bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fatal JC-virus Granular Cerebellar Neuronopathy associated with Autoimmune Lymphoproliferative Syndrome and Common Variable Immunodeficiency
Authors: Helweg-Larsen Jannik , Rasmussen Morten , Rosenstierne Maiken , Bay Jakob Thaning , Gjerdrum Lise Mette Rahbek , Bangsgaard Regitze , Gideon Peter , Marvig Rasmus L. , Selleberg Finn , Marquart Hanne Vibeke , Ryder Lars Peter , Fomsgaard Anders , Kondziella Daniel 
Published: September 2020

Abstract
Background: JC-virus (JCV) associated granular cerebellar neuronopathy (JCV-GCN), which causes severe ataxia, is a rare complication of severe immunodeficiency and caused by a variant of JCV with a VP1-deletion. JCV-GCN has not yet been reported in patients with autoimmune lymphoproliferative syndrome (ALPS-FAS). We report a 34-year old woman with autoimmune lymphoproliferative syndrome (ALPS-FAS) and common variable immunodeficiency (CVID) who developed JCV-GCN which progressed to fatal progressive multifocal leukoencephalopathy (PML).Methods: Extensive longitudinal virologic, genetic and immunologic characterisation by JCV CSF quantification and sequencing, peripheral blood flowcytometry and exome sequencing. Results: A diagnosis of JCV-GCN was established by findings of severe cerebellar vermis atrophy on MRI and a JCV variant with a VP1-deletion (JCV-VP1) in CSF. During a period of 18 months, at which treatment with high dose immunoglobulin, cidofovir, mirtazapine and high dose fucidic acid were given, cerebellar ataxia was relatively stable. In CSF a mixture of predominantly JCV-VP1 with only low levels of wildtype JCV was found. However, classic PML ensued, with rising JCV- CSF levels and a complete change to JCV-wildtype quasi species without JCV-VP1. Immunological findings were unusual, with disappearance of the original ALPS-FAS phenotype. Trio-exome sequencing identified a heterozygote de novo variant of unknown significance in RAG1. FAS mutations were not detected in the patient or in the parents, suggesting that her previously diagnosed ALPS-FAS-FAS was caused by somatic mosaicism. At the progression to PML, increased expression of T-cell PD-1 was demonstrated, suggesting T-cell exhaustion. Treatment with pembrolizumab, an inhibitor of PD-1, was attempted but followed by rapid and fatal PML progression. Conclusion: JCV-GCN may complicate ALPS and may progress to PML. In JCV-GCN, wild-type and JCV-VP-1 can co-exist in CSF. Quantification and sequencing of JCV in CSF is helpful to characterize and monitor disease and treatment. Progression of disease may be associated with development of T-cell exhaustion, but the benefit PD-1 inhibitor treatment is uncertain.
MiR-545-3p Upregulated in Osteoporosis and Regulates The Apoptosis of Osteoblasts by Targeting SIRT6
Authors: Ma Qi-Ming , Li Xiao-Jing , Pei Shao-Bao , Li Bo-Wen , Han Guo-Song , Cao Shuang , Jiang Ting 
Published: September 2020

Abstract
Background: The imbalance of proliferation and apoptosis plays an important role in the pathogenesis of osteoporosis. MicroRNAs play an important role in the apoptosis of osteoblasts cells. However, the role and potential mechanism of miR-545-3p in regulating osteoblast apoptosis remain unclear. The purpose of this study was to investigate the effect of miR-545-3p on osteoblast cells apoptosis and explore the mechanism of osteoporosis.Methods: Osteogenic medium was used to induce the differentiation of osteoblasts MC3T3-E1 to construct the osteoporosis model, and the expression of ALP, Runx2, OCN were detected by western blot; miR-545-3p mRNA was detected by RT-PCR. Transfected with miR-545-3p mimics into MC3T3-E1, then flow cytometry was used to detected the changes of apoptosis status. The expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot. Bioinformatics was used to analyze the binding protein of miR-545-3p, and luciferase reporter gene experiment was used to verify whether miR-545-3p directly targets SIRT6; RT-qPCR and western blot were used to detect the expression level of SIRT6 after transfection of miR-545-3p mimics or miR-545-3p inhibitor. After co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6, the apoptosis status of osteoblasts was analyzed by flow cytometry, and the expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot.Results: The expression of miR-545-3p in patients with osteoporosis was significantly higher than that of normal in GEO database (P<0.05). After osteoblasts were cultured in osteogenic medium, the expression of ALP, Runx2 and OCN was increased, and the expression of miR-545-3p was decreased. Flow cytometry analysis showed that overexpression of miR-545-3p promoted the apoptosis of osteoblasts. Western blot results showed that overexpression of miR-545-3p promoted the expression of Bax and decreased the expression of Bcl-2. Bioinformatics analysis showed that miR-545-3p could target SIRT6. The results of real-time PCR and western blot showed that SIRT6 expression was significantly inhibited by miR-545-3p mimics (P<0.05). Luciferase reporter gene assay showed that miR-545-3p significantly inhibited luciferase activity of wild-type SIRT6-3'UTR plasmid transfected cells (P<0.05), but had no effect on luciferase activity of mutant SIRT6-3'UTR plasmid transfected cells (P<0.05). However, co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6 could reduce the apoptosis, and western blot results showed that co-transfection promoted the expression of Bcl-2 and decreased the expression of Bax.Conclusions: miR-545-3p can promote the apoptosis of osteoblasts by inhibiting the expression of SIRT6, which provides a certain idea for the treatment of osteoporosis.
Investigation of the Relationship Between Sagittal Curvature and Lumbar Extensor Muscle Volume in Patients with Lower Back Pain
Authors: Yurdaisik Isil , Aksoy Süleyman Hilmi 
Published: September 2020

