bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of High Pressure-Assisted Extraction on Yield, Antioxidant, Antimicrobial and Anti-Diabetic Properties of Chlorogenic Acid and Caffeine Extracted From Green Coffee Beans
Authors: Lin Yan-Han , Huang Hsiao-Wen , Wang Chung-Yi 
Published: March 2022

Abstract
The bioactive ingredients of green coffee beans were extracted using high pressure-assisted extraction (HPE) and compared against those derived from the traditional heat reflux (HR) extraction method. The effect of extraction conditions on the extraction efficiency of functional components (chlorogenic acids, caffeine, total phenols, and flavonoids); the free radical-scavenging activity of the extract; and the inhibition of α-glucosidase, α-amylase, and food pathogenic bacteria were measured. Using water as the solvent, the high-pressure extraction rates of chlorogenic acid (CGA) and caffeine were 3.20–5.75 mg/100 g and 4.32–7.95 mg/100 g, respectively, which were significantly higher than the rates obtained using the traditional method (2.92 mg/100 g and 3.54 mg/100 g, respectively). Under optimal extraction conditions of 25°C and 600 MPa for 2.5 min, inhibition of α-glucosidase and α-amylase by the extract reached rates of 27% and 26%, respectively, with the highest free radical-scavenging activity of 81.5%. HPE samples exhibited antibacterial activity against both gram-positive (Staphylococcus aureus and Listeria innocua) and gram-negative (Escherichia coli and Salmonella enterica) bacteria, and the lowest minimum inhibitory concentration (4.69 mg/mL) against S. aureus was achieved. Scanning electron microscopic observations evidenced that high pressure partially damaged the intercellular compartments of coffee beans, increased solvent permeability, and improved the extraction rate of bioactive ingredients. The outcomes of the study demonstrated that, HPE can be employed as an efficient extraction technique for production of chlorogenic acids and caffeine that might have a potential application in food and related industries.
Machine Learning Model for Predicting Antibiotic Resistance in the Emergency Department in Patients With Urinary Tract Infection
Authors: Lee Hyun-Gyu , Seo Youngho , Han Seung Baik , Kim Ji Hye , Im Jae Hyoung , Durey Areum 
Published: March 2022

Abstract
Background: Increasing antimicrobial resistance in uropathogens is a clinical challenge to emergency physicians as antibiotics should be selected before an infecting pathogen or its antibiotic resistance profile is confirmed. This single-center retrospective study evaluated patients diagnosed with upper urinary tract infection (UTI) in the emergency department (ED) between January 2020 and June 2021 to develop a predictive model for antibiotic resistance of uropathogens, using machine learning (ML) algorithmsResults: Forty variables were used to train the model for predicting resistance to ciprofloxacin and the presence of ESBL of urinary pathogens. Model performance with the XGBoost Gradient-Boosted Decision Tree (GBDT) was compared with that of empirical treatment (ET) according to effectiveness of antibiotic selected and appropriateness of selection with respect to antibiotic stewardship. Two prediction models using different decision thresholds were developed. The probability of using ineffective antibiotics in the ED was significantly lowered by 13.3% in the GDBT 0.25 using a decision threshold of 0.25 than in the ET model. Further, the rate of appropriate use of narrow-spectrum antibiotics was higher by 7.4 times in the GBDT 0.44 model than in the ET model, while the ineffectiveness level was maintained.Conclusions: An ML model is potentially useful for predicting antibiotic resistance, improving the effectiveness and appropriateness of empirical antimicrobial treatment in patients with upper UTI in the ED. The model could be a point-of-care decision support tool to guide clinicians towards individualized antibiotic prescription.
Repurposing alpelisib, an anti-cancer drug, for the treatment of severe TIE2-mutated venous malformations: preliminary pharmacokinetics and pharmacodynamic data
Authors: Kleiber Niina , Remy Amandine , Tran Thai Hoa , Dubois Josée , Lapointe Chantal , Gavra Paul , Garcia-Bournissen Facundo , Théorêt Yves , Winikoff Rochelle 
Published: March 2022

