bluuebunny/crossref_metadata_2025 huggingface dataset:
PEG-BCT-100 in Combination With Capecitabine and Oxaliplatin (PACOX) in Patients With Advanced Hepatocellular Carcinoma: A Phase I Study Results
Authors: Yau Thomas , Cheng Paul N.M. , Chiu Joanne , Kwok Gin Wai , Leung Roland , Liu Angela M , Cheung Tan To , Ng Chi Tao
Published: July 2021

Introduction: We investigated the safety and efficacy of PEG-BCT-100 in combination with oxaliplatin and capecitabine (PACOX) in advanced HCC patients.Methods: This was a single centre phase 1 trial to assess the safety and tolerability of PACOX. All the enrolled subjects received treatment in 3-weekly cycles: IV PEG-BCT-100 2.7 mg/kg on day 1, 8 and 15 of each cycle; oral capecitabine 1000 mg/m2 twice daily on day 1-14 of each cycle and IV oxaliplatin on day 1. Three dose levels of oxaliplatin (85 mg/m2, 100 mg/m2 or 130 mg/m2) were studied to define the maximum tolerated dose (MTD). Adverse events (AEs), efficacy by RECIST v1.1, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were studied.Results: Seventeen patients were enrolled at 3 doses of oxaliplatin: 85 mg/m2 (8 patients), 100 mg/m2 (3 patients), and 130 mg/m2 (6 patients). The median age was 55 years; all had local-regional chemotherapy or target therapy such as sorafenib, but no systemic chemotherapy. Most common AEs were nausea (82%), injection site reaction (76%), palmar-plantar erythrodysesthesia (59%), oral mucositis (53%) and vomiting (53%). There was no dose-limiting toxicity (DLT). Median duration on study was 8 weeks overall. In 14 evaluable cases, one achieved partial response (PR), 4 had stable disease (SD); disease control rate was 36% (5/14); most responses were observed in the 130 mg/m2 cohort with 1 PR and 2 SDs (3/6 or 50%). The median TTP, PFS were both 7.0 weeks. Overall median OS was 10.7 months; the median OS was not reached at 19.4 months of follow-up in the third cohort.Conclusion: The PACOX regimen demonstrated good anti-cancer activity and survival advantage in advanced pre-treated HCC with favourable safety profile. It warrants further phase II/III studies.
Increased Soil Fertility in Tea Plantations Leads to Declines in Fungal Diversity and Complexity in Subsoils
Authors: yan peng , Shen Chen , Zou Zhenhao , Fan Lichao , Li Xin , Zhang Liping , Zhang Lan , Dong Chunwang , Fu Jianyu , Han Wenyan , Shi Lingling
Published: July 2021

Purpose The effects of fertilization of tea plantations on soil quality and the diversity and composition of microbial communities have received increased attention in recent years. Despite their important role as decomposers of organic matter, the responses of soil fungi to fertilization and soil fertility, particularly in subsoils, remain unknown. In this study, the effects of land-use change and fertilization on fungal diversity and function in both of topsoil and subsoils were evaluated.Methods We sampled soil profiles (0–60 cm) from tea plantations in southeastern China with low, moderate, and high inputs of mineral and organic fertilizers, as well as a nearby natural (unfertilized) forest. 18s rRNA Illumina sequencing was used to evaluate how soil fertility and land-use impacted fungal diversity and function. Results Following conversion from forest to tea plantation, soil fungal diversity increased with fertility in topsoil but declined in subsoils, resulting in significant vertical variation in highly fertile soils. The dominant fungal groups shifted from Solicoccozyma and Trichoderma in the forest to Pseudogymnoascus and Umbelopsis in tea plantation soils. Relative abundance of Pseudogymnoascus increased with soil fertility, while Mortierella and opportunistic saprotrophs exhibited the opposite pattern. Fungal network complexity was enhanced in topsoil under increased soil fertility, but decreased in the subsoil, suggesting an increased selective effect along the soil horizon. Land-use changes have altered the dominant fungal groups, particularly in topsoil. Soil fertility not only regulated fungal diversity but also shifted community composition toward that found in the forest. With increased soil fertility, plants have a greater influence on the soil fungal community.
A double-hit in vivo model of GBA viral microRNA-mediated downregulation and human alpha-synuclein overexpression demonstrates nigrostriatal degeneration
Authors: Polissidis Alexia , Nikolopoulou Georgia , Koronaiou Effrosyni , Nikatou Maria , Viel Catherine , Bogiongko Marios , Sardi S. Pablo , Xilouri Maria , Vekrellis Kostas , Stefanis Leonidas
Published: July 2021

