bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound-guided implantation of radioactive 125 I seed in radioiodine refractory differentiated thyroid carcinoma
Authors: Chen Wei , Luo Yu Kun , Zhang Ying , Song Qing , Tang Jie
Published: March 2021

Background: Treatment for radioiodine refractory differentiated thyroid carcinoma (RR-DTC) is challenging. The purpose of this study was to assess the efficacy and safety of ultrasound-guided implantation of radioactive 125I-seed in radioiodine refractory differentiated thyroid carcinoma.Methods: 36 cervical metastatic lymph nodes (CMLNs) diagnosed as RR-DTC from 18 patients were enrolled in this retrospective study. US and contrast-enhanced ultrasound (CEUS) examinations were performed before implantation. Follow-up consisted of US, CEUS, thyroglobulin (Tg) level and routine hematology at 1-3, 6, 9 and 12 months and every 6 months thereafter. The volumes of the nodules were compared before implantation and at each follow-up point. The volume reduction rate (VRR) of nodules was also recorded.Results: The median volume of the nodules was 522.8 mm3 (147.5, 2009.6mm3) initially, which decreased significantly to 53.0mm3 (0, 285.7mm3) (P < 0.01) at the follow-up point of 24 months with a mean VRR as 87.4±18.1% (the range was 32–100%). During the follow-up period (the range was 24–50 months), 25 (69%) nodules had VRR greater than 90%, of which 12 (33%) nodules had VVR≈100% with structures unclear and only 125I seeds images visible. At the last follow-up visit, the serum Tg level decreased from 57.0 (8.6, 114.8) ng/ml to 4.9 (0.7, 50.3) ng/ml, (P < 0.01).Conclusion: US-guided 125I seed implantation is safety and efficacy in treating RR- DTC. It could be an effective supplement for the comprehensive treatment of thyroid cancer.
The (1-x)BiFeO3-xBaTiO3-Bi(Zn0.5Ti0.5)O3 high temperature lead-free piezoelectric ceramics with strong piezoelectric properties
Authors: Sun Yuanyuan , Yang Huabin , Xu Jiwen , Huang Weiran , Jiang Minhong , Chen Qiaohong
Published: March 2021

The structure, microstructure, piezoelectric properties, ferroelectric properties and Curie temperature of (1- x )BiFeO 3 - x BaTiO 3 -Bi(Zn 0.5 Ti 0.5 )O 3 +MnO 2 +Li 2 CO 3 ceramics were investigated experimentally by improved solid-state reaction approach. The crystalline structures were examined by X-ray diffractometry. When x = 0.3, the rhombohedral and pseudocubic phases coexist in the ceramic structure. It is considered that the morphotropic phase boundary was formed here. At the same time, the piezoelectric performance d 33 , Curie temperature T C , and depolarization temperature are as high as 184 pC/N, 550°C, 530°C at x = 0.3, respectively. It is worth noting that when x = 0.24, the ceramics have a high T C = 580°C and low dielectric loss tan δ = 1.9%. These results show that the BFBT-BZT system ceramics are applicable ceramics with high piezoelectric properties in high temperature fields.
Icotinib, an Effective Treatment Option for Patients With Lung Adenocarcinoma Harboring Compound EGFR L858R and A871G Mutation
Authors: Jin Lin-ling , Wu Zhen-zhen , Wang Yan-li , Chen Dong-sheng , Li Si , Xiao Mingzhe , Zhao Xin
Published: March 2021

Compound epidermal growth factor receptor (EGFR) mutations are defined as double or multiple independent mutations of the EGFR tyrosine kinase domain (TKD), in which an EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutation is identified together with a mutation of unclarified clinical significance. Lung adenocarcinoma with compound EGFR mutation shows poor clinical response to EGFR-TKIs. Kobayashi et al. reported a non-small-cell lung cancer (NSCLC) patient whose tumor had EGFR exon21 L858R/A871G mutation presented rapid disease progression to erlotinib. However, in this case, we present an EGFR exon21 L858R/A871G mutation patient exerted significant benefit to icotinib, another first-generation EGFR-TKI, indicating that different EGFR-TKIs have diversiform sensitive sites and therapeutic effects, consistent mutation sites might achieve heterogeneous benefits from different EGFR-TKIs. Our case report provides promising EGFR-TKI for clinical treatment with EGFR exon21 L858R/A871G mutation in NSCLC. More dedicated efforts are needed to clarify their biologic effects on disease course and drug responsiveness.
Different mechanisms underlying divergent responses of autotrophic and heterotrophic respiration to long-term throughfall reduction in a warm-temperate oak forest
Authors: Zhang Jinglei , Liu Shirong , Liu Cuiju , Wang Hui , Luan Junwei , Liu Xiaojing , Guo Xinwei , Niu Baoliang
Published: March 2021