Abstract
Extensive venous malformations (VM) involving limbs severely impact quality of life, mostly due to chronic pain and functional limitations. Patients can also display coagulopathy with associated risks of life-threatening thromboembolism and bleeding. Current pharmacological VM treatments (e.g. sirolimus) are not universally effective as 10% of patients present intractable debilitating and/or critical disease. Novel therapies are therefore highly needed for treatment-resistant VM. Over 70% of sporadic VM are attributed to activating mutations in the TEK gene, encoding the receptor tyrosine kinase TIE2 expressed by venous endothelial cells. Despite in vitro studies showing the superiority of alpelisib over sirolimus in inhibiting TIE2 signalling pathway and vein remodelling, there are currently no clinical reports of alpelisib use in VM. Our aim was therefore to assess the effect of alpelisib in TIE-2 mutated VM and to assess its pharmacokinetics. Three patients with a VM harboring the TEK L914F mutations were treated with alpelisib in an open-label compassionate use study. All patients experienced significant improvement. Pain was controlled, gait improved, size of the abnormal venous network decreased, and coagulopathy showed dramatic improvement. Drug exposure was highly variable despite similar weight-adjusted doses, suggesting that alpelisib dosing should be individualized to patient’s characteristics and guided by therapeutic drug monitoring to improve clinical response.
AR12 increases BAG3 expression via ER stress signaling which is essential for Tau and APP degradation via LC3-associated phagocytosis and macroautophagy
Authors: Dent Paul , Booth Laurence , Roberts Jane L. , Poklepovic Andrew , Martinez Jennifer , Cridebring Derek , Reiman Eric 
Published: March 2022

Abstract
Background
We defined the mechanisms by which the chaperone ATPase inhibitor AR12 and the multi-kinase inhibitor neratinib interacted to reduce expression of Tau and amyloid-precursor protein (APP) in microglia and neuronal cells.
Methods
In vitro cell culture; in-cell immunostaining using a Hermes wide-field microscope with densitometric imaging software; transfection of siRNA and plasmids; assessments of autophagy using a plasmid to express LC3-GFP-RFP.
Results
AR12 and neratinib interacted to increase the phosphorylation of eIF2A S51 and the expression of BAG3, Beclin1 and ATG5, and in parallel, enhanced autophagosome formation and autophagic flux. Knock down of BAG3, Beclin1 or ATG5 abolished autophagosome formation and significantly reduced degradation of p62, LAMP2, Tau, APP, and GRP78 (total and plasma membrane). Knock down of Rubicon, a key component of LC3-associated phagocytosis (LAP), significantly reduced autophagosome formation but not autophagic flux and prevented degradation of Tau, APP, and cell surface GRP78, but not ER-localized GRP78. Knock down of Beclin1, ATG5 or Rubicon or over-expression of GRP78 prevented the significant increase in eIF2A phosphorylation. Knock down of eIF2A prevented the increase in BAG3 expression and significantly reduced autophagosome formation, autophagic flux, and it prevented Tau and APP degradation.
Conclusions
We conclude that AR12 has the potential to reduce Tau and APP levels in neurons and microglia via the actions of LAP, endoplasmic reticulum stress signaling and macroautophagy. We hypothesize that the initial inactivation of GRP78 catalytic function by AR12 facilitates an initial increase in eIF2A phosphorylation which in turn is essential for greater levels of eIF2A phosphorylation, greater levels of BAG3 and macroautophagy and eventually leading to significant amounts of APP/Tau degradation.
Attention-LSTM Based Prediction Model for Aircraft 4-D Trajectory
Authors: Jia Peiyan , Chen Huiping , Zhang Lei , Han Daojun 
Published: March 2022

Abstract
With the increase of aviation activities, airspace constraints and flight delays have become increasingly prominent in the process of air traffic management (ATM). How to increase airspace capacity within the limited airspace resources while ensuring smooth and safe aircraft operations is a challenge for civil aviation today. In order to accelerate the intelligent operation of air traffic control and promote the development of intelligent ATM systems, it becomes very important to improve the accuracy of trajectory prediction, which becomes very difficult due to the problems of sparse aircraft flight trajectory and different flight altitudes. In order to solve this problem, an Attention-LSTM trajectory prediction model is proposed in this paper. This model can extract the time series features of the trajectory using an long short-term memory (LSTM) network and improve the accuracy of trajectory prediction by extracting the important factors affecting the current point change using an attention mechanism. To verify the accuracy of our proposed model, this paper uses real trajectory data, and uses LSTM, support vector machine, and other models for comparison. The comparison results show that this model is better than the most advanced model, which further promotes the process of intelligent ATM systems.
Segregated transmission of co-occluded baculoviruses limits cellular coinfection and virus-virus interactions
Authors: Pazmiño-Ibarra Verónica , Herrero Salvador , Sanjuán Rafael 
Published: March 2022

