bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel composite scaffolds based on alginate and Mg‐doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions
Authors: Stojkovska Jasmina , Zvicer Jovana , Andrejevic Milica , Janackovic Djordje , Obradovic Bojana , Veljovic Djordje N. 
Published: May 2021

AbstractIn the present study, we synthesized hydroxyapatite (HAP) powders followed by the production of alginate based macroporous scaffolds with the aim to imitate the natural bone structure. HAP powders were synthesized by using a hydrothermal method, and after calcination, dominant phases in the powders, undoped and doped with Mg2+ were HAP and β‐tricalcium phosphate, respectively. Upon mixing with Na‐alginate, followed by gelation and freeze‐dying, highly macroporous composite scaffolds were obtained with open and connected pores and uniformly dispersed mineral phase as determined by scanning electron microscopy. Mechanical properties of the scaffolds were influenced by the composition of calcium phosphate fillers being improved as Ca2+ concentration increased while Mg2+ concentration decreased. HAP formation within all scaffolds was investigated in simulated body fluid (SBF) during 28 days under static conditions while the best candidate (Mg substituted HAP filler, precursor solution with [Ca + Mg]/P molar ratio of 1.52) was investigated under more physiological conditions in a biomimetic perfusion bioreactor. The continuous SBF flow (superficial velocity of 400 μm/s) induced the formation of abundant HAP crystals throughout the scaffolds leading to improved mechanical properties to some extent as compared to the initial scaffolds. These findings indicated potentials of novel biomimetic scaffolds for use in bone tissue engineering.
AnARHGAP25variant links aberrantRac1function to early‐onset skeletal fragility
Authors: Mäkitie Riikka E. , Henning Petra , Jiu Yaming , Kämpe Anders , Kogan Konstantin , Costantini Alice , Välimäki Ville‐Valtteri , Medina‐Gomez Carolina , Pekkinen Minna , Salusky Isidro B. , Schalin‐Jäntti Camilla , Haanpää Maria K. , Rivadeneira Fernando , Bassett John H. Duncan , Williams Graham R. , Lerner Ulf H. , Pereira Renata C. , Lappalainen Pekka , Mäkitie Outi 
Published: May 2021

ABSTRACTRas homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase‐activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Here, we report defective RhoGTPase regulation as a cause of severe, early‐onset, autosomal‐dominant skeletal fragility in a three‐generation Finnish family. Affected individuals (n = 13) presented with multiple low‐energy peripheral and vertebral fractures despite normal bone mineral density (BMD). Bone histomorphometry suggested reduced bone volume, low surface area covered by osteoblasts and osteoclasts, and low bone turnover. Exome sequencing identified a novel heterozygous missense variant c.652G>A (p.G218R) inARHGAP25, encoding a GAP for Rho‐family GTPase Rac1. Variants in theARHGAP255′ untranslated region (UTR) also associated with BMD and fracture risk in the general population, across multiple genomewide association study (GWAS) meta‐analyses (lead variant rs10048745).ARHGAP25messenger RNA (mRNA) was expressed in macrophage colony‐stimulating factor (M‐CSF)–stimulated human monocytes and mouse osteoblasts, indicating a possible role for ARHGAP25 in osteoclast and osteoblast differentiation and activity. Studies on subject‐derived osteoclasts from peripheral blood mononuclear cells did not reveal robust defects in mature osteoclast formation or resorptive activity. However, analysis of osteosarcoma cells overexpressing the ARHGAP25 G218R‐mutant, combined with structural modeling, confirmed that the mutant protein had decreased GAP‐activity against Rac1, resulting in elevated Rac1 activity, increased cell spreading, and membrane ruffling. Our findings indicate that mutated ARHGAP25 causes aberrant Rac1 function and consequently abnormal bone metabolism, highlighting the importance of RhoGAP signaling in bone metabolism in familial forms of skeletal fragility and in the general population, and expanding our understanding of the molecular pathways underlying skeletal fragility. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta
Authors: Liu Yi , Wang Zihan , Ju Mingyan , Zhao Yuxia , Jing Yaqing , Li Jiaci , Shao Chenyi , Fu Ting , Lv Zhe , Li Guang 
Published: May 2021

