bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural evolution and the partitioning of deformation during basin growth and inversion: A case study from the Mizen Basin Celtic Sea, offshore Ireland
Authors: Rodríguez‐Salgado Pablo , Childs Conrad , Shannon Patrick M. , Walsh John J. 
Published: August 2019

AbstractThe Celtic Sea basins lie on the continental shelf between Ireland and northwest France and consist of a series of ENE–WSW trending elongate basins that extend from St George’s Channel Basin in the east to the Fastnet Basin in the west. The basins, which contain Triassic to Neogene stratigraphic sequences, evolved through a complex geological history that includes multiple Mesozoic rift stages and later Cenozoic inversion. The Mizen Basin represents the NW termination of the Celtic Sea basins and consists of two NE–SW‐trending half‐grabens developed as a result of the reactivation of Palaeozoic (Caledonian, Lower Carboniferous and Variscan) faults. The faults bounding the Mizen Basin were active as normal faults from Early Triassic to Late Cretaceous times. Most of the fault displacement took place during Berriasian to Hauterivian (Early Cretaceous) times, with a NW–SE direction of extension. A later phase of Aptian to Cenomanian (Early to Late Cretaceous) N–S‐oriented extension gave rise to E–W‐striking minor normal faults and reactivation of the pre‐existing basin bounding faults that propagated upwards as left‐stepping arrays of segmented normal faults. In common with most of the Celtic Sea basins, the Mizen Basin experienced a period of major erosion, attributed to tectonic uplift, during the Paleocene. Approximately N–S Alpine regional compression‐causing basin inversion is dated as Middle Eocene to Miocene by a well‐preserved syn‐inversion stratigraphy. Reverse reactivation of the basin bounding faults was broadly synchronous with the formation of a set of near‐orthogonal NW–SE dextral strike‐slip faults so that compression was partitioned onto two fault sets, the geometrical configuration of which is partly inherited from Palaeozoic basement structure. The segmented character of the fault forming the southern boundary of the Mizen Basin was preserved during Alpine inversion so that Cenozoic reverse displacement distribution on syn‐inversion horizons mirrors the earlier extensional displacements. Segmentation of normal faults therefore controls the geometry and location of inversion structures, including inversion anticlines and the back rotation of earlier relay ramps.
Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma
Authors: Maekawa Keiko , Ri Masaki , Nakajima Miki , Sekine Akihiro , Ueda Ryuzo , Tohkin Masahiro , Miyata Naoki , Saito Yoshiro , Iida Shinsuke 
Published: August 2019

AbstractAlthough the proteasome inhibitor bortezomib (BTZ) shows excellent efficacy in multiple myeloma (MM), a fraction of patients has a suboptimal or no response to this agent. In addition, BTZ‐induced peripheral neuropathy (BiPN), a frequent side‐effect of this therapy, limits its use in some patients. This study aimed to explore serum lipid biomarker candidates to predict the response to BTZ and the severity of BiPN. Fifty‐nine serum samples were collected from patients with MM prior to receiving BTZ plus low‐dose dexamethasone therapy. Serum levels of phospholipids, sphingolipids, neutral lipids, and polyunsaturated fatty acids and their oxidation products were measured by a comprehensive lipidomic study. Overall, 385 lipid metabolites were identified in patients’ sera; lower levels of several glycerophospholipids, sphingolipids, and cholesteryl esters were associated with a poor treatment response. Metabolites related to platelet‐activating factor biosynthesis and cholesterol metabolism appeared particularly relevant. Furthermore, several lysophosphatidylcholines, phosphatidylcholines, ceramides, neutral lipids, and oxidative fatty acids were significantly increased or decreased in patients with BiPN grades ranging from G0 to G3. Among these compounds, mediators reportedly inducing myelin breakdown and stimulating inflammatory responses were prominent. Although further study is necessary to validate these biomarker candidates, our results contribute to the development of predictive biomarkers for response to BTZ treatment, or ensuing severe BiPN, in patients with MM.
Triterpenes from Poria cocos are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence
Authors: Xu Hui , Wang Yuchen , Zhao Junnan , Jurutka Peter W. , Huang Dechun , Liu Liangyun , Zhang Lange , Wang Suilou , Chen Yadong , Cheng Shujie 
Published: August 2019

