bluuebunny/crossref_metadata_2025_split huggingface dataset:
Budget impact analysis of lens material on the posterior capsule opacification (PCO) as a complication after the cataract surgery
Authors: Raulinajtys-Grzybek Monika , Grabska-Liberek Iwona , Opala Aleksandra , Słomka Marta , Chrobot Michał 
Published: June 2020

AbstractBackgroundOver 300,000 cataract operations are performed in Poland every year, and the most common, late complication of cataract removal surgery is posterior capsule opacification (PCO). The risk of PCO depends on the lens material. Hydrophobic acrylic lenses cause PCO less frequently as lymphatic endothelial cells show lower affinity for the surface of the lens made of silicone. The objective of this study is to assess the economic impact of using hydrophobic acrylic lenses compared to using hydrophilic acrylic lenses for cataract treatment in the Polish inpatient and outpatient settings.MethodsA budget impact analysis (BIA) compared the economic outcomes associated with using hydrophobic acrylic lenses versus using hydrophilic lenses for patients undergoing cataract surgery. The BIA predicted annual expenses in the following scenarios: performing Nd:YAG to treat PCO within 2 and 3 years after implantation of hydrophobic or hydrophilic acrylic lenses for different lens structure. Data used to assess the frequency of PCO was determined in systematic literature review. Costs of current and predicted interventions were estimated based on average data from 19 Polish hospitals. Prices of health services were taken from official public tariff lists.ResultsThe use of a hydrophobic lens significantly limits the number of complications after cataract surgery relative to a hydrophilic lens. As hydrophobic lenses have a higher unit price their use increases the cost of treatment which currently is not reflected by adequate difference in price of the service. Total annual National Health Fund (NHF) expenses for 3-year follow-up model range from 139.1 million EUR to 143.1 million EUR depending on the lens structure, due to the cost of complications.ConclusionsBIA indicates the possibility of introducing surcharge for the use of hydrophobic lenses, which could increase the frequency of their use and reduce the number of complications after cataract surgery. It was estimated that total NHF expenses reach the minimum value for the surcharge at the level of 9 EUR. The surcharge of 14 EUR is the maximum value that does not increase the initial NHF expenses.
Failure of anti Interleukin-1 β monoclonal antibody in the treatment of recurrent pericarditis in two children
Authors: Signa Sara , D’Alessandro Matteo , Consolini Rita , Miniaci Angela , Bustaffa Marta , Longo Chiara , Tosca Maria A. , Bizzi Martina , Caorsi Roberta , Mendonça Leonardo Oliveira , Pession Andrea , Ravelli Angelo , Gattorno Marco 
Published: June 2020

Abstract
Background
Recurrent pericarditis (RP) is a complication (15–30%) of acute pericarditis with an unknown etiology. Treatment regimen consists of a combination of non-steroidal anti-inflammatory drugs (NSAIDs) and colchicine, with the addition of corticosteroids in resistant or intolerant cases. In the last decade anakinra was shown as an effective treatment in patients with colchicine resistant and steroid-dependent RP, initially in anecdotal reports in children and more recently in a randomized trial. Canakinumab is a monoclonal antibody selectively blocking IL-1β and its use is only anecdotally reported to treat pericarditis. We report two pediatric patients with refractory recurrent pericarditis, who presented an optimal response to anakinra treatment but prompt relapse after switch to canakinumab.

Case presentation
The first patient is a girl with Recurrent Pericarditis started in April 2015, after heart surgery. NSAIDs and oral steroids were started, with prompt relapse after steroid suspension. The child showed a steroid-dependent RP; anakinra was therefore started with excellent response, but discontinued after 2 weeks for local reactions. In July 2016 therapy with canakinumab was started. She experienced four relapses during canakinumab therapy despite dosage increase and steroid treatment. In January 2018 a procedure of desensitization from anakinra was performed, successfully. Anakinra as monotherapy is currently ongoing, without any sign of flare.
The second patient is a girl with an idiopathic RP, who showed an initial benefit from NSAIDs and colchicine. However, 10 days after the first episode a relapse occurred and therapy with anakinra was established. Two months later, while being in complete remission, anakinra was replaced with canakinumab due to patient’s poor compliance to daily injections. She experienced a relapse requiring steroids 10 days after the first canakinumab injection. Anakinra was subsequently re-started with complete remission, persisting after 24 months follow-up.