Background: Preclinical and clinical studies support a strong association between mutations in the GBA1 gene that encodes beta-glucocerebrosidase (GCase) (EC 3.2.1.45; glucosylceramidase beta) and Parkinson’s disease (PD). Alpha-synuclein (AS), a key player in PD pathogenesis, and GBA1 mutations may independently and synergistically cause lysosomal dysfunction and thus, embody clinically well-validated targets of the neurodegenerative disease process in PD. However, double-hit in vivo models, recapitulating pathological features of PD that can be used to dissect the nature of the complex relationship between GCase and AS on the nigrostriatal axis, the region particularly vulnerable in PD, are direly needed. Methods: To address this, we implemented a bidirectional approach in mice to examine the effects of: 1) GCase overexpression (wild-type and mutant N370S) on endogenous AS levels and 2) downregulation of endogenous GCase combined with AS overexpression. Results: Striatal delivery of viral-mediated GCase overexpression revealed minimal effects on cortical and nigrostriatal AS tissue levels and no significant effect on dopaminergic system integrity. On the other hand, microRNA (miR)-mediated GBA1 downregulation (miR GBA), combined with virus-mediated human AS overexpression (+AS), yields decreased GCase activity in the cortex, mimicking levels seen in GBA1 heterozygous carriers (30-40%), increased astrogliosis and microgliosis, decreased striatal dopamine levels (50% compared to controls) and loss of nigral dopaminergic neurons (~33%)- effects that were all reversible with miR rescue. Most importantly, the synergistic neurodegeneration of miR GBA+AS correlated with augmented AS accumulation and extracellular release in the striatum. Conclusion: Collectively, our results suggest that GCase downregulation alone is not sufficient to recapitulate key pathological features of PD in vivo, but its synergistic interplay with AS, via increased AS levels and release, drives nigrostriatal neurodegeneration. Furthermore, we demonstrate a novel double-hit model that can be used to identify putative mechanisms driving PD pathophysiology and can be subsequently used to test novel therapeutic approaches.
The Improved Techniques of Holding the Lens in Endoscopic Thyroidectomy via Bilateral Areola Approach
Authors: wang junxiao , Lin Qisheng , Wu Xiaolan , Lin Yuxiang , liu ezhang
Published: July 2021

Background: Inexperienced endoscope holder often greatly affect the time and quality of endoscopic thyroidectomy (ET) via bilateral areola approach. We summarized some techniques of holding the endoscopic lens to evaluate the value of the technique in ET.Methods: We retrospectively enrolled 200 eligible patients during two time peroids: 2015.6-2018.6 (Control group:inexperienced endoscope holder,n = 100) and 2019.9-2021.2 (Improved group:assistants who master the techniques of holding the endoscopic lens,n = 100). Surgery approach:unilateral lobectomy and isthmus resection plus ipsilateral cervical central lymph nodes dissection via bilateral areola approach of ET. Perioperative indicators included Volume of intraoperative blood loss,the time of three stages in the operation, the indwelling time of drainage tube and postoperative hospitalization time were compared. Postoperative complications were simultaneously compared involved temporary hoarseness, tetany, postoperative bleeding, postoperative infection and postoperative subcutaneous effusion.Results: The time of stage 1 (p < 0.001), stage 2 (p < 0.001) and stage 3 (p < 0.001) in the operation in improved group were significantly shorter than those in control group. The volume of intraoperative blood loss was smaller (p < 0.001), postoperative hospitalization time was shorter (p < 0.001) and the indwelling time of drainage tube was shorter (p < 0.001) for improved group. In terms of postoperative complications, the control group had more cases of temporary hoarseness (p = 0.002), tetany (p = 0.008) and postprocedure subcutaneous effusion (p = 0.009), but there was no difference in postoperative bleeding (p = 0.477) and infection (p = 1.000) between the two groups.Conclusions: The skills of holding the endoscopic lens which shorten the operation time and improve the quality of the operation are effective and suitable for novices.
Study on the techniques of wallpaper (“Biaohu”) in the Palace Museum: Case on Lodge of Bamboo Fragrance(Zhu Xiangguan)
Authors: Yue Ma , Zhao Congshan , Lei Yong
Published: July 2021

"Biao Hu" was one of the eight famous traditional crafts in the late Qing dynasty.Its function was decorating the interior of ancient buildings and making burial objects, including ceilings, walls and windows. It was popular in the buildings of northern China in the early Qing dynasty. There were white and patterned wallpaper in the Forbidden City, the latter included traditional and rare patterns in the Palace. Take the wallpaper in Lodge of Bamboo Fragrance( Zhuxiang Guan ) as an example, in this article, its structure and composition are studied by morphological observation and spectral analysis. Combined with the analysis of the patterned wallpaper in other buildings of the Forbidden City, the traditional technology is studied .
Seismic Performance of Prefabricated Beam-to-column Joint with Replaceable Energy-dissipating Steel Hinge
Authors: Zheng Lianqiong , Chen Xiaoyang , Wei Changgui , Yan Guiyun
Published: July 2021

This study presents a novel energy-dissipating prefabricated joint for connecting beam to column in a precast frame structure. The joints are characterized by a replaceable steel hinge and a prefabricated steel tube confined joint core, providing advantages for precast concrete reinforced frames, such as complete assembly, damage control, and maintainability of the structure after an earthquake. The hysteretic behavior of the proposed prefabricated joint was studied through two tests. First, a full-scale prefabricated joint was tested under cyclic loading until failure. On the basis of the initial test, only four weakened dissipaters of the steel hinges in the prefabricated joint were replaced and the second test was conducted to investigate the restorable functional characteristics of the proposed prefabricated joints. For comparison, a reference monolithic joint was also tested. The experimental results demonstrate that the novel prefabricated beam-to-column joint displayed excellent hysteretic performance, and corresponding to the monolithic joint, the load-bearing, energy dissipation, and deformation capacity were improved. The damage of the prefabricated joint was concentrated on the weakened dissipaters of the steel hinges, indicating that the failure mode and damage degree of the prefabricated joint can be controlled. In the second test, the prefabricated joint exhibited similar hysteretic behavior to that of the first test; however, the initial stiffness was slightly lower. Therefore, the prefabricated joint can meet the replaceability requirement and achieve satisfactory beam-to-column joint function recovery after an earthquake.
Study Protocol: Traditional Chinese Medicine (TCM) Syndrome Differentiation for Heart Failure patients and its Implication for Long-term Therapeutic Outcome of Qiliqiangxin Capsules
Authors: Leung Alice Yeuk Lan , Chen Hoiyong , Jia Zhenhua , Li Xinli , Shen Jiangang
Published: July 2021

