bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Macular Vessel Densities in Patients with Birdshot Chorioretinopathy Using Optical Coherence Tomography Angiography
Authors: Seminel M , Mehanna C , Gerardy M , Hoogewoud F , Touboul A , Somisetty S , Monnet D , Brezin A , Bousquet E
Published: February 2022

Objectiveto quantify macular vessel densities (VD) in patients with birdshot chorioretinopathy (BSCR) and investigate the correlation of these parameters with other features of the disease.DesignSingle-center cross-sectional studyMethodPatients with BSCR and healthy controls underwent projection-resolved OCT-angiography (PR-OCTA, RTVue XR Avanti, Optovue). The foveal avascular zone (FAZ) area, the macular VD in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were recorded. Univariate and multivariate analyses were performed to evaluate the association between PR-OCTA parameters and other clinical and imaging findings.Resultsseventy-five patients (138 eyes) with BSCR and 27 healthy age and sex-matched controls (27 eyes) were included in the study. The VD in both SCP and DCP were significantly lower in the BSCR group compared to the control group (p< 0.001). The FAZ area was similar between both groups. Multivariate analysis showed visual acuity and visual field mean defects to be associated with VD in the SCP, while central macular thickness and the visual field were associated with VD in the DCP. Eyes with a disrupted macular ellipsoid zone had a lower VD in the SCP and DCP (p<0.001).ConclusionsQuantitative evaluation of the macular vessel density might be a new promising tool for monitoring BSCR severity.
Risk factors for conversion to open approach during laparoscopic reduction of intussusception in children who failed fluoroscopy-guided pneumatic enema reduction: experience from a single‐center experience in 94 consecutive patients- an original article.
Authors: Sun Jun , Liu Ying-Hua , Xu Wei-Jue , Liu Jiang-Bin , Sheng Qing-Feng , Lv Zhi-Bao
Published: February 2022

Objective To summarize our experience in laparoscopic treatment of intussusception in children who failed fluoroscopy-guided pneumatic enema reduction, and to identify the independent risk factors that may relate to conversion to open approach.Methods A retrospective analysis of patients with intussusception who failed pneumatic enema reduction was performed from August 2014 to March 2021. Patients who completed laparoscopic intussusception reduction were compared with those who converted to open approach regarding demographic (age, gender), history (previous abdominal surgery history, number (No.) of intussusception before), clinical manifestations (preoperative pneumatic enema attempts, abdominal pain, irritable crying, emesis, bloody stool, abdominal mass, fever, diarrhea, duration of symptoms, body mass index, American Society of Anesthesiologists fitness grade), work-up (Leukocyte counts), and intra-operative findings (anatomic type of intussusception, number (No.) of intussusceptions, length of intussusception, outcome (operative time, complications, postoperative hospital stay). Statistic analyze was performed using univariate and Logistic regression analysis. Results Univariate analysis showed that small bowel intussusception was associated with conversion to laparotomy (p < 0.05). Logistic regression analysis indicated that bloody stool (odds ratio (OR)26.071; 95% confidence interval (CI)2.341,290.33; p < 0.01) and small bowel intussusception (odds ratio (OR)39.194; 95% confidence interval (CI)3.562,431.281; p < 0.01) may be independent risk factors related to the conversion from laparoscopic intussusception to open procedure (p < 0.01).Conclusion Bloody stool and small bowel intussusception may be the independent risk factors associated with the conversion to laparotomy in laparoscopic treatment for intussusception in children who failed fluoroscopy-guided pneumatic enema reduction.
Hyper Expression of Active, GFP-fused HFGF21 in Tobacco Chloroplasts
Authors: Wang Yunpeng , Fan Jieying , Xu Nuo , Xin Wen , Wei Zhengyi , Xing Shaochen
Published: February 2022

Human fibroblast growth factor 21 (hFGF21) is a promising candidate for metabolic diseases. In this study, a tobacco chloroplast transformation vector, pWYP21406, was constructed. In the vector, the codon optimized encoding gene hFGF21 fused with GFP at its 5’ terminal was driven by the promoter of plastid rRNA operon (Prrn) and terminated by the terminator of plastid rps16 gene (Trps16). Spectinomycin resistant gene (aadA) as the selectable marker was placed in the same cistron between hFGF21 and the terminator Trps16. Transplastomic plants were generated by biolistic bombardment method and proven to be homoplastic by Southern Blotting analyses. The expression of GFP was detected under UV light and laser confocal microscope. The expression of GFP-hFGF21 was confirmed by immunoblotting and quantified by ELISA. The accumulation of was GFP-hFGF21confirmed to be 12.44 ± 0.45% of total soluble protein (i.e., 1.9232 ± 0.0673 g kg− 1 of fresh weight). The GFP-hFGF21 was confirmed to be capable of promoting the proliferation of hepatoma cell line HepG2, inducing the expression of glucose transporter 1 in hepatoma HepG2 cells and improve the glucose uptakes. The above results suggested that chloroplast expression is a promising approach for bioactive recombinant hFGF21 production.
Monocyte subsets and their activation markers in Kawasaki disease – A Study from a Tertiary care Center in North India
Authors: Gupta Aarchie , Sairam Kaki , Vignesh Pandiarajan , Sil Archan , Das Jhumki , Arora Kanika , Shandilya Jitendra K. , Kumrah Rajni , Suri Deepti , Rawat Amit , Singh Surjit
Published: February 2022