Abstract
Objective: The objective of this study was to investigate the relationship between spinal curvature and extensor muscle volume in patients who presented to our hospital with lower back pain and were referred to our radiology clinic for imaging investigations.Methods: A total of 150 patients with 87 being female and 63 male who presented to our hospital with the complaint of lower back pain and were referred to our radiology clinic were included in this study. Lumbar angle, lumbosacral angle, wedge angle, sacral horizontal angle, the volume of the right and left PSOAS muscles and the volume of the right and left extensor muscles were calculated and analyzed. Results: A total of 150 patients with lower back pain were included in the study. The mean lumbar angle was found as 44.2±10.6 degrees, and the mean lumbosacral angle as 56.7±10.9 degrees. The mean wedge angle of all patients included in the study was measured as 9.3±3.7 degrees. The mean sacral horizontal angle was found as 33.6±7.1 degrees. The mean right lumbar extensor muscle volume was measured as 2169.6±489.6 mm3, while the mean left lumbar extensor volume was calculated as 2286.5±1452.8 mm3. Conclusion: Our findings indicate a significant positive correlation between the volume of extensor muscles in the lower half of the lumbar spine and sagittal curvature in the same region. Clarifying the relationship between sagittal curvature and lower lumbar muscle size will provide contribution to the management of patients with lower back pain and will be helpful in determining whether these patients would benefit from intensive treatment.
Ultrasonic Evaluation of Muscle Recovery Following Free Functioning Gracilis Transfer, A Preliminary&nbsp;Study
Authors: Hou Yi , Yang Jiantao , Qin Bengang , Gu Liqiang , Zheng Jia 
Published: September 2020

Abstract
Background: Ultrasonic measurement has not been utilized to assess functional recovery of transplanted muscle. This study aimed to investigate the feasibility of B-ultrasound measurement for evaluation of muscle recovery following free functioning gracilis transfer.Methods: From January 2009 to January 2014, 35 patients receiving free functioning gracilis transfer due to total brachial plexus injury were enrolled. B-ultrasound was utilized to measure the cross-sectional area (CSA) of transplanted gracilis muscle at rest and contraction state. The ratio of pre- to post-transplant CSA value at rest state was defined as muscle bulk ratio (MBR). The ratio of CSA value at the contraction state to that at rest state was defined as contraction ratio (CR). Results: Patients with muscle strength M≥4 had significantly higher CR1 (post-transplant), CR2 (pre-transplant), and range of motion (ROM, joint mobility) than those with muscle strength M＜4. The CR1>CR2 group had significantly higher CR1, muscle strength, and ROM than the CR1≤CR2 group. The MBR>1 group had significantly higher muscle strength than the MBR≤1 group. CR1 value was highly correlated with muscle strength and with ROM. CR2 value was moderately correlated with muscle strength and ROM. Multivariate linear regression analysis showed that higher CR1/CR2 value was associated with higher muscle strength and higher joint mobility. The CR1>CR2 group had better muscle strength and ROM than the CR1≤CR2 groups.Conclusion: B-ultrasound measurement can quantitatively reflect muscle strength following gracilis transfer, and CR but not MBR value could be a potential indicator for functional recovery of the transplanted gracilis muscle.Level of Evidence: Prognostic studies, Level II.
Whole Exome Sequencing Identifies genetic variants in Chinese Han pregnant women with Venous thromboembolism-a case control study
Authors: Shen Yupei , Zhang Yan , Xiong Ying , Zhang Zhiping , Zhang Baohua , Li Aihong , Zhang Zhaofeng , Du Jing , Che Yan 
Published: September 2020