ABSTRACT
Osteogenesis imperfecta (OI) is a congenital genetic disorder mainly manifested as bone fragility and recurrent fracture. Mutation of COL1A1/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose-derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1+/−365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes-associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone-forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo/YAP signaling and effectively rescued YAP-mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1+/−365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).
Expression profiles of circular RNAs in colon biopsies from Crohn's disease patients by microarray analysis
Authors: Hu Yu‐an , Zhu Yan , Liu Guorui , Yao Xinyue , Yan Xiaoling , Yang Yang , Wang Weiping , Zou Xiaoping , Li Xiaojun 
Published: May 2021

AbstractBackgroundCircular RNAs (circRNAs) are involved in various diseases and serve as biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in colon tissues of Crohn's disease (CD) and search novel biomarkers for the diagnosis.MethodsDifferentially expressed (DE) circRNAs in biopsies from four CD patients, four ulcerative colitis (UC) patients, and four healthy controls (HC) were screened by microarray. Hsa_circ_0062142 and hsa_circ_0001666 were verified in another expanded validation cohort. Bioinformatics analysis was applied to predict the function of two DE circRNAs. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of CD.ResultsThe top 10 upregulated circRNAs in CD compared with HC were hsa_circ_0000691, hsa_circ_0001666, hsa_circ_0004183, hsa_circ_0009024, hsa_circ RNA_405324, hsa_circ_0002003, hsa_circ_0085323, hsa_circ_0040994, hsa_circ_0062142, and hsa_circ_0048148; the top 10 downregulated circRNAs were hsa_circ_0049356, hsa_circ RNA_405443, hsa_circ RNA_403556, hsa_circ_0092328, hsa_circ_0003979, hsa_circ_0074491, hsa_circ_0023461, hsa_circ RNA_406237, hsa_circ_0034044, and hsa_circ RNA_400564 (fold change in descending order). The expression levels of hsa_circ_0001666 and hsa_circ_0062142 in CD were significantly higher than those in UC and HC (p < 0.01). ROC curves suggested the favorable diagnostic value of hsa_circ_0062142 and hsa_circ_0001666 (AUC = 0.803 and 0.858, respectively, p < 0.01). In silico analysis indicated that these circRNAs may be involved in the progress of CD.ConclusionHsa_circ_0062142 and hsa_circ_0001666 may play critical roles in the pathogenesis and serve as potential biomarkers of CD.
The role and significance of angiotensin‐converting enzyme 2 peptides in the treatment of coronavirus disease 2019
Authors: Liu Yang , He Huanzhong , Huang Huilian 
Published: May 2021

AbstractSince the end of 2019, coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus (2019‐nCoV) posed a serious threat to human health and life. Therefore, the discovery of drugs that can effectively prevent and treat COVID‐19 is urgently warranted. In this article, the role and significance of angiotensin‐converting enzyme 2 in drug development and the treatment of COVID‐19 are discussed. It was found that the binding of ACE2 to SARS‐CoV‐2‐RBD involved two core regions (31st and 353rd lysine) and 20 amino acids of the ACE2 protein. The mutation of these amino acids could lead to a great change of the binding ability of ACE2 and SARS‐CoV‐2‐RBD. This information was important for us to find more efficient ACE2 peptides to block the 2019‐nCoV infection. So during this study, we summarized the role of ACE2 in the regulation of 2019‐nCoV infection and stress, and hypothesized that the development and optimization of ACE2 peptide can effectively block 2019‐nCoV infection and reliably treat the COVID‐19.
A culture of care: How Lotus House Women's Shelter heals program participants through genuineness, space, high expectations, dignity, individualized attention, and community
Authors: Eaton Asia A. , Stephens Dionne P. , Ruvalcaba Yanet , Banks Jasmine ,   Sundari Foundation Inc.
Published: May 2021

