bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasonography of sudden swollen tongue in a calf
Authors: Tsuka Takeshi , Okamoto Yoshiharu , Sunden Yuji , Morita Takehito , Yamashita Masamichi , Osaki Tomohiro , Azuma Kazuo , Amaha Takao , Ito Norihiko , Murahata Yusuke , Imagawa Tomohiro
Published: June 2020

Background

In cattle, the lingual diseases are primarily diagnosed postmortem by histopathological examination of the affected tongues obtained after the death or during necropsy. In humans, ultrasonography has been used to provide differential diagnoses, and for preoperative or intraoperative planning of glossectomy in various lingual diseases. This is a bovine clinical case report, in which ultrasonography for sudden swelling of the tongue, which was possibly caused by snake bite, was utilized as a preoperative indication to perform a glossectomy.

Case presentation

An eight-month-old female Japanese black calf presented with sudden swelling of the tongue with well-defined discoloration in the cranial region. A 10-MHz linear probe on a portable-type ultrasound machine (MyLabOne VET, Esaote Co., Genova, Italy) was applied to the ventral surface of the tongues in the affected case, and also in five healthy calves under sedation to observe normal tongues. Ultrasonography of the swollen tongue in this case revealed that the ventral lingual muscular layers were severely thickened compared with those of normal tongues. However, the muscle layers were regularly aligned with the echogenic muscular fibers. This resembled the lingual muscular architectures of normal tongues. Color-flow Doppler ultrasonography revealed that blood flow was weakened in the small peripheral vessels in the spaces between the lingual muscular structures, and was lacking in the deep lingual artery between the apex and base of the tongue. This finding was very different than that of normal tongues, which exhibited weakened or rich blood flows. Based on ultrasonographic findings, this case was treated with glossectomy. After recovery, the calf grew up normally with a normal appetite and rumination, and did not exhibit mouth pain behavior. Histopathologically, hemorrhagic necrotic changes, together with focal formation of fibrin thrombus in the lingual blood vessels in the affected tongue, were noted.

Conclusions

To the best of our knowledge, the present report is the first description of lingual ultrasonography performed in cattle. In this case, ultrasonography enabled visualization of decreased vascularity, which might be associated with hemorrhage or formation of fibrin thrombus in the suddenly swollen tongue presented.
Metabolic role of pyrophosphate-linked phosphofructokinase pfk for C1 assimilation in Methylotuvimicrobium alcaliphilum 20Z
Authors: Nguyen Anh Duc , Nam Gayoung , Kim Donghyuk , Lee Eun Yeol
Published: June 2020

Background

Methanotrophs is a promising biocatalyst in biotechnological applications with their ability to utilize single carbon (C1) feedstock to produce high-value compounds. Understanding the behavior of biological networks of methanotrophic bacteria in different parameters is vital to systems biology and metabolic engineering. Interestingly, methanotrophic bacteria possess the pyrophosphate-dependent 6-phosphofructokinase (PPi-PFK) instead of the ATP-dependent 6-phosphofructokinase, indicating their potentials to serve as promising model for investigation the role of inorganic pyrophosphate (PPi) and PPi-dependent glycolysis in bacteria. Gene knockout experiments along with global-omics approaches can be used for studying gene functions as well as unraveling regulatory networks that rely on the gene product.

Results

In this study, we performed gene knockout and RNA-seq experiments in Methylotuvimicrobium alcaliphilum 20Z to investigate the functional roles of PPi-PFK in C1 metabolism when cells were grown on methane and methanol, highlighting its metabolic importance in C1 assimilation in M. alcaliphilum 20Z. We further conducted adaptive laboratory evolution (ALE) to investigate regulatory architecture in pfk knockout strain. Whole-genome resequencing and RNA-seq approaches were performed to characterize the genetic and metabolic responses of adaptation to pfk knockout. A number of mutations, as well as gene expression profiles, were identified in pfk ALE strain to overcome insufficient C1 assimilation pathway which limits the growth in the unevolved strain.

