bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Mini‐DMEK versus predescemetal sutures as treatment of acute hydrops in keratoconus
Authors: Händel Alexander , Siebelmann Sebastian , Hos Deniz , Ögrünc Ferdi , Matthaei Mario , Cursiefen Claus , Bachmann Björn 
Published: May 2021

AbstractPurposeTo compare two surgical treatment options for acute corneal hydrops in keratoconus: Mini‐DMEK versus predescemetal sutures.MethodsSixteen patients were treated by either Mini‐Descemet membrane endothelial keratoplasty (Mini‐DMEK) (n = 7, group 1) or predescemetal sutures (n = 9, group 2) early after onset of acute hydrops. Visual acuity, maximum corneal thickness (SD‐OCT) in the affected oedematous area, complications and recurrence rates were retrospectively compared between both groups. Measurements were taken immediately preoperatively as well as 1 day, 1 week and 1 month postoperatively (Table 1).ResultsBoth groups showed reductions in corneal thickness and increased visual acuity shortly after surgery. In group 1 (average age 33 years ± 7 years), the best corrected visual acuity (BCVA) increased from logMAR 1.65 ± 0.7 before Mini‐DMEK to logMAR 0.93 ± 0.6 30 days after Mini‐DMEK (p = 0.046). During that period, maximum corneal thickness decreased from 1159 ± 338 µm before surgery to 531 ± 75 µm after Mini‐DMEK (p = 0.046). Patients from group 2 (average age 34 ± 10 years) had a BCVA of logMAR 1.59 ± 0.8 which increased to logMAR 0.97 ± 0.5 (p = 0.014) 30 days after surgery. At the same time, the preoperative maximum corneal thickness decreased from 1439 ± 272 µm to 476 ± 162 µm (p = 0.014). There was no difference in corneal thickness or BCVA one month after the surgical intervention between both groups (p = 0.394 and p = 0.871).ConclusionsBoth techniques, Mini‐DMEK and predescemetal sutures, are effective in the treatment of an acute hydrops in keratoconus. Mini‐DMEK appears to be beneficial in large DM tears.
Muscarinic M4 and M5 receptors in the ventral subiculum differentially modulate alcohol seeking versus consumption in male alcohol‐preferring rats
Authors: Walker Leigh C. , Huckstep Kate L. , Chen Nicola A. , Hand Lexi J. , Lindsley Craig W. , Langmead Christopher J. , Lawrence Andrew J. 
Published: May 2021

Background and PurposeMuscarinic acetylcholine receptors mediate alcohol consumption and seeking in rats. While M4 and M5 receptors have recently been implicated to mediate these behaviours in the striatum, their role in other brain regions remain unknown. The ventral tegmental area (VTA) and ventral subiculum (vSub) both densely express M4 and M5 receptors and modulate alcohol‐seeking, via their projections to the nucleus accumbens shell (AcbSh).Experimental ApproachIn Indiana alcohol‐preferring (iP) male rats, we examined Chrm4 (M4) and Chrm5 (M5) expression in the VTA and vSub following long‐term alcohol consumption and abstinence using RT‐qPCR. Using a combination of retrograde tracing and RNAscope, we examined the localisation of Chrm4 and Chrm5 on vSub cells that project to the AcbSh. Using selective allosteric modulators, we examined the functional role of M4 and M5 receptors within the vSub in alcohol consumption, context‐induced alcohol‐seeking, locomotor activity, and food/water consumption.Key ResultsLong‐term alcohol and abstinence dysregulated the expression of genes for muscarinic receptors in the vSub, not in the VTA. Chrm4 was down‐regulated following long‐term alcohol and abstinence, while Chrm5 was up‐regulated following long‐term alcohol consumption. Consistent with these data, a positive allosteric modulator (VU0467154) of intra‐vSub M4 receptors reduced context‐induced alcohol‐seeking, but not motivation for alcohol self‐administration, while M5 receptor negative allosteric modulator (ML375) reduced initial motivation for alcohol self‐administration, but not context‐induced alcohol‐seeking.Conclusion and ImplicationsCollectively, our data highlight alcohol‐induced cholinergic dysregulation in the vSub and distinct roles for M4 and M5 receptor allosteric modulators to reduce alcohol consumption or seeking.
Intelligent identification of sequence stratigraphy constrained by multipopulation genetic algorithm and dynamic time warping technique: A case study of Lower Cretaceous Qingshuihe Formation in hinterland of Junggar Basin (NW China)
Authors: Shi Bingbing , Chang Xiangchun , Liu Zhongquan , Pang Yumao , Xu Youde , Mao Lixin , Zhang Pengfei , Chen Guo 
Published: May 2021

