bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnetic resonance imaging and neurological findings in dogs with disc‐associated cervical spondylomyelopathy: a case series
Authors: Bonelli Marília de Albuquerque , da Costa Luciana Bignardi de Soares Brisola , da Costa Ronaldo Casimiro 
Published: April 2021

AbstractBackgroundCanine cervical spondylomyelopathy can be separated into osseous and disc-associated (DA-CSM) forms. Our aim was to describe the magnetic resonance imaging (using a high-field scanner) and neurological findings in dogs with DA-CSM and investigate a relationship between these findings.ResultsSixty-three dogs were included: 60/63 (95 %) were large breeds, with Doberman Pinschers and males over-represented (70 %). Mean and median age at the time of diagnosis was 7.25 and 7.2 years (range 0.41–12 years). Chronic signs were noted in 52/63 (83 %) dogs, with proprioceptive ataxia the most common. Main site of spinal cord compression was commonly C6-7 or C5-6. Thirty-six (57 %) dogs had various sites of spinal cord compression. Most dogs younger than 6 years of age had a single affected site. Foraminal stenosis was present in 51/63 dogs (81 %). T2-weighted hyperintensity was present in 40/63 dogs (63 %). 88 % of the articular processes showed degenerative changes, which correlated strongly with intervertebral disc degeneration. Ligamentum flavum hypertrophy was seen in 38 % of dogs. No correlation was observed between neurologic signs and number of affected sites. A moderate positive correlation was observed between severity of spinal cord compression and neurologic grade (r0.48;p < 0.001).ConclusionsDA-CSM was predominantly observed in older, male Dobermans, with lesions located in the caudal cervical vertebral region. It was also seen in dogs 3 years of age or even younger (8 %). Single compressive lesions were more common in dogs younger than 6 years of age. Many dogs had concomitant changes (e.g.: ligamentum flavum hypertrophy and foraminal stenosis). Most dogs with ligamentum flavum hypertrophy were 6 years or older. A positive correlation was observed between severity of spinal cord compression and neurologic grade, but multilevel compression was not associated with more severe neurologic signs. A very high percentage of dogs had articular process degenerative changes. Possible biomechanical or genetic relationships between degenerative changes in articular processes, ligamentum flavum, and intervertebral discs warrants further investigation.
Topical ophthalmic atropine in horses, pharmacokinetics and effect on intestinal motility
Authors: Ström L. , Dalin F. , Domberg M. , Stenlund C. , Bondesson U. , Hedeland M. , Toutain P-L , Ekstrand C. 
Published: April 2021

AbstractBackgroundTopical ophthalmic atropine sulfate is an important part of the treatment protocol in equine uveitis. Frequent administration of topical atropine may cause decreased intestinal motility and colic in horses due to systemic exposure. Atropine pharmacokinetics are unknown in horses and this knowledge gap could impede the use of atropine because of the presumed risk of unwanted effects. Additional information could therefore increase safety in atropine treatment.ResultsAtropine sulfate (1 mg) was administered in two experiments: In part I, atropine sulfate was administered intravenously and topically (manually as eye drops and through a subpalpebral lavage system) to six horses to document atropine disposition. Blood-samples were collected regularly and plasma was analyzed for atropine using UHPLC-MS/MS. Atropine plasma concentration was below lower limit of quantification (0.05 μg/L) within five hours, after both topical and IV administration. Atropine data were analyzed by means of population compartmental modeling and pharmacokinetic parameters estimated. The typical value was 1.7 L/kg for the steady-state volume of distribution. Total plasma clearance was 1.9 L/h‧kg. The bioavailability after administration of an ophthalmic preparation as an eye drop or topical infusion were 69 and 68%, respectively. The terminal half-life was short (0.8 h). In part II, topical ophthalmic atropine sulfate and control treatment was administered to four horses in two dosing regimens to assess the effect on gastro-intestinal motility. Borborygmi-frequency monitored by auscultation was used for estimation of gut motility. A statistically significant decrease in intestinal motility was observed after administration of 1 mg topical ophthalmic atropine sulfate every three hours compared to control, but not after administration every six hours. Clinical signs of colic were not observed under any of the treatment protocols.ConclusionsTaking the plasma exposure after topical administration into consideration, data and simulations indicate that eye drops administrated at a one and three hour interval will lead to atropine accumulation in plasma over 24 h but that a six hour interval allows total washout of atropine between two topical administrations. If constant corneal and conjunctival atropine exposure is required, a topical constant rate infusion at 5 μg/kg/24 h offers a safe alternative.
Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China
Authors: Luo Xi , Zhang Xiang-mei , Wu Liu-song , Chen Jindong , Chen Yan 
Published: April 2021

Abstract
Background
α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation

Methods
A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data.