BackgroundSyndrome differentiation is a commonly used methodology and practice in Traditional Chinese Medicine (TCM) guiding the diagnosis and treatment of diseases including heart failure (HF). However, previous clinical trials seldom consider the impact of syndrome patterns on the outcome evaluation of TCM formulae. Qiliqiangxin (QLQX) capsule is a TCM formula with cardiotonic effect to improve the cardiovascular function for heart failure with proven efficacy from well-designed clinical trials. Though, there is no clinical trial with a large sample size and long assessment period that considers the relationship between TCM syndrome differentiation and the treatment efficacy of QLQX. In the present study, we design a study protocol to evaluate the relationship between TCM syndrome differentiation and the severity of heart failure as well as its progression. Furthermore, we will evaluate the impact of the TCM syndrome patterns on the efficacy of QLQX in the outcome of heart failure. MethodsThis is a clinical study conducted in conjunction with an ongoing clinical trial (QUEST Study 1 ) to evaluate the efficacy of QLQX to improve the outcome of HF treatment through the assessment of morbidity and re-hospitalization, which involves over 100 hospitals in mainland China and Hong Kong SAR with 3,080 HF patients. Firstly, we will apply a modified TCM Questionnaire to collect the clinical manifestations of HF and acquire the tongue images of the patients to facilitate the syndrome differentiation. We will base on the “2014 Consensus from TCM experts on diagnosis and treatment of chronic heart failure” to evaluate the TCM syndromes for the patients. Secondly, we will investigate the characteristic of TCM syndrome distribution of HF patients and its correlation with the functional and biochemical data. Furthermore, we will evaluate the relationship between the TCM syndrome patterns and the efficacy of QLQX in the treatment of heart failure. Lastly, we will investigate the implication of tongue diagnosis in the severity and therapeutic outcome of HF. Expect OutcomesTo our knowledge, this will be the latest and well-designed clinical trial to evaluate the rules of TCM syndrome differentiation in the progression and therapeutic outcome of HF patients. We expect to obtain direct clinical evidence to verify the importance of TCM syndrome differentiation for the diagnosis and treatment of HF.Trial Registration1The trial was registered at Chinese Clinical Trial Registry, http://www.chictr.org.cn. (Registration No.: ChiCTR1900021929); Date: 2019-03-16.
A Rare Case of Right Upper Lung Cancer With Azygos Lobe and Partial Anomalous Pulmonary Venous Return: A Case Report
Authors: SU Xiaoyang , Huang Qianzhun , Luo Zhiqiang , Fang Ning , Huang Jian
Published: July 2021

Background: The azygos lobe (AL) combined with partial anomalous pulmonary venous return (PAPVR) is comparatively uncommon as well as in radical surgery for right lung cancer.Case presentation: We herein present an extremely rare case of lung cancer coexisting with AL and asymptomatic PAPVC, which was diagnosed with preoperative contrast three-dimensional reconstruction and received radical surgery by thoracoscopy. During the surgery, we preserved azygos vein successfully and found a split type of PAPVR in right upper pulmonary vein.Conclusions: AL combined with PAPVR may cause confusion on the vascular separation and disconnection of the right pulmonary hilar. However, preoperative 3D reconstruction are more conducive to the correct performing of this type of surgery.
Clinical Outcomes of Limited-repair Strategy and Conservative Approach for the Elderly With Acute Type A Aortic Dissection
Authors: Maze Yasumi , Tokui Toshiya , Murakami Masahiko , Nakamura Bun , Inoue Ryosai , Hirano Reina , Hirano Koji
Published: July 2021

BackgroundThere is controversy regarding surgical indication and surgical procedure of acute type A aortic dissection for the elderly. We examined surgical outcomes for the elderly.MethodsFrom January 2012 to December 2019, 174 patients underwent surgical repair for acute type A aortic dissection. We compared the surgical outcomes between the elderly group (≧80 years old) and the non-elderly group (≦79 years old). Additionally, we compared the surgical treatment group with the conservative treatment group.ResultsThe primary entry was found in the ascending aorta in 51.6% of the elderly group and in 32.8% of the non-elderly group (p= 0.049). In the elderly group, ascending or hemiarch replacement was performed in all cases, while in the non-elderly group, ascending or hemiarch replacement was performed in 57.3% (p<0.001). The hospital mortality was similar in both groups. The 5-year survival rate was 48.4±10.3% in the elderly group and 86.7±2.9% in the non-elderly group (p<0.001). The rates of freedom from aortic event at 5 years was 86.9±8.7% in the elderly group and 86.5±3.9% in the non-elderly group (p=0.771). The 5-year survival rate of conservative treatment group was 19.2±8.0% in the elderly. There was no significant difference from the surgical treatment group (p=0.103).ConclusionsThe surgical approach may not always be the reasonable treatment of choice for the elderly because the significant survival merit was not achieved compared with the conservative approach.
Magnetic Composite of γ-Fe2O3 Hollow Sphere and Palladium Doped Nitrogen-rich Mesoporous Carbon as a Recoverable Catalyst for C-C Coupling Reactions
Authors: Malmir Masoume , Heravi Majid M. , Amiri Zahra , Kafshdarzadeh Kosar
Published: July 2021