Conclusions

This study first revealed the regulatory roles of PPi-PFK on C1 metabolism and then provided novel insights into mechanism of adaptation to the loss of this major metabolic enzyme as well as an improved basis for future strain design in type I methanotrophs.
Matrine inhibits cell growth, migration, invasion and promotes autophagy in hepatocellular carcinoma by regulation of circ_0027345/miR-345-5p/HOXD3 axis
Authors: Lin Shaobing , Zhuang Jie , Zhu Liping , Jiang Zongsheng
Published: June 2020

Background

Matrine has been reported to exert anti-tumor effects in multiple types of cancers containing hepatocellular carcinoma (HCC). However, the anti-tumor molecular mechanisms of matrine in HCC is still not fully revealed.

Methods

Cell viability, apoptosis, cycle, migration and invasion were determined by Cell counting kit-8 (CCK-8), Flow cytometry and Transwell assays, respectively. Levels of all protein were analyzed by western blot analysis. The levels of circular RNA_0027345 (circ_0027345), microRNA-345-5p (miR-345-5p) and homeobox-containingD3 (HOXD3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circ_0027345 and circ_0027345 was identified using dual-luciferase reporter assay. The mouse xenograft model was constructed to explore the effect of matrine on tumor growth in vivo.

Results

Matrine suppressed cell growth, migration and invasion, while promoted apoptosis and autophagy in HCC cells. Matrine down-regulated the levels of circ_0027345 and HOXD3, and up-regulated miR-345-5p expression. Besides, circ_0027345 overexpression could reverse the inhibitory effect of matrine on cell progression. As the target gene of circ_0027345, miR-345-5p elevation counteracted the promotion effect of circ_0027345 overexpression on development of HCC cells. Moreover, miR-345-5p knockdown could facilitate cell growth, migration, invasion and repress cell apoptosis and autophagy by targeting HOXD3. Meanwhile, matrine restrained tumor growth of HCC by regulating circ_0027345/miR-345-5p/HOXD3 axis in vivo.

Conclusion

Matrine inhibited cell development and tumorigenesis in HCC by increasing miR-345-5p and decreasing circ_0027345 and HOXD3.
A low coefficient of variation in hepatic triglyceride concentration in an inbred rat strain
Authors: Shimoda Tomoko , Hori Shota , Maegawa Kenta , Takeuchi Akari , Lee Yeonmi , Joe Ga-Hyun , Tanaka Yasutake , Shimizu Hidehisa , Ishizuka Satoshi
Published: June 2020

Background

Inbred strains are characterized by less genetic variation, which suggests usefulness of inbred strains for evaluations of various parameters. In this study, experimental reproducibility in several parameters was compared between an outbred Wistar rat and Wistar King A Hokkaido (WKAH/HkmSlc) rat, the inbred strain that is originated from Wistar rats.

Methods

Difference of variations was investigated in parameters of body compositions and liver functions such as body weight, liver weight, liver triglycerides (TG), liver cholesterol and plasma alanine aminotransferase activity (ALT) between WKAH rats and outbred Wistar rats by using the coefficient of variation (CV).

Results

There was no difference in the CVs of body weight and relative liver weight between WKAH and Wistar rats. The CVs of body weight and relative liver weight were below 10% in both WKAH and Wistar rats. The CVs of TG, cholesterol, and ALT in Wistar rats were between 30 and 40%, whereas those in WKAH rats were between 10 and 25%. A low CV level of TG was observed in WKAH rats compared to that in Wistar rats regardless of the duration of the experimental period in those rat strains.

Conclusion

The low CV values in metabolic parameters involved in liver functions in the inbred rats suggested an advantage of using inbred rather than outbred rats for the evaluation of liver lipid metabolism.
Defining and classifying public health systems: a critical interpretive synthesis
Authors: Jarvis Tamika , Scott Fran , El-Jardali Fadi , Alvarez Elizabeth
Published: June 2020

Background

The introduction of the determinants of health has caused a shift towards understanding health from a holistic perspective as well as increased recognition of public health’s contributions to the health of the population. Several frameworks exist to conceptualise healthcare systems, highlighting the stark contrast of frameworks unique to public health systems. The objectives of this study were to define public health systems and assess differences between healthcare systems and public health systems within established health systems frameworks.

