, China from 2018 to 2020: a cross sectional study
Authors: Zhao Gaichan , Zhang Faxue , Zhang Xupeng , Zhu Shijie , Zhang Xiaowei , Zhu Wei , Li Dejia 
Published: March 2022

Abstract
Background: Small for gestational age (SGA) defined as below 10th percent of birth weight of sex-specific gestational age, will bring large burden to the child. Large epidemiological studies have shown that exposure to air pollutants during pregnancy is associated with SGA, but the conclusions are inconsistent.Objective: To further investigate the relationship between prenatal exposure to air pollutants and SGA in Xuzhou, China.Methods: Our study included 2,039 pairs of mothers and their fetuses from January 1, 2018 to December 31, 2020 at the Affiliated Hospital of Xuzhou Medical University. A total of six air pollutants were acquired from the Xuzhou Department of Environmental Protection including particulate matter, nitrogen dioxide (NO2), and sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO). Adjusted for the confounders referring gestation, parity, gestational diabetes mellitus and Meteorological factors. We performed binomial logistic regression to test the odds ratio between air pollutants and the risk of SGA. Results: We found strong positive association of exposure to SO2 with SGA over the entire pregnancy and during the 1th, 2nd trimester (OR, 95% confidence interval: 1.204(1.091-1.328), 1.165(1.073-1.266), 1.110(1.033-1.193)). The other pollutants exception of O3 and NO2 were also found moderate relation with SGA over the entire pregnancy.Conclusions: The SGA incidence in Xuzhou was still high and even exposure to low levels of SO2 will pose a significant risk to infants. The government should focus on relevant policies to further improve air quality to reduce the burden of medical and health work and promote maternal health.