AbstractThe division and correlation of sequence stratigraphy are one of the essential steps in petroleum exploration. To comprehensively utilize the sequence stratigraphic information implied in multiple wireline well logs and improve the accuracy and reliability of sequence stratigraphic division, based on the edge detection, optimal partition, and natural evolution theories, and realizes the information fusion (formed one ‘chromosome’) of multiple wireline well logs (named as ‘genes’) which can reflect the feature information of sequence stratigraphy by using multipopulation genetic algorithm (MPGA) based on Fisher algorithm, in this study, geophysical data (wireline well logs and 3D seismic data) were used for spectral trend attribute analyses (wavelet transform, maximum entropy spectrum, time‐frequency analyses, and integrated prediction error filter). Since the seismic reflection characteristics of K1qwere difficult to identify and considering subjective factors in conventional methods, a MPGA was also used to intelligently identify the sequence stratigraphy framework of the Lower Cretaceous Qingshuihe (K1q) Formation. Since the MPGA is an optimization algorithm, the code was run 10 times for accuracy with changes in the dividing layers. The optimal parameters in the process of data fusion (gene combination process) are selected. The sequence boundaries (SBs) searched by the MPGA matched those of the spectral trend attribute analyses, confirming that the MPGA was an effective, fast, and user‐friendly tool for defining the main SBs. MPGA can provide an optimal layering scheme (‘elite population’) through simultaneous searching at multiple depth ranges (‘multipopulation’), recording the optimal SBs (‘elite individuals’) of each population and making the results more convinced. Although simulation solutions may not be unique, the MPGA still provides us a chance to gain some insights into the details of the stratigraphy. Based on this intelligent identification, the maximum flooding surface, two first flooding surfaces (FFS), and three SBs were defined in K1q. The cyclic patterns (prograding, aggrading, and retrograding) were identified. They showed the relationship between accommodation space (related to tectonic subsidence of the Chemo paleo‐uplift) and sediment supply. In addition, dynamic time warping (DWT) technique was used for sequence discrimination and correlation on the integrated prediction error filter analyses curve. A massive pebbly sandstone set, named ‘bottom sandstone,’ was identified in the lowstand system tract of SQ1 (K1q1), constrained by SB1 and FFS1, which was a favourable hydrocarbon exploration target.
Global variation in freshwater physico‐chemistry and its influence on chemical toxicity in aquatic wildlife
Authors: Pinheiro João Paulo S. , Windsor Fredric M. , Wilson Rod W. , Tyler Charles R. 
Published: May 2021

ABSTRACTChemical pollution is one of the major threats to global freshwater biodiversity and will be exacerbated through changes in temperature and rainfall patterns, acid–base chemistry, and reduced freshwater availability due to climate change. In this review we show how physico‐chemical features of natural fresh waters, including pH, temperature, oxygen, carbon dioxide, divalent cations, anions, carbonate alkalinity, salinity and dissolved organic matter, can affect the environmental risk to aquatic wildlife of pollutant chemicals. We evidence how these features of freshwater physico‐chemistry directly and/or indirectly affect the solubility, speciation, bioavailability and uptake of chemicals [including via alterations in the trans‐epithelial electric potential (TEP) across the gills or skin] as well as the internal physiology/biochemistry of the organisms, and hence ultimately toxicity. We also show how toxicity can vary with species and ontogeny. We use a new database of global freshwater chemistry (GLORICH) to demonstrate the huge variability (often >1000‐fold) for these physico‐chemical variables in natural fresh waters, and hence their importance to ecotoxicology. We emphasise that a better understanding of chemical toxicity and more accurate environmental risk assessment requires greater consideration of the natural water physico‐chemistry in which the organisms we seek to protect live.
Radiological model based on the standard magnetic resonance sequences for detecting methylguanine methyltransferase methylation in glioma using texture analysis
Authors: Huang Wei‐yuan , Wen Ling‐hua , Wu Gang , Pang Pei‐pei , Ogbuji Richard , Zhang Chao‐cai , Chen Feng , Zhao Jian‐nong 
Published: May 2021