Background: Kawasaki disease (KD) is a common childhood vasculitis and autopsy studies have shown monocyte infiltration in affected blood vessels. Role of monocyte subsets and their activation status in KD have not been completely explored. Materials and methods: Sixteen children diagnosed with KD were included in our study along with 16 age and sex-matched controls. We studied subpopulations of monocytes (classical, intermediate and non-classical), early and late monocyte activation markers during acute and convalescent stages. We also assessed soluble markers of monocyte activation (sCD14, sCD163, CCL2). Results: Significant elevation in absolute number of classical [CD14+CD16-] and intermediate monocytes [CD14++CD16+] were noted in KD and febrile controls in comparison to healthy controls. CD69 expression in classical, intermediate and non-classical monocytes were higher in KD when compared to healthy controls. Absolute counts of classical and intermediate monocytes expressing CD69 and HLA-DR were significantly lower in the convalescent stage as compared to acute KD. We observed no significant elevation in sCD14 and sCD163 levels in KD as compared to controls. However, median CCL2 levels were highest in children with KD. Conclusion: Our results suggest that both early and late monocyte activation occur in acute phase of KD that subsides in convalescent phase.
Dietary Resistant Starch Alleviates Escherichia Coli-induced Bone Loss in Meat Ducks by Promoting Short-chain Fatty Acid Production and Inhibiting Malt1/NF-κB Inflammasome Activation
Authors: Zhang Huaiyong , Qin Simeng , Zhang Xiangli , Du Pengfei , Zhu Yao , Huang Yanqun , Michiels Joris , Zeng Quifeng , Chen Wen
Published: February 2022

Background: Escherichia coli (E. coli) infection in humans and animals usually comes with gut dysbiosis, which is potential culprit to skeletal health, it is still unclear to whether diet interfered gut microbiome changes can be a protective strategy to bone loss development. Here, the effects of resistant starch from raw potato starch (RPS), a type of prebiotic, on E. coli-induced bone loss and gut microbial composition in meat ducks were evaluated. Results: The results showed that dietary 12% RPS treatment improved bone quality, depressed bone resorption, and attenuated the pro-inflammatory reaction in both ileum and bone marrow. Meanwhile, the 12% RPS diet also increased the abundance of Firmicutes in E. coli-treated birds, along with higher production of short-chain fatty acids (SCFAs) especially propionate and butyrate. Whereas addition of β-acid, an inhibitor of bacterial SCFAs production, to the drinking water of ducks fed 12% RPS diet significantly decreased SCFAs level in cecum content and eliminated RPS-induced tibial mass improvement. Further, treatment with MI-2 to abrogate mucosa-associated lymphoid tissue lymphoma translocation protein 1 (Malt1) activity replicated the protective role of dietary 12% RPS in E. coli-induced bone loss including reduced the inhibition on nuclear factor κB (NF-κB) inflammasome activation, decreased bone resorption, and improved bone quality, which were correlated with comparable and higher regulatory T cells (Treg) frequency in MI-2 and 12% RPS group, respectively. Conclusions: These findings suggested that the diet with 12% RPS could alleviate E. coli-induced bone loss in meat ducks by changing the gut microbial composition and promoting concomitant SCFAs production, and consequently inhibiting Malt1/NF-κB inflammasome activation and Treg cells expansion.
Insecticidal features displayed by the beneficial rhizobacterium Pseudomonas chlororaphis PCL1606
Authors: Arrebola Eva , Aprile Francesca R. , Calderón Claudia E. , de Vicente Antonio , Cazorla Francisco M.
Published: February 2022

The biocontrol rhizobacterium Pseudomonas chlororaphis is one of the bacterial species of the P. fluorescens group where insecticide fit genes have been found. Fit toxin, supported with other antimicrobial compounds, gives the bacterial capacity to repel and fight against predators, such as nematodes and insect larvae, thus protecting the plant host and itself. Pseudomonas chlororaphis PCL1606 is an antagonistic rhizobacterium isolated from avocado roots with efficient biocontrol against fungal soil-borne disease. The main antimicrobial compound produced by P. chlororaphis PCL606 is 2-hexyl,5-propyl resorcinol (HPR), which plays a crucial role in effective biocontrol against fungal pathogens. Further analysis of the P. chlororaphis PCL1606 genome showed the presence of hydrogen cyanide (HCN), pyrrolnitrin (PRN) and homologous fit genes. To test the insecticidal activity and to determine the bases for such activity, single and double mutants on the biosynthetic genes of these four compounds were tested in a Galleria mellonella larval model using inoculation by injection. The results revealed that fit toxin and HPR are the main compounds responsible for the insecticide phenotype in P. chlororaphis PCL1606, and HCN and PRN could be considered supporting compounds.
Exposure to Job-related Violence Among Young Female Sex Workers in Urban Slums of Southwest Nigeria
Authors: Ikuteyijo Olutoyin Opeyemi , Akinyemi Akanni Ibukun , Merten Sonja
Published: February 2022