Abstract
Background: Venous thromboembolism (VTE) is a common health problem, causing considerable morbidity and mortality. The incidence of VTE is higher in pregnant women than in those who are not pregnant. However, genetic factors for VTE in pregnant women are largely unknown.Methods: We performed a large-scale prospective cohort study of 65138 pregnancies. Pregnant patients with VTE and pregnant women without VTE were enrolled in the study and sequenced by whole exome sequencing. Functional and enrichment analyses were performed using the DAVID online database. The protein-protein interaction network was constructed using the STRING database. Results: 5810 significant variants were associated with pregnant patients with VTE, including 4874 single nucleotide variants and 936 short deletions which were annotated in 3417 genes (P < 0.05). Fifty-six variants annotated in 46 genes (P < 0.001) and the top 3 variants, including rs2706258 (RNA LOC102724050, p = 1.25 × 10-6), rs17057520 (SCARA3, p = 4.64 × 10-5), and rs3739550 (CAAP1, p = 4.64 × 10-5), were identified. Fourteen low frequency variants had a minor allele frequency (MAF) of less than 1%. Logistic analysis revealed that rs7099478 (GRK5), rs8041208 (WDR72), rs17215792 (KLF7), rs13035688 (KLF7), rs6725221 (KLF7), and rs3214417 (KLF7) were associated with an increased risk of developing VTE (P < 0.05, OR > 1). In addition, combined pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA replication were associated with VTE in pregnant individuals.Conclusion: The study identified a series of variants and genes that may contribute to VTE in the Chinese pregnant population. Several genes may be risk factors for VTE including KLF7, GRK5, and WDR72. CDC7 and MCM6 may be related to the potential functions of VTE in pregnant women. Notably, the KLF7 gene had 4 genetic variants that were found to be associated with lipid metabolism and cardiovascular diseases. Therefore, further validation is required to reveal the KLF7 mechanism in pregnant women with VTE.
Risk factors and population attributable risk percent for lactation mastitis in Chinese women: a systematic review and meta-analysis
Authors: Lai Baoyong , Yu Bo-Wen , Chu Ai-Jing , Liang Shi-Bing , Jia Li-Yan , Liu Jian-Ping , Fan Ying-Yi , Pei Xiao-Hua 
Published: September 2020

Abstract
Background: Lactation mastitis (LM) is one of the most common breast disorders experienced by postpartum women, affecting approximately 3% to 20% breastfeeding mothers. Although a few researches have studied the risk factors related to LM, there are still some inconsistent problems on this topic and nationally representative evidence is scarce. This study was aimed to determine the well-accepted risk factors for LM in Chinese women. Methods: Six electronic literature databases were searched from their inception to June 1st, 2020. We used RevMan5.3 and Stata14.0 for data analysis. The strength of the association was summarized using odds ratio (OR) with 95% confidence intervals (CI). The population attributable risk (PAR) percent was calculated for significant risk factors. The fail-safe number (Nfs) was used to estimate publication bias and robustness of the current results. Results: Twelve studies involving 6539 participants were included. A total of 18 potential risk factors were eventually evaluated. Significant risk factors for LM included improper breastfeeding posture (OR 2.47, 95%CI 2.09-2.92; PAR 26.51%), improper milking method (OR 6.79, 95%CI 3.45-13.34; PAR 59.14%), repeated milk stasis (OR 6.08, 95%CI 3.75-9.88; PAR 37.42%), little or no cleaning of nipples (OR 2.38, 95%CI 1.88-3.03; PAR 31.28%), abnormal nipple or crater nipple (OR 2.94, 95%CI 1.76-4.91; PAR 33.99%), primipara (OR 1.91, 95%CI 1.26-2.90; PAR 39.06%), history of breast trauma (OR 3.57, 95%CI 2.86-4.46; PAR 13.36%), experience of cesarean section (OR 1.77, 95%CI 1.32-2.38; PAR 28.34%), low educational level (OR 1.85, 95%CI 1.04-3.28, PAR 23.67%), breast massage experience of non-medical personnel (OR 1.90, 95%CI 1.36-2.65, PAR 20.89%), postpartum within 6 months (OR 5.11, 95%CI 2.66-9.82; PAR 65.93%), prone sleeping position (OR 2.53, 95%CI1.51-4.22; PAR 22.72%) and postpartum rest time less than 3 months (OR 4.71, 95%CI 3.92-5.65; PAR 56.95%). There seemed to be good robustness of the pooled results for most of the included risk factors.Conclusion: This study found several important risk factors of LM in Chinese women. In particular, the incidence of LM can be reduced by controlling several modifiable factors such as breastfeeding posture, milking method, milk stasis situation and nipple cleaning condition, etc.
Risk stratification in PAH
Authors: Corris Paul A 
Published: September 2020