AbstractThis study aims to build a radiological model based on standard MR sequences for detecting methylguanine methyltransferase (MGMT) methylation in gliomas using texture analysis. A retrospective cross‐sectional study was undertaken in a cohort of 53 glioma patients who underwent standard preoperative magnetic resonance (MR) imaging. Conventional visual radiographic features and clinical factors were compared between MGMT promoter methylated and unmethylated groups. Texture analysis extracted the top five most powerful texture features of MR images in each sequence quantitatively for detecting the MGMT promoter methylation status. The radiomic signature (Radscore) was generated by a linear combination of the five features and estimates in each sequence. The combined model based on each Radscore was established using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve, nomogram, calibration, and decision curve analysis (DCA) were used to evaluate the performance of the model. No significant differences were observed in any of the visual radiographic features or clinical factors between different MGMT methylated statuses. The top five most powerful features were selected from a total of 396 texture features of T1, contrast‐enhanced T1, T2, and T2 FLAIR. Each sequence’s Radscore can distinguish MGMT methylated status. A combined model based on Radscores showed differentiation between methylated MGMT and unmethylated MGMT both in the glioblastoma (GBM) dataset as well as the dataset for all other gliomas. The area under the ROC curve values for the combined model was 0.818, with 90.5% sensitivity and 72.7% specificity, in the GBM dataset, and 0.833, with 70.2% sensitivity and 90.6% specificity, in the overall gliomas dataset. Nomogram, calibration, and DCA also validated the performance of the combined model. The combined model based on texture features could be considered as a noninvasive imaging marker for detecting MGMT methylation status in glioma.
Suppression of lysosomal acid alpha‐glucosidase impacts the modulation of transcription factor EB translocation in pancreatic cancer
Authors: Hamura Ryoga , Shirai Yoshihiro , Shimada Yohta , Saito Nobuhiro , Taniai Tomohiko , Horiuchi Takashi , Takada Naoki , Kanegae Yumi , Ikegami Toru , Ohashi Toya , Yanaga Katsuhiko 
Published: May 2021

AbstractLysosomal degradation plays a crucial role in the metabolism of biological macromolecules supplied by autophagy. The regulation of the autophagy‐lysosome system, which contributes to intracellular homeostasis, chemoresistance, and tumor progression, has recently been revealed as a promising therapeutic approach for pancreatic cancer (PC). However, the details of lysosomal catabolic function in PC cells have not been fully elucidated. In this study, we show evidence that suppression of acid alpha‐glucosidase (GAA), one of the lysosomal enzymes, improves chemosensitivity and exerts apoptotic effects on PC cells through the disturbance of expression of the transcription factor EB. The levels of lysosomal enzyme were elevated by gemcitabine in PC cells. In particular, the levels of GAA were responsive to gemcitabine in a dose–dependent and time–dependent manner. Small interfering RNA against the GAA gene (siGAA) suppressed cell proliferation and promoted apoptosis in gemcitabine‐treated PC cells. In untreated PC cells, we observed accumulation of depolarized mitochondria. Gene therapy using adenoviral vectors carrying shRNA against the GAA gene increased the number of apoptotic cells and decreased the tumor growth in xenograft model mice. These results indicate that GAA is one of the key targets to improve the efficacy of gemcitabine and develop novel therapies for PC.
Low-density neutrophils in chronic graft versus host disease (cGVHD) are primarily immature CD10– and enhance T cell activation
Authors: Matthews Nick C , Burton Charlotte S , Alfred Arun 
Published: May 2021