Background: In Nigeria, many young girls are engaged in commercial sex work as a means of livelihood and support of dependent relatives. Although studies have documented some of the violence related issues among commercial sex workers, the plight of adolescent and young sex workers particularly in urban slums may be different in context and depth. Objective: This study explored the experiences of violence among young female sex workers and their coping strategies in urban slums in Ibadan and Lagos, Southwest Nigeria.Design: The study applied an interpretive phenomenological approach through in-depth interviews. Settings: Young female sex workers ages (15-24 years) who reported having experienced violence were recruited. Data were transcribed using a phenomenological framework analysis. Participants’ reports based on life experiences were identified: lived experience “daily brothel life experience”; sources of violence such as law enforcement agents’ intermittent raids; violence experience with clients who often demanded sexual acts beyond the agreed scope; and coping strategies employed to mitigate the challenges.Participants: 12 participants completed the interviews out the 20 initially contacted. Results: The results showed that the major motivation for engaging in commercial sex work was for economic reasons in order to sustain their livelihood. The risks involved, exposure to violence and other social vices were enormous.Conclusion: In conclusion, the study raised the need for targeted interventions to mitigate violence against young sex workers. Working with law enforcement officials and health care providers may be the most promising next steps. It should also be made a human rights and public health priority.
Rapid, High Throughput, Automated Detection Of SARS-Cov-2 Neutralizing Antibodies Against Native-Like Vaccine And Delta Variant Spike Trimers
Authors: Cheedarla Narayanaiah , Verkerke Hans , Potlapalli Sindhu , McLendon Kaleb , Patel Anamika , Frank Filipp , Damhorst Gregory , Wu Huixia , O'Sick William , Graciaa Daniel , Hudaib Fuad , Alter David , Bryksin Jeannette , Ortlund Eric , Guarner Jeannette , Auld Sara , Shah Sarita , Lam Wilbur , Mattoon Dawn , Johnson Joseph , Wilson David , Dhodapkar Madhav , Stowell Sean , Neish Andrew , Roback John
Published: February 2022

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of hACE-2 binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using vaccine and delta variant viral strains showed strong correlation with cell-based pseudovirus and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta variant resistance to neutralization in samples with paired vaccine and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.
Low-Grade Albuminuria and Its Relationship with Cardiovascular Disease Risk in Hypertensive and Diabetic Patients in Primary Health Care
Authors: Souza Ramon Augusto Ferreira , Silva Eunice Ferreira , Oliveira Deíse Moura , Colodette Renata Maria , Cotta Rosângela Minardi Mitre , Silva Luciana Saraiva , Moreira Tiago Ricardo
Published: February 2022

Objective: To evaluate the presence of LGA and the relationship with the 10-year risk of a cardiovascular event in hypertensive and diabetic patients in Primary Health Care. Study Design: The study design used in the study is a cross-sectional study. Methods: This study was based on the application of questionnaires, anthropometric measurements, and laboratory tests carried out from August 2017 to April 2018. Logistic regression was used to evaluate the odds ratio of the explanatory variables in relation to the highest tercile of LGA. The Framingham risk score was used to assess the 10-year risk of cardiovascular event. The comparison of this score with the LGA terciles was analyzed by using ANOVA. Results: An increase in the 10-year risk of cardiovascular event score was observed with an increasing LGA tercile, and this pattern prevailed after adjusting for confounding variables. Conclusion: An association between LGA and 10-year risk of cardiovascular event was observed in a representative sample of hypertensive and diabetic patients.
In-hospital Initiation of PCSK9 Inhibitor and Short-term Lipid Profile Alteration, as well as In-hospital Mortality and Readmission Rate in Patients with Acute Myocardial Infarction
Authors: She Jianqing , Lou Bowen , Liu Hui , Luo Yongbai , Jiang Gulinigaer Tuerhong , Wu Haoyu , Wang Chen , Wu Yue , Zhou Bo , Yuan Zuyi , Liu Junhui
Published: February 2022

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes when added to conventional statin therapy. This study aims to investigate the efficacy and safety of in-hospital initiation of PCSK9 inhibitor among patients with acute myocardial infarction(AMI) based on real-world experience.Methods and Results Data were collected from the Biobank of the First Affiliated Hospital of Xi’an Jiaotong University between January 2016 and December 2020. 7556 AMI patients were screened for eligibility. Propensity Score Match(PSM) was employed and covariates were age, sex, admission blood pressure and lipid profiles. Eligible participants were (1) propensity-matched 1:2:2 of Statin plus Evolocumab (dual therapy) vs. Statin vs. Statin plus Ezetimibe. 95 Statin plus Evolocumab users achieved significant decreased LDL level (0.92±0.62 mmol/L in the 1st month and 1.17±0.73 in the 3rd month) and a promising attainment rate of LDL(79.5% in 1st month and 80.0% in the 3rd month ) as compared to the other two groups. (2) propensity-matched 1:2:2 of Statin plus Ezetimibe Evolocumab (triple therapy) vs. Statin vs. Statin plus Ezetimibe. Similarly, 75 triple medication users achieved significantly decreased LDL levels and a promising attainment rate of LDL as compared to the other two groups. In-hospital mortality, readmission rate within 3 months were then analyzed and decreased readmission rate was observed through PCSK9i therapy.Conclusions Based on the present single-centre real-world PSM-adjusted study, PCSK9i has been effective in short-term lipid control among AMI patients. The long-term effectiveness for reducing major cardiovascular events among AMI patients based on real-world experience remains to be explored.Trial registration: The study was registered at ClinicalTrials.gov, Unique Protocol ID: 82100477-1.
CDK7 inhibition augments the response against multidrug chemotherapy in pancreatic cancer
Authors: Zeng Siyuan , Lan Bin , Ren Xiaofan , Zhang Shuman , Schreyer Daniel , Eckstein Markus , Yang Hai , Britzen-Laurent Nathalie , Dahl Andreas , Debabrata Mukhopadhyay , Chang David , Kutschick Isabella , Pfeffer Susanne , Bailey Peter , Biankin Andrew , Grützmann Robert , Pilarsky Christian
Published: February 2022

