bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel therapeutics in myeloproliferative neoplasms
Authors: Venugopal Sangeetha , Mascarenhas John 
Published: December 2020

AbstractHyperactive signaling of the Janus-Associated Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway is central to the pathogenesis of Philadelphia-chromosome-negative myeloproliferative neoplasms (MPN), i.e., polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) which are characterized by inherent biological and clinical heterogeneity. Patients with MPNs suffer from substantial symptom burden and curtailed longevity due to thrombohemorrhagic complications or progression to myelofibrosis or acute myeloid leukemia. Therefore, the management strategies focus on thrombosis risk mitigation in PV/ET, alleviation of symptom burden and improvement in cytopenias and red blood cell transfusion requirements, and disease course alteration in PMF. The United States Food and Drug Administration’s (USFDA) approval of two JAK inhibitors (ruxolitinib, fedratinib) has transformed the therapeutic landscape of MPNs in assuaging the need for frequent therapeutic phlebotomy (PV) and reduction in spleen and symptom burden (PV and PMF). Despite improving biological understanding of these complex clonal hematopoietic stem/progenitor cell neoplasms, none of the currently available therapies appear to modify the proclivity of the disease per se, thereby remaining an urgent unmet clinical need and an ongoing area of intense clinical investigation. This review will highlight the evolving targeted therapeutic agents that are in early- and late-stage MPN clinical development.
HDAC2 inhibits EMT-mediated cancer metastasis by downregulating the long noncoding RNA H19 in colorectal cancer
Authors: Hu Xue-ting , Xing Wei , Zhao Rong-sen , Tan Yan , Wu Xiao-feng , Ao Luo-quan , Li Zhan , Yao Meng-wei , Yuan Mu , Guo Wei , Li Shang-ze , Yu Jian , Ao Xiang , Xu Xiang 
Published: December 2020

Abstract
Background
Emerging evidence suggests that epithelial mesenchymal transition (EMT) and epigenetic mechanisms promote metastasis. Histone deacetylases (HDACs) and noncoding RNAs (ncRNAs) are important epigenetic regulators. Here, we elucidated a novel role of histone deacetylase 2 (HDAC2) in regulating EMT and CRC metastasis via ncRNA.

Methods
The expression of HDACs in CRC was analyzed using the public databases and matched primary and metastatic tissues, and CRC cells with different metastatic potentials (DLD1, HCT116, SW480 and SW620). Microarray analysis was used to identify differential genes in parental and HDAC2 knockout CRC cells. EMT and histone modifications were determined using western blot and immunofluorescence. Migration ability was assessed by transwell assay, and metastasis was assessed in vivo using a tail vain injection. Gene expression and regulation was assessed by RT-PCR, chromatin immunoprecipitation and reporter assays. Protein interaction was assessed by immunoprecipitation. Specific siRNAs targeting H19, SP1 and MMP14 were used to validate their role in HDAC2 loss induced EMT and metastasis.

Results
Reduced HDAC2 expression was associated with poor prognosis in CRC patients and found in CRC metastasis. HDAC2 deletion or knockdown induced EMT and metastasis by upregulating the long noncoding RNA H19 (LncRNA H19). HDAC2 inhibited LncRNA H19 expression by histone H3K27 deacetylation in its promoter via binding with SP1. LncRNA H19 functioned as a miR-22-3P sponge to increase the expression of MMP14. HDAC2 loss strongly promoted CRC lung metastasis, which was suppressed LncRNA H19 knockdown.