Summary
Chronic graft-versus-host disease (cGVHD) is a frequent complication of allogeneic haematopoietic stem cell transplantation. Low density neutrophils (LDNs) in autoimmunity, which shares disease features with cGVHD, are proinflammatory, whereas those in cancer and sepsis suppress T cell immunity. Mature LDNs can be distinguished from immature LDNs on the basis of expression of CD10 and suppressive neutrophils can be identified using lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression. The functionality of LDNs in cGVHD has not been specifically investigated. Here, we have determined the relative contribution of immature and mature neutrophils to LDNs in cGVHD and assessed whether these were suppressive or potentially proinflammatory. Peripheral blood LDNs and normal density neutrophils (NDNs) from 30 cGVHD patients and NDNs from 10 healthy controls (HCs) were immunophenotyped by flow cytometry. The ability of LDNs and NDNs to influence T cell proliferation and cytokine production in co-cultures was quantified. To further characterize LDNs, their propensity to undergo constitutive apoptosis and differentiate ex vivo was assessed.
LDNs were elevated in cGVHD versus HCs, heterogeneous in phenotype, with a predominance of immature CD10– cells in most patients, but some mature CD10+ LOX-1+ LDNs were also detected. LDNs enhanced autologous T cell proliferation, interleukin (IL)-6 and interferon (IFN)-γ production. LDN, but not NDN, CD10 expression was inversely correlated with LOX-1, which correlated with IL-6 production. LDNs resisted apoptosis and differentiated into antigen-presenting/neutrophil-hybrid-like cells, which co-expressed major histocompatibility complex (MHC) class II HLA-DR and immuno-inhibitory programmed cell death ligand 1 (PD-L1), but did not suppress T cell proliferation. These data suggest LDNs in cGVHD are predominantly immature, proinflammatory and may have pathogenic potential.
Inhibitor of apoptosis-stimulating p53 protein protects against inflammatory bowel disease in mice models by inhibiting the nuclear factor kappa B signaling
Authors: Qian Ke , Yuan Lianwen , Wang Shalong , Kuang Yong , Jin Qianqian , Long Dongju , Jiang Yuhong , Zhao Hua , Liu Kuijie , Yao Hongliang 
Published: May 2021

Summary
Drugs and therapies available for the treatment of inflammatory bowel disease (IBD) are not satisfactory. Our previous study has established the inhibitor of apoptosis-stimulating p53 protein (iASPP) as an oncogenic regulator in colorectal cancer by forming a regulatory axis or feedback loop with miR-124, p53, or p63. As iASPP could target and inhibit nuclear factor kappa B (NF-κB) activation, in this study the role and mechanism of iASPP in IBD was investigated. The aberrant up-regulation of iASPP in IBD was subsequently confirmed, based on online data sets, clinical sample examinations and 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and dextran sulfate sodium (DSS)-induced colitis mice models. TNBS or DSS stimulation successfully induced colon shortness, body weight loss, mice colon oxidative stress and inflammation. In both types of colitis mice models, iASPP over-expression improved, whereas iASPP knockdown aggravated TNBS or DSS stimulation-caused colon shortness, body weight loss and mice colon oxidative stress and inflammation. Meanwhile, in both types of colitis mice models, iASPP over-expression inhibited p65 phosphorylation and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand (CXCL)1 and CXCL2 in mice colons, whereas iASPP knockdown exerted opposite effects.
The role of NOTCH3 variants in Alzheimer's disease and subcortical vascular dementia in the Chinese population
Authors: Guo Lina , Jiao Bin , Liao Xinxin , Xiao Xuewen , Zhang Weiwei , Yuan Zhenhua , Liu Xixi , Zhou Lu , Wang Xin , Zhu Yuan , Yang Qijie , Wang Junling , Tang Beisha , Shen Lu 
Published: May 2021

AbstractAimsNOTCH3 gene mutations predominantly cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, a common etiology of subcortical vascular dementia (SVaD). Besides, there may be a pathogenic link between NOTCH3 variants and Alzheimer's disease (AD). We aimed to study the role of NOTCH3 variants in AD and SVaD patients.MethodsWe recruited 763 patients with dementia (667 AD and 96 SVaD) and 365 healthy controls from the Southern Han Chinese population. Targeted capture sequencing was performed on NOTCH3 coding and adjacent intron regions to detect the pathogenic variants in AD and SVaD. The relationship between common or rare NOTCH3 variants and AD was further analyzed using Plink1.9.ResultsFive known pathogenic variants (p.R182C, p.C201S, p.R544C, p.R607C, and p.R1006C) and two novel likely pathogenic variants (p.C201F and p.C1061F) were detected in 16 SVaD patients. Additionally, no pathogenic or likely pathogenic variants were found in AD patients. NOTCH3 was not associated with AD in either single‐variant association analysis or gene‐based association analysis.ConclusionOur findings broaden the mutational spectrum of NOTCH3 and validate the pathogenic role of NOTCH3 mutations in SVaD, but do not support the notion that NOTCH3 variation influences the risk of AD.
Lipocalin 2 regulates iron homeostasis, neuroinflammation, and insulin resistance in the brains of patients with dementia: Evidence from the current literature
Authors: Lim Daejin , Jeong Jae‐ho , Song Juhyun 
Published: May 2021