Methods

A critical interpretive synthesis was conducted. Databases searched included EBSCOhost, OVID, Scholars Portal, Web of Science, Cochrane Library and Health Systems Evidence. Data extraction, coding and analysis followed a best-fit framework analysis method. Initial codes were based on a current leading health systems and policy classification scheme – health systems arrangements (governance, financial and delivery arrangements).

Results

A total of 5933 unique documents were identified and 67 were included in the analysis. Definitions of public health and public health systems varied significantly as did their roles and functions across jurisdictions. Public health systems arrangements generally followed those of health systems, with the addition of partnerships (community and inter-sectoral) and communication playing a larger role in public health. A public health systems framework and conceptualisation of how public health currently fits within health systems are presented.

Conclusions

Public health systems are unique and vital entities within health systems. In addition to examining how public health and public health systems have been defined within the literature, this review suggests that establishing the scope of public health is crucial to understanding its role within the larger health system and adds to the discourse around the relationship between public health, healthcare and population health. More broadly, this study addresses an important gap in understanding public health systems and provides conceptual and practical contributions as well as areas for future research.
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

Background

Over 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.

Methods

A 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.

Results

The 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.

Conclusions

BIA 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

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

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

Background

The 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.

Methods

Data 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.

Results

Optimal 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.

Conclusions

SNAC 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

We 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

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

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

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

Background

Silver-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.

Results

Multigene 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.

Conclusions

We 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

We 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

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

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.
BRS cS: a hybrid recommendation model fusing multi-source heterogeneous data
Authors: Ji Zhenyan , Yang Chun , Wang Huihui , Armendáriz-iñigo José Enrique , Arce-Urriza Marta
Published: June 2020

Recommendation systems are often used to solve the problem of information overload on the Internet. Many types of data can be used for recommendations, and fusing different types of data can make recommendations more accurate. Most existing fusion recommendation models simply combine the recommendation results from different data instead of fully fusing multi-source heterogeneous data to make recommendations. Furthermore, users’ choices are usually affected by their direct and even indirect friends’ preferences. This paper proposes a hybrid recommendation model BRS cS (an acronym for BPR-Review-Score-Social). It fully fuses social data, score, and review together; uses improved BPR model to optimize the ranking; and trains them in a joint representation learning framework to get the top-N recommendations. User trust model is used to introduce social relationships into the rating and review data, PV-DBOW model is used to process the review data, and fully connected neural network is used to process the rating data. Experiments on Yelp public dataset show that the BRS cS algorithm proposed outperforms other recommendation algorithms such as BRS c, UserCF, and HRS c. The BRS cS model is also scalable and can fuse new types of data easily.
EU wine policy in the framework of the CAP: post-2020 challenges
Authors: Pomarici Eugenio , Sardone Roberta
Published: June 2020

The EU Common Agricultural Policy (CAP), and with it the EU wine policy, is experiencing a reform process, started in 2018, in order to address ambitious environmental and social objectives, in conjunction with the goal of a competitive agricultural sector.

Given the role of the EU in wine supply, the aim of this paper is to present the design, the rationale and the potential effect of the proposed reform with specific reference to wine sector. To better understand the forthcoming process, it is firstly presented how CAP and its wine policy evolved in terms of objectives and tools over time.

The EU wine policy is a paradigmatic example of a combination between the horizontal measures, valid for all agricultural sectors, and vertical measures, peculiarly encompassing the whole wine supply chain. The reform proposal confirms, with some interesting modifications, the set of tools already operating in the sector; however, it calls for a planning of the implementation of the available tools for all products in a unitary frame represented by a national CAP Strategic Plan, applying a lean administrative procedure.

