bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study
Authors: Garcia-Manero Guillermo , Griffiths Elizabeth A. , Steensma David P. , Roboz Gail J. , Wells Richard , McCloskey James , Odenike Olatoyosi , DeZern Amy E. , Yee Karen , Busque Lambert , O’Connell Casey , Michaelis Laura C. , Brandwein Joseph , Kantarjian Hagop , Oganesian Aram , Azab Mohammad , Savona Michael R. 
Published: April 2020

Abstract
This phase 2 study was designed to compare systemic decitabine exposure, demethylation activity, and safety in the first 2 cycles with cedazuridine 100 mg/decitabine 35 mg vs standard decitabine 20 mg/m2 IV. Adults with International Prognostic Scoring System intermediate-1/2- or high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) were randomized 1:1 to receive oral cedazuridine/decitabine or IV decitabine in cycle 1, followed by crossover to the other treatment in cycle 2. All patients received oral cedazuridine/decitabine in subsequent cycles. Cedazuridine and decitabine were given initially as separate capsules in a dose-confirmation stage and then as a single fixed-dose combination (FDC) tablet. Primary end points: mean decitabine systemic exposure (geometric least-squares mean [LSM]) of oral/IV 5-day area under curve from time 0 to last measurable concentration (AUClast), percentage long interspersed nuclear element 1 (LINE-1) DNA demethylation for oral cedazuridine/decitabine vs IV decitabine, and clinical response. Eighty patients were randomized and treated. Oral/IV ratios of geometric LSM 5-day AUClast (80% confidence interval) were 93.5% (82.1-106.5) and 97.6% (80.5-118.3) for the dose-confirmation and FDC stages, respectively. Differences in mean %LINE-1 demethylation between oral and IV were ≤1%. Clinical responses were observed in 48 patients (60%), including 17 (21%) with complete response. The most common grade ≥3 adverse events regardless of causality were neutropenia (46%), thrombocytopenia (38%), and febrile neutropenia (29%). Oral cedazuridine/decitabine (100/35 mg) produced similar systemic decitabine exposure, DNA demethylation, and safety vs decitabine 20 mg/m2 IV in the first 2 cycles, with similar efficacy. This study is registered at www.clinicaltrials.gov as #NCT02103478.
Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736
Authors: Moore Andrew S. , Faisal Amir , Mak Grace W. Y. , Miraki-Moud Farideh , Bavetsias Vassilios , Valenti Melanie , Box Gary , Hallsworth Albert , de Haven Brandon Alexis , Xavier Cristina P. R. , Stronge Randal , Pearson Andrew D. J. , Blagg Julian , Raynaud Florence I. , Chopra Rajesh , Eccles Suzanne A. , Taussig David C. , Linardopoulos Spiros 
Published: April 2020

AbstractInternal tandem duplication of FLT3 (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML); it causes constitutive activation of FLT3 kinase and is associated with high relapse rates and poor survival. Small-molecule inhibition of FLT3 represents an attractive therapeutic strategy for this subtype of AML, although resistance from secondary FLT3 tyrosine kinase domain (FLT3-TKD) mutations is an emerging clinical problem. CCT241736 is an orally bioavailable, selective, and potent dual inhibitor of FLT3 and Aurora kinases. FLT3-ITD+ cells with secondary FLT3-TKD mutations have high in vitro relative resistance to the FLT3 inhibitors quizartinib and sorafenib, but not to CCT241736. The mechanism of action of CCT241736 results in significant in vivo efficacy, with inhibition of tumor growth observed in efficacy studies in FLT3-ITD and FLT3-ITD-TKD human tumor xenograft models. The efficacy of CCT241736 was also confirmed in primary samples from AML patients, including those with quizartinib-resistant disease, which induces apoptosis through inhibition of both FLT3 and Aurora kinases. The unique combination of CCT241736 properties based on robust potency, dual selectivity, and significant in vivo activity indicate that CCT241736 is a bona fide clinical drug candidate for FLT3-ITD and TKD AML patients with resistance to current drugs.
Cavernous malformation hemorrhage due to trans-mural pressure alterations after cerebrospinal fluid diversion: a case report
Authors: Hartley Benjamin R. , Birnbaum Corinne , Hoffman Caitlin E. 
Published: April 2020

Abstract
Background
Cavernous malformations are rare cerebral pseudo-vascular lesions with annualized bleeding rates of 0.5–3% in most studies. Of the various explored risk factors for bleeding to date, only prior hemorrhage has shown significant correlation.