In this article, Palladated-magnetic nitrogen doped porous carbon was prepared from nano magnetic γ-Fe2O3 hollow sphere (h-Fe2O3) with high specific surface area and pore volume. To the purpose, initially h-Fe2O3 was prepared and covered with glucose via hydrothermal treatment with subsequent polymerization of organic shell. The polymerization of melamine-resorcinol-formaldehyde (MRF) was achieved in the presence of Cl-functionalized glucose coated h-Fe2O3 (h-Fe2O3@glu-MRF). Next, the prepared magnetic core-shell hollow sphere was palladated followed by carbonization to yield Pd@h-Fe2O3@C introducing more pores in its structure. The resulted compound, Pd@h-Fe2O3@C, was fully characterized, showing that carbonization process expressively increased the specific surface area. The resulted Pd@h-Fe2O3@C was successfully used for promoting C-C coupling reactions under mild reaction conditions as a heterogeneous catalyst and its activity was compared with some prepared control catalysts. This novel catalyst was magnetically separated simply by a magnet bar and recycled and reused at least in five consecutive runs, without considerable loss of its activity. It is note mentioning that, high recyclability with low Pd leaching are another gains of this protocol.
Analysis and Prediction of Sulfate Erosion Damage of Concrete in Service Tunnel based on ARIMA Model
Authors: Liu Dunwen , Chen Haofei , Tang Yu , Chun Gong , Jian Yinghua , Cao Kunpeng
Published: July 2021

Sulfate erosion is a major cause of concrete durability deteriorations, especially for the service tunnels which are in sulfate erosion for a long time. Accurately predicting the concrete damage failure under sulfate erosion has been a challenging problem in the evaluation and maintenance of concrete structures. Here we design the dry-wet cycle test of service tunnel concrete under sulfate erosion, and analyze the Elastic relative dynamic modulus(Erd) and mass under 35 times cycle periods. Then we develop an autoregressive integrated moving average (ARIMA) prediction model linking damage failure to Erd and mass. The results show that the deterioration of concrete first increased and then decreased with an extension of the dry–wet cycle period. Moreover, based on a finite set of training data, the proposed prediction approach shows high accuracy for the changes of concrete damage failure parameters in or out of the training dataset. The ARIMA method is proven to be feasible and efficient for predicting the concrete damage failure of service tunnel under sulfate erosion for a long time.
Oral Supplementation With Selected Lactobacillus Acidophilus Triggers Antimicrobial Response, Activation of Innate Lymphoid Cells Type 3 And Improves Colitis
Authors: Hrdý Jiří , Couturier-Maillard Aurélie , Boutillier Denise , Lapadatescu Carmen , Blanc Philippe , Pot Bruno , Ryffel Bernhard , Grangette Corinne , Chamaillard Mathias
Published: July 2021

Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that are illustrated by direct and indirect antimicrobial activity against several pathogens and improvement of intestinal inflammation. In this study, we evaluated the anti-inflammatory properties of the L. acidophilus strain BIO5768 and assessed the underlying mechanisms of action. BIO5768 was able to counteract the acute colitis that is induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was also able to alleviate intestinal inflammation induced by Citrobacter rodentium infection. Supplementation of naïve mice with either strain BIO5768 alone or as mixture, increased the gene expression of several target genes involved in immune signaling, including c-type lectin Reg3 gamma. Consistently, the ability of innate lymphoid cells to secrete IL-22 was enhanced in response to BIO5768. Interestingly, the aforementioned responses were shown to be independent of NOD2 and Th17 signaling in mice that were mono-colonized with BIO5768. In conclusion, we identify a new potential probiotic strain with the ability for the management of inflammatory bowel diseases, and provide some insights into its mode of action.
One-pot Synthesis of (R)- and (S)-phenylglycinol From Bio-based L-phenylalanine by an Artificial Biocatalytic Cascade
Authors: Zhang Jiandong , Qi Ning , Gao Lili , Li Jing , Zhang Chaofeng , Chang Honghong
Published: July 2021