Conclusions
We describe two cases of failure of the treatment with anti-IL-1β monoclonal antibodies in steroid- dependent idiopathic RP. This anecdotal and preliminary observation suggests a different efficacy of the two IL-1 blockers in the management of RP and support a possible pivotal role of IL-1α in the pathogenesis of this condition.
Regulation of Hippo-YAP signaling by insulin-like growth factor-1 receptor in the tumorigenesis of diffuse large B-cell lymphoma
Authors: Zhou Xiangxiang , Chen Na , Xu Hongzhi , Zhou Xiaoming , Wang Jianhong , Fang Xiaosheng , Zhang Ya , Li Ying , Yang Juan , Wang Xin 
Published: June 2020

Abstract
Background
Hippo-Yes-associated protein (YAP) signaling is a key regulator of organ size and tumorigenesis, yet the underlying molecular mechanism is still poorly understood. At present, the significance of the Hippo-YAP pathway in diffuse large B-cell lymphoma (DLBCL) is ill-defined.

Methods
The expression of YAP in DLBCL was determined in public database and clinical specimens. The effects of YAP knockdown, CRISPR/Cas9-mediated YAP deletion, and YAP inhibitor treatment on cell proliferation and the cell cycle were evaluated both in vitro and in vivo. RNA sequencing was conducted to detect dysregulated RNAs in YAP-knockout DLBCL cells. The regulatory effects of insulin-like growth factor-1 receptor (IGF-1R) on Hippo-YAP signaling were explored by targeted inhibition and rescue experiments.

Results
High expression of YAP was significantly correlated with disease progression and poor prognosis. Knockdown of YAP expression suppressed cell proliferation and induced cell cycle arrest in DLBCL cells. Verteporfin (VP), a benzoporphyrin derivative, exerted an anti-tumor effect by regulating the expression of YAP and the downstream target genes, CTGF and CYR61. In vitro and in vivo studies revealed that deletion of YAP expression with a CRISPR/Cas9 genome editing system significantly restrained tumor growth. Moreover, downregulation of IGF-1R expression led to a remarkable decrease in YAP expression. In contrast, exposure to IGF-1 promoted YAP expression and reversed the inhibition of YAP expression induced by IGF-1R inhibitors.

Conclusions
Our study highlights the critical role of YAP in the pathogenesis of DLBCL and uncovers the regulatory effect of IGF-1R on Hippo-YAP signaling, suggesting a novel therapeutic strategy for DLBCL.
The value of secondary neoadjuvant chemotherapy in platinum-sensitive recurrent ovarian cancer: a case-control study post GOG-0213 trial
Authors: Gu Hongyuan , Zhou Rui , Ni Jing , Xu Xia , Cheng Xianzhong , Li Yan , Chen Xiaoxiang 
Published: June 2020

AbstractBackgroundThe prognostic value and optimal resection outcome related factors of the secondary cytoreduction surgery (SCR) in Platinum-sensitive recurrent ovarian cancer (PSOC) patients were still in doubt. The present retrospective study aims to determine the relationship between the objective response of secondary neo-adjuvant chemotherapy (SNAC) and the resection outcome of SCR.MethodsData were reviewed from 142 type II PSOCs who underwent SCR in Jiangsu Institute of Cancer Research between 1996 and 2016. Among them, 55 cases received preliminary Platinum based SNAC before SCR. Logistic regression analysis was used to explore optimal SCR related factors. Cox proportional hazards model and log-rank test were used to assess the associations between the survival durations and covariates.ResultsOptimal initial CRS (p = 0.02), disappearance of ascites after SNAC (p = 0.04) recurrent status (p = 0.02) and longer Platinum-free interval (p = 0.01) were the independent indicators of optimal SCR. Optimal SCR was associated with time to progression (TTP) but not overall survival (OS) (p = 0.04 andp = 0.41). The TTP and OS of PSOCs underwent SNAC were similar to those patients underwent SCR (p = 0.71, andp = 0.77, respectively) directly.ConclusionsSNAC might be another choice for PSOCs were not suitable for directly SCR. Optimal SCR had survival benefit in PSOCs whenever underwent SNAC or not.
SWISS: multiplexed orthogonal genome editing in plants with a Cas9 nickase and engineered CRISPR RNA scaffolds
Authors: Li Chao , Zong Yuan , Jin Shuai , Zhu Haocheng , Lin Dexing , Li Shengnan , Qiu Jin-Long , Wang Yanpeng , Gao Caixia 
Published: June 2020