Case presentation
In this case, we describe a 65-year old man with a peri-ventricular atrial cavernous malformation that hemorrhaged after CSF diversion via ventriculoperitoneal shunting. Serial imaging showed that bleeding continued until the shunt was revised with a programmable valve set at maximum resistance with the addition of a gravitational unit, thereby lowering the trans-mural pressure differential across the cavernous malformation.

Conclusions
Given that other vascular lesions are subject to hemorrhage from alterations in trans-mural pressure dynamics, we hypothesize that cavernous malformations are similarly affected by trans-mural pressure gradients as they are composed of primitive vascular elements. This hypothesis is corroborated by the temporal correlation of interventions, imaging, and exam findings in the present case, and suggests a potentially important risk factor for hemorrhage in CM patients that affects prognostication and management.
Scaling left ventricular mass in adolescent female soccer players
Authors: V. Martinho Diogo , Valente-dos-Santos João , Coelho-e-Silva Manuel J. , Gutiérrez Arturo O. , Duarte João P. , Lourenço-Farinha Pedro , Luz Leonardo G. O. , Gonçalves-Santos João , Machado Dalmo R. L. , Leite Neiva , Conde Jorge , Castanheira Joaquim M. , Cumming Sean P. , Sherar Lauren B. , Malina Robert M. 
Published: April 2020

Abstract
Background
The aim of the study was to examine the contribution of chronological age (CA), skeletal maturation, training experience and concurrent body size descriptors, to inter-individual variance in left ventricular mass (LVM) among female adolescent soccer players.

Methods
The sample included 228 female soccer players 11.8–17.1 years. Training experience defined as years of participation in competitive soccer (range 2–9 years), was obtained by interview. Stature, body mass and skinfolds (triceps, medial calf) were measured. Fat mass was estimated; Fat-free mass was derived. LVM was assessed by echocardiography. Skeletal maturity status was as the difference of skeletal age (SA, Fels method) minus CA.

Results
Fat-free mass was the most prominent single predictor of LVM (R2 = 36.6%). It was associated with an allometric coefficient close to linearity (k = 0.924, 95%CI: 0.737 to 1.112). A significant multiplicative allometric model including body mass, fat-free mass, CA, training experience and skeletal maturity status was also obtained (R = 0.684; R2 = 46.2%).

Conclusion
Stature has limitations as a valid size descriptor of LVM. Body mass, fat-free mass, training experience, CA, body mass and skeletal maturity status were relevant factors contributing to inter-individual variability in LVM.
A narrative review and content analysis of functional and quality of life measures used to evaluate the outcome after TSA: an ICF linking application
Authors: Lu Ze , MacDermid Joy C. , Rosenbaum Peter 
Published: April 2020

Abstract
Background
Total shoulder arthroplasty (TSA) is considered as the standard reconstructive surgery for patients suffering from severe shoulder pain and dysfunction caused by arthrosis. Multiple patient-reported outcome measures (PROMs) have been developed and validated that can be used to evaluate TSA outcomes. When selecting an outcome measure both content and psychometric properties must be considered. Most research to date has focused on psychometric properties. Therefore, the current study aims to summarize what PROMs are being used to assess TSA outcomes, to classify the type of measure (International society for quality of life (ISOQOL) using definitions of functioning, disability, and health (FDH), quality of life (QoL) and health-related quality of life (HRQoL)) and to compare the content of these measures by linking them to the International Classification of Functioning, Disability and Health (ICF) framework.

Methods
A literature review was performed in three databases including MEDLINE, EMBASE, and CINAHL to identify PROMs that were used in TSA studies. Meaningful concepts of the identified measures were extracted and linked to the relevant second-level ICF codes using standard linking rules. Outcome measures were classified as being FDH, HRQoL or QoL measures based on the content analysis.