Chiral phenylglycinol is a very important chemical in the pharmaceutical manufacturing. Current methods for synthesis of chiral phenylglycinol often suffered from unsatisfied selectivity, low product yield and using the non-renewable resourced substrates, then the synthesis of chiral phenylglycinol remain a grand challenge. Design and construction of synthetic microbial consortia is a promising strategy to convert bio-based materials to high value-added chiral compounds. In this study, we reported a six-step artificial cascade biocatalysis system for conversion of biobased L-phenylalanine to yield chiral phenylglycinol. The cascade biocatalysis system was conducted by a microbial consortium composed of two engineered recombinant Escherichia coli cells modules, one recombinant E. coli cell module co-expression of six different enzymes (phenylalanine ammonia lyase/ferulic acid decarboxylase/phenylacrylic acid decarboxylase/styrene monooxygenase/epoxide hydrolase/alcohol dehydrogenase) for efficient conversion of L-phenylalanine into 2-hydroxyacetophenone. The second recombinant E. coli cell module expression of an (R)-ω-transaminase or co-expression of the (S)-ω-transaminase, alanine dehydrogenase and glucose dehydrogenase for conversion of 2-hydroxyacetophenone to (S)- or (R)-phenylglycinol, respectively. Combining the two engineered E. coli cell modules, after the optimization of bioconversion conditions (including pH, temperature, glucose concentration, amine donor concentration and cell ratio), L-phenylalanine could be easily converted to (R)-phenylglycinol and (S)-phenylglycinol with up to 99% conversion and >99% ee. Preparative scale biotransformation was also conducted on 100 mL scale, (S)-phenylglycinol and (R)-phenylglycinol were obtained in 71.0% and 80.5% yield, >99% ee, and 5.19 g/L.d and 4.42 g/L.d productivity, respectively. The salient features of this biocatalytic cascade system are good yields, excellent ee, mild reaction conditions and no need for additional cofactor (NADH/NAD+), provide a practical biocatalytic method for sustainable synthesis of (S)-phenylglycinol and (R)-phenylglycinol from biobased L-phenylalanine.
Synthesis, crystal structure, and quantum mechanical studies regarding a new metal–organic complex based on Cd (II)
Authors: razmara zohreh , Shiri Fereshteh , Karimi Pouya , Necas Marek
Published: July 2021

A novel metal-organic complex formulated as [Cd (phen)(dipic) (H2O)2]. 3 H2O (phen = 1, 10-phenanthroline; dipic2−= pyridine-2,6-dicarboxylate) has been hydrothermally synthesized at 150°C for 48h. The structure of Cd complex was characterized by elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential thermal analysis (DTA), and single-crystal X-ray diffraction (SC-XRD). The crystal system of Cd complex is monoclinic with space group C 2/c. The pentagonal bipyramid (seven coordinate) around Cd2+ center filled by two terminal water ligands, one 1,10-phenanthroline, and one pyridine-2,6-dicarboxylate anion. Extensive O–H···O hydrogen bonding interactions involving all coordinated water molecules, dipicolinate oxygens, and crystallization water molecules further stabilize the complex units by linking them to form three-dimensional polymeric networks. Indeed, quantum mechanical studies were performed to understand effective factors on stability of the Cd(II) complex.
Study of Hollow ZnO Nanoparticles by Flame Spray Synthesis
Authors: Hui Li
Published: July 2021

Hollow ZnO nanoparticles prepared by flame spray synthesis(FSP) have been reported in this letter. By the results obtained from X-Ray diffraction(XRD) pattern and high-resolution transmission electron microscopy(HR-TEM) picture, it is concluded that the hollow ZnO nanoparticles were successfully synthesized at high temperature. The size of hollow nanoparticles distributed between 20 and 30 nm, and the formation mechanism of this hollow structure was discussed in the synthesis process. The strong ultra-visible(UV) emission was shown in photoluminescence(PL) spectra, while the mechanism had been explained in detail.
Transcriptomic comparison of ovarian granulosa cells between adult sheep and prepubertal lambs
Authors: Tian Hao , Ren Panyu , Liu Kailing , Qiu Lijuan , Fan Lihong , Li Junlong , Hou Jian
Published: July 2021

Background
The oocyte development ability of prepubertal animals is significantly lower than that of adult animals. Granulosa cells (GCs) have an important function on regulation of follicular and oocyte development. Therefore, analysis of GCs characteristics can be used to explore the developmental mechanism of follicles and oocytes.
Results
In order to understand the possible reasons for the differences in follicles and oocytes development between lambs and adult sheep, we utilized high-throughput sequencing technique to analyze the transcriptome of GCs from follicle-stimulating hormone (FSH) superstimulated adult ewes and prepubertal lambs. Adult ewes were stimulated with FSH for 3 days (group A) and lambs were FSH-stimulated for 2 days (group B) or 3 days (group C). Transcriptome analysis of GCs showed that there were 405 and 159 differentially expressed genes from A vs. B and A vs. C, respectively. The results indicated that prolonging the FSH-stimulation of lambs made the GC state of lambs more similar to the adult sheep, but there were still a large number of differentially expressed genes between adult sheep and lambs. Further analysis showed that many differently expressed genes were implicated in cell proliferation and apoptosis, oocyte development and follicular ovulation. Cellular examination demonstrated that fatty acid binding protein 4 (FABP4), which was highly expressed in lamb GCs, had a potential of promoting cell apoptosis. Cytoplasmic phospholipase A2 (PLA2G4A), which was expressed lowly in lamb GCs, may be responsible for reduced synthesis of prostaglandins in cells and impaired follicle/oocyte development. In contrast, glutathione S-transferase β-1 (GSTT2B) and forkhead boxO6 (FOXO6) had no apparent effect on the proliferation and apoptosis of GCs.
Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant
Authors: Lu Jing , Li Baisheng , Deng Aiping , Li Kuibiao , Hu Yao , Li Zhencui , Xiong Qianlin , Liu Zhe , Guo Qianfang , Zou Lirong , Zhang Huan , Zhang Meng , Ouyang Fangzhu , Su Juan , Su Wenzhe , Xu Jing , Lin Huifang , Sun Jing , Peng Jinju , Jiang Huimin , Zhou Ping-Ping , Zheng Huanying , Xiao Jianpeng , Liu Tao , Che Rongfei , Zeng Hanri , Zheng Zhonghua , Huang Yushi , Yu Jianxiang , Yi Lina , Wu Jie , Chen Jingdiao , Zhong Haojie , Deng Xiaoling , Kang Min , Pybus Oliver , Hall Matthew , Lythgoe Katrina , Li Yan , Yuan Jun , He Jianfeng
Published: July 2021