AbstractWe describe here a CRISPR simultaneous and wide-editing induced by a single system (SWISS), in which RNA aptamers engineered in crRNA scaffold recruit their cognate binding proteins fused with cytidine deaminase and adenosine deaminase to Cas9 nickase target sites to generate multiplexed base editing. By using paired sgRNAs, SWISS can produce insertions/deletions in addition to base editing. Rice mutants are generated using the SWISS system with efficiencies of cytosine conversion of 25.5%, adenine conversion of 16.4%, indels of 52.7%, and simultaneous triple mutations of 7.3%. The SWISS system provides a powerful tool for multi-functional genome editing in plants.
Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis
Authors: Kralemann Lejon E. M. , Liu Shujing , Trejo-Arellano Minerva S. , Muñoz-Viana Rafael , Köhler Claudia , Hennig Lars 
Published: June 2020

Abstract
Background
Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&2 system, but its functional role remains elusive.

Results
We show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1.

Conclusions
Our data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.
Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial
Authors: Knobel Darryn , Odita Christianah Ibironke , Conan Anne , Barry Donna , Smith-Anthony Marshalette , Battice Juliet , England Shianne , Gessner Bradford D. 
Published: June 2020

Abstract
Background
Vaccines may cause non-specific effects (NSEs) on morbidity and mortality through immune-mediated mechanisms that are not explained by the prevention of the targeted disease. Much of the evidence for NSEs comes from observational studies with a high risk of bias, and there is a clear need for new data from randomized controlled trials. Recently, it was proposed that rabies vaccine has protective NSEs in people and in animals. The aim of the proposed study is to determine whether rabies vaccine reduces the incidence rate of episodes of common infectious disease syndromes in a population of veterinary students on the island of St. Kitts.

Methods
The trial design is a single-site, two-arm, parallel-group, participant-blinded, randomized, placebo-controlled, two-sided comparative study, with an internal pilot study for blinded sample size re-estimation. Allocation to study arm is by block randomization stratified by sex within cohort with a 1:1 allocation ratio. The primary study outcome is the number of new weekly episodes of common infectious diseases including respiratory, diarrheal and febrile illnesses. A vaccine immunogenicity ancillary study is planned.

Discussion
Demonstration of a non-specific protective effect of rabies vaccine against unrelated respiratory, gastrointestinal and febrile illnesses would provide supportive evidence for the design of similar studies in children in populations with a high burden of these illnesses.

Trial registration
ClinicalTrials.gov, ID: NCT03656198. Registered on 24 August 2018.
Detection of DNA of filariae closely related to Mansonella perstans in faecal samples from wild non-human primates from Cameroon and Gabon
Authors: Gaillard Colette Marie , Pion Sebastien David , Hamou Hadjira , Sirima Constant , Bizet Charlotte , Lemarcis Thomas , Rodrigues Jules , Esteban Amandine , Peeters Martine , Mpoudi Ngole Eitel , Mombo Illich , Liégeois Florian , Martin Coralie , Boussinesq Michel , Locatelli Sabrina 
Published: June 2020

Abstract
Background
The Onchocercidae is a family of filarial nematodes with several species of medical or veterinary importance. Microfilariae are found in the blood and/or the dermis and are usually diagnosed in humans by microscopy examination of a blood sample or skin biopsy. The main objectives of this study were to evaluate whether filariae DNA can be detected in faecal samples of wild non-human primates (NHPs), whether the detected parasites were closely related to those infecting humans and whether filarial DNA detection in faeces is associated with co-infections with nematodes (Oesophagostumum sp. and Necator sp.) known to cause blood loss while feeding on the host intestinal mucosa.

Methods
A total of 315 faecal samples from 6 species of NHPs from Cameroon and Gabon were analysed. PCRs targeted DNA fragments of cox1 and 12S rDNA genes, to detect the presence of filariae, and the internal transcribed spacer 2 (ITS2), to detect the presence of Oesophagostomum sp. and Necator sp. infections.