AbstractPoria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXR‐dependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α‐hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR‐specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL‐60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 μM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXR‐dependent pathway may play an important role in their anti‐acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti‐cancer activity. These results suggest a novel approach to the treatment or prevention of APL.
Discovery of small molecule agonists targeting neuropeptide Y4 receptor using homology modeling and virtual screening
Authors: Kang Ning , Wang Xiao‐Lei , Zhao Yaxue 
Published: August 2019

AbstractNeuropeptide Y4 receptor has the most significant effect on body weight and fat mass in its physiological functions, and the activation of Y4 receptor has explicit role on losing weight. The Y4 receptor has been successfully applied in the development of anti‐obesity agent, thus representing a potential therapeutic target for obesity treatment. Here, we reported the first discovery of small molecule agonists targeting Y4 receptor: three Y4 receptor models with active and inactive conformations were built, each model was submitted following structure‐based virtual screening, and finally six hits were identified as Y4 receptor agonists. These results confirm the reliability of the constructed Y4 receptor models and the proposed computational strategy for investigating novel Y4 receptor agonists. These new small molecule Y4 receptor agonists will contribute to the further development of Y4 agonists as potential therapeutics and functional probes.
Prospective randomized controlled clinical study comparing two types of two‐piece dental implants supporting fixed reconstructions—Results at 5 years of loading
Authors: Ioannidis Alexis , Heierle Linda , Hämmerle Christoph H. F. , Hüsler Jürg , Jung Ronald E. , Thoma Daniel S. 
Published: August 2019

AbstractObjectivesCompare clinical outcomes of two types of dental implants with non‐matching implant–abutment junctions loaded with fixed implant‐borne reconstructions at 5 years of loading.Materials and methodsIn 64 patients, one of two implant systems (S1, S2) was randomly used to support fixed dental prostheses (FDP). At loading (TL), after 1 (T1), 3 (T3) and 5 years (T5), the implant and reconstruction survival, biological and technical complications, radiographic marginal bone levels, clinical outcomes were recorded. The implants of the groups S1 and S2 contained of two‐piece titanium implants with a non‐matching implant–abutment junction. Data were analyzed on the patient level (1 implant/patient) using the non‐parametric Wilcoxon–Mann–Whitney test.ResultsNinety‐seven implants were placed and loaded with fixed reconstructions in 64 patients. At T5, 29 S1 and 28 S2 implants were available for the patient‐level analysis. Two implants in group S1 had to be removed in the same patient due to severe peri‐implantitis, resulting in a survival rate of 96.1% on the implant level and 96.6% on the patient level. No implant in group S2 was lost. The technical complication rate on patient‐level amounted of 24.2% (S1) and of 6.5% (S2) (p > .05). Biological complications on patient‐level were observed in 15.2% (S1) and 16.1% (S2) (p > .05). From TL to T5, the medians of the mean marginal bone level changes wer a gain of 0.15 mm in group S1 and a loss of 0.14 mm in group S2 (p > .05).Conclusions and clinical implicationsBoth implant systems revealed high survival rates and minimal changes of the marginal bone levels during 5 years. Few biological complications occurred in both groups. S1 revealed a high rate of technical complications. Therefore, both implant systems can be recommended for fixed reconstructions.
The up‐to‐11‐year survival and success of implants and abutment teeth under solely implant‐supported and combined tooth–implant‐supported double crown‐retained removable dentures
Authors: Fobbe Hannah , Rammelsberg Peter , Lorenzo Bermejo Justo , Kappel Stefanie 
Published: August 2019