Result
Thirty-five measures were identified across 400 retrieved studies. The most frequently used PROM was the American Shoulder and Elbow Society score accounting for 21% (246) of the total citations, followed by the single item pain-related scale like visual analog scale (17%) and Simple Shoulder Test (12%). Twelve PROMs with 190 individual items fit inclusion criteria for conceptual analysis. Most codes (65%) fell under activity and participation categories. The top 3 most predominant codes were: sensation of pain (b280; 13%), hand and arm use (d445; 13%), recreational activity (d920; 8%). Ten PROMs included in this study were categorized as FDH measures, one as HRQoL measure, and one as unknown.

Conclusions
Our study demonstrated that there is an inconsistency and lack of clarity in conceptual frameworks of identified PROMs. Despite this, common core constructs are evaluated. Decision-making about individual studies or core sets for outcome measurement for TSA would be advanced by considering our results, patient priorities and measurement properties.
Enhanced recovery care versus traditional non-ERAS care following osteotomies in developmental dysplasia of the hip in children: a retrospective case-cohort study
Authors: Li Jin , Rai Saroj , Ze Renhao , Tang Xin , Liu Ruikang , Hong Pan 
Published: April 2020

Abstract
Background
Enhanced recovery after surgery (ERAS) has been shown to shorten the length of hospital stay and reduce the incidence of perioperative complications in many surgical fields. However, there has been a paucity of research examining the application of ERAS in major pediatric orthopaedic surgeries. This study aims to compare the perioperative complications and length of hospital stay after osteotomies in children with developmental dysplasia of the hip (DDH) between ERAS and traditional non-ERAS group.

Methods
The ERAS group consisted of 86 patients included in the ERAS program from January 2016 to December 2017. The Control group consisted of 82 DDH patients who received osteotomies from January 2014 to December 2015. Length of hospital stay, physiological function, postoperative visual analogue scale (VAS) score, and postoperative complications were compared between the two groups.

Results
The mean duration of hospital stay was significantly reduced from 10.0 ± 3.1 in the traditional care group to 6.0 ± 0.8 days in the ERAS(P < 0.001). The average VAS score in the first 3 days was significantly lower in the ERAS group (2.9 ± 0.8) than the traditional non-ERAS group (4.0 ± 0.8) (P < 0.001). However, there was no significant difference in the frequency of break-out pain (VAS > 4) between two groups (29.5 ± 6.3 times vs.30.6 ± 6.5 times, P = 0.276). The frequency of postoperative fever was lower in the ERAS group. The frequency of urinary tract infection in both groups were not noticeable because the catheter was removed promptly after the surgery.

Conclusion
The ERAS protocol is both safe and feasible for pediatric DDH patients undergoing osteotomies, and it can shorten the length of hospital stay without increasing the risk of perioperative complications.
Total knee arthroplasty with simultaneous tibial shaft osteotomy in patient with multiple hereditary osteochondromas and multiaxial limb deformity – a case report
Authors: Grzelecki Dariusz , Szneider Jan , Marczak Dariusz , Kowalczewski Jacek 
Published: April 2020

AbstractBackgroundHereditary multiple osteochondromas (hereditary multiple exostoses, HME) is a rare genetic disease characterized by the development of benign osteocartilaginous tumors that may cause severe limb deformities and early onset osteoarthritis. Total knee arthroplasty (TKA) is the method of choice for the treatment of advanced gonarthrosis, however the surgical management with coexisting severe axial limb deformity remains unclear.Case presentation65-year-old man with HME and extra-articular multi-axial limb deformity was admitted to the orthopedic department due to chronic knee pain and limited range of motion caused by secondary osteoarthritis. Regarding to the clinical and radiological examinations, after preoperative planning he was qualified to a one-stage TKA combined with tibial shaft osteotomy (TSO). In a one year follow-up full bone union was confirmed with no signs of implant loosening or prosthesis displacement. Patient was very satisfied, did not report any joint pain and has sufficient range of motion without knee instability.ConclusionThe improvement of mechanical axis during TKA is a crucial factor for achieve operative success and long implant survival. Despite the higher risk of complication rate in comparison to two-stage treatment, one-stage TKA with simultaneous TSO should be a considerable method for patients with osteoarthritis and multiaxial limb deformities. This method can give a good clinical and functional outcomes, however should be performed subsequently to careful preoperative planning and proper patient qualification.
Investigating carbon dioxide absorption by urban trees in a new park of Bangkok, Thailand
Authors: Tor-ngern Pantana , Leksungnoen Nisa 
Published: April 2020

Abstract
Background
Trees remove atmospheric carbon dioxide through photosynthesis, hereafter CO2 absorption (A). Despite growing urban green areas, only a few studies have quantified A of urban trees and assessed their dynamical changes with varying atmospheric conditions. Hence, we investigated A in nine dominant tree species in a new park of Bangkok.