Conclusion
Our study supports HDAC2 as a CRC metastasis suppressor through the inhibition of EMT and the expression of H19 and MMP14.
Giardia duodenalis multi-locus genotypes in dogs with different levels of synanthropism and clinical signs
Authors: Uiterwijk Mathilde , Mughini-Gras Lapo , Nijsse Rolf , Wagenaar Jaap A. , Ploeger Harm W. , Kooyman Frans N. J. 
Published: December 2020

AbstractBackgroundIn dogs, infections withGiardia duodenalisare mainly caused by assemblages C and D, but also by the potentially zoonotic assemblages A and B. The aims of this study were to assess differences in assemblages (i) between dogs living mainly in close proximity to humans (synanthropic dogs)versusdogs living mainly among other dogs, (ii) between samples of dogs with or without loose stool, and (iii) related to the amount of cysts shedding.MethodsOne hundred eighty-nine qPCRGiardiapositive fecal samples of dogs originating from four groups (household, sheltered, hunting, and dogs for which a veterinarian sent a fecal sample to a diagnostic laboratory) were used for genotyping. For this, multi-locus genotyping of beta-giardin, triose phosphate isomerase, and glutamate dehydrogenase and genotyping ofSSU rDNAgene fragments were performed. Fecal consistency was scored (loose or non-loose stool), and cysts per gram of feces were determined with qPCR.ResultsAssemblage D was the most prevalent in all groups, followed by the other canid assemblage C. Also, mixed C/D was common. In two (synanthropic) household dogs, the potentially zoonotic assemblage AI was present. Although occurrence of assemblage AI in household dogs was not significantly different from dogs living among other dogs (sheltered and hunting dogs), it was significantly higher compared to dogs for which a sample was sent to a diagnostic laboratory. Dogs with assemblage D shed significantly more cysts than dogs with other assemblages (except for mixed C/D results) or dogs in which no assemblage could be determined. None of the assemblages was significantly associated with loose stool.ConclusionNot only do dogs mainly shed the canidGiardia duodenalisassemblages D and/or C, the numbers of cysts per gram for the canid assemblage D were also higher than for the potential zoonotic assemblage AI. Based on the assemblages shed by dogs, the risk to public health posed by dogs is estimated to be low, even though the dogs that shed AI were synanthropic household dogs. Loose stool in infected dogs was not associated with any particularGiardiaassemblage.
Effects of Bacillus subtilis on growth performance, serum parameters, digestive enzyme, intestinal morphology, and colonic microbiota in piglets
Authors: Deng Bo , Wu Jie , Li Xiaohui , Zhang Cheng , Men Xiaoming , Xu Ziwei 
Published: December 2020

AbstractThe present study was conducted to investigate effects of Bacillus subtilis on growth performance, serum parameters, digestive enzymes, intestinal morphology, and colonic microbiota in piglets. A total of 72 piglets were weighed and randomly allotted into three treatments (four replication pens per treatment with six piglets/pen) for a 28-day experiment. The dietary treatments were as follows: basal diet (control group, CTR), basal diet supplementation with antibiotic (antibiotic group, ABT), and basal diet supplementation with 0.1% Bacillus subtilis (probiotic group, PBT). The average daily gain of body weight increased in both the ABT and PBT groups, and dietary antibiotics decreased the feed:gain ratio (F:G), as compared to the CTR group (P < 0.05). Both ABT and PBT piglets had increased serum triglycerides and lipase, amylase, maltase activities and villus height:crypt depth ratio (V/C) in ileum (P < 0.05). The PBT group also showed an increase in serum glucose and villus height in the ileum (P < 0.05). Dietary antibiotics increased Lactobacillus johnsonii, as compared to the CTR group, but decreased bacterial diversity and increased Escherichia coli, as compared to the PBT group (P < 0.05). Piglets dietary with B. subtilis modulated the microbiota by increasing the abundance of Firmicutes (L. johnsonii, L. reuteri) and decreasing the abundance of E. coli, as compared to the control group (P < 0.05). These results indicate that dietary of B. subtilis improves growth performance and intestinal health and can be a promising alternative to antibiotics in piglets diet.
Does respiratory co-infection facilitate dispersal of SARS-CoV-2? investigation of a super-spreading event in an open-space office
Authors: Weissberg Dana , Böni Jürg , Rampini Silvana K. , Kufner Verena , Zaheri Maryam , Schreiber Peter W. , Abela Irene A. , Huber Michael , Sax Hugo , Wolfensberger Aline 
Published: December 2020