AbstractThe present study was designed to examine perceptions of Lotus House Women's Shelter from the perspective of former program participants, for the purpose of informing shelter programming and policies. Our qualitative research followed a community‐based participatory research framework. Fifty diverse women graduates of Lotus House Women's Shelter participated in eight focus groups to discuss their experiences with Lotus House and other shelters. Findings from this study highlight the elements that create a “culture of care” within an organization. Participants described Lotus House shelter culture as genuine, defined by dignity and respect, having high expectations for guest independence and accountability, giving space to rest and recuperate, recognizing and accommodating individual needs and experiences, and fostering a sense of community. Creating an organizational “culture of care” is an avenue by which any shelter or related organization can enhance the experience of program participants.
The new periodontal disease classification: Level of agreement on diagnoses and treatment planning at various dental education levels
Authors: Abou‐Arraj Ramzi V. , Kaur Maninder , Alkhoury Shadi , Swain Thomas A. , Geurs Nicolaas C. , Souccar Nada M. 
Published: May 2021

AbstractPurpose/objectivesUsing the periodontal diseases classification published in 2018, this study evaluated the level of agreement among predoctoral and postgraduate students of different education levels and specialties in the diagnosis and treatment planning of periodontal conditions.MethodsSecond‐year (D2) and fourth‐year (D4) dental students, postgraduate orthodontic students (OS), and periodontology students (PS) were presented with an anonymous survey of 10 cases, each with five choices of diagnosis and seven therapeutic approaches. The cases included a patient summary, photographs, radiographs, periodontal charting, and ranged from health to periodontitis. Consensus diagnosis, used as a gold standard, was established between two experienced periodontists. Diagnosis and treatment choices for each case were compared across educational groups using Fisher's exact test. The level of agreement among educational groups was assessed using a multirater kappa coefficient.ResultsThe survey was completed in 2020 with a 72.4% overall response rate (57‐D2, 45‐D4, 17‐OS, and 12‐PS). The overall level of agreement on diagnosis was fair (κ = 0.24, p <.0001) with PS showing the most agreement (κ = 0.55, p <.0001). There were tendencies to prioritize stage over grade and extent in assigning diagnoses and to overdiagnose disease severity and underdiagnose localized periodontitis. Nonsurgical periodontal therapies had the highest overall agreement (κ = 0.63 for scaling/root planing and κ = 0.44 for maintenance, p <.0001). Response distribution per case and per level of education indicated that PS more consistently agreed with the gold standard than any other group.ConclusionsOS, D2, and D4 students demonstrated inferior agreement levels compared to PS, successfully recognized health from disease, suggested appropriate treatment plans, and tended to overdiagnose milder periodontal conditions.
Diagnostic challenge of chlamydial Fitz‐Hugh‐Curtis syndrome and cervicitis complicated by appendicitis: Case report
Authors: Ishimaru Naoto , Kanzawa Yohei , Nakajima Takahiro , Seto Hiroyuki , Ando Masayuki , Kinami Saori 
Published: May 2021

AbstractOur patient had appendicitis complicated by Chlamydia trachomatis‐induced Fitz‐Hugh‐Curtis syndrome and cervicitis. Differential diagnosis was challenging. A 22‐year‐old Japanese woman was febrile and presented with vomiting and subsequent abdominal pain. She had unprotected sexual intercourse with multiple partners. She had high Alvarado score and lack of cervical motion pain, despite cervical inflammation. Noncontrast CT showed enlarged appendix. Laparoscopic appendectomy revealed acute suppurative appendicitis and perihepatic adhesion. Cervical PCR assay was positive for C. trachomatis. She remained febrile but defervesced after azithromycin therapy. Clinicians should confirm whether females with abdominal pain are sexually active in view of screening for C. trachomatis.
Real‐world data on treatment concepts in classical Hodgkin lymphoma in Sweden 2000–2014, focusing on patients aged >60 years
Authors: Wahlin Björn Engelbrekt , Övergaard Ninja , Peterson Stefan , Digkas Evangelos , Glimelius Ingrid , Lagerlöf Ingemar , Johansson Ann‐Sofie , Palma Marzia , Hansson Lotta , Linderoth Johan , Goldkuhl Christina , Molin Daniel 
Published: May 2021