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Although combined treatment with gemcitabine and albumin-bound paclitaxel has improved the prognosis of PDAC, both intrinsic and acquired chemoresistance cloud the outcomes. Hence, there is an urgent need to explore new therapeutic targets and formulate innovative strategies for the more effective treatment of PDAC.Methods: We transduced pancreatic cancer cells with a protein kinase library, and transfected cells were selected by puromycin treatment, followed by continuous exposure to vehicle control or gemcitabine/paclitaxel chemotherapy for 21 days. Next-generation sequencing as well as MAGeCK-VISPR analysis were performed to the identify candidate genes. Finally, we used the CRISPR-Cas9 to knockout the target gene, confirming that it is a viable target for overcoming chemoresistance in vivo and in vitro.Results: We identified several cell cycle checkpoint kinases and DNA damage-related kinases as targets for overcoming chemoresistance. Among them, cyclin-dependent kinase 7 (CDK7) ranked highly in both screenings. We demonstrated that both gene knockout and pharmacological inhibition of CDK7 by THZ1 result in cell cycle arrest, apoptosis induction. Furthermore, THZ1 synergized with gemcitabine and paclitaxel in vitro and in vivo, resulting in enhanced antitumor effects.Conclusions: Our findings support the application of CRISPR-Cas9 screening in identifying novel therapeutic targets and provide new strategies for overcoming chemoresistance in pancreatic cancer.
Spatial distribution and extent of environmental risks of strontium metal concentration in water and bottom sediments of Nile River, Egypt
Authors: Khalifa Moutaz , elsaadani zozo , qi wang ming
Published: February 2022

Strontium is one of the rare heavy metals found in the sediments and water of the Nile River. By examining the metal concentration in 69 sampling points along the river between two Nile banks and the Middle, we could throw further light on its dispersion in the current study. High Sr concentrations were found in the eastern>western>middle regions with average concentrations of 344.3, 338.39, and 327.57ppm, respectively, due to the point sources such as industrial activities, sewage wastes, and agricultural discharge. High Sr concentrations were found in the West and East of Cairo (Samalut and Beni Suef) (395, 397, and 392 ppm). Various pollution indices, such as the Geo-accumulation index, Contamination factor, and Enrichment factor depiction, were used to determine the pollution level caused by this metal, ranging from low to moderate contamination. According to the extraction fractions, the occurrence nature of the element is as follows: Acid soluble > residual >Fe- Mn oxy-hydroxides (reducible)> organic (Oxidizable). The risk assessment code based on the Acid soluble fraction indicates moderate to high risk. Renal failure and baby bone growth problems are common in Egypt, impacting Sr concentration in sediments. The average Sr concentration in water is around (221.58µg/l), indicating that the water is perfectly safe to drink. The study's findings are useful in determining the extent of Sr metal pollution in the river. If not monitored, Sr concentration will be an issue in Egypt and Ethiopia following dam construction. After the dam is built, this study will serve as a baseline.
Previous Cesarean Delivery Affect Pregnancy Outcomes After in Vitro Fertilization and Frozen-thawed Embryo Transfer: a Retrospective Cohort Study
Authors: Zhang Yinfeng , Ziegler Dominique , Hu Xinyu , Tai Xiaomei , Han Ying , Ma Junfang , Zhang Yunshan , Luo Haining
Published: February 2022

Background: To investigate the impact of previous cesarean delivery (CD) on pregnancy outcomes after in vitro fertilization (IVF) and frozen-thawed embryo transfer (FET).Methods: We conducted a retrospective cohort study that included 1122 women aged <40 years who had a history of only one parturition (after 28 weeks of pregnancy) and were undergoing their first FET cycle between January 2014 and January 2020. Live birth, clinical pregnancy, multiple pregnancy, ectopic pregnancy, pregnancy loss, pregnancy complications, preterm birth, and neonatal birth weight were compared among patients treated with IVF and FET. Multivariate logistic regression was performed to evaluate the relationship between pregnancy outcomes and FET.Results: After adjustment for confounders, in the single embryo transfer (SET) patients, the adjusted OR for a subsequent live birth was 0.75(95% CI: 0.39–1.42, P=0.370) in women with previous CD and 0.48 (95% CI: 0.18–1.27, P=0.140) in women with a cesarean scar defect (CSD), compared to women with previous vaginal delivery (VD). In the double embryo transfer (DET) patients, the adjusted OR for a subsequent live birth was 0.57(95% CI: 0.41–0.81, P=0.001) in women with previous CD and 0.37(95% CI: 0.20–0.70, P=0.002) in women with a CSD, compared to women with previous VD.Conclusions: Previous CD and the presence of a CSD reduced the success of clinical pregnancy and live birth among patients who received IVF-FET treatment, especially in DET patients.
Lymphocyte Population in Peripheral Blood in Children and Adolescents with Graves Disease. Potential Predictive Tool for Severity of The Disease
Authors: Tuli Gerdi , Munarin Jessica , Mazzucco Beatrice , Matarazzo Patrizia , De Sanctis Luisa
Published: February 2022