Results
We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia.

Conclusions
These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.
Overexpression of DSCR1 prevents proliferation and predicts favorable prognosis in colorectal cancer patients
Authors: Li Wen-Xiang , Zheng Jia-Jia , Zhao Gang , LYU Chen-Tao , Lu Wei-Qi 
Published: April 2021

Abstract
Objectives
Down syndrome critical region 1 (DSCR1) is associated with carcinogenesis and tumor growth in several types of malignancy. However, little is known about the role of DSCR1 in CRC progression. The present study aimed to elucidate the clinicopathological significance, prognostic, and function roles of DSCR1 in CRC.

Methods
Firstly, we analyzed DSCR1 expression in 58 paired CRC samples and Oncomine database. Then, we analyzed DSCR1 expression in two independent CRC cohorts (test cohort: n = 70; validation cohort: n = 58) and tested its overall survival (OS) by Kaplan-Meier survival analyses. Finally, we overexpressed DSCR1 in two CRC cell lines DLD1 and LoVo and analyzed its effect on cell cycle and senescence.

Results
DSCR1 expression was significantly decreased in CRC samples and associated with clinicopathologic features of CRC patients, such as tumor size, lymph node metastasis, and TNM stage. CRC patients with low expression of DSCR1 had shorter overall survival (OS). Kaplan-Meier survival analyses showed that the expression of DSCR1 was significant factor for OS in both cohorts. Multiple Cox regression analysis showed that DSCR1 expression was an independent prognostic marker for OS in test cohort. Overexpression of DSCR1 isoform 4 (DSCR1-4) increased p21, p16, p-NFAT1, and p-NFAT2, while decreased CDK2, CDK4, and Cyclin D1 in CRC cells. In addition, overexpression of DSCR1-4 prevented proliferation and colony formation, and induced senescence in vitro. Moreover, overexpression of DSCR1-4 inhibited tumor growth and tumor angiogenesis in vivo.

Conclusions
Our study found high expression of DSCR1 contributes to favorable prognosis of CRC patients and prevents cell cycle and proliferation of CRC cells, indicating a critical tumor suppressive role in CRC progression.
Implementing care coordination in a large dental care organization in the United States by upskilling front office personnel
Authors: Kottek Aubri M. , Hoeft Kristin S. , White Joel M. , Simmons Kristen , Mertz Elizabeth A. 
Published: April 2021

AbstractBackgroundCare coordination is a key strategy used to improve health outcomes and efficiency, yet there are limited examples in dentistry. A large dental accountable care organization piloted care coordination by retraining existing administrative staff to coordinate the care of high-risk patients. Following the pilot’s success, a formal “dental care advocate” (DCA) role was integrated system-wide. The goal of this new role is to improve care, patient engagement, and health outcomes while integrating staff into the clinical care team. We aim to describe the process of DCA role implementation and assess staff and clinician perceptions about the role pre- and post-implementation.MethodsGuided by the Consolidated Framework for Implementation Research, semi-structured interviews with clinical and operational administrative staff and observation at the company-wide training session were combined with pre- and post-implementation electronic surveys. Descriptive statistics and mean scores were tested for significance between each survey sample (t-tests), and qualitative data were thematically analyzed.ResultsWith preliminary evidence from the pilot and strong executive support, a dedicated leadership team executed a stepwise rollout of the DCA role over 6 months. Success was facilitated by an organizational culture of frequent interventions deployed rapidly through a centralized system, along with supportive buy-in from managerial teams and high staff acceptance and enthusiasm for the DCA role before implementation. Following implementation, significant changes in attitudes and beliefs about the role were measured, though managers held stronger positive impressions than DCAs. DCAs reported high confidence in new skills and dental knowledge post-implementation, including motivational interviewing and the ability to confidently answer patients’ questions about their oral health. Overall, the fast-paced implementation of this new role was well received, although consistent and significant differences in mean attitudes between managers and DCAs indicate more work to fine-tune the role is needed.ConclusionsSuccessful implementation of the new DCA role was facilitated by a strong organizational commitment to team-based dentistry and positive impressions of care coordination among staff and managers. Upskilling existing administrative staff with the necessary training to manage some high-risk patient needs is one method that can be used to implement care coordination efforts in dentistry.
Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model
Authors: Wu Jianjun , Xie Shoupin , Li Hailong , Zhang Yanxia , Yue Jia , Yan Chunlu , Liu Kai , Liu Yongqi , Xu Rui , Zheng Guisen 
Published: April 2021