Results
Results revealed that A of two tree species (Millingtonia hortensis and Afzelia xylocarpa) significantly increased with vapor pressure deficit (VPD) until it reached a maximum and declined when VPD decreased, with no seasonal difference. Five of them (Dalbergia cochinchinensis, Tabebuia rosea, Lagerstroemia floribunda, Dipterocarpus alatus and Bauhinia purpurea) exhibited different response patterns of A to VPD between wet and dry seasons. In contrast, the A of two tree species (Samanea saman and Homalium tomentosum) did not respond to changing VPD in either season.

Conclusions
Comparing planting scenarios of insensitive (i.e. no response to VPD) versus sensitive (i.e. significant response to VPD) species, we found that planting a mixture of sensitive and insensitive tree species would improve the park’s capacity of A across seasons, allowing climate change adaptation to adverse environmental impacts such as droughts and the urban heat island effects, and would increase biodiversity. Additionally, planting insensitive tree species would significantly increase the capacity of the park for CO2 mitigation. These findings are useful for those who design parks and expand urban green areas to fully benefit ecosystem services from trees.
Rectal neuroendocrine tumor developing lateral lymph node metastasis after curative resection: a case report
Authors: Tokumaru Yoshihisa , Matsuhashi Nobuhisa , Takahashi Takao , Imai Hisashi , Tanaka Yoshihiro , Okumura Naoki , Yamaguchi Kazuya , Yoshida Kazuhiro 
Published: April 2020

AbstractBackgroundAmong gastrointestinal neuroendocrine tumors (NETs), rectal NETs account for about one-third of all tumors. Despite the occasional observation of lateral lymph node metastasis in patients with rectal NETs, lateral lymph node recurrence is rare. We present a rare case of lateral lymph node recurrence after curative resection of a rectal NET.Case presentationA 55-year-old man presented with fecal occult blood and colonoscopy revealed a mass in the distal rectum. Systematic computed tomography scan showed no evidence of regional lymph node or distant metastasis. The patient underwent laparoscopicintersphincteric resectionand D2 lymph node dissection with diverting stoma. Diverting stoma closure was performed 6 months after the initial operation. Pathological diagnosis was NET of the rectum, grade 2, T1b, N0, Stage I without lymphovascular invasion. At 54 months after the surgery, recurrence in a left lateral lymph node was suspected and lymph node dissection was performed. The pathological diagnosis of the specimen was consistent with lateral lymph node metastasis of a recurrent rectal NET. To our best knowledge, there are no case reports in English of lateral lymph node recurrence after curative resection of a rectal NET, grade 2, T1b, N0, Stage I without lymphovascular invasion.ConclusionConsidering that patients with lateral lymph node metastasis have worse survival than those without metastasis in rectal cancer, if complete resection of the tumor can be achieved for lateral lymph node recurrence, surgery may be an important option in the strategy to treat this condition.
MiR-489 inhibited the development of gastric cancer via regulating HDAC7 and PI3K/AKT pathway
Authors: Zhang Haiyan , Li Lingyun , Yuan Cuicui , Wang Congcong , Gao Tiantian , Zheng Zhiwei 
Published: April 2020

Abstract
Background
Mounting evidences have displayed that the dysregulation of miRNAs plays important roles in the pathogenesis of gastric cancer (GC). The purpose of this study was to explore the biological functions and potential mechanism of miR-489 in GC progression.

Methods
Quantitative real-time PCR (qRT-PCR) and western blot were performed to examine the mRNA expression and protein levels of miR-489 and HDAC7. The relationship between miR-489 and HDAC7 was analyzed by Spearman rank correlation. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays were conducted for determining the effect of miR-489 and HDAC7 on GC cell viability, migration, and invasion. TargetScan and luciferase reporter assay were used to confirm the target gene of miR-489 in GC cells.

