bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated longitudinal analysis of glioblastomas with long-term relapse interval revealed upregulation of the Tumor Growth Factor β signaling pathway in the recurrent tumor
Authors: Kashani Elham , Schnidrig Désirée , Gheinani Ali Hashemi , Ninck Martina Selina , Zens Philipp , Maragkou Theoni , Baumgartner Ulrich , Schucht Philippe , Rätsch Gunnar , Rubin Mark Andrew , Berezowska Sabina , Ng Charlotte K. Y. , Vassella Erik 
Published: February 2022

Abstract
Background. Glioblastoma (GBM) is the most aggressive primary brain tumor and represents a particular challenge of therapeutic intervention. Methods. In a single-center retrospective study of matched pairs of initial and post-therapeutic GBM cases with a recurrence period greater than one year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent GBM. Results. Expression and mutational profiling of recurrent GBM revealed evidence for early branching evolution in seventy-five percent of patients. SBS1 signature was reduced in the recurrent tumor and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in the recurrent GBM. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration and stemness. In contrast, TGF-β-induced expression of pro-apoptotic proteins and repression of anti-apoptotic proteins were uncoupled in the recurrent tumor. Conclusions. Our results suggest an important role of TGF-β signaling in recurrent GBM. This may have clinical implication, since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent GBM show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles.
Severe acute cholecystitis (Tokyo III) in high risk patients : Should cholecystectomy be preferred over percutaneous drainage?
Authors: Giron Felipe , Venegas David , Rey Carlos , Rodriguez Lina , Vanegas Marco , Peña David , Puello Sebastian , Rodriguez Barbara , Rojas Susana , Conde Danny 
Published: February 2022

Abstract
Background Current guidelines advise the use of less aggressive procedures for the solution of cholecystitis in high risk patients. However, recent literature has shown better results in those patients managed with laparoscopic cholecystectomy . We aim to describe outcomes in high-risk patients with severe acute cholecystitis (Tokyo III) according to 2018 guidelines. MethodsPatients that underwent laparoscopic cholecystectomy and percutaneous drainage by cholecystostomy between January 2018 and January 2020 were included in descriptive analysis. Bivariate analysis of Tokyo III patients was performed between variables involved. Results A total of 622 patients were included. 54.66% of patients were female. The mean age was 66.6 ± 16.52 years. 288 patients were classified as grade III in Tokyo classification, 28.98% underwent cholecystostomy and 71.02% cholecystectomy. Mortality and complication rate had no significant differences between the groups (p = 0.09 - p = 0.1 respectively). The in-hospital length of stay was significantly higher in patients that required cholecystostomy with a mean of 15.43 days versus 9.97 days in the LC group, with a statistically significant difference (p 0.000 CI 95%) .ConclusionsLaparoscopic cholecystectomy seems to be a feasible treatment choice over percutaneous cholecystostomy in terms of mortality, reintervention and in-hospital stay length.
Efficacy of Ustekinumab on perianal fistulizing Crohn’s disease: a retrospective single-center real-world analysis
Authors: Zhi Min , Yao Jiayin , Zhang Heng , Hu Bang , Peng Xiang , Zhao Junzhang , Liu Tao , Wang Wei , Hu Pinjin , Zhang Min 
Published: February 2022

Abstract
Aim: Data of Ustekinumab (UST) in treating perianal fistulizing Crohn’s disease (CD) are limited in China. We aimed to evaluate the efficacy of UST in the real-world setting. Methods: We retrospectively analyzed patients with perianal fistulizing CD and receiving UST treatment from March 1, 2020 to October 30, 2021. Patients’ characteristics, biomarker, and imaging were extracted from digital databases. Results: Twenty patients were eligible (18 males; mean age of 29.4±2.6 years; mean disease duration of 6.3±0.9 years; 45.0% diagnosed as complex fistula; mean baseline Van Assche score of 7.7±1.1). Perianal Crohn’s disease activity index (5.4±1.0 vs 8.7±1.0, P=0.027) and Crohn’s anal fistula quality of life (29.4±4.8 vs 38.9±4.2, P=0.011) reduced significantly. Clinical remission appeared in 60.0% and clinical response in 85.0%; clinical fistula remission in 30.0%, clinical fistula response in 35.0%, and no response in 35.0% of patients. Eight patients received post-treatment MRI. Healing, partial response, no change, and deterioration appeared in 37.5%, 25.0%, 12.5% and 25.0% of the patients, respectively. The cut-off UST trough concentration predicting clinical fistula remission was 2.6 μg/ml (an area under the curve of 0.821, sensitivity 66.7%, specificity 85.7%). Conclusions: UST is efficacious in promoting clinical and radiological fistula remission in patients with CD.
Structural, DFT calculations, photophysical and photochemical characteristics of 1-((E)-2-phenylethenyl)-2-(4-(2-((E)-2-phenylethenyl) phenoxy) butoxy) benzene (PPPBB)
Authors: Bayoumy Rasha M. , Abdel-Halim Shakir T. , El-Daly Samy A. , Saad Mohamed A. , Awad Mohamed , Ebeid El-Zeiny M. 
Published: February 2022

Abstract
X- ray single crystal structure, spectroscopic and photophysical parameters of the titled compound were studied. Photophysical parameters include singlet electronic absorption, molar absorption coefficient, oscillator strength and dipole moment of electronic transition, fluorescence spectra, excited state lifetime and fluorescence quantum yield for PPPBB in different solvents. PPPBB displays a little change in maximum absorption and emission spectra with solvent polarity, indicating a slight change in dipole moment of dye molecules upon excitation. The dipole moments (Δ\(\mu\) ) difference between the excited and ground state was obtained from Lippert-Mataga method. Ground and electronic excited states geometric optimization was performed using density functional theory (DFT) and time-dependent density functional theory (TD-DFT), complemented with spectral findings. A good agreement between theoretical data and experimental observations was found. The net photochemical quantum yield (ϕc) of PPPBB dye was calculated in various solvents.
Obtaining large numbers of predatory mites, namely Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae), from cotton fields rich in it, and accumulating them on a few leaves
Authors: Elshazly Mohamed Mahrous Youssef 
Published: February 2022

Abstract
Preliminary studies on the population density of Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae) existing in a cotton field revealed that spraying Chlorpyrifos-methyl 48% E. C. and lambda-cyhalothrin 5% E. C. didn't affect the mite population density significantly. As regards the pesticide-untreated area, the maximum population density was recorded in September; meanwhile, the minimum one was recorded in June. The mites were at the highest population density on the leaves of the middle section of the plants; meanwhile, they were at the lowest population density on the leaves of the top section. The mite population found on the lower surfaces of the leaves was significantly more than the mite population found on the upper ones. The majority of the mite individuals existed at the pleats and the bases of the lower surfaces of the leaves. After spraying a defoliant by a week, the population density of the mites existing on the fresh leaves found beneath the defoliant-treated plants were 13.5 mites per leaf, which is considered to be comparatively high. Hence, large numbers of that mite could be obtained from that leaf category. By collecting 15 fresh leaves from the ground located under the plants treated with the pesticides and the defoliant, and stacking them in a jar, in certain conditions, for three days, most individuals congregated on the upper ones. The average population density of the mites found on the upper three leaves was 39.89 mites per leaf. Hence, large numbers of that mite could be accumulated on a few leaves.
Limit Cycles and Chaos in the Hybrid Atom-Optomechanics System
Authors: Xu Xingran , Krisnanda Tanjung , Liew Timothy C. H. 
Published: February 2022

Abstract
We consider atoms in two different periodic potentials induced by different lasers, one of which is coupled to a mechanical membrane via radiation pressure force. The atoms are intrinsically two-level systems that can absorb or emit photons, but the dynamics of their position and momentum are treated classically. On the other hand, the membrane, the cavity field, and the intrinsic two-level atoms are treated quantum mechanically. We show that the mean excitation of the three systems can be stable, periodically oscillating, or in a chaotic state depending on the strength of the coupling between them. We define regular,time-periodicl, and chaotic phases, and present a phase diagram where the three phases can be achieved by manipulating the field-membrane and field-atom coupling strengths. The first and second-order correlation functions in different phases are also calculated, which can be observed in experiments. Our proposal offers a new way to generate and tune time-periodic and chaotic phases in a well-established atom-optomechanics system.
A causal role for the parietal cortex in ambiguity computations in humans
Authors: Valdebenito-Oyarzo Gabriela ,   María Paz Martínez-Molina1, Soto-Icaza Patricia , Zamorano Francisco , Figueroa-Vargas Alejandra , Larraín-Valenzuela Josefina , Stecher Ximena , Salinas César , Valero-Cabré Antonie , Polania Rafael , Billeke Pablo 
Published: February 2022

Abstract

Humans must often estimate reward values in the presence of ambiguous information to determine the best course of action. The degree of ambiguity during decision-making has been related to levels of activity in the parietal cortex, however, its specific computations and causal role remain unknown. We tested the hypothesis that the parietal cortex is causally related in the computation of ambiguous probabilities during decision-making, studied via fMRI and concurrent TMS-EEG recordings. We found that the parietal cortex computes the degree of ambiguity assigned to subjective probability estimates. Disruption of these parietal signals selectively increased the assignment of unknown probabilities to choice outcomes, and these effects were accompanied by a modulation of frontal theta oscillations related to prediction error signals emerging from ambiguous choices. These results contribute to evidence supporting a fundamental causal role for the parietal cortex in the computations of ambiguous information during risky decisions and learning in humans.
Autonomous Decision Making Over Reproductive Health Service Utilization and Associated Factors Among Married Women in Illuababora Zone, South West Ethiopia:
Authors: Nigatu Dessalegn , Bayabil Zerihun , Fekede Tarekegn 
Published: February 2022

Abstract
Objective፡ Assess autonomous decision-making on RH-service utilization and its associated factors among married women in Illubabor zone, South West Ethiopia.Methods: Community based comparative cross-sectional study was conducted among married women of 584(urban 292 and rural 292) married women of reproductive age group. The data were entered into EPI data version 3.1 and exported to SPSS version 20 computer software for analysis. Both Bivariate and multivariable logistic regression analysis was used. Level of significance was declared at a p value of <0.05Results: A total of 288 in urban and 288 in rural married women were interviewed and yields a response rate of 98.6% both in urban and rural. Autonomous decision making in urban and rural was 55.2% [95% CI (52.7-64.6)] and 40.3% [95% CI (39.9-52.5)] respectively. In urban, being wives of government employed spouses [AOR 2.102 95% CI (1.16, 3.81)], knowledge on RH [AOR 3.33, 95% CI (1.20, 12.49)], above five years in marriage [AOR 1.91, 95% CI (1.19, 7.70)], were found to be predictors of women’s autonomous decision making.Conclusion: Urban women had better anonymously make decisions than rural on reproductive health service utilization. The study revealed that in urban settings those women who had marriage duration five and more than five years, being wives of government employed spouses had more likely decision making anonymously on reproductive health utilization but not in rural settings. Reproductive health interventions in the area should be promoted by considering empowering of married women on reproductive health service utilization.
GPR97-mediated PAR2 transactivation via a mPR3-associated macromolecular complex induces inflammatory activation of human neutrophils
Authors: Lin Hsi-Hsien , Chu Tai-Ying , Zheng-Gérard Céline , Huang Kuan-Yeh , Chang Yu-Chi , Chen Ying-Wen , I Kuan-Yu , Lo Yu-Ling , Chiang Nien-Yi , Chen Hsin-Yi , Stacey Martin , Gordon Siamon , Tseng Wen-Yi , Sun Chiao-Yin , Wu Yen-Mu , Pan Yi-Shin , Huang Chien-Hao , Lin Chun-Yen , Chen Tse-Ching , Antonelou Marilina , Henderson Scott , salama Alan , Seiradake Elena 
Published: February 2022

Abstract
Neutrophils play essential anti-microbial and inflammatory roles in host defense, however their activities are tightly regulated as neutrophil dysfunction often leads to detrimental inflammatory and autoimmune diseases. Here, we identified a novel PR3/CD177/GPR97/PAR2/CD16b interactome as a critical modulator of neutrophil activation. Using multiple approaches, we deorphanized GPR97, a human neutrophil-restricted adhesion G protein-coupled receptor (aGPCR), as the interacting protein and allosteric activator of CD177-associated membrane proteinase 3 (mPR3). Structural and deletion analysis of the GPR97 extracellular region disclosed two independent mPR3-binding domains. The efficient binding and activation of mPR3 by GPR97 required a macromolecular CD177/GPR97/PAR2/CD16b interactome and resulted in the transactivation of PAR2, another GPCR. GPR97-mediated PAR2 transactivation in neutrophils elicited strong inflammatory activation, triggering anti-microbial activities and endothelial dysfunction. Altogether, we identify a novel aGPCR-GPCR transactivation mechanism that directs neutrophil activation and inflammation. The PR3/CD177/GPR97/PAR2/CD16b interactome represents a potential therapeutic target for neutrophil-mediated inflammatory diseases.
AMX-1 is necessary for proper fertility and lack of its expression induced sterility in a p53/CEP-1 dependent manner by modulating piwi expression in C. elegans
Authors: Ren Xiaojing , Tian Sisi , Meng Qinghao , Kim Hyun-Min 
Published: February 2022

Abstract
Background
Histone methylation shapes the epigenetic configuration and adjusts multiple fundamental nuclear processes, including transcription, cell cycle control and DNA repair. The absence of histone demethylase LSD1/SPR-5 leads to progressive fertility defects as well as a reduction in brood size. Similarly, C. elegans LSD2 homolog AMX-1 has been implicated in regulating H3K4me2 and maintaining ICL susceptibility. However, the mechanisms of how lack of AMX-1 induces sterility have not been addressed so far.
Results
This study investigated the histone demethylase AMX-1 in C. elegans and uncovered how amx-1 contributes to sterility in a p53/CEP-1 dependent manner. We show that while sterility in spr-5 mutants exhibited progressive over generations, amx-1 mutants displayed non-transgenerational fertility defects. Also, amx-1 mutants exhibited a reduced number of sperms and produced low brood size (LBS) or sterile worms that retain neither sperms nor germline nuclei, suggesting that fertility defects originated from germline development failure. Surprisingly, sterility exhibited in amx-1 was mediated by p53/CEP-1 in a DNA damage independent manner, indicating p53/CEP-1's roles beyond DNA damage repair. Consistent with this result, upregulation of Piwi expression in amx-1 mutants suggested that AMX-1 is essential for germline development by regulating Piwi gene expressions.
Conclusions
We propose that AMX-1 is required for proper Piwi expression and transposon silencing in a p53/CEP-1 dependent manner; thus, the absence of AMX-1 expression leads to defective meiotic development and sterility. This study elucidates how LSD2/ AMX-1 contributes sterility for the first time, therefore, expanding the boundaries of histone demethylase function.
Downregulation of circBIRC6 and circCORO1C During Differentiation of Human Cord Blood-derived CD34 Cells
Authors: Karimi Roqaye , Atashi Amir , Zomorrod Mina Soufi , Ajami Monireh , Ajami Mansoureh 
Published: February 2022

Abstract
Umbilical cord blood hematopoietic stem cells (UCB HSCs) transplantation has attracted the attention of many researchers due to the low probability of GVHD and HLA mismatching; however, the use of this resource for adults has been limited due to the inadequate number of CD34+ HSC from any individual donor. Recent reports indicate that circular RNAs (circRNAs) are involved in stem cell properties. In this study, the functional role of several candidate circRNAs, including circCORO1C and circBIRC6 in CD34+ HSCs was investigated. The results showed that the expression levels of circBIRC6 and circCORO1C and simultaneously, the expression of transcription factors such as NANOG and SOX2 were significantly downregulated during differentiation. Taken together, these findings suggested that circBIRC6 and circCORO1C were involved in the process of self-renewal of CD34+ HSCs, and their expression is downregulated by differentiating these cells.
m6A modification-tuned sphingolipid metabolism regulates postnatal liver development
Authors: Yuan Detian , Wang Shiguan , Chen Shanze , Sun Jianfeng , Han Pan , Xu Bowen , Zhong Youquan , Xu Zaichao , Zhang Peng , Mi Ping , Zhang Cuijuan , Xia Yuchen , Li Shiyang , Heikenwälder Mathias 
Published: February 2022

Abstract
Different organs undergo distinct transcriptional, epigenetic and physiological alterations that guarantee their functional maturation after birth. However, the roles of epitranscriptomic machineries in these processes remain elusive. Here, we show that RNA methyltransferase enzymes Mettl3 and Mettl14 highly express in murine hepatocytes at embryonic and neonatal stages, and gradually decline during the postnatal development. Liver-specific Mettl3 deficiency causes hepatocyte hypertrophy, liver injury and growth retardation. Transcriptomic and N6-methyl-adenosine (m6A) profiling identify the neutral sphingomyelinase, Smpd3, as a target of Mettl3. Decreased decay of Smpd3 transcripts due to Mettl3 deficiency results in sphingolipid metabolism rewiring, characterized by toxic ceramide accumulation and excessive sphingomyelin hydrolysis, leading to mitochondrial damage and elevated ER stress. Pharmacological inhibition of Smpd3 ameliorates the abnormality of Mettl3-deficent liver. Our findings demonstrate that Mettl3/m6A fine-tunes sphingolipid metabolism, highlighting the pivotal role of an epitranscriptomic machinery in coordinating metabolic homeostasis and functional maturation during postnatal liver development.
Comparison of the Efficacy of Oral and Intramuscular Vitamin D Therapy in Obese Children with Vitamin D Deficiency
Authors: Korkmaz Hüseyin Anil , Karaarslan Utku , Özkan Behzat 
Published: February 2022

Abstract
Introduction:
The efficacy of oral versus intramuscular (IM) vitamin D administration in obese children is debatable. The purpose of this study was to compare the efficacy of oral versus IM administration of a single dose of cholecalciferol (300,000 IU) in obese children with vitamin D deficiency.
Methods
In an open-label, randomized, and cross-sectional clinical study, 96 obese patients with vitamin D deficiency and body mass index (BMI) > + 2 standard deviation scores (SDS) for their age and gender were recruited. Sixty-one children received a single IM dose of cholecalciferol (300,000 IU), while 35 children received an oral single dose of cholecalciferol (300,000 IU). At the initial clinic visit, baseline serum calcium (Ca), phosphorus (PO4), alkaline phosphatase (ALP), parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD) concentrations were measured. After 12 weeks, serum biochemical and hormone levels were determined. The study’s primary endpoint was a change in serum 25OHD hormone levels.
Results
There was no statistically significant difference between the IM and oral groups and baseline in the median 25OHD levels (8 (4) vs. 10.3 (1.8) ng/mL) and PTH levels (70 (28) vs. 68 (22) pg/ml). Compared to the oral group, the IM group showed a statistically significant increase in the 25OHD levels (IM Δ25OHD: 31 (10) vs. oral Δ25OHD: 20 (6.7) ng/ml, p < 0.01), while the PTH levels were significantly reduced from their baseline levels (IM ΔPTH: 53.2 (31.5) vs. oral ΔPTH: 37.4 (27.2) pg/ml, p < 0.01).
Conclusion
In obese children, a single IM dose of vitamin D (300,000 IU) had a greater bioavailability than a similar dose given orally. Supplementation of vitamin D (300,000 IU), either IM or orally, was found to normalize 25OHD levels in vitamin D deficient obese children.
Investigation of micronutrients and heavy metals in rice farms of Ahvaz and Bawie Counties, Khuzestan Province, Iran
Authors: Rastmanesh Fatemeh , Ghazalizadeh Soraya , Shalbaf Fatemeh , Zarasvandi Alireza 
Published: February 2022

Abstract
This research was conducted to determine the status of micronutrients (Fe, Zn, Cu, Mn, Co) and heavy metals (As, Pb) in the soil and rice crop in Ahvaz and Bawie counties, Iran. Twenty-eight composite soil and grain samples from selected rice farms were collected during the harvest time. The concentrations of elements in samples were determined by Inductively coupled plasma - optical emission spectrometry and in the grains by Inductively coupled plasma mass spectrometry device. Physicochemical properties of soil, bioconcentration factor, daily intakes and health risk assessment for elements were calculated. The results showed that the area is covered by alkaline saline soils, which is poor in micronutrients. The bioconcentration factor values of all elements were less than 1. Low levels of bioconcentration factor may be due to the low levels of nutrients in the soil as well as the physicochemical conditions of the soil. Furthermore, the results showed that the daily intake of Co (in the adults’ group) and Fe and Zn (in the children group) is very low. Health risk assessment showed that only adults are at the risk of non-cancerous and cancerous diseases caused by excess of As and Pb. Considering that Khuzestan province is the fourth largest producer of rice in Iran, the lack of micronutrients and presence of heavy metals in the rice produced in the study area can have adverse health effects on consumers. Investigation of this issue requires more detailed studies in the region.