We report the first local transmission of the SARS-CoV-2 Delta variant in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of the quarantined subjects indicated that the viral loads of Delta infections, when they first become PCR+, were on average ~1000 times greater compared to A/B lineage infections during initial epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. We performed high-quality sequencing on samples from 126 individuals. Reliable epidemiological data meant that, for 111 transmission events, the donor and recipient cases were known. The estimated transmission bottleneck size was 1-3 virions with most minor intra-host single nucleotide variants (iSNVs) failing to transmit to the recipients. However, transmission heterogeneity of SARS-CoV-2 was also observed. The transmission of minor iSNVs resulted in at least 4 of the 30 substitutions identified in the outbreak, highlighting the contribution of intra-host variants to population level viral diversity during rapid spread. Disease control activities, such as the frequency of population testing, quarantine during pre-symptomatic infection, and level of virus genomic surveillance should be adjusted in order to account for the increasing prevalence of the Delta variant worldwide.
Malaria Trigram: Improving the Visualisation of Recurrence Data for Malaria Elimination
Authors: de Morais Cleber Matos , Monteiro Kayo Henrique de Carvalho , Brito-Sousa Jose Diego , Monteiro Wuelton Marcelo , Sampaio Vanderson Souza , Endo Patricia Takako , Kelner Judith
Published: July 2021

Background: Although considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualisation tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon.Methods: Action Research methodology was employed to deal with the complex malaria surveillance problem in the Amazon region. Iterative cycles were used, totalling four cycles with a formal validation of an operational version of the Malaria Trigram tool at the end of the process. Further probabilistic data linkage was carried out so that information on the same patients could be linked, allowing for follow-up analysis since the official system was not planned in such way that includes this purpose.Results: An infographic user interface was developed for the Malaria Trigram that incorporates all the visual and descriptive power of the Trigram concept. It is a multidimensional and interactive historical representation of malaria cases historical per patient over time and provides visual input to decision-makers on recurrences of malaria.Conclusions: The Malaria Trigram is aimed to help public health professionals and policy makers to recognise and analyse different types of patterns in malaria events, including recurrences and reinfections, based on the current Brazilian health surveillance system, the SIVEP-Malária system, with no additional primary data collection or change in the current process. By using the Malaria Trigram, it is possible to plan and coordinate interventions for malaria elimination that is integrated with other parallel actions in the Brazilian Amazon region, such as vector control management, developing of an effective drugs for treatment and effective vaccine.
A Comparative Study of Total Knee Arthroplasty Outcome for Stiff Knee with or without Sequential Antirheumatic Drug Treatment
Authors: Jia Cheng-Qi , Guan Xiao-Rui , Zhao Zhi-Lai , Chen Ji-Ying , Li Xiang
Published: July 2021

BackgroundTo evaluate influence of antirheumatic drug treatment on knee function of patients with stiff knee after total knee arthroplasty (TKA). MethodsTwenty-seven patients (44 knees) of active RA (rheumatoid arthritis) or AS (ankylosing spondylitis) with stiff knee were included in this study. And they were divided into two groups according to continue antirheumatic drug treatment or not after TKA: the therapeutic group (16 patients, 27 knees) and the controlled group (11 patients, 17 knees). The outcomes were assessed by Knee Society Score (KSS), Visual Analogue Scale (VAS), range of motion (ROM) (at week 6, month 6, year 1 and year 2), “Forgotten Joint” Scale (FJS), with or without crutch, satisfaction and revision (at year 2). The knee prosthetic loosening was evaluated by the followed X-ray at each following time. ResultsThe mean follow-up time was 51 months (34-69 months). The KSS were higher at week 6 after TKA in the therapeutic group (p < 0.05), however, the functional scores of KSS at month 6, year 1 and year 2 in the controlled group were more points improved. The therapeutic patients preferred the knee more at month 6, year 1 and year 2. The differences of KSS clinical scores (at month 6, year 1 and year 2), VAS, ROM, Crutch and FJS between the two groups were not statistically significant (p＞0.05). ConclusionFor patients with stiff knees, the sequential antirheumatic drug treatment after TKA had no effect on postoperative KSS, but can improve the satisfaction.Level of evidence﻿Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Analysis of the Function of the Loops in G-quadruplex in the Promoter of the Transcription Factor BmPOUM2 in the Silkworm, Bombyx Mori
Authors: Chen Yanfei , Niu Kangkang , Song Qisheng , Feng Qili
Published: July 2021