In the hypothesis that the COVID-19 outbreak will not cause a radical change in the global agri-food system, the proposed planning process should stimulate shared strategies. These are intended to effectively coordinate, according to the principle of complementarity, the implementation of available policy tools, in order to obtain a better use of resources and a more balanced achievement of all policy objectives.
Retraction Note: Application of 4% chlorhexidine to the umbilical cord stump of newborn infants in lower income countries: a systematic review and meta-analysis
Authors: Roba Aklilu Abrham , Tefera Maleda , Worku Teshager , Dasa Tamirat Tesfaye , Estifanos Abiy Seifu , Assefa Nega
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Tailoring of the ongoing water, sanitation and hygiene interventions for prevention and control of COVID-19
Authors: Mushi Vivian , Shao Magdalena
Published: June 2020

Water, sanitation, and hygiene (WASH) interventions remain to be important in the prevention of further spread of coronavirus disease-2019 (COVID-19). Basic hygiene interventions such as handwashing with water and soap (HWWS) when applied consistently will deactivate and remove the virus particles from the hands. Realizing the efforts that have been made by countries world over in controlling the COVID-19, this letter seeks to discuss how the available WASH services can be used in the fight against further spread of COVID-19. The letter highlights the challenges being faced by the current WASH services in middle- and low-income countries and suggests measures that can be employed to strengthen the WASH services in this period of the COVID-19 pandemic.
The protective effect of propolis against aluminum chloride-induced hepatorenal toxicity in albino rats
Authors: Okail Hanan A. , Ibrahim Ahmed S. , Badr Amira H.
Published: June 2020

Background

The use of natural products is an essential way to new pharmaceutical leads for the discovery and development of new drugs to treat diseases. Propolis (Pro) is a natural resinous product produced by honey bees. It has a strong cytoprotective effect against various exogenous toxic agents. The current study was designed to evaluate the possible protective effect of propolis against the toxicity of aluminum chloride (AlCl3) on hepatorenal structure and function in male white albino rats.

Methods

Thirty mature males of albino rat, Rattus rattus, weighing about 80-90g were divided into five groups contained 6 rats each. The first group acts as a control (received only saline solution); the second group (Al) had given orally 40 mg/kg b.w. of AlC13, the third group (Pro) had administrated orally 150 mg/kg b.w. of propolis and the fourth group (Al+Pro) had given 40 mg/kg b.w. of AlCl3 in the morning and 150 mg/kg b.w. of propolis in the evening. These four groups had given the treatments for two months. The fifth group (Al-Pro) had given 40 mg/kg b.w. of AlC13 chloride for one month then had given 40 mg/kg b.w. of AlCl3 combined with 150 mg/kg b.w. of propolis for another month.

Results

The AlCl3-treated group showed a significant increase in the activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), acid phosphatase (AP), and lactate dehydrogenase (LDH) in the plasma. Also, glucose, total protein, albumin, creatinine, uric acid, urea, cholesterol, and triglycerides in the plasma were significantly increased. The histological examination for the liver and kidney sections revealed marked histopathological alternations. The treatment with propolis combined with AlCl3 improved the previous mentioned biochemical and histological alterations induced by AlCl3.

Conclusion

It can be concluded that the combination of propolis with AlCl3 alleviated the toxic effects of AlCl3. The propolis has protective influences on the hepatorenal structure and function and could be able to resist AlCl3 intoxication.
Evaluation and future framework of green mine construction in China based on the DPSIR model
Authors: Chen Jinhui , Jiskani Izhar Mithal , Jinliang Chen , Yan Hui
Published: June 2020

The idea of green mining was proposed as a practical approach to make the mining industry more sustainable than before. Green mining is a contemporary mining model centered on the sustainability of resources, environment, and socio-economic benefits. Its purpose is to develop and apply technologies and processes that increase environmental performance while maintaining competitiveness throughout the entire mining cycle from exploration to post-closure. Although the green mining strategy has achieved considerable significance, there is still a considerable gap between its research and practice. This study evaluates the situation of green mine construction in China and suggests a future framework. First, based on the Driver–Pressure–State–Impact–Response model, an evaluation index system composed of 20 indicators was established. The principal component analysis was used to analyze the data collected from mines situated in Yongcheng, China. The results show that the construction of green mines has improved significantly over the years. Energy consumption and pollutant emissions were minimized, the protection of the ecological environment was realized, and secondary processing of mining waste was practiced. However, there are still some unresolved problems, such as the utilization of solid waste, the recovery ratio from ore processing, and the reuse ratio of coal washing water. Thus, the strategic framework has been proposed for improving green mine construction and the sustainability of the mining industry.
Awareness of obstructive sleep apnea among critical care physicians in Sharkia Governorate, Egypt
Authors: Embarak Sameh , Zake Lamiaa G. , Abd-El-Azem W. , Sileem Ashraf E.
Published: June 2020