Purpose: To date, few data are available on the prognostic role of lymphocyte subsets in pediatric Graves’ Disease (GD). The aim of this retrospective study is to analyze the role of lymphocyte subtypes in predicting the severity of GD.Methods: Data of 10 pediatric subjects aged <18 years with GD onset in the period November 2017- April 2021 were collected. The lymphocyte population was assessed at the onset of GD as well as hormonal and clinical data. The follow-up period was 2.4 ± 0.8 years. Results: Pearson correlation coefficient between CD4+/CD8+ ratio and fT3 levels and thyroid volume at diagnosis was 0.72 (p=0.04) and 0.81 (p=0.004) respectively; that between CD4+/CD8+ ratio and the TRAb titer at diagnosis and after 6, 12 and 24 months was 0.89, 0.89, 0.73 and 0.77 respectively (p=0.02, p=0.01, p=0.03 and 0.04). The correlation coefficient of anti-thyroid drug (ATD) dose after 6 and 12 months with CD4+/CD8 ratio was 0.88 and 0.78 (p=0.001 and p=0.02 respectively). Patients with a higher CD4+/CD8+ ratio at diagnosis displayed higher fT3 levels (28.73 ± 2.18 vs 13.48 ± 2.19 pmol/L, p = 0.03) and higher TRAb titers (28.9 ± 11.2 vs 4.88 ± 0.97, p=0.01).Conclusion: CD4+/CD8+ ratio appears as a promising predictive tool to be considered together with other prognostic factors to better manage pediatric GD. These preliminary data need to be confirmed over a longer follow-up period and in larger cohorts.
Clinical efficacy and feasibility of simple navigation technology with an ordinary laser pen and surgical instrument box in open-wedge high tibial osteotomy
Authors: Xu Zhe , Tian Guang , Zhang Ruguo , Wu Zhanyu , Liu Chen , Ye Chuan
Published: February 2022

Background: The clinical outcomes of open-wedge high-tibial osteotomy (OWHTO) for medial knee osteoarthritis depend mainly on the precision of correction. The present study aimed to determine the efficacy and feasibility of simple navigation technology with an ordinary laser pen and surgical instrument box.Methods: Seventy-one patients were randomly divided into the navigation (n=36) and traditional groups (n=35). In the navigation group, the hip, knee (Fujisawa point), and ankle centers were located preoperatively using the lid of the surgical instrument box. The leg was aligned with an ordinary laser pen. Radiation exposure, operative time and cost, required labor and postoperative complications were evaluated. The visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were recorded. After 24 months, the femoral tibial angle (FTA), medial proximal tibial angle (MPTA), posterior slope angle (PSA), and rate of excellent correction were recorded. The Kaplan-Meier method was used to evaluate the survival time of affected knees.Results: Radiation exposure, operative time and cost, required labor, rate of excellent correction, and postoperative complications were better in the navigation group than in the traditional group (P < 0.05). Six months postoperatively, the VAS and WOMAC scores were significantly improved in both groups (P < 0.001). At 24 months, the FTA, MPTA and PSA were corrected in both groups (P < 0.001), and no between-group differences were found (P > 0.05). There was no difference in the postoperative knee survival time between the traditional and laser navigation groups (P = 0.533).Conclusions: Simple laser navigation technology can effectively increase the rate of excellent leg alignment correction and reduce radiation exposure, operative time and cost, required labor, and postoperative complications.
Triglyceride Glucose-Waist Circumference to Height Ratio Exceeds Commonly Used Anthropometric Markers in Predicting 10-Year Diabetes Risk: the REACTION Research
Authors: Lin Jie , Li Hang , Qin Yahui , Xiang Xin , Wan Qin
Published: February 2022

Purpose
Although Triglyceride glucose-waist-to-height ratio (TyG-WHtR) is an indicator for insulin resistance, the relationship between TyG-WHtR and newly diagnosed diabetes is unclear. The intention of this research is to examine the causative association between TyG-WHtR and new-onset diabetes.
Methods
We conducted a retrospective 10-year cohort study of 10150 Chinese adults. After screening out the unqualified people, the TyG-WHtR level of 8279 participants was calculated in this study, and a multivariate logistic regression model was used to investigate the possibility that it has a connection with diabetes.
Results
Within 10 years, 271 men (3.27%) and 532 women (6.43%) were newly diagnosed with diabetes. Multivariate Cox regression analysis reveals a linear relationship between TyG-WHtR index and newly diagnosed diabetes mellitus (HR=8.889, 95% CI: 4.703 to 16.801, P < 0.001), and TyG-WHtR shows great AUC (0.750, 95% CI: 0.733-0.767). Addionally, TyG-WHtR associated diabetes was shown to be substantially more prevalent in people aged 71 to 80, with a BMI below 24 kg/m2 and no hypertensive condition (P < 0.05), according to subgroup analysis.
Conclusion
According to the study, TyG-WHtR might be an accuracy indicator of future diabetes risk and outperform other commonly used anthropometric indices.
Comparing behavioral performance and physiological responses of Sebastes schlegelii with different aggressive strengths
Authors: Li Haixia , Wang Jie , Zhang Xu , Hu Yu , Liu Ying , Ma Zhen
Published: February 2022