Background: There are many studies on disentangling the responses of autotrophic (AR) and heterotrophic (HR) respiration components of soil respiration (SR) to long-term drought, but few studies have focused on the mechanisms underlying its responses.Methods: To explore the impact of prolonged drought on AR and HR, We conducted the 2-year measurements on soil CO2 effluxes in the 7th and 8th year of manipulated throughfall reduction (TFR) in a warm-temperate oak forest. Results: Our results showed long-term TFR decreased HR, which was positively related to bacterial richness. More importantly, some bacterial taxa such as Novosphingobium and norank Acidimicrobiia, and fungal Leptobacillium were identified as major drivers of HR. In contrast, long-term TFR increased AR due to the increased fine root biomass and production. The increased AR accompanied by decreased HR appeared to counteract each other, and subsequently resulted in the unchanged SR under the TFR. Conclusions: Our study shows that HR and AR respond in the opposite directions to long-term TFR. Soil microorganisms and fine roots account for the respective mechanisms underlying the divergent responses of HR and AR to long-term TFR. This highlights the contrasting responses of AR and HR to prolonged drought should be taken into account when predicting soil CO2 effluxes under future droughts.
Impact of Spatio-Temporal change in landuse/landcover on Groundwater Quality and Human Health; A case study of District Peshawar, Khyber Pakhtunkhwa, Pakistan.
Authors: Ahmad Waqas , Iqbal Javed , Nasir Muhammad Jamal , Ahmad Burhan , Khan Muhammad Tasleem , Khan Shahid Nawaz
Published: March 2021

The quality and quantity of groundwater resources are affected by landuse/landcover (LULC) dynamics, particularly the increasing urbanization coupled with high household wastewater discharge and decreasing open lands. This study evaluates temporal changes of groundwater quality for 2012 and 2019, its relation to Landuse/landcover, and its impact on Peshawar's residents (study area), Pakistan. A total of 105 and 112 groundwater samples were collected from tube wells in 2012 and 2019. Samples were then analyzed for seven standard water quality parameters (i.e., pH, Electric Conductivity (EC), Turbidity, Chloride, Calcium, Magnesium, and Nitrate). Patient data for waterborne diseases were also collected for the years 2012 and 2019 to relate the impact of groundwater quality on human health. Landsat satellite images were classified for the years 2012 and 2019 to observe Landuse/landcover dynamics concerning groundwater quality. Results manifested a decrease in groundwater quality for the year 2019 compared to 2012 and were more highlighted in highly populated areas. The nitrate concentration level was found high in the vicinity of agricultural areas due to the excessive use of nitrogenous fertilizers and pesticides, and thus the methemoglobinemia patients ratio increased by 14% (48- 62% for the year 2012 and 2019, respectively). Besides, Urinary Tract Infections, Peptic Ulcer, and Dental Caries diseases increased due to the high calcium and magnesium concentration. The overall results indicate that anthropogenic activities were the main driver of Spatio-temporal variability in groundwater quality of the study area. The study could help district health administration understand groundwater quality trends, make appropriate site-specific policies, and formulate future health regulations.
The Ontology-Based Modeling and Evolution of Digital Twin for Assembly Workshop
Authors: Bao Qiangwei , Zhao Gang , Yu Yong , Dai Sheng , Wang Wei
Published: March 2021

Digital twin (DT) technology has been entrusted with the tasks of modeling and monitoring of the product, process and production system. Moreover, the development of semantic modeling and digital perception provides the feasibility for the application of DT in the manufacturing industry. However, the application of DT technology in assembly workshop modeling and management is immature for the discreteness of assembly process, diversity of assembly resource and complexity of dataflow in the assembly task execution. A method of ontology-based modeling and evolution of DT for the assembly workshop is proposed to deal with this situation. Firstly, the ontology-based modeling method is given for the assembly resource and process. By instantiating in the ontology, resources and processes can be involved in the modeling and evolution of the DT workshop. Secondly, the DT assembly workshop framework is introduced with the detailed discussions of dataflow mapping, DT evolution, storage and tracing of historical data generated during the operation of the workshop. In addition, a case study is illustrated to show the entire process of construction and evolution of DT modeled on an experimental field, indicating the feasibility and validity of the method proposed.
The Effect of Tool Pin Size and Taper Angle on the Thermal Process and Plastic Material Flow in Friction Stir Welding
Authors: Chen Jie , Shi Lei , Wu Chuansong , Jiang Yuanning
Published: March 2021

Friction stir welding (FSW) tool pin, as a critical component of FSW tool, plays an important role in determining the final joint properties by affecting the heat generation, plastic material flow, welding loads and so on. However, the influence of tool pin on heat and mass transfer in FSW are not elucidated. In the present study, a validated model was adopted to quantitatively analyze the effects of pin size and taper angle on the thermal process and plastic material flow in FSW. It reveals that the torque and transverse force imposed on the pin are increased with the increase of the pin diameters (including its root diameter, its tip diameter and its size in condition of constant taper angle), while the total tool torque various a little for the tool pin diameter considered in this study. When the pin diameters increase, the viscosity of the materials near the pin is decreased, while the temperature as well as the flow velocity is increased. More plastic material near the tool could rotate around the tool with an increase of the pin diameter. The TMAZ boundary is enlarged with larger pin diameters in FSW. Particularly, the shear layer thickness of the same horizontal plane in the range of 1 mm < z < 5 mm is significantly enlarged with an increase of pin root diameters. However, the shear layer thickness of the same horizontal plane in the region of z < 5 mm is increased when using a larger pin tip diameter. In addition, maximum width of TMAZ boundary at the top surface of workpiece was not affected by pin diameters. The model is validated by experimental results. It lays solid foundation for optimizing the tool pin size and taper angle in FSW.
Impacts of ENSO On The Seasonal Transition From Summer to Winter in East Asia
Authors: Kim Sunyong , Kug Jong-Seong
Published: March 2021