[No abstract. Showing first paragraph of article]Pulmonary arterial hypertension (PAH) is a chronic disease of the pulmonary vasculature characterized by progressive narrowing of the pulmonary arteries leading to increased pulmonary vascular resistance, right heart failure, and ultimately premature death.There has been a significant improvement in the available medical therapeutic options in this field that have impacted the short-term survival and morbidity in these patients. However, the median survival post-diagnosis remains unacceptable at 7 years.Physicians’ ability to predict PAH disease progression and risk allows them to determine the patient’s prognosis, make informed adjustments to therapy, and monitor his or her response to therapy . If widely adopted, risk prediction can enhance the consistency of treatment approaches and improve the timeliness of referral for lung transplantation. This approach should lead optimal, directed care that ultimately reduces morbidity and improves mortality in patients with PAH.
Toxicity of apple juice and its components in the model plant system
Authors: Samoylov Artem , Suraeva Natal’ya , Zaytseva Mariya , Rachkova Vera , Kurbanova Madinat , Belozerov Georgy 
Published: September 2020

Introduction. In view of the ongoing research into the negative effects of fruit juice on human health, we aimed to study the subchronic toxicity of apple juice, a model mixture based on its components, and ethanol on biomass growth, cellular oxidative enzymes, and chromosomal abnormalities in Allium cepa roots.
Study objects and methods. Our objects of study included clarified apple juice and its components such as fructose, glucose, sucrose, D-sorbitol, and malic acid. After treating Allium cepa roots with apple juice and a model mixture in different concentrations, we analyzed their toxic effects on biomass growth, malondialdehyde levels, as well as the nature and frequency of proliferative and cytogenetic disorders in the plant tissues.
Results and discussion. The incubation in an aqueous solution of apple juice at a concentration of 1:5 inhibited the growth in root mass by 50% compared to the control (water). The mitotic index of cells decreased with higher concentrations of juice, reaching zero at a 1:5 dilution. The fructose and model solutions in the same concentrations appeared less toxic in relation to cell mitosis and root mass growth. Although malondialdehyde levels increased in the onion roots treated with juice and model solutions, they were twice as low as in the control due to the juice’s antioxidant activity. Adding 1% ethanol to the 1:2 diluted juice abolished the effect of acute toxicity on root growth and reduced malondialdehyde levels by 30%.
Conclusion. The study revealed a complex of interdependent biomarkers of apple juice responsible for its subchronic toxicity in Allium cepa roots. These data can be used to create biological response models based on the approaches of systems biology and bioinformatics.
Instant tea from Condonopsis javanica L. root extract via spray drying
Authors: Nhan Nguyen Phu Thuong , Vu Nguyen Duong , Thanh Le Van , Phuong Than Thi Minh , Bach Long Giang , Toan Tran Quoc 
Published: September 2020

Introduction. Codonopsis javanica L. root is a gingsen-like medicinal material with valuable bioactive compounds and alkaloids in its composition. However, the diversification of commercial products from Codonopsis javanica root extract is limited and poorly represented on the market. This study presents a new production process of an instant tea product from Codonopsis javanica root extract, which involved spray drying with maltodextrin as a drying additive.
Study objects and methods. The research featured different process parameters including a drying additive concentration, a drying temperature, and a feed flow rate. Moisture content and drying yield were selected as the main outcomes.
Results and discussion. In general, the improved drying yield was associated with an increased drying additive concentration, a lower drying temperature, and a higher feed flow rate. The best drying yield (78.35%) was obtained at the drying additive concentration of 30% (w/w), the drying temperature of 140°C, and the feed flow rate of 300 mL/h. The total saponin content in the product was 0.29% (w/w), and the ABTS free radical scavenging ability reached 59.48 μgAA/g. The obtained powder was spherical and exhibited fairly uniform particle morphology with shriveled and concave outer surface.
Conclusion. The research results justified the use of Codonopsis javanica as an ingredient in beverage industry and suggested maltodextrin as an appropriate substrate for spray-drying natural extracts.
An investigation of the possible scenarios for the optimal locating of quality sensors in the water distribution networks with uncertain contamination
Authors: Jafari Hamideh , Rajaee Taher , Nazif Sara 
Published: September 2020