Fish aggression has significant individual differences, and different personalities exhibit distinct behavioral performances and physiological stress responses. Under intensive culture conditions, Sebastes schlegelii juveniles display severe aggression and cannibalism, causing fish welfare and economic loss. Herein, we investigated the alterations in behavioral performance and physiological stress indicators of Sebastes schlegelii juveniles with different aggressive strengths. The results revealed that latency to the first movement, distance to center-point, mobile frequency, and immobile frequency were significantly lower in high-aggressive individuals than low-aggressive individuals. In contrast, the immobile time was significantly higher in high-aggressive individuals compared to low-aggressive individuals. PCA was performed to identify the key parameters of fish behavior. From the results of PCA, position, motion state, and physical status could be used as behavioral screening indicators for individuals with different aggressions. The 5-HIAA/5-HT ratio was significantly lower in high-aggressive individuals than in low-aggressive individuals. Moreover, cortisol levels were positively correlated with immobile time, and the ratio of 5-HIAA/5-HT was significantly and positively correlated with the distance to the central point. These results suggest that different aggressive individuals can be identified according to position, motion state, and physical status in a short period of time, while the distance to center-point associated with brain monoaminergic activity may be a more accurate indicator. The results not only provide a non-invasive method for reducing fish aggression but also help to enhance precise management in aquaculture.
Geoarchaeological and palaeoenvironmental interpretation of residual hills and relict slopes in the Central Ebro Basin, Spain
Authors: Peña-Monné José Luis , Sampietro-Vattuone Maria Marta , Picazo-Millán Jesús
Published: February 2022

The cyclical evolution of the testimonial buttes in the central area of the Ebro depression (Los Monegros) is analysed. It is a semiarid environment that favours high erosive rates. The aim of this paper is to obtain an evolutionary model of the Jubierre hills that shows the environmental cycles represented by aggradational and degradative processes on the slopes that produced the present arrangement of talus flatiron rings. In the four studied cases, the talus relicts are composed of detritic material from a disappeared caprock pediment. Four slope stages (S4 to S1) formed under more stable climate conditions are identified. Older stages ages (S4 and S3) are estimated by comparison with other talus flatiron systems from the region. The S2 stage contains Bronze Age archaeological remains and the radiocarbon age obtained was 1608 − 1446 years cal BC (2σ), while S1 is younger. A climate genesis is established for these aggradational stages (S4 to S1). The active erosion of these hills led to a relief inversion and talus flatirons remain as the only features revealing the presence of the old hills and past human occupations.
Evaluating Body Weight In Predicting Initial Gn Dosage During IVF For Women With PCOS: A Retrospective Study
Authors: Zeng Rujun , Chen Hanxiao , Zeng Xun , Qin Lang
Published: February 2022

Background: Polycystic ovarian syndrome (PCOS) is the major cause of anovulatory infertility. Since women with PCOS are often accompanied by increased body weight and infertility, Individualized gonadotropin (Gn) dose is required to achieve therapeutic effect while minimizing the risk of ovarian hyperstimulation simultaneously. We aimed to investigate the essential role of body weight in optimizing initial Gn dosage for PCOS patients during in vitro fertilization (IVF).Methods: We retrospectively included 227 infertile PCOS patients who used gonadotropin-releasing hormone (GnRH)-antagonist fixed protocol underwent their first cycle of IVF in West China Second University Hospital from January 2019 to December 2020. Baseline characteristics controlled ovarian stimulation parameters, and reproductive outcomes were compared between patients with different body weights and different ovarian responses. Multivariable logistic regression analyses were adopted to investigate the relationship between body weight and initial Gn dosage. Receiver operating characteristic (ROC) curves were drawn to find the optimal cut-off value of body weight in predicting the starting Gn dosage so as to prevent high ovarian response (HOR).Results: Circulating testosterone (T) level was increased and Anti-Mullerian hormone (AMH) level was decreased in higher weight groups compared to lower weight groups. Increased body weight was significantly correlated to the rise of initial Gn dosage (OR = 1.113, 95% CI = 1.021-1.227, p = 0.016). Normal ovarian response (NOR) patients had significantly less fresh cycle cancel rate and ovarian hyperstimulation syndrome (OHSS) rate which outweighed the slightly fewer embryos compared with HOR patients. Using ROC curves, 55.5 kg and 70.5 kg were identified as the optimal cut-off values to predict the initial Gn dosage no more than 150 IU (sensitivity, 72.5%; specificity, 63.4%) and 225 IU (sensitivity, 75.0%; specificity, 95.2%), respectively.Conclusion: Body weight was an independent factor for initial Gn dosage. Adjusting initial Gn dosage based on body weight is crucial to achieving better reproductive outcomes for PCOS patients during IVF.
Phase II Trial of Metronomic Capecitabine and Cyclophosphamide with Lapatinib and Trastuzumab in Patients with HER2 Positive Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen
Authors: Kang Irene , Zang Peter D. , Spicer Darcy V. , Lu Janice M. , Groshen Susan , Tsao-Wei Denice , Garcia Augustin A.
Published: February 2022