AbstractDementia accompanied by memory loss is considered one of the most common neurodegenerative diseases worldwide, and its prevalence is gradually increasing. Known risk factors for dementia include genetic background, certain lifestyle and dietary patterns, smoking, iron overload, insulin resistance, and impaired glucose metabolism in the brain. Here, we review recent evidence on the regulatory role of lipocalin 2 (LCN2) in dementia from various perspectives. LCN2 is a neutrophil gelatinase‐associated protein that influences diverse cellular processes, including the immune system, iron homeostasis, lipid metabolism, and inflammatory responses. Although its functions within the peripheral system are most widely recognized, recent findings have revealed links between LCN2 and central nervous system diseases, as well as novel roles for LCN2 in neurons and glia. Furthermore, LCN2 may modulate diverse pathological mechanisms involved in dementia. Taken together, LCN2 is a promising therapeutic target with which to address the neuropathology of dementia.
Prevalence of sarcopenic obesity and association with metabolic syndrome in an adult Iranian cohort: The Fasa PERSIAN cohort study
Authors: Siervo Mario , Rubele Sofia , Shannon Oliver M , Prado Carla M. , Donini Lorenzo Maria , Zamboni Mauro , Homayounfar Reza , Farjam Mojtaba , Faghih Shiva , Mazidi Mohsen 
Published: May 2021

SummarySarcopenic obesity (SO) is characterised by a concomitant high fat mass (FM) and low fat free mass (FFM) leading to an increased cardio‐metabolic risk. This analysis aims to estimate the SO prevalence in Iranian adults and evaluate the association of SO with metabolic syndrome (MetS) risk. This cross‐sectional analysis included 4296 subjects (age 35‐70 years, 55.2% females). Body composition parameters, measured by bioelectrical impedance included: FM, FFM, appendicular lean mass (ALM) and skeletal mass index. SO was classified according to five criteria: (1) FM%‐SMI; (2) FM%‐ALM/% weight (wt%); (3) FM%‐ALM/body mass index (BMI); (4) Residuals of ALM and FM and (5) FM/FFM Ratio. Multivariate logistic regression was applied to explore the association between SO models with MetS risk stratified by gender. Receiving operating characteristic (ROC) curves were used to identify the best FM/FFM ratio cut‐off value for detecting MetS cases in males and females. The prevalence of SO varied between 4% and 26% depending upon the classification method. The prevalence of MetS was 12.8% and 31.6% in males and females, respectively. SO models based on ALM/wt% and FM/FFM ratio showed the strongest association with MetS risk in males (OR: 11.5, 95%CI: 7.5‐17.7, p < 0.001 and OR: 10.1, 95%CI: 6.9‐14.7, p < 0.001, respectively) and females (OR: 4.1, 95%CI: 3.0‐5.6, p < 0.001 and OR: 4.6, 95%CI: 3.5‐5.9, p < 0.001, respectively). SO is a prevalent condition in an adult Iranian population and the ALM/wt% and the FM/FFM ratio models of SO appeared to be associated with higher MetS risk.
Toward integrating private conservation lands into national protected area systems: Lessons from a megadiversity country
Authors: da Silva José Maria Cardoso , Pinto Luiz Paulo , Scarano Fábio Rubio 
Published: May 2021

AbstractPrivate conservation lands are essential for protecting biodiversity, but few national‐level studies have assessed their coverage and the legal frameworks that support them. Here, we review the legal mechanisms enabling conservation on private lands in Brazil and evaluate these lands' potential to reinforce the national protected area system. We found that conserving native vegetation on private lands is the most important mechanism to protect biodiversity in five out of the six Brazilian biomes. Because Brazil has a law that mandates landowners to set aside conservation areas, remnants of native vegetation were protected rather than converted to other land uses in areas of old economic frontiers. These remnants can be the cornerstones of effective regional conservation systems. Still, upgrading these remnants to privately protected areas and integrating these privately protected areas into the national protected area system remains a challenge. We suggest that the Brazilian experience provides important lessons on how other countries can design innovative policies to recognize and expand private land conservation.