Bachguound: A G4 structure in the promoter of the transcription factor BmPOUM2 was identified in Bombyx mori. This G4 structure binds with the transcription factor BmLARK and is involved in the transcription of BmPOUM2. However, the structure and functional domains of the BmPOUM2 G4 remain to be clarified.Results: In this study, the relationship between the loop structure and the function of the BmPOUM2 G4 was examined using mutation, CD analysis, EMSA, MST and luciferase assay. The results revealed that the loop mutations could not suppress the G4 structure formation, but loop C does influence the LARK binding affinity and the promoter activity.Conclusions: the results of this study are suggesting that the structure and function of BmPOUM2 G4 are mainly determined by the G-quartets, which maintain the framework of the structure and were targeted by BmLARK. Nevertheless, the loops, which are relatively variable in G4, may entitle the variability of the structure, especially the loop C, which is the one-nucleotide-loop.
The Impact of the COVID-19 Pandemic on Anxiety and Depression in Breast Cancer Patients in Tunisia
Authors: KSONTINI Feryel letaief , Lajnef Ines , Zenzri Yosr , Gabsi Azza , Ayadi Mouna , Mezlini Amel
Published: July 2021

Objective : The COVID-19 generated an unprecedented set of emotional challenges for cancer patients. We aimed to investigate the impact of COVID-19 on anxiety and depression in breast cancer patients.Method: Between September and December 2020, women aged 18 years old or older with breast cancer (stage I to IV) who have started treatment before the onset of the pandemic were included. They must have an evaluation of anxiety and depression with the HAD scale before the onset of COVID-19. After inclusion, each patient was asked to complete the HAD scale to evaluate her mental health during the pandemic.Results: 100 patients were included. The mean age was 51 years. The prevalence of anxiety and depression before the COVID-19 pandemic were 63% and 43 % respectively. Under pandemic, the prevalence of anxiety was 77% : 25 women had mild anxiety, 29 moderate anxiety and 23 severe anxiety. For depression, the prevalence was 62% : 25 were experiencing mild anxiety, 20 moderate anxiety and 17 severe anxiety. The COVID 19 was significantly correlated with the increase of anxiety and depression rate ( p=0,027 and p=0,005) respectively. Other clinical factors were significantly associated with the increase of the anxiety and depression. In multivariate Analysis including the incidence of anxiety and depression during the pandemic and these factors, COVID-19 was an independent factor affecting the incidence of anxiety and depression (p<0.05, IC=95%).Conclusions: this study underlined the negative psychological impact of COVID-19 in breast cancer patient, showing the importance of the psychological support.
The effects of rapid mass vaccination against SARS-CoV-2 and its Variants-of-Concern: Evidence from an early VoCs hotspot
Authors: paetzold joerg , Krammer Florian , von Laer Dorothee , winner Hannes , Kimpel Janine , Bates Katie , Hummer Michael
Published: July 2021

We studied the real-life effect of an unprecedented rapid mass vaccination campaign. Following a large outbreak of B.1.351 and B.1.1.7/E484K in the district of Schwaz/Austria, 100,000 BNT162b2 doses were procured to mass vaccinate the entire adult population (16+) of the district between the 11th and 16th of March 2021. This made the district the first widely inoculated region in Europe. We examined the effect of this unique campaign on the number of infections including VoCs, hospital and intensive care unit (ICU) admissions. We compared Schwaz with (i) a control group of highly similar districts, and (ii) with populations residing in municipalities along the border of Schwaz which were just excluded from the campaign. We find large and significant decreases for all outcomes after the campaign, including VoCs cases. The reduction relative to the control regions was largest for younger age cohorts, which were mostly non-vaccinated in the rest of the country due to the age-gradient in the national vaccination plan. Our results demonstrate that rapid population-wide mass vaccination can be an effective tool to curb overall infections as well as VoCs.
Interleukin-1 Receptor Antagonist Inhibits Matastatic Potential by Down-Regulating CXCL12/CXCR4 Signaling Axis in Colorectal Cancer
Authors: Ma Jiachi , Liang Wanqing , Qiang Yaosheng , Li Lei , Du Jun , Pan Chengwu , Chen Bangling , Zhang Chensong , Chen Yuzhong , Wang Qingkang
Published: July 2021

Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.
Diagnostic Utility of Cord Blood Serum Procalcitonin in Early Onset Neonatal Sepsis in Comparision to Sepsis Screening Parameters
Authors: MEENA CHIRANJI LAL , SHARMA RAMBABU , BAGRI DHAN RAJ , SINGH NEELAM
Published: July 2021