AbstractTreatment for patients > 60 years with classical Hodgkin lymphoma (cHL) is problematic; there is no gold standard, and outcome is poor. Using the Swedish Lymphoma Registry, we analysed all Swedish patients diagnosed with cHL between 2000 and 2014 (N = 2345; median age 42 years; 691 patients were >60 years). The median follow‐up time was 6.7 years. Treatment for elderly patients consisted mainly of ABVD or CHOP, and the younger patients were treated with ABVD or BEACOPP (with no survival difference). In multivariable analysis of patients > 60 years, ABVD correlated with better survival than CHOP (p = 0.027), and ABVD became more common over time among patients aged 61–70 years (p = 0.0206). Coinciding with the implementation of FDG‐PET/CT, the fraction of advanced‐stage disease increased in later calendar periods, also in the older patient group. Survival has improved in cHL patients > 60 years (p = 0.027), for whom ABVD seems superior to CHOP.
Socioeconomic cost of AML in Sweden—A population‐based study using multiple nation‐wide registers
Authors: Hernlund Emma , Redig Josefine , Paulsson Björn , Rangert Derolf Åsa , Höglund Martin , Vertuani Simona , Juliusson Gunnar 
Published: May 2021

AbstractAcute myeloid leukemia (AML) is associated with a high economic and clinical burden. Recently novel therapies have been added to standard treatment regimens. Here, we evaluated the economic impact of AML up until the introduction of these novel therapies. Individual data on 2954 adult patients diagnosed from 2007 to 2015 from five Swedish national population‐based registers were used, enabling analyses from diagnosis to either death or 5‐year follow‐up for survival, inpatient and outpatient costs, costs of prescribed drugs, sick leave, and early retirement. Costs per patient were stratified by age group, treatment options, and FLT3‐ITD status. The expected 5‐year costs per patient differed substantially between age groups. Patients aged 18–59 years had an expected mean cost per patient of €170,748, while age groups 60–69 years, 70–79 years, and >80 years incurred an expected mean cost of €92,252, €48,344, and €24,118, respectively, over 5 years. Patients <60 years undergoing stem cell transplantation had the highest costs (€228,525 over 5 years). About 60% of costs for these patients were from hospitalizations and 20% from sick leave and early retirement; cost per day was highest from the first admission to complete remission. This study provides a baseline for socioeconomic evaluations of novel therapies in AML in Sweden.
Synthesis and antitumor activity of novel pyridino[2,3‐d]pyrimidine urea derivatives
Authors: Chen Dongmei , Chen Yumei , Yang Di , Zheng Zhaopeng , Zhou Zhixu 
Published: May 2021

AbstractA series of novel N‐(3‐((6‐bromopyrido[2,3‐d]pyrimidin‐4‐yl)oxy)phenyl)pyrrolidine‐1‐carboxamide and 1‐(3‐((6‐bromopyrido[2,3‐d]pyrimidin‐4‐yl)oxy)phenyl)‐3‐propylurea derivatives were synthesized. Their antitumor activities against human breast carcinoma cells (MCF‐7) and human colon cancer cells (HCT‐116) in vitro were evaluated, using sorafenib as a positive control drug. Anticancer bioassays indicated that several compounds exhibited appreciable anticancer activity against MCF‐7 and HCT‐116 cells. Particularly, compounds 9g and 8b demonstrated the most significant inhibitory effect against HCT‐116 and MCF‐7 cells, with inhibition ratios of 25.56% and 26.46%, respectively. Additionally, the synthesized pyridine[2,3‐d]pyrimidine derivatives containing a urea group moieties exhibited antitumor activities against MCF‐7 and HCT‐116 cells in vitro.
A cluster‐randomized controlled trial of a combination HIV risk reduction and microfinance intervention for female sex workers who use drugs in Kazakhstan
Authors: El‐Bassel Nabila , McCrimmon Tara , Mergenova Gaukhar , Chang Mingway , Terlikbayeva Assel , Primbetova Sholpan , Kuskulov Azamat , Baiserkin Bauyrzhan , Denebayeva Alfiya , Kurmetova Kulpan , Witte Susan S. 
Published: May 2021