Abstract
One of the ways to reduce the risk of contaminated water consumption is to optimally locate the quality sensors. These sensors warn users in the case of contamination detection. Analyzing the actual conditions of the contamination which enters the network is faced with many uncertainties. These uncertainties include the dose of contamination, time and location of its entry which have received less attention. Also, the uncertainty in the nodes' water demand causes changes in the distribution and contamination diffusion within the network. The main impetus of the present study is to determine the optimal quality sensor locations in the water distribution network in order to reduce the damage caused by contaminated water consumption prior to the contamination event detection. For this purpose, a parameter is defined as the maximum possible damage for calculating which the vulnerability and importance of the nodes have been considered in addition to the uncertainties in the location and time of the contamination entry. The importance of each node differs from that of other ones. Ranking the importance of the nodes is influenced by both land use and covered population ratio. In this study, six scenarios are defined for the contamination event in the water distribution network. These scenarios consider the effects of varying pollutant dose and the contamination input from nodes which are prone to its entry. Also, the NSGA-II has been utilized in order to minimize the damage with minimum number of sensors. The proposed model is evaluated on a real network in Iran. The results indicate that adding only one or two contamination warning sensors to the proposed locations can lead to the decreasing damage caused by the contaminated water consumption from 54 to 82%. According to the proposed method, the best answer for scenarios 1–6 was obtained for 7, 6, 6, 2, 2 and 2 sensors, respectively. The results showed that the slope of the pollution rate diagram does not change much from 6 sensors upwards in the first three scenarios, and from 4 sensors upwards in the second three scenarios. In scenarios 1–3, with 7, 6 and 6 sensors, respectively, in different nodes, the best placement is for 203–224 equivalent attack population, and in scenarios 4–6, with sensors in nodes 4 and 43, the best placement is for 225–279 equivalent attack population.
Two-level games on the trans-boundary river Indus: obstacles to cooperation
Authors: Rigi Hanifeh , Warner Jeroen F. 
Published: September 2020

Abstract
This synthesis paper explores the reasons hindering water cooperation between India and Pakistan on the Indus River Basin. It argues that both domestic and international-level elements narrow the size of the ‘win-sets’ which make water cooperation between the two states highly challenging. Not only state actors but also the domestic actors in both India and Pakistan have repeatedly played ‘water games’. Further, due to long-standing geopolitical and territorial conflicts between India and Pakistan, the strategies pursued so far by these states including ‘securitization’, ‘issue-linkage’ and ‘alliance strategies’ as leverage mechanisms, have also contributed to the lack of cooperation in their water realm.
Application of composite degradable modified starch-based flocculant on dewatering and recycling properties
Authors: Liu Jianbo , Jia Shouhao , Xu Liming , Zhu Feifei , Ren Shan , Liu Yuanfeng , Sun Ziqi 
Published: September 2020

Abstract
Sludge dewatering is an important step for wastewater treatment. Composite degradable flocculant (CDF) was prepared by cationic polyacrylamide (PAM) grafting onto modified starch with a novel initiator, and characterized by Fourier transform infrared spectroscopy. The microstructure of flocculated sludge was characterized by scanning electron microscopy. The study investigated the properties of CDF compared to PAM, which showed that the prepared CDF exhibited a highly effective flocculation on sludge dewatering, a higher transmittance and chemical oxygen demand removal rate, and a lower value of effluent ammonia nitrogen and total phosphorus. The fermentation process was also analyzed by testing the performance of dewatered sludge (temperature, pH, ammonia nitrogen, E4/E6 (humic acid absorbance at 465 nm (E4) and 665 nm (E6))). The dehydrated sludge with CDF could be easily compressed into cakes by belt-filter for easy transportation and storage. With the continuous addition of CDF and PAM, the corresponding index of capillary suction time (CST) increased. Moreover, the total value of CST with CDF was low, showing a good dewaterability. In addition, the sludge index of pumping time and moisture content with CDF were low in contrast with PAM. Fermentation experiments demonstrated that sludge with CDF had a comparatively high temperature and low value of E4/E6. Such novel CDF shows enormous potential in wastewater treatment and sludge fermentation.