Abstract
Background
Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice

Methods
The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured

Results
There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05)

Conclusions
This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.
Development of an immunochromatographic strip for rapid detection of H7 subtype avian influenza viruses
Authors: Li Ge , Wang Xun , Li Qingmei , Yang Jifei , Liu Xiao , Qi Wenbao , Guo Junqing , Deng Ruiguang , Zhang Gaiping 
Published: April 2021

Abstract
Background
H7N9 avian influenza virus (AIV) including highly and low pathogenic viruses have been detected in China since 2013. H7N9 AIV has a high mortality rate after infection in humans, and most human cases have close contacted with poultry in the live poultry market. Therefore, it is necessary to develop a rapid point-of-care testing (POCT) technique for H7N9 AIV detection.

Methods
The H7N9 AIV was inactivated and purified, and was used as the antigen to immunize BALB/c. Twelve H7-HA specific monoclonal antibodies (McAbs) were produced through the hybridoma technique. The McAb 10A8 was conjugated with colloid gold as detecting antibody; McAb 9B6 was dispensed on the nitrocellulose membran as the capture test line and the Goat-anti mouse IgG antibody was dispensed as control line respectively. The immunochromatographic strip was prepared.

Results
The analysis of ELISA and virus neutralization test showed that the obtained McAbs specifically recognized H7 HA. Based on the prepared strip, the detection of H7 AIV was achieved within 10 min. No cross-reaction occurred between H7 AIVs and other tested viruses. The detection limit of the strip for H7 was 2.4 log10EID50/0.1 mL for chicken swab samples.

Conclusion
The McAbs were specific for H7 and the immunochromatographic strip developed in this study was convenient, rapid and reliable for the detection of H7 AIV. The strip could provide an effective method for the rapid and early detection of H7 AIV.
An in vitro model for assessment of SARS-CoV-2 infectivity by defining the correlation between virus isolation and quantitative PCR value: isolation success of SARS-CoV-2 from oropharyngeal swabs correlates negatively with Cq value
Authors: Sonnleitner Sissy Therese , Dorighi Julian , Jansen Bianca , Schönegger Carmen , Gietl Sarah , Koblmüller Stephan , Sturmbauer Christian , Posch Wilfried , Walder Gernot 
Published: April 2021

Abstract
Background
At the beginning of the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), little was known about its actual rate of infectivity and any COVID-19 patient positive in laboratory testing was supposed to be highly infective and a public health risk factor.

Methods
One hundred oropharyngeal samples were obtained during routine work flow of testing symptomatic persons by quantitative polymerase chain reaction (qPCR) and were inoculated onto cell culture of VeroB4 cells to study the degree of infectivity of SARS-CoV-2 in vitro. Quantification by virus titration and an external standard using synthetic RNA gave the breaking point of infectivity in SARS-CoV-2 in vitro.

Results
A clear negative correlation (r = − 0.76; p < 0.05) could be asserted between the viral load in quantitative polymerase chain reaction (qPCR) and the probability of a successful isolation in serial isolation experiments of specific oropharyngeal samples positive in qPCR. Quantification by virus titration and an external standard using synthetic RNA indicate a Cq between 27 and 30 in E-gene screening PCR as a breaking point in vitro, where infectivity decreases significantly and isolations become less probable.