Results
Among the 315 samples analysed, 121 produced sequences with > 90% homology with Onchocercidae reference sequences. However, 63% of the 12S rDNA and 78% of the cox1 gene sequences were exploitable for phylogenetic analyses and the amplification of the 12S rDNA gene showed less discriminating power than the amplification of the cox1 fragment. Phylogenetic analyses showed that the cox1 sequences obtained from five chimpanzee DNA faecal samples from Gabon and two from Cameroon cluster together with Mansonella perstans with high bootstrap support. Most of the remaining sequences clustered together within the genus Mansonella, but the species could not be resolved. Among the NHP species investigated, a significant association between filarial DNA detection and Oesophagostomum sp. and Necator sp. infection was observed only in gorillas.

Conclusions
To our knowledge, this is the first study reporting DNA from Mansonella spp. in faecal samples. Our results raise questions about the diversity and abundance of these parasites in wildlife, their role as sylvatic reservoirs and their potential for zoonotic transmission. Future studies should focus on detecting variants circulating in both human and NHPs, and improve the molecular information to resolve or support taxonomy classification based on morphological descriptions.
Contribution of gene mutations to Silver-Russell syndrome phenotype: multigene sequencing analysis in 92 etiology-unknown patients
Authors: Inoue Takanobu , Nakamura Akie , Iwahashi-Odano Megumi , Tanase-Nakao Kanako , Matsubara Keiko , Nishioka Junko , Maruo Yoshihiro , Hasegawa Yukihiro , Suzumura Hiroshi , Sato Seiji , Kobayashi Yoshiyuki , Murakami Nobuyuki , Nakabayashi Kazuhiko , Yamazawa Kazuki , Fuke Tomoko , Narumi Satoshi , Oka Akira , Ogata Tsutomu , Fukami Maki , Kagami Masayo 
Published: June 2020

AbstractBackgroundSilver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features. Major (epi)genetic causes of SRS are loss of methylation on chromosome 11p15 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). However,IGF2,CDKN1C,HMGA2, andPLAG1mutations infrequently cause SRS. In addition, other imprinting disturbances, pathogenic copy number variations (PCNVs), and monogenic disorders sometimes lead to SRS phenotype. This study aimed to clarify the frequency and clinical features of the patients with gene mutations among etiology-unknown patients with SRS phenotype.ResultsMultigene sequencing was performed in 92 out of 336 patients referred to us for genetic testing for SRS. The clinical features of the patients were evaluated based on the Netchine-Harbison clinical scoring system. None of the patients showed 11p15 LOM, upd(7)mat, abnormal methylation levels for six differentially methylated regions (DMRs), namely,PLAGL1:alt-TSS-DMR on chromosome 6,KCNQ1OT1:TSS-DMR on chromosome 11,MEG3/DLK1:IG-DMR on chromosome 14,MEG3:TSS-DMR on chromosome 14,SNURF:TSS-DMR on chromosome 15, andGNAS A/B:TSS-DMR on chromosome 20, PCNVs, or maternal uniparental disomy of chromosome 16. Using next-generation sequencing and Sanger sequencing, we screened four SRS-causative genes and 406 genes related to growth failure and/or skeletal dysplasia. We identified four pathogenic or likely pathogenic variants in responsible genes for SRS (4.3%:IGF2in two patients,CDKN1C, andPLAG1), and five pathogenic variants in causative genes for known genetic syndromes presenting with growth failure (5.4%:IGF1Rabnormality (IGF1R), SHORT syndrome (PIK3R1), Floating-Harbor syndrome (SRCAP), Pitt-Hopkins syndrome (TCF4), and Noonan syndrome (PTPN11)). Functional analysis indicated the pathogenicity of theCDKN1Cvariant. The variants we detected inCDKN1CandPLAG1were the second and third variants leading to SRS, respectively. Our patients withCDKN1CandPLAG1variants showed similar phenotypes to previously reported patients. Furthermore, our data confirmedIGF1Rabnormality, SHORT syndrome, and Floating-Harbor syndrome are differential diagnoses of SRS because of the shared phenotypes among these syndromes and SRS. On the other hand, the patients with pathogenic variants in causative genes for Pitt-Hopkins syndrome and Noonan syndrome were atypical of these syndromes and showed partial clinical features of SRS.ConclusionsWe identified nine patients (9.8%) with pathogenic or likely pathogenic variants out of 92 etiology-unknown patients with SRS phenotype. This study expands the molecular spectrum of SRS phenotype.
Treatment of vocal fold scarring with autologous bone marrow-derived human mesenchymal stromal cells—first phase I/II human clinical study: commentary to response
Authors: Hertegård Stellan , LeBlanc Katarina 
Published: June 2020