AbstractBackgroundSuper-spreaders are individuals infecting disproportionately large numbers of contacts. They probably play a crucial role in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe a super-spreading event within a team working in an open-space office and investigate factors potentially having facilitated SARS-CoV-2 transmission.MethodsIn this retrospective cohort study, semi-structured telephone interviews with all team members were carried out to identify symptoms, contacts, and adherence to basic hygiene measures. During site visits, we gathered information about workplace and seating arrangements. The secondary attack rate in office and households was calculated. Potential respiratory viral co-infections were assessed by multiplex PCR. SARS-CoV-2 whole-genome sequencing was performed using a tiled-amplicon sequencing approach.ResultsOf 13 team members, 11 fell ill with Coronavirus disease 2019 (COVID-19). Due to the sequence of events and full genome sequence data, one person was considered the index case for this outbreak, directly infecting 67 to 83% of the teammates. All team members reported repetitive close contacts among themselves during joint computer work, team meetings and a “Happy Birthday” serenade. Two individuals shared nuts and dates. The arrangement of the office and meeting rooms precluded sufficient adherence to physical distancing. The index case and a further individual were diagnosed with an adenovirus serotype 4 co-infection.ConclusionWe identified several environmental and behavioral factors that probably have facilitated the transmission of SARS-CoV-2. The relevance of the adenovirus co-infection remains unclear and merits further investigation.
Crime script analysis for adult image-based sexual abuse: a study of crime intervention points for retribution-style offenders
Authors: O’Hara Abigail C. , Ko Ryan K. L. , Mazerolle Lorraine , Rimer Jonah R. 
Published: December 2020

AbstractObjectiveThis research uses crime scripts to understand adult retribution-style image-based sexual abuse (RS-IBSA) offender decision-making and offending in offline and online environments. We explain the crime-commission process of adult RS-IBSA and identify crime intervention points at eight crime script stages.MethodsPublicly released court transcripts of adult RS-IBSA prosecution cases (n = 18) in New Zealand from 2015 to 2018 were utilised to examine the crime-commission process of adult RS-IBSA. We analysed the court transcripts thematically at offence-level prior to constructing the crime scripts.FindingsThe study identified four types of adult RS-IBSA acts including the non-consensual dissemination of a victim’s intimate images, violent cyber sextortion, covert intimate photography, and unauthorised access of a victim’s phone/media. From our analysis, we identified three script tracks and constructed three distinct crime scripts: (1) threats, sextortion and dissemination; (2) unauthorised access of a victim’s mobile device and dissemination; and (3) covert intimate filming. We highlight areas for potential intervention for law enforcement agencies and policy makers to increase deterrence and personal security in online and offline spaces.ConclusionAdult RS-IBSA occurs in a range of dating and domestic contexts. This study develops crime scripts for adult RS-IBSA and advances our understanding of how the Internet/smartphones/digital media translates into virtual crime scenes with opportunities for maximum harm infliction. We offer several policy implications including revising current RS-IBSA legislation and supporting law enforcement agencies with policing online and offline intimate relationship spaces through situational prevention.
Protective effects of Erythronium japonicum and Corylopsis coreana Uyeki extracts against 1,3-dichloro-2-propanol-induced hepatotoxicity in rats
Authors: Kim Seunghyun , Boo Hee-Ock , Ahn Taeho , Bae Chun-Sik 
Published: December 2020

AbstractErythronium japonicum (E. japonicum) and Corylopsis coreana Uyeki (C. coreana Uyeki, Korean winter hazel) have been shown to significantly decrease 1,3-dichloro-2-propanol (1,3-DCP)-induced generation of reactive oxygen species and CYP2E1 activity in HuH7, human hepatocytes. In this study, we expanded upon the previous study and investigated the effects of E. japonicum and C. coreana Uyeki extracts on 1,3-DCP-induced liver damage in rats. The pre-treatment of rats with these extracts alleviated a decrease in body weight and reduced 1,3-DCP-induced increase in catalytic activities of hepatic enzymes, such as aspartate aminotransferase and alanine aminotransferase, in the serum. Moreover, treatment with the extracts restored the 1,3-DCP-induced decreases in anti-oxidant enzyme activities, such as the activities of superoxide dismutase and catalase, in the rat liver. Histopathological studies also strongly supported the results of enzyme activities. These results suggest a possibility that the extracts of E. japonicum and C. coreana Uyeki can be a remedy for alleviating 1,3-DCP-induced liver damage in animals.
Diagnostic accuracy of contrast-enhanced digital mammography in comparison with sonomammography for characterization of focal asymmetries
Authors: Soliman Gelan Ali Mahmoud , Mohammad Shaimaa Abdelsattar , El-Shinawi Mohamed , Keriakos Nermeen Nasry 
Published: December 2020