Background

Patients with symptoms of obstructive sleep apnea (OSA) present to nearly all physicians irrespective of their specialties. A basic knowledge of OSA is considered essential to identify those patients for appropriate referral and treatment. This study aimed to assess the knowledge and attitude of Sharkia Governorate Critical Care physicians regarding OSA using a standard validated questionnaire.

Results

This cross-sectional survey study was performed on a sample of Sharkia Governorate physicians, from all critical care units in tertiary and secondary hospitals including the following specialties: chest, internal medicine, neurology, cardiology, pediatric, and anesthesia. The OSA knowledge and attitudes (OSAKA) questionnaire that consists of 18 knowledge assessment questions and the OSA attitude questionnaire that consists of 6 attitude assessment questions were used. A total of 231, out of 296 invited physicians, completed the given questionnaire with a response rate of 78%. The mean score for knowledge assessment was 10.05 ± 2.3 with a 33.3% adequate response, while the mean score for attitude assessment was 3.75 ± 1.22 with a 59.3% adequate response. The mean OSA knowledge (12.5 ± 2.42) and attitude (5 ± 0.78) scores were highest among chest physicians when compared to physicians from other specialties (p < 0.001). A significant positive correlation between knowledge and attitude scores was found among Sharkia Governorate critical care physicians (r = 0.55, p < 0.001).

Conclusions

The level of knowledge of OSA among Sharkia Governorate critical care physicians was far from optimal whereas the attitude regarding OSA was acceptable.
The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses
Authors: Amore Mario , Murri Martino Belvederi , Calcagno Pietro , Rocca Paola , Rossi Alessandro , Aguglia Eugenio , Bellomo Antonello , Blasi Giuseppe , Carpiniello Bernardo , Cuomo Alessandro , dell’Osso Liliana , di Giannantonio Massimo , Giordano Giulia Maria , Marchesi Carlo , Monteleone Palmiero , Montemagni Cristiana , Oldani Lucio , Pompili Maurizio , Roncone Rita , Rossi Rodolfo , Siracusano Alberto , Vita Antonio , Zeppegno Patrizia , Corso Alessandro , Arzani Costanza , Galderisi Silvana , Maj Mario ,   Italian Network for Research on Psychoses
Published: June 2020

Background.

Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions.

Methods.

Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression.

Results.

After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms.

Conclusions.

In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem.
Mending Disconnects in Cancer Care: Setting an Agenda for Research, Practice, and Policy
Authors: Alfano Catherine M. , Mayer Deborah K. , Beckjord Ellen , Ahern David K. , Galioto Michele , Sheldon Lisa K. , Klesges Lisa M. , Aronoff-Spencer Eliah , Hesse Bradford W.
Published: June 2020

Cancer in the United States accounts for $600 billion in health care costs, lost work time and productivity, reduced quality of life, and premature mortality. The future of oncology delivery must mend disconnects to equitably improve patient outcomes while constraining costs and burden on patients, caregivers, and care teams. Embedding learning health systems into oncology can connect care, engaging patients and providers in fully interoperable data systems that remotely monitor patients; generate predictive and prescriptive analytics to facilitate appropriate, timely referrals; and extend the reach of clinicians beyond clinic walls. Incorporating functional learning systems into the future of oncology and follow-up care requires coordinated national attention to 4 synergistic strategies: (1) galvanize and shape public discourse to develop and adopt these systems, (2) demonstrate their value, (3) test and evaluate their use, and (4) reform policy to incentivize and regulate their use.