The El Niño-Southern Oscillation (ENSO) has seasonally distinct impacts on the East Asian climate so that its seasonal transition depends on the phases of El Niño and La Niña. Here, we investigate the seasonal transition of surface temperature in East Asia from boreal summer to winter based on the warm/cold ENSO developing phases. During La Niña years, from summer to winter the continuous temperature drop in East Asia tends to be faster than that during El Niño, indicating a latter start and earlier termination of fall. This different seasonal transition in East Asia according to phases of ENSO is mostly explained by atmospheric responses to the seasonally-dependent tropical/subtropical precipitation forcings in ENSO developing phases. The anomalous positive precipitation in the subtropical North Pacific exists only in September and leads to the subtropical cyclonic flow during El Niño years. The resultant northerly anomalies on the left side of subtropical cyclone are favorable for transporting cold advection towards East Asia. However, the positive subtropical precipitation disappears and teleconnection to East Asia is strongly controlled by the negative precipitation anomalies in the western North Pacific, modulating the anticyclonic anomalies in East Asia during the early winter (November). Therefore, these seasonally sharp precipitation changes associated with ENSO evolution induce distinctive teleconnection changes from northerly (summer) to southerly (winter) anomalies, which eventually affect seasonal transition in East Asia. Also, the Coupled Model Intercomparison Project Phase 5 models reasonably simulate the relatively rapid temperature transition in East Asia during La Niña years, supporting the observational argument.
Endothelial progenitor cells overexpressed with omentin-1 enhance the inhibition of neointimal hyperplasia via anti-inflammation
Authors: Xiang Yuan , Zhou Zheng-Shi , Li Chuan-Chang , Luo Ying , Zhou Ji Peng
Published: March 2021

Background

Endothelial progenitor cells (EPCs) play an important role in vascular repair. However, the functions of EPCs are obviously weakened in inflammatory microenvironment during restenosis. Therefore, we investigated whether omentin-1, an anti-inflammatory factor, can reduce neointima formation after carotid artery injury (CAI) in rats via improving EPCs functions damaged by inflammation and the underlying mechanisms.
Methods

Rats bone marrow-derived EPCs were isolated and cultured. EPCs were transfected with adenovirus vectors expressing human omentin-1 or green fluorescent protein (GFP). Rats received 2×106 EPCs with expressing omentin-1 or GFP by tail vein injection directly after CAI and again 24 h later. Hematoxylin-eosin staining and immunohistochemistry were used for analyzing neointimal hyperplasia. Besides, EPCs were treated with omentin-1 and tumor necrosis factor-α (TNF-α) in order to explore the underlying mechanism.
Results

Omentin-1 could significantly promote EPCs proliferation and tube formation, as well as inhibit apoptosis. EPCs overexpressed with omentin-1 using adenovirus vectors could extremely reduce the neointimal hyperplasia after CAI in rats. Besides, TNF-α could notably induce EPCs dysfunction including reduced proliferation, migration tube formation and increased apoptosis, which can be remarkably attenuated by omentin-1 via inhibiting of p38/CREB pathway. Besides, p38 agonist (anisomycin) could significantly reverse the protective effects of omentin-1 which attenuated the injury effects of TNF-α on EPCs.
Conclusions

EPCs overexpressed with omentin-1 can significantly reduce neointima formation after arterial injury by enhancing the functions of EPCs via inhibiting the p38/CREB pathway. Our results indicate that gene modified EPCs with omentin-1 may be an alternative strategy for the treatment of restenosis.
Application of Bone Collagen Matrix combined with HUC-MSCs for Alveolar Process Cleft in a Rabbit Model
Authors: Sun Xue-Cheng , Wang Hu , Zhang Dan , Li Jian-Hui , Yin Li-Qiang , Yan Yu-Fang , Ma Xu , Xia Hong-Fei
Published: March 2021

Background: Most materials used clinically for filling severe bone defects lack the ability to induce bone regeneration or low bone conversion rate, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (HUC-MSCs) have good osteoinduction. The mechanism of heterogeneous bone collagen matrix combined with HUC-MSCs in repairing bone defects of alveolar process cleft is still unclear.Methods: Here, a rabbit alveolar process cleft model was established to evaluate the repair effect and molecular mechanism of bone collagen matrix and its combination with HUC-MSCs on critical-sized bone defects in the alveolar process. We randomly divided 48 young Japanese white rabbits (JWRs) into normal, control