Abstract
Background
Mammographic focal asymmetry represents normal breast tissue, benign, or malignant lesions. Accurate characterization is important for better management. The study evaluates diagnostic accuracy of contrast-enhanced digital mammography (CEDM) for characterization of focal asymmetries seen in 2D mammography.

Results
The study was done prospectively on 38 females among 360 patients who underwent baseline sonomammographic assessment for diagnostic and screening purposes. Complementary ultrasound was performed only when a finding was detected in cases of screening mammograms. Focal asymmetries were evaluated according to Breast Imaging Reporting and Data System (BI-RADS) lexicon 2013. CEDM was performed and followed by ultrasound (US) guided core biopsy for solid lesions or aspiration for cystic lesions. CEDM processing resulted in recombined image showing enhancing abnormality. Low energy image and recombined image findings were analyzed blindly and classified into focus enhancement, mass enhancement, non-mass enhancement, and non-enhanced lesions. CEDM and sonomammography findings were compared regarding pathological probability and multiplicity. Histopathology was the reference standard.
Mass enhancement showed strong correlation with malignant pathology. Non-mass enhancement showed no correlation with particular pathology. All non-enhanced focal asymmetries were benign in pathology or normal tissue. Rim enhancement needed second look ultrasound evaluation. CEDM was superior to sonomammography with higher sensitivity (77.8%, 65.7% respectively), NPV (0.8, 0.6), accuracy (0.6, 0.2) but lower specificity (81.8% vs. 100%). Multiplicity detection by CEDM was 26.3% and by sonomammography was 10.5%.

Conclusion
CEDM is more accurate than sonomammography in determination of normal tissue, benign, or malignant lesions in cases of mammographic focal asymmetry. CEDM is more accurate in detection of multiplicity. Undesired biopsies were avoidable with proper management of suspicious and malignant lesions.
Immunohistochemical analysis of stem cells from human exfoliated deciduous teeth seeded in carbonate apatite scaffold for the alveolar bone defect in Wistar rats (Rattus novergicus)
Authors: Saskianti Tania , Nugraha Alexander Patera , Prahasanti Chiquita , Ernawati Diah Savitri , Suardita Ketut , Riawan Wibi 
Published: December 2020

Background: Stem cells from human exfoliated deciduous teeth (SHED) seeded in carbonate apatite scaffold (CAS) may have multiple functions that could be used to regenerate the alveolar bone defects. The purpose of this study is to examine the ability of SHED and CAS in alveolar bone defects using an immunohistochemical analysis. Methods: ten three-month-old healthy male Wistar rats (R. novergicus) that weighed between 150–250 grams (g) were used as animal models. A simple blind random sampling method was used to select the sample that was assigned to the study group for CAS and SHED seeded in CAS (n=5). The animal study model of the alveolar bone was established by extracting the anterior mandible teeth. Rodent anesthesia was applied to relieve the pain during the procedure for all test animals. Immunohistochemistry was performed after seven days to facilitate the examination of the receptor activator of NF-κβ ligand (RANKL), osteoprotegrin (OPG), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin, and osteopontin expression. The data was analyzed using the unpaired t-test (p<0.01) and Pearson’s correlation test (p<0.05). Results: The OPG, RUNX2, TGF-β, VEGF, ALP, osteocalcin, and ostepontin expressions were higher in SHED seeded in CAS than CAS only with a significant difference between the groups (p<0.01). Furthermore, the RANKL expression was lower in SHED seeded in CAS compared to CAS only. There was a strong reverse significant correlation between OPG and RANKL expression (p<0.05). Conclusions: The number of osteogenic marker expressing cells, such as OPG, RUNX2, TGF-β, VEGF, ALP, osteocalcin, and ostepontin, increased. However, RANKL expression in the alveolar bone defects that were implanted with SHED seeded in CAS did not increase after seven days.
Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC
Authors: Garzón-Castaño Sandra Catalina , Jiménez-González Francisco Javier , Veloza Luz Angela , Sepúlveda-Arias Juan Carlos 
Published: December 2020