AbstractIntroductionFemale sex workers (FSW) who use drugs are a key population at risk of HIV in Kazakhstan, and face multiple structural barriers to HIV prevention. More research is needed on the role of structural interventions such as microfinance (MF) in reducing HIV risk. This paper describes the results of a cluster‐randomized controlled trial to test the efficacy of a combination HIVRR + MF intervention in reducing biologically confirmed STIs and HIV risk behaviours.MethodsThis study took place from May 2015 to October 2018 in two cities in Kazakhstan. We screened 763 participants for eligibility and enrolled 354 FSW who use drugs. Participants were randomized in cohorts to receive either a four‐session HIVRR intervention, or that same intervention plus 30 additional sessions of financial literacy training, vocational training and asset‐building through a matched‐savings programme. Repeated behavioural and biological assessments were conducted at baseline, 3‐, 6‐ and 12‐months post‐intervention. Biological and behavioural primary outcomes included HIV/STI incidence, sexual risk behaviours and drug use risk behaviours, evaluated over the 12‐month period.ResultsOver the 12‐month follow‐up period, few differences in study outcomes were noted between arms. There was only one newly‐detected HIV case, and study arms did not significantly differ on any STI incidence. At post‐intervention assessments compared to baseline, both HIVRR and HIVRR + MF participants significantly reduced sexual and drug use risk behaviours, and showed improvements in financial outcomes, condom use attitudes and self‐efficacy, social support, and access to medical care. In addition, HIVRR + MF participants showed a 72% greater reduction in the number of unprotected sex acts with paying partners at the six‐month assessment (IRR = IRR = 0.28, 95% CI = 0.08, 0.92), and a 10% greater reduction in the proportion of income from sex work at the three‐month assessment (b = −0.10, 95% CI = −0.17, −0.02) than HIVRR participants did. HIVRR + MF participants also showed significantly improved performance on financial self‐efficacy compared to HIVRR over the 12‐month follow‐up period.ConclusionsCompared to a combination HIVRR + MF intervention, a robust HIVRR intervention alone may be sufficient to reduce sexual and drug risk behaviours among FSW who use drugs. There may be structural limitations to the promise of microfinance for HIV risk reduction among this population.
Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID‐19 neuropathy patients
Authors: Manganotti Paolo , Bellavita Giulia , Tommasini Valentina , D′Acunto Laura , Fabris Martina , Cecotti Laura , Furlanis Giovanni , Sartori Arianna , Bonzi Lucia , Buoite Stella Alex , Pesavento Valentina 
Published: May 2021

AbstractThis case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID‐19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin‐6 (IL‐6) and IL−8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL‐6 and IL‐8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL‐8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL‐6 and IL‐8 as prognostic biomarkers in COVID‐19.
Design and performance of a dark‐field probe with confocal Raman spectroscopy for ophthalmic applications
Authors: Zhang Shuo , Erckens Roel J. , Jongsma Franciscus H.M. , Webers Carroll A.B. , Berendschot Tos T.J.M. 
Published: May 2021

AbstractA dark‐field ophthalmic contact probe for analysis of aqueous humor (AH) was designed by ray tracing and constructed in quartz glass for experimental use as a prototype probe in a confocal Raman spectroscopic setup. The misalignment tolerance of this probe was theoretically evaluated, whereas the optical performance was experimentally evaluated by a concentration curve of the ocular drug phenylephrine HCl in an artificial eye model. The results indicated a ninefold improvement in misalignment tolerance and a 36‐fold improvement in the signal‐to‐noise ratio at the phenylephrine HCl 1002 cm−1 peak compared with a previous design. The prototype showed a good linear fit with the phenylephrine HCl concentration, with an R2 of 0.996. Phenylephrine HCl concentration down to 0.1% is detectable.