Neonatal sepsis is an important cause of neonatal deaths globally. Diagnosis of neonatal sepsis is established based on microbiological tests of sepsis screen and clinical status. Mid phase markers of inflammation like CRP & Serum Procalcitonin are considered useful and sensitive for diagnosis. Most of the studies evaluating serum PCT as a diagnostic marker for neonatal septicemia have been carried out in peripheral venous blood with smaller sample sizes with inclusion of neonates without considering perinatal sepsis score. This hospital based, prospective study compares the diagnostic utility of cord blood Procalcitonin (PCT) with venous blood PCT; alone and as part of sepsis screening parameters currently in use in perinatal sepsis score positive neonates. Statistical analysis for cord blood Serum Procalcitonin (PCT) for detecting blood culture positive patients showed that PCT has a sensitivity of 44.4%, a high specificity of 86.4%, a low PPV of 33.3% and a high NPV of 91.1%. Overall diagnostic accuracy is 80.9%, indicating that cord blood PCT is a good test for identifying these patients (p < 0.05). However, venous blood PCT failed to demonstrate similar results. Conclusions- Umbilical blood sampling protects the neonates from pain of venipunctures. Cord blood PCT estimations have statistically significant correlation with blood culture and other sepsis screen parameters and better sensitivity and specificity than venous blood PCT. This early serological biomarker is valuable for the diagnostic armamentarium of neonatal septicemia for early diagnosis and management while awaiting blood culture reports and helps in reducing separation of probable sepsis neonates from mother, thus contributing in developmental supportive care.
Newly Developed Dual Topoisomerase Inhibitor P8-D6 is Highly Active in Ovarian Cancer
Authors: Flörkemeier Inken , Steinhauer Tamara N. , Hedemann Nina , Ölander Magnus , Artursson Per , Clement Bernd , Bauerschlag Dirk O.
Published: July 2021

Background: Ovarian cancer (OvCa) constitutes a rare and highly aggressive malignancy and is one of the most lethal of all gynaecologic neoplasms. Due to chemotherapy resistance and treatment limitations because of side effects, OvCa is still not sufficiently treatable. Hence, new drugs for OvCa therapy such as P8-D6 with promising antitumour properties have a high clinical need. The benzo[c]phenanthridine P8-D6 is an effective inductor of apoptosis by acting as a dual topoisomerase I/II inhibitor. Methods: In the present study, the effectiveness of P8-D6 on OvCa was investigated in vitro. In various OvCa cell lines and ex vivo primary cells, the apoptosis induction compared to standard therapeutic agents was determined in 2D monolayers. Expanded by 3D and co-culture, the P8-D6 treated cells were examined for changes in cytotoxicity, apoptosis rate and membrane integrity via scanning electron microscopy (SEM). Likewise, the effects of P8-D6 on non-cancer human ovarian surface epithelial cells and primary human hepatocytes were determined. Results: This study shows a significant P8-D6-induced increase in apoptosis and cytotoxicity in OvCa cells which surpasses the efficacy of standard therapeutic drugs. Non-cancer cells were affected only slightly by P8-D6. Moreover, no hepatotoxic effect in in vitro studies was detected.Conclusions: P8-D6 is a strong and rapid inductor of apoptosis and might be a novel treatment option for OvCa therapy.
Single Incision Approach for Decompression of Greater, Lesser and Third Occipital Nerves in Migraine Surgery
Authors: Olla Danielle , Mailey Brian
Published: July 2021

Background

The traditional approach for occipital migraine surgery encompasses 3 separate surgical incisions in the posterior neck to decompress the great occipital nerves (GON), lesser occipital nerves (LON) and third occipital nerves (TON). We sought to evaluate a single midline incision approach for decompression of all 6 occipital nerves.
Methods

Using 10 cadaveric hemi-sides (5 fresh cadaver head and necks). Anatomic landmarks and the location of the bilateral GON, LON and TON were marked according to previous anatomic studies. A single midline 9-cm incision was made and lateral skin flaps were raised to decompress or avulse all 6 nerves.
Results

The GON and TON were identified 3.5 and 6.2 cm, respectively inferior to a line bisecting the external auditory canal (EAC) and 1.5 cm lateral to the midline. The LON was identified 6-cm inferior and 6.5-cm medial to a line bisecting the EAC in the plane just above the investing layer of the deep cervical fascia until the posterior boarder of the sternocleidomastoid was encountered. The LON had the greatest amount of variation, but was identified lateral to the posterior border of the SCM.
Conclusions

A single midline incision approach allows for successful identification and decompression of all 6 occipital nerves in migraine surgery.
Role of FRG1 in predicting the overall survivability in cancers using multivariate based optimal model
Authors: Khan Rehan , Palo Ananya , Dixit Manjusha
Published: July 2021

FRG1 has a role in tumorigenesis and angiogenesis. Our preliminary analysis showed FRG1 expression is associated with the overall survival (OS) in cancers the effect varies. In cervix and gastric cancers, we found a clear difference in the OS between the low and high FRG1 expression groups, but in breast, lung, and liver cancers the difference was not prominent. We hypothesized that the functionality of the genes correlated with FRG1 could be getting affected by FRG1 or vice versa, which might mask the effect of a single gene on the OS analysis in cancer patients. We used the multivariate Cox regression, risk score, and Kaplan Meier analyses to determine OS in a multigene model. STRING, Cytoscape, and HIPPIE were used to deduce FRG1 associated pathways. In breast, lung, and liver cancer we found a distinct difference in the OS, between the low and high FRG1 expression groups in the multigene model, suggesting an independent role of FRG1 in survival. Risk scores were calculated based upon regression coefficients in the multigene model. Low and high-risk score groups revealed a significant difference in the FRG1 expression and survival. HPF1, RPL34, and EXOSC9 were the most common genes present in FRG1 associated pathways across the cancer types. Validation of the effect of FRG1 expression on these genes by qRT-PCR, supports that FRG1 might be an upstream regulator of their expression. These genes may have multiple regulators which also affect their expression, leading to the masking effect in the survival analysis. In conclusion, our study highlights the role of FRG1 in the survivability of cancer patients in tissue-specific manner and the use of multigene models in prognosis.