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H2O2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 μM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H2O2-induced oxidative stress in HepG2 cells.
The financial burden of reverse shoulder arthroplasty for proximal humerus fractures
Authors: Packer Timothy Wallace , Sabharwal Sanjeeve , Griffiths Dylan , Reilly Peter 
Published: December 2020

Aims The purpose of this study was to evaluate the cost of reverse shoulder arthroplasty (RSA) for patients with a proximal humerus fracture, using time-driven activity based costing (TDABC), and to compare treatment costs with reimbursement under the Healthcare Resource Groups (HRGs). Methods TDABC analysis based on the principles outlined by Kaplan and a clinical pathway that has previously been validated for this institution was used. Staffing cost, consumables, implants, and overheads were updated to reflect 2019/2020 costs. This was compared with the HRG reimbursements. Results The mean cost of a RSA is £7,007.46 (£6,130.67 to £8,824.67). Implants and staffing costs were the primary cost drivers, with implants (£2,824.80) making up 40% of the costs. Staffing costs made up £1,367.78 (19%) of overall costs. The total tariff, accounting for market force factors and high comorbidities, reimburses £4,629. If maximum cost and minimum reimbursement is applied the losses to the trust are £4,828.67. Conclusion RSA may be an effective and appropriate surgical option in the treatment of proximal humerus fractures; however, a cost analysis at our centre has demonstrated the financial burden of this surgery. Given its increasing use in trauma, there is a need to work towards generating an HRG that adequately reimburses providers. Cite this article: Bone Jt Open 2020;1-12:731–736.
Refinement of the CS6-expressing enterotoxigenic Escherichia coli strain B7A human challenge model: A randomized trial
Authors: Talaat Kawsar R. , Porter Chad K. , Jaep Kayla M. , Duplessis Christopher A. , Gutierrez Ramiro L. , Maciel Milton , Adjoodani Brittany , Feijoo Brittany , Chakraborty Subhra , Brubaker Jessica , Trop Stefanie A. , Riddle Mark S. , Joseph Sabrina S. , Bourgeois A. Louis , Prouty Michael G. 
Published: December 2020

Background
Human challenge models for enterotoxigenic Escherichia coli (ETEC) facilitate vaccine down-selection. The B7A (O148:H28 CS6+LT+ST+) strain is important for vaccine development. We sought to refine the B7A model by identifying a dose and fasting regimen consistently inducing moderate-severe diarrhea.

Methods
An initial cohort of 28 subjects was randomized (1:1:1:1) to receive B7A following an overnight fast at doses of 108 or 109 colony forming units (cfu) or a 90-minute fast at doses of 109 or 1010 cfu. A second cohort included naïve and rechallenged subjects who had moderate-severe diarrhea and were given the target regimen. Immune responses to important ETEC antigens were assessed.

Results
Among subjects receiving 108 cfu of B7A, overnight fast, or 109 cfu, 90-minute fast, 42.9% (3/7) had moderate-severe diarrhea. Higher attack rates (71.4%; 5/7) occurred in subjects receiving 109 cfu, overnight fast, or 1010 cfu, 90-minute fast. Upon rechallenge with 109 cfu of B7A, overnight fast, 5/11 (45.5%) had moderate-severe diarrhea; the attack rate among concurrently challenge naïve subjects was 57.9% (11/19). Anti-CS6, O148 LPS and LT responses were modest across all groups.

Conclusions
An overnight fast enabled a reduction in the B7A inoculum dose; however, the attack rate was inconsistent and protection upon rechallenge was minimal.