Conclusions
This study showed that only the 21% of samples with the highest viral load were infectious enough to transmit the virus in vitro and determined that the dispersion rate in vitro is surprisingly close to those calculated in large retrospective epidemiological studies for SARS-CoV-2. This raises the question of whether this simple in vitro model is suitable to give first insights in dispersion characters of novel or neglected viral pathogens. The statement that SARS-CoV-2 needs at least 40,000 copies to reliably induce infection in vitro is an indication of its transmissibility in Public Health decisions. Applying quantitative PCR systems in diagnosis of SARS-CoV2 can distinguish between patients providing a high risk of transmission and those, where the risk of transmission is probably limited to close and long-lasting contacts.
Clinical and genetic characteristics of hypophosphatasia in Chinese children
Authors: Liu Meijuan , Liu Min , Liang Xuejun , Wu Di , Li Wenjing , Su Chang , Cao Bingyan , Chen Jiajia , Gong Chunxiu 
Published: April 2021

Abstract
Background
Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children.

Methods
The clinical and genetic characteristics of 10 Chinese children with HPP who were referred to the Beijing Children’s Hospital were described. Previously reported HPP cases of children in China were also reviewed.

Results
A total of 33 cases were identified, which included 2 perinatal lethal HPP, 10 infantile HPP, 10 childhood HPP, and 11 odonto HPP. The male-to-female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 h after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 h after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with perinatal lethal/infantile HPP when compared with those with the mild forms of HPP childhood/odonto HPP (P < 0.01). Although serum phosphate levels were not different (P > 0.05), serum calcium levels were elevated, and serum intact parathyroid hormone levels were decreased in patients with perinatal lethal/infantile HPP in comparison with those with the childhood/odonto HPP (P all < 0.01). Genetic analyses identified 40 mutations in 31 HPP cases, including 28 missense mutations, 9 frameshift mutations, 2 splice junction alterations, and 1 regulatory mutation. Of which, 5 novel mutations were identified in our present study: 2 frameshift mutations (p.Arg138GlyfsTer27, p.Leu511Profs*272); 2 missense mutations (p.Ala176Val, p.Phe268Leu), and 1 splice junction alteration (c.297+5G>A). Compound heterozygous mutations accounted for 80.6% of all variants. No mutational “hot-spot” was found. Most mutations of ALPL were located in exons 5, 7, 10, and 3. Notably, subjects that carrying single heterozygous mutations showed milder phenotypes of HPP, while subjects with nonsense mutations were associated with a severer phenotype.

Conclusions
HPP is a rare disease with often delayed diagnosis, and the incidence of HPP in China may be seriously underestimated. The present study expands the phenotypic and genotypic spectrum and the understanding of HPP in Chinese children. These findings will be useful for clinical assessment and shorten the diagnosis time for pediatric HPP in China.
Lactoferrin is required for early B cell development in C57BL/6 mice
Authors: Wei Lingyu , Liu Can , Wang Jia , Zheng Xiang , Peng Qiu , Ye Qiurong , Qin Zailong , Li Zhengshuo , Zhang Xiaoyue , Wu Yangge , Wen Yuqing , Zhang Xuemei , Yan Qun , Ma Jian 
Published: April 2021

AbstractLactoferrin (Lf) is widely distributed in mammalian milk, various tissues, and their exocrine fluids and has many physiological functions, such as bacteriostasis, antivirus, and immunoregulation. Here, we provide evidence that lactoferrin is required for early stages of B cell development in mice. Lactoferrin-deficient (Lf−/−) C57BL/6 mice showed systematic reduction in total B cells, which was attributed to the arrest of early B cell development from pre-pro-B to pro-B stage. Although the Lf−/− B cell “seeds” generated greater pro-B cells comparing to wild type (WT) littermates, the Lf−/− mice bone marrow had less stromal cells, and lower CXCL12 expression, produced a less favorable “microenvironment” for early B cell development. The underlying mechanism was mediated through ERK and AKT signalings and an abnormality in the transcription factors related to early differentiation of B cells. The Lf−/− mice also displayed abnormal antibody production in T cell-dependent and T cell-independent immunization experiments. In a pristane-induced lupus model, Lf−/− mice had more serious symptoms than WT mice, whereas lactoferrin treatment alleviated these symptoms. This study demonstrates a novel role of lactoferrin in early B cell development, suggesting a potential benefit for using lactoferrin in B cell-related diseases.