Background:Breast cancer is the most common cancer and second most common cause of cancer mortality in women. Around 25% of all breast cancers have overexpression of Human Epidermal growth factor 2 (HER2), which is associated with earlier recurrence and shorter overall survival. ‘Metronomic chemotherapy’ is an emerging paradigm in cancer therapy, in which frequent low doses of chemotherapeutic agents are administered at frequent intervals. We proposed a regimen with metronomic chemotherapy with dual HER2 inhibition in HER2 positive patients with MBC. We hypothesize that this regimen will be highly active in MBC and have a favorable toxicity profile.Methods:This was a single-center, phase II, single arm, open-label study. Female patients 18 years of age and older who had histologically confirmed HER2-positive metastatic breast cancer with prior trastuzumab use in the adjuvant or metastatic setting were eligible. Patients were treated on a 21-day cycle with capecitabine 1500mg PO daily, cyclophosphamide 50mg PO daily, lapatinib 1000mg PO daily and trastuzumab 6mg/kg IV once per 21-day cycle. The primary objective of this study was to estimate the progression free survival (PFS). Secondary objectives were to evaluate the overall response rate (ORR), to evaluate the clinical benefit rate (CBR; complete response, partial response, and stable disease for ≥24 weeks), to estimate the overall survival (OS) and to assess the safety and tolerability of this regimen in the study population. Results:Ten patients were accrued for the study. PFS was 13.7 (95% CI: 2.6, 16.6) months. ORR was 40% (95% CI: 15%, 70%), and CBR was 70%. Median OS was 29.6 (95% CI: 11.8, 81.9+) months. Several grade 3 toxicities were identified in 5 patients (50%): diarrhea, weight loss, fatigue, infusion related reaction, abdominal pain, oral mucositis, paronychia, AST and ALT increase, neutropenia, leukopenia and palmar-plantar erythrodysesthesia.Conclusions:The proposed regimen of metronomic capecitabine and cyclophosphamide with lapatinib and trastuzumab appears to be active in patients with HER2 positive MBC but with toxicity in line with other standard therapies. Trial Registration: ClinicalTrials.gov # NCT01873833 Date: June 10, 2013
Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition
Authors: Liu Xue , Li Jiao , Yang Xuesong , Li Xiaojie , Kong Jing , Qi Dongyuan , Zhang Fuyin , Sun Bo , Liu Yuehua , Liu Tingjiao
Published: February 2022

Background: Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Methods: sEVs separation was performed by differential ultracentrifugation. Normal fibroblasts (NFs) were treated with sEVs and the content of collagen crosslinking were performed by ELISA. Active LOX (αLOX) was enriched in sEVs were performed by western blot and ELISA. TCI-15 was used to inhibited sEVs bind to collagen I and triggered collagen crosslinking. CAF sEV-induced collagen crosslinking promoted the epithelial-mesenchymal transition (EMT) of OSCC cells was confirmed both in vitro and in vivo. Results: Here, we demonstrate, for the first time, that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting EMT. CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. αLOX, but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC cells in vitro and in vivo. Conclusions: This work reveals that CAF sEV-αLOX interacted with FN, POSTN, and BMP-1 on the surface of sEVs. Integrin α2β1 mediated the binding of CAF sEVs to collagen I, and αLOX triggered collagen crosslinking directly. Collagen crosslinking induced by CAF sEVs promoted the EMT of OSCC cells.
Quantitative Analysis of Heat Release during Coal Oxygen-Lean Combustion in a O2/CO2/N2 atmosphere by TG-DTG-DSC
Authors: Shi Jingdong , Su Hetao , Li Yunzhuo , Huang Zijun , Wang Yiru , Gao Lintao
Published: February 2022

Coal combustion in an oxygen-lean and multi-gas environment is a common exothermic phenomenon for coalfield fires, leading to serious environmental destruction and loss of coal resources. Simultaneous thermal analysis experiments for Bulianta (BLT, high-volatile bituminous coal) and Yuwu coal (YW, anthracite) in 21vol.%O2/79vol.%N2 and 15vol.%O2/5vol.%CO2/80vol.%N2 were carried out to study the law of heat release. Based on the TG-DTG-DSC curves, the combustion characteristic parameters were analyzed. A delay of ignition and heat release existed during the coal oxygen-lean combustion in O2/CO2/N2. Decreasing O2 concentration caused a significant reduction of local reactivity and further the decreasing maximum heat release rate for low-rank coal, while increasing CO2 concentration caused a significant thermal lag effect and further the increasing maximum heat release rate for high-rank coal. The relationship between the heat release rate and the reaction rate constant was quantitatively analyzed. At the increasing stage of the heat release rate, the heat release rate of the two coals increased conforming to ExpGro1 exponential model. At the decreasing stage of the heat release rate, the heat release rate of YW coal decreased exponentially with the reaction rate constant, while the heat release rate of BLT coal decreased linearly. Regardless of the atmospheres, the conversion rates corresponding to maximum heat release rate of BLT and YW coal were about 0.80 and 0.50, respectively, indicating that the coal rank played a dominant role. The results are helpful to understand the heat release process of coal oxygen-lean combustion in O2/CO2/N2.
Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission
Authors: Lopaticki Sash , McConville Robyn , John Alan , Geoghegan Niall , Mohamed Shihab Deen , Verzier Lisa , Steel Ryan , Evelyn Cindy , O'Neill Matthew , Caiazzo Sabrina , Soler Niccolay Madiedo , Scott Nichollas , Rogers Kelly , Goddard-Borger Ethan , Boddey Justin
Published: February 2022