AbstractObjectiveThis retrospective analysis was designed to compare the survival and success of dental implants in solely implant‐supported, double crown‐retained removable dentures (DCRDs) and combined tooth–implant‐supported DCRDs, due to a lack of data on the latter.Material and methodsFrom 2002, patients were consecutively admitted for treatment at the Department of Prosthodontics, University of Heidelberg. Surgical and prosthodontic treatment and scheduled and unscheduled visits were recorded on standardized documentation forms. Kaplan–Meier analysis was used to estimate success (survival without major complications). Cox regression was applied to assess risk factors.ResultsFrom this clinical study, 139 DCRDs on 412 implants and 239 teeth met the inclusion criteria. Fifty‐three dentures were implant‐supported (213 implants). Eighty‐six were supported by teeth and implants. The DCRDs were placed in 126 patients. After an observation period of up to 11.2 years (median: 4.2 years), total implant survival was 99.5% for tooth–implant‐supported DCRDs and 93.4% for implant‐supported ones. The estimated cumulative success was 97.2% (standard error/SE ± 1.2%) and 85.9% (SE ± 2.4%) at five years, respectively. Complications included implant or tooth loss, peri‐implantitis, apical periodontitis and tooth fracture. In terms of abutments, results from multiple Cox regression revealed lower failure rates in tooth–implant‐supported dentures (p = .04). No other risk factors were identified.ConclusionsWithin the limitations of this study, survival and success are high for both treatment options. Combining teeth and implants in one DCRD might have a positive effect on the prognosis of the implant and the survival of remaining teeth.
Daratumumab added to standard of care in patients with newly diagnosed multiple myeloma: A network meta‐analysis
Authors: Xu Wenjun , Li DianFang , Sun Yanhua , Ran Xuehong , Wang Baohong , Wu Wei , Sheng Zhixin , Liu Liping 
Published: August 2019

AbstractPurposeTo investigate the activity and safety of daratumumab added to standard of care and evaluate the relative efficacy of DRd vs DVMP and other regimens on survival endpoints for untreated myeloma, we undertook this meta‐analysis.MethodsWe searched published reports that described the activity and safety of daratumumab added to standard of care for untreated myeloma.ResultsSix daratumumab trials were identified, covering 5106 subjects. Daratumumab containing combinations for untreated myeloma attained an impressive complete response or better (≥CR) rate of 24%, very good partial response or better (≥VGPR) rate of 67%, overall response rate (ORR) of 92%. Daratumumab added to standard of care significantly improved progression free survival (PFS): the HR for PFS was 0.52 [0.44, 0.61], P < .001. The HR for overall survival (OS) was 0.73 [0.52, 1.04], P = .09. In the network meta‐analysis for patients ineligible for autologous stem‐cell transplantation (ASCT), DRd regimen produced significant PFS advantage vs other first‐line treatments (VMP HR:0.39 P < .001, Rd HR:0.55 P < .001, MPT HR:0.38 P < .001, and MP HR:0.22 P < .001); DVMP regimen also produced significant PFS advantage vs VMP (HR:0.50 P < .001), MPT (HR:0.49 P < .001), and MP (HR:0.28 P < .001). Among these first‐line regimens (DRd, DVMP, VMP, Rd, MPT, and MP), DRd regimen had the highest probability to be the best intervention, with 83.4% and 91.0% probability to reach the longest PFS and OS, respectively. Toxicity consisted primarily of myelosuppression. And, the vital non‐hematologic adverse events (AEs) were peripheral sensory neuropathy (41% of all grades) and upper respiratory tract infection (39% of all grades).ConclusionsDaratumumab added to standard of care could produce clinical benefits in newly diagnosed patients with multiple myeloma. DRd and DVMP could be good combination options for those patients ineligible for ASCT.
Carbon storage in a rainfed Mediterranean vertisol: Effects of tillage and crop rotation in a long‐term experiment
Authors: López‐Bellido Luis , López‐Bellido Rafael , Fernández‐García Purificación , Muñoz‐Romero Verónica , Lopez‐Bellido Francisco Javier 
Published: August 2019