Abstract
Baculovirus occlusion bodies (OBs) are polyhedrin-rich structures that mediate the collective transmission of tens of viral particles to the same insect host. In addition, in multiple nucleopolyhedroviruses, occlusion-derived viruses (ODVs) form nucleocapsid aggregates that are delivered to the same host cell. It has been suggested that, by favoring coinfection, this transmission mode promotes evolutionarily stable interactions between different baculovirus variants. To investigate this, we obtained OBs from cells coinfected with two viral constructs, each encoding a different fluorescent reporter, and used them for inoculating Spodoptera exigua larvae. Microscopy analysis of midguts revealed that the two reporter genes were typically segregated into different infection foci, suggesting that ODVs do not promote the coinfection of cells with different baculovirus genetic variants. However, a polyhedrin-deficient mutant underwent inter-host transmission by exploiting the OBs of a fully-functional virus and re-acquired the lost gene through recombination, demonstrating cellular coinfection. Our results suggest that viral spatial segregation during transmission and primary infection limits interactions between different baculovirus variants, but that these interactions still occur episodically.
Joint effect of Maternal Pre-pregnancy Body Mass Index and Folic Acid Supplements on Gestational Diabetes Mellitus Risk: A prospective cohort study
Authors: Li Minyu , Wang Lijiang , Du Zhanhui , Shen Qianqian , Jiang Lu , Sui Lun , Zhang Nan , Wang Hong , Li Guoju 
Published: March 2022

Abstract
Background: The joint effect of folic acid (FA) supplements and maternal pre-pregnancy body mass index (ppBMI) on gestational diabetes mellitus (GDM) has not been fully addressed. We aimed to examine the joint effect of FA supplements and ppBMI on GDM.Methods: Pregnant women at 4 to 14 weeks of gestation (n=3186) were recruited to this study during their first prenatal visit in Qingdao from May 1, 2019, to June 27, 2021. The main outcome was GDM and GDM screening based on 75g 2-hour OGTT, a fasting glucose ≥5.1 mmol/L, or a 1-hour result ≥10.0 mmol/L, or a 2-hour result ≥8.5 mmol/L at 24-28 weeks’ gestation. The interactive effect of FA supplements and ppBMI on GDM was examined by logistic regression models.Results: A total of 2095 pregnant women were included analysis, and GDM incidence was 17.76%. The joint effect of ppBMI and FA supplements was statistically significant on GDM. The risk effect was most prominent among pregnant women with FA-D and pre-pregnant obese (adjusted OR [aOR]=5.10, 95% CI: 1.83-14.19). This synergistic effect was more obvious when stratified by FA intake time. The aORs of FA-S and FA-D among the obesity women were 2.75 (95% CI: 1.42-5.34) vs. 4.49 (95% CI: 1.22-16.50) in FA intake <3 months. An increased risk of GDM was more apparent for obesity women with FA-D in FA intake ³3 months (aOR=9.83, 95%CI: 1.52-63.47). However, as for pre-pregnant overweight, FA-D appeared to be positively associated with GDM only in the group of FA supplements ³3 months (aOR= 2.13, 95% CI: 1.46-3.11).Conclusion: Coexistence of pre-pregnancy overweight or obese and deficiency of FA supplements increased risk of GDM compared with each of these risk factors alone. Public awareness about the risk effects of FA deficiency, especially among pregnant women with a higher BMI, are necessary.
Cross-National Comparison Of Religion As A Predictor Of COVID-19 Vaccination Rate
Authors: Trepanowski Radosław , Drążkowski Dariusz 
Published: March 2022

Abstract
We examined the effects of religiosity on COVID-19 vaccination rate using a cross-national comparison while controlling for socio-economic factors and culture. Our analysis, conducted on data from 90 countries representing 86% of the world population showed that the proportion of Christians was negatively related with vaccination, while there was no relation with the proportion of Muslims, Buddhists, Hindus, and nonbelievers. The importance of religion, freedom of expression and belief, sex ratio, median age, and almost all cultural factors were not related to vaccination, whereas Human Development Index was. The influence of different religions on vaccination rate has also been described.
Proving Riemann Hypothesis by Elementary Equivalents
Authors: Kader Syed Abdul 
Published: March 2022