C-mannosylation stabilizes proteins bearing a thrombospondin repeat (TSR) domain in metazoans. Here we show that Plasmodium falciparum expresses a DPY19 C-mannosyltransferase in the endoplasmic reticulum and that DPY19-deficiency abolishes C-glycosylation, destabilizes members of the TRAP adhesin family and inhibits transmission to mosquitoes. P. falciparum gametogenesis was imaged in its entirety in four dimensions using lattice light-sheet microscopy. This revealed defects in egress and exflagellation for DDPY19 microgametes. While exflagellation was diminished, DDPY19 microgametes still fertilized macrogametes, forming ookinetes but these were abrogated for mosquito infection. The gametogenesis defects corresponded with destabilization of MTRAP, which we show is C-mannosylated in P. falciparum, and the ookinete defect was concordant with defective CTRP secretion on the DDPY19 background. Genetic complementation of DPY19 restored ookinete infectivity, sporozoite production and C-mannosylation activity. Therefore, tryptophan C-mannosylation by DPY19 in the early secretory pathway ensures TSR protein quality control at two lifecycle stages for successful transmission of the human malaria parasite.
Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the IL-11/MEK/ERK signaling pathway
Authors: Song Cheng , Liu Xiaofan , Tan Weijun , Guo Xiaoqun , Mao Yahui , Zhou Qi , Geng Shuang , Hu Yi
Published: February 2022

Background: Idiopathic pulmonary ﬁbrosis (IPF) is a special type of interstitial lung diseases with unknown cause. Interleukin (IL)-11 is a new therapeutically target for fibrosis diseases. In this experiment, we further explored the pharmacology mechanism and molecular target of ﬂuorofenidone (FD) in vivo and in vitro.
Methods: Male C57BL/6J mice were intratracheally injected with Bleomycin (BLM) or saline. FD was administered throughout the course of the experiment. Lung tissue sections were stained with haemotoxylin and eosin, Masson’s trichrome and Immunohistochemistry. Cytokines were measured by ELISA, and phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated mitogen-activated protein kinase (p-MEK), IL-11RA and gp130 were measured by Western blot. The RAW264.7 cells and the normal human lung fibroblasts (NHLFs) were treated with IL-11 and/or FD, IL-11RA-siRNA, MEK Inhibitor. The expressions of p-ERK, p-MEK, IL-11RA, gp130, α-SMA, ﬁbronectin and collagenⅠwere measured by Western blot and/or RT-PCR, the cytokines were measured by ELISA.
Results: FD attenuated pulmonary inﬂammation and ﬁbrosis, and decreased the expressions of IL-8, IL-18, IL-11, MCP-1, p-ERK and p-MEK in the bleomycin mouse model. Moreover, the protein expressions of IL-11RA and gp130 were inhibited by FD in IL-11-induced RAW264.7 cells. Additionally, FD attenuated IL-11-induced expressions of p-ERK and p-MEK in IL-11-induced RAW264.7 cells and IL-11-induced normal human lung fibroblasts. Meanwhile, FD reduced IL-11-induced the levels of IL-8, IL-18 and MCP-1, blocked IL-11-induced the activation of fibroblasts.
Conclusion: These findings demonstrated that FD attenuates BLM-induced pulmonary inﬂammation and ﬁbrosis in mice via inhibiting the IL-11/MEK/ERK signaling pathway.
Reducing uncertainty in local climate projections
Authors: Qasmi Saïd , Ribes Aurélien
Published: February 2022

Planning for adaptation to climate change requires accurate climate projections. Recent studies have shown that the uncertainty in global mean surface temperature projections can be considerably reduced by using historical observations. However, the transposition of these new results to the local scale is not yet available. We adapt an innovative statistical method that combines the latest generation of climate model simulations, global observations, and local observations to reduce uncertainty in local temperature projections. By taking advantage of the tight links between local and global temperature, we can derive the local implications of global constraints. The model uncertainty is reduced by 30% up to 50% at any location worldwide, allowing to substantially improve the quantification of risks associated with future climate change. A rigorous evaluation of these results within a perfect model framework indicates a robust skill, leading to a high confidence in our constrained climate projections.
Redesign of E-Commerce Mobile Application with Design Thinking Method: A Case Study of RP2, Online Household Retailer
Authors: Limantara Natalia , Renaldi Renaldi , Filicia Cynthia
Published: February 2022

RP2 is one of the growing e-commerce sites in Indonesia offering products for home and living. Recently, RP2 launches a mobile application to reach users by using mobile devices to facilitate purchases on RP2. However, the development of this mobile application has not been through a good application development process, so several weaknesses are found. The aim of the research was to redesign the RP2 mobile application using the design thinking method. The method had five stages: empathize, define, ideate, prototype, and test. However, the research only focused on the first four stages. Moreover, a survey using a questionnaire and interviews were done with 34 users of the RP2 mobile application. The research results are a prototype of the RP2 mobile application, which has been tailored to users’ needs and the project owner’s input. Changes have been made to the RP2 mobile application using the design thinking method. Changes are applied in several views, such as home, navigation and notifications, search bar, Product Detail Page (PDP), cart and payment, and profiles. With these changes, it is expected that users of the RP2 mobile application will increase, so the number of transactions through the RP2 mobile application will increase too.