AbstractThe storage of carbon (C) in cultivated soils can be increased with the adoption of different practices. The objective of this study was to determine soil organic carbon (SOC) storage in the 0‐ to 90‐cm depth profile, in four different soil layers (0–15, 15–30, 30–60 and 60–90 cm) in a long‐term (29 years) experiment established in 1986 on a rainfed Mediterranean Vertisol in southern Spain. The treatments studied were: conventional tillage (CT) versus no‐tillage (NT); five 2‐year crop rotations (wheat–chickpea, wheat–sunflower, wheat–bare fallow, wheat–faba bean, and continuous wheat; and nitrogen (N) fertilizer applied to wheat at four rates (0, 50, 100 and 150 kg N ha−1). The SOC accumulation was higher in the 30–60‐cm layer (9.2 Mg ha−1) due to the size of the characteristic cracks of Vertisols under semiarid conditions. Over the 29‐year study period, the SOC in the 0–90‐cm layer increased by 23.6 Mg ha−1 due to the change in residue management. The NT treatment exhibited a higher mean annual rate of organic C accumulation compared with the CT treatment (1.0 and 0.66 Mg ha−1 year−1, respectively) due to the retention of the mulched residue. Additionally, crop rotation influenced the rate of organic C accumulation, with wheat‐faba bean, wheat‐sunflower and continuous wheat exhibiting the highest levels of C storage in comparison to the other treatments. In rainfed Mediterranean agriculture, the selection of no‐tillage along with a rotation with legumes is key to improving soil fertility and increasing C reserves and the rate of C accumulation by soil.Highlights
The SOC increase over the 29‐year study period was 23.6 Mg ha−1 in the 0–90‐cm soil profile.
The characteristic cracks of Vertisol increase SOC stocks in deeper soil layers.
No tillage accumulated 66.2% more SOC than conventional tillage in the 0–90‐cm profile.
The wheat–sunflower rotation had the highest annual rate of C sequestration (1 Mg ha−1 year−1) and wheat–chickpea the lowest (0.6 Mg ha−1 year−1) over 29 years.
Haplotype analysis encompassing HTT gene in Chinese patients with Huntington's disease
Authors: Li X.‐Y. , Li H.‐L. , Dong Y. , Gao B. , Cheng H.‐R. , Ni W. , Gan S.‐R. , Liu Z.‐J. , Burgunder J.‐M. , Wu Z.‐Y. 
Published: August 2019

Background and purposeHuntington's disease (HD) is a dominantly inherited neurodegenerative disorder with varied prevalence in different populations, which may be associated with specific haplotypes. This study aimed to explore the haplotypes encompassing the HTT gene in the Chinese population.MethodsA total of 406 individuals with HD and 59 normal relatives from 253 families with HD were enrolled. A total of 29 tag single nucleotide polymorphisms (tSNPs) were selected and genotyped for the haplotype analysis.ResultsIn stage one, we used 18 tSNPs to replicate the distribution of three major haplogroups (A, B, C). We found that risk‐associated haplogroup variants A1 and A2, enriched on Caucasian HD chromosomes, were totally absent from both Chinese HD and control chromosomes, and the distributions of haplogroups between HD and control chromosomes were similar. Therefore, in stage two, we used 29 tSNPs (including the18 tSNPs) to define new haplogroups (I, II, III) and found that haplogroup I accounted for 61.4% on HD chromosomes and 34.4% on control chromosomes, indicating that haplogroup I was enriched on Chinese HD chromosomes.ConclusionsThis is the first haplotype analysis encompassing HTT in the Chinese population. The results contribute to explaining the low prevalence of HD in China and provide a better understanding of genetic diversity in the HTT region.
Effect of cholinergic pathway disruption on cortical and subcortical volumes in subcortical vascular cognitive impairment
Authors: Lim J.‐S. , Kwon H.‐M. , Lee Y.‐S. 
Published: August 2019