AbstractWe would like to thank for the interest for the article and comments in the response. We believe that cell therapy may offer a treatment for severe voice problems in patients with vocal fold scarring and MSC treatment is a valuable alternative.
In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT
Authors: Tsartsalis Stergios , Tournier Benjamin B. , Millet Philippe 
Published: June 2020

Abstract
Background
[123I]epidepride is a high-affinity radiotracer used in single-photon emission computed tomography (SPECT) imaging of the D2/3 receptors. It binds with high affinity to striatal and extrastriatal receptors. Nevertheless, its slow kinetics in the striatum impedes quantification in this region. Thus, an approach that would allow a simultaneous quantification of both striatal and extrastriatal D2/3 receptors would be of interest for preclinical and clinical SPECT neuroimaging. We describe a partial saturation protocol that allows us to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately in both striatal and extrastriatal regions, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]epidepride using a two-tissue compartment, 5-parameter model (2T-5k).

Methods
Eighteen male rats were used. Binding parameters were estimated using the multi-injection protocol. Various simulations were performed to estimate the optimal conditions for the partial saturation protocol, which was applied at the region and voxel level. The results of the partial saturation study were compared to those obtained with the 2T-5k model. To illustrate the interest of the partial saturation approach, we performed a preliminary study of the effect of a chronic, subcutaneous administration of haloperidol (1 mg/kg/day), a D2 receptor antagonist, on the Bavail of [123I]epidepride in the rat striatum.

Results
A series of simulations demonstrated that a mass of 3 ug/kg of unlabeled epidepride allows the formation of an in vivo Scatchard plot. The partial saturation study led to robust estimations of Bavail in all brain regions that highly correlated (r = 0.99) with the corresponding values from the multi-injection study. A chronic haloperidol treatment resulted in a 17.9% increase in the Bavail values in the left Caudate Putamen nucleus (CP) (p = 0.07) and a 13.8% increase in the right CP (p = 0.12).

Conclusion
A partial saturation method allowed the robust quantification of D2/3 receptors in striatal and extrastriatal D2/3 receptors with a single-scan approach. This approach may be applied in the mapping of the D2/3 receptor in translational biological studies and potentially, in clinical SPECT imaging.
Combination of intramuscular alfaxalone, butorphanol, and midazolam as a novel immobilization protocol in 3 ring-tailed lemurs (Lemur catta)
Authors: Pentsou Kyratsoula , Huuskonen Vilhelmiina 
Published: June 2020

Abstract
Background
There is very little data on the optimal anaesthetic management of ring-tailed lemurs, and the available information is mostly based on extrapolation from other species. In addition, a thorough pre-anaesthetic assessment of lemurs might not be possible without prior chemical immobilization, making a safe immobilization protocol essential.

Case presentation
Three ring-tailed lemurs (Lemur catta) were immobilized using a combination of intramuscular alfaxalone (5 mg/kg), butorphanol (0.2 mg/kg), and midazolam (0.2 mg/kg), at the University College Dublin Veterinary Hospital. One lemur was anaesthetised once, two lemurs twice, amounting to five anaesthetic events. Conversion to general anaesthesia was warranted in all five occasions, and anaesthesia was maintained with either sevoflurane in oxygen or alfaxalone infusion. The immobilization protocol provided an adequate duration of deep sedation for diagnostic procedures and in some occasions allowed the intubation of the trachea. Analgesia was also provided for minor procedures. No major complications were noted with the protocol used.

Conclusions
The combination of intramuscular alfaxalone, butorphanol and midazolam provided a clinically useful sedation/immobilization in ring-tailed lemurs with only minor complications such as mild hypothermia, hypotension, hypoventilation and bradycardia. This protocol could be considered in ring-tailed lemurs that need to be immobilized for minor procedures, or as a pre-anaesthetic premedication, especially if a full pre-anaesthetic clinical exam is not possible.