Results
The findings showed that miR-489 was dramatically decreased in GC tissues and GC cell lines (SGC-7901 and MKN45). Moreover, it was closely correlated with overall survival (OS) and progression-free survival (PFS) of GC patients. Downregulation of miR-489 significantly promoted GC cell proliferation, invasion, and migration. Additionally, HDAC7 was confirmed as the direct target of miR-489. Knockdown of HDAC7 exerted inhibited effect on GC progression and it markedly overturned miR-489 inhibitor-medicated effect on GC cells. More interestingly, via targeting HDAC7, miR-489 blocked the activation of PI3K/AKT pathway in GC cells.

Conclusions
Correctively, miR-489 played as a tumor suppressor in GC cell growth by targeting HDAC7, and miR-489 might function as a novel biomarker for diagnosis or therapeutic targets of human GC.
Succession of physiological stages hallmarks the transcriptomic response of the fungus Aspergillus niger to lignocellulose
Authors: van Munster Jolanda M. , Daly Paul , Blythe Martin J. , Ibbett Roger , Kokolski Matt , Gaddipati Sanyasi , Lindquist Erika , Singan Vasanth R. , Barry Kerrie W. , Lipzen Anna , Ngan Chew Yee , Petzold Christopher J. , Chan Leanne Jade G. , Arvas Mikko , Raulo Roxane , Pullan Steven T. , Delmas Stéphane , Grigoriev Igor V. , Tucker Gregory A. , Simmons Blake A. , Archer David B. 
Published: April 2020

Abstract
Background
Understanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer Aspergillus niger over its life time to six substrates important for biofuel production.

Results
We analysed the response of A. niger to the feedstock Miscanthus and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the Aspergillus nidulans fatty acid beta-oxidation transcriptional regulator farA, there was a reduction in expression of selected lignocellulose degradative CAZyme-encoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds.

Conclusion
In this study, which includes the first transcriptional response of Aspergilli to Miscanthus, we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism.
Molecular epidemiology of rotavirus A and adenovirus among children with acute diarrhea in Hangzhou, China
Authors: Li Wei , Xiang Wenqing , Li Cixiu , Xu Jialu , Zhou Dongming , Shang Shiqiang 
Published: April 2020

Abstract
Background
Rotavirus A (RVA) and adenovirus (Adv) are important causes of acute diarrhea in children. RVAs are classified into G and P genotypes based on viral proteins (VP)7 and VP4 gene and Adv contains over 70 genotypes based on hexon and fiber gene. This study aimed to characterize the molecular epidemiology of RVA and Adv in children with acute diarrhea during 2017–2018 in Hangzhou.

Methods
The stool samples were collected and tested for RVA and Adv by reverse transcription-quantitative PCR (RT-qPCR) assay. The RVA positive samples were detected by RT-PCR for VP7(G) and VP4([P]) genotypes, and the Adv positive samples were detected by PCR for genotyping by the target to hexon gene.

Results
Among 228 RVA-positive samples, G9 was detected as the most frequent genotype (195/228, 85.5%), followed by G3 (20/228, 8.8%), G2 (7/228, 3.1%) and G1 (6/228, 2.6%). G9 strains were closely related to strains from China and neighboring countries, as well as the USA. On the other hand, P[8] strains were detected in 219 (96.1%) samples with most closely related to one strain from Malawi, and P[4] in 9 (3.9%) samples. G9P[8] (84.6%, 193/228) was the most prevalent rotavirus A strains, followed by G3P[8] (8.8%, 20/228), G2P[4] (3.1%, 7/228), G1P[8] (2.6%, 6/228) and G9P[4] (0.9%, 2/228). Of 167 Adv-positive cases, 2 different genotypes were identified with 152 (91.0%) of Adv-41and 15 (9%) of Adv-40. All Adv strains were closely related to prototype strains of Adv types 40 and 41 in India.

Conclusions
G9P[8] of RVA and Adv-41 were the most common genotypes that caused children’s acute diarrhea in Hangzhou, 2017–2018.