Background and purposeThe brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor to subcortical vascular cognitive impairment (scVCI). We aimed to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI.MethodsWe enrolled patients with scVCI, defined as moderate to severe WMH or multiple (>2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores was obtained using multiple linear regression.ResultsIn total, 80 patients were enrolled. The mean age was 78.4 ± 6.5 years, median Mini‐Mental State Examination score was 17 (interquartile range, 13–20) and median CHIPS score was 11 (interquartile range, 7–17). CHIPS scores were positively correlated with subcortical volumes of the putamen (rʹ = 0.46, P = 0.002) and pallidum (rʹ = 0.45, P = 0.002), and were negatively associated with inferior temporal (rʹ = −0.35, P = 0.002) and medial orbitofrontal (rʹ = −0.32, P = 0.002) cortical thickness.ConclusionOur study suggested that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons.
Contribution of Otoacoustic Emissions for Diagnosis of Atypical or Recurrent Intracranial Hypotension. A Cases Series
Authors: Redon Sylvain , Elzière Maya , Kaphan Elsa , Donnet Anne 
Published: August 2019

BackgroundThe diagnosis of spontaneous or post‐traumatic intracranial hypotension mainly rely on clinical features and neuroimaging. In atypical presentations, other non‐invasive tests are missing to support the diagnosis of intracranial hypotension. The assessment of otoacoustic emissions (OAE) shown interest to monitor intracranial pressure mainly in cases of intracranial hypertension. This non‐invasive method was also assessed in response to pressure change after lumbar puncture. A few reports showed abnormal results of distortion product otoacoustic emissions (DPOAE) in cases of spontaneous or post‐traumatic intracranial hypotension. We describe additional results in a series of intracranial hypotension cases. We discuss the interest of DPOAE assessment in atypical presentations of intracranial hypotension. We review the other non‐invasive tests reported in literature.MethodsWe studied 4 atypical or recurrent cases of spontaneous or post‐traumatic intracranial hypotension by recording OAE in sitting then supine position.ResultsUnilateral or bilateral abnormal changes of DPOAE were recorded in all cases, in response to postural test. These changes were present even in the absence of vestibular symptoms.ConclusionThe study of OAE may be a non‐invasive tool for the diagnosis of spontaneous intracranial hypotension.
SOX17 expression and its down‐regulation by promoter methylation in cervical adenocarcinoma in situ and adenocarcinoma
Authors: Hopman Anton N H , Moshi Jobran M , Hoogduin Klaas J , Ummelen Monique , Henfling Mieke E R , van Engeland Manon , Wouters Kim A D , Stoop Hans , Looijenga Leendert H J , Ramaekers Frans C S 
Published: August 2019

AimsSOX17 expression has not been studied in glandular lesions of the uterine cervix like adenocarcinoma in situ (AIS) and invasive adenocarcinomas (AdC), whereas SOX17 promoter CpG island methylation has been reported. Therefore, the aim of this study was to relate the topographical distribution of SOX17 expression and SOX17 methylation status to each other, and to SOX2 expression, human papillomavirus (HPV) type, and physical status of the virus.Methods and resultsImmunohistochemistry was used in 45 cases to assess expression of SOX17 and SOX2. SOX17 promoter methylation was determined in 25 cases by means of bisulphite conversion and methylation‐specific polymerase chain reaction. SOX17 and SOX2 showed a mutually exclusive expression pattern in normal epithelium, with a sharp delineation in the squamocolumnar junction. SOX17 was found in endocervical columnar and reserve cells, whereas SOX2 was exclusively found in squamous epithelium. In both glandular lesions and cases with coexisting glandular and squamous intraepithelial components, a complex combination of SOX17 and SOX2 expression patterns was seen and mutually exclusive expression was lost. Frequently, gain of expression of SOX2 was found and expression of SOX17 was lost. Methylation of the CpG island in the SOX17 promoter was shown to be strongly associated with loss of expression of SOX17 (P = 0.0016).ConclusionsIn this study, we show for the first time a direct correlation between the topographical distribution of SOX17 expression and the methylation status of its gene promoter. This explains the heterogeneity of SOX17 expression in the glandular lesions of the cervix. No correlation was found between HPV type and physical status of the virus on the one hand and methylation status on the other.