Abstract
One of the most elusive unsolved problems of today is Riemann hypothesis. For long mathematicians have struggled to prove this problem, and also tried to devise an elementary version of the problem, proof of which indirectly proves Riemann hypothesis. In 2002 J. C. Lagarias published such an elementary version of the hypothesis which has been widely accepted as an elementary equivalent of Riemann hypothesis. This article attempts to prove Lagarias's condition, a proof of Guy Robin's inequality has also been provided in the end, any of which consequently proves Riemann hypothesis.
Indications and pivotal trials of the FDA approved small-molecular kinase inhibitors in cancer therapies with and without biomarker of cancer driver gene
Authors: Huang Yafang , Xiong Weiyi , Ma Li , Wu Hao 
Published: March 2022

Abstract
Background: Cancer precision medicine with biomarker of cancer driver gene (CDG) has been achieved by many small-molecular kinase inhibitors (SMKIs) approved by the US Food and Drug Administration (FDA). We characterized their indications and pivotal trials with and without CDG biomarker. Methods: Publicly available FDA documents were collected for all SMKI cancer drugs approved between January 2001 and December 2021. Characteristics of indication and pivotal trial were compared in terms of trends in the number of approval, special expedited development and review pathways as determined by the FDA, cancer types, line of treatment, trial design features. Results: We identified 62 SMKI cancer drugs with 150 indications approved by the FDA between 2001 and 2021. Of these, 55 indications (36.7%) were CDG biomarker-directed. There was a significant increase of 20.5% per year in the number of approved CDG biomarker-directed indications. CDG biomarker-directed indications were associated with significantly higher odds in receiving accelerated approval (odds ratio [OR] = 2.728; 95% CI, 1.246 to 5.973; P = .012), designating orphan drug (OR = 3.952; 95% CI, 1.758 to 8.883; P < .001) and in solid cancer (OR = 7.613; 95% CI, 2.958 to 19.590; P < .001), and were associated with significantly lower odds in using randomized controlled trials (RCTs) (OR = 0.103; 95% CI, 0.032 to 0.338; P < .001) with less number of entered patients. In solid cancer, CDG biomarker-directed indications were associated with significantly higher overall response rates (ORRs). Conclusion: The number of CDG biomarker-directed indications in approved SMKIs increased significantly in past two decades, with higher proportion of approvals using special expedited development and approval pathways at the FDA, less proportion of trials with RCT, less number of entered patients but better ORRs.
A Prospective Cohort Study: Platelet-Rich Plasma Combined with Carpal Tunnel Release Treating Carpal Tunnel Syndrome short (running) title: PRP-CTR Treating Carpal Tunnel Syndrome
Authors: Chen Hua , Gao Yan-chun , Wang Qi-yang , Wang Chen-chen 
Published: March 2022

Abstract
Background: PRP injection was proved to promote the health condition of individuals with mild to moderate Carpal Tunnel Syndrome （CTS）. However, carpal tunnel release (CTR) was still an important treatment for individuals with moderate, as well as severe CTS.Methods: To explore whether adjuvant PRP treatment would improve the prognosis while using CTR, we included 82 patients in this study. Preoperative and postoperative visual analog scale (VAS), Boston carpal tunnel syndrome questionnaire-symptom severity scale (BCTQ-SSS), Boston carpal tunnel syndrome questionnaire-functional status scale (BCTQ-FSS), and grip strength was used to examine the patient's symptoms and function.Results: CTR combined with PRP treatment improved the VAS (1.9±0.5 versus 1.4±0.4, P<.05), BCTQ-SSS (1.8±0.4versus 1.5±0.3, P<.05) and BCTQ-FSS (1.8±0.5 versus 1.4±0.6, P<.05) in patients with moderate symptoms within one month after surgery. At the same time, it does not show any advantages in treating individuals with severe carpal tunnel syndrome.Conclusions: The use of PRP does not affect long-term prognosis while increasing the surgery cost. To conclude, PRP as an adjuvant treatment of CTR has limited effect. Considering the additional financial burden on patients, CTR combined with PRP should be cautious in CTS treatment.
The Gonial Angle as a Predictive Marker of Mandibular Fossa Depth: A Diagnostic Accuracy Study
Authors: KOLSUZ Mehmet Eray , BOZKURT Poyzan , SEKİ Umut 
Published: March 2022

Abstract
Purpose
The aim of the study is to evaluate the relationship between submandibular fossa depth and gonial angle measurements in cone beam computed tomography examinations in terms of dental implant applications and whether the results can be transferred to panoramic radiographs.
Methods
Cone-beam computed tomography images of 51 dry human mandibles were included. Gonial angle and fossa depths were determined and evaluated separately for left and right sides. Gonial angle was measured on Cone-beam computed tomography images as the angle between the tangent line drawn posterior to the border of the ramus of the mandible and the tangent line drawn to the lower border of the mandible. Determination of the submandibular fossa depth was made with a line was drawn to connect the most dislocated upper and lower points on the inner surface of the mandible in the coronal plane sections, and the length of the line drawn at a right angle from the deepest point of the fossa to this line. Measurements were made separately for left and right sides.
Results
No statistically significant correlation was found between the angle measurement and the depth measurements from the left and right sides. There was no statistically significant correlation between mean angle measurement and mean depth measurement. No statistically significant correlation was found between all angle measurements and all depth measurements.
Conclusion
The mandibular gonial angle is not a suitable marker to be used to predict the depth of the submandibular fossa on panoramic radiographs.
Demography and Clinical Pattern of Newly Diagnosed Uveitis Patients in Malaysia
Authors: Rajan Rajasudha Sawri , Mohamed Shelina Oli , Salowi Mohamad Aziz 
Published: March 2022

Abstract
Introduction:Uveitis is one of the common causes of visual impairment in Malaysia and it remains a challenging entity to diagnose and manage. This study aims to observe the demographic and clinical pattern of uveitis cases that are referred to most ophthalmology units in Malaysia Methods:This was an observational, multicenter study with a total of 1199 newly diagnosed uveitis patients. Data collected and analyzed included age, gender, ethnicity, nationality, state of origin, laterality, granulomatous or non-granulomatous uveitis, and etiology of uveitis.Results:The results showed that majority of the patients across all age groups had anterior uveitis (n=560; 46.7%). The higher the age group, the higher the percentage of anterior uveitis patients (39.0% among 20-40 age group vs 61.3% among the >60 age group). Sixty three percent of the patients presented with unilateral uveitis (n= 760, p <0.001). Non granulomatous uveitis comprised 84.5% of all patients (n=1013, p< 0.001). Non-infectious etiology contributed to 65.7% of all patients (n=788, p<0.001) with idiopathic (57.2%, n=686) as the most common cause followed by Vogt-Koyanagi-Harada (VKH) syndrome (2.1%, n=25). Infectious uveitis comprised 34.3% (411 patients) in total with Tuberculous (TB) related uveitis (105 patients with 8.8%) and Viral related uveitis (107 patients with 8.9%) contributing the most followed by Ocular Toxoplasmosis (n=93,7.8%). The likelihood of posterior uveitis being more infectious was statistically significant (Odds ratio (OR) 12.54, 95% CI 8.81-18.13) (p-value <0.001)Conclusion:This study has highlighted the demographic data and common causes of uveitis in Malaysia
Testing microbiome associations with survival times at both the community and individual taxon levels
Authors: Hu Yingtian , Li Yunxiao , Satten Glen A. , Hu Yi-Juan 
Published: March 2022

Abstract
Background: Finding microbiome associations with possibly censored survival times is an important problem, especially as specific taxa could serve as biomarkers for disease prognosis or as targets for therapeutic interventions. The two existing methods for survival outcomes, MiRKAT-S and OMiSA, are restricted to testing associations at the community level and do not provide results at the individual taxon level. An ad hoc approach testing each taxon with a survival outcome using the Cox proportional hazard model may not perform well in the microbiome setting with sparse count data and small sample sizes.Methods: We have previously developed the linear decomposition model (LDM) for test- ing continuous or discrete outcomes that unifies community-level and taxon-level tests into one framework. Here we extend the LDM to test survival outcomes. We propose to use the Martingale residuals or the deviance residuals obtained from the Cox model as continu- ous covariates in the LDM. We further construct tests that combine the results of analyzing each set of residuals separately. Finally, we extend PERMANOVA, the most commonly used distance-based method for testing community-level hypotheses, to handle survival outcomes in a similar manner.Results: Using simulated data, we showed that the LDM-based tests preserved the false dis- covery rate for testing individual taxa and had good sensitivity. The LDM-based community- level tests and PERMANOVA-based tests had comparable or better power than MiRKAT-S and OMiSA. An analysis of data on the association of the gut microbiome and the time to acute graft-versus-host disease revealed several dozen associated taxa that would not have been achievable by any community-level test, as well as improved community-level tests by the LDM and PERMANOVA over those obtained using MiRKAT-S and OMiSA.Conclusions: Unlike existing methods, our new methods are capable of discovering individ- ual taxa that are associated with survival times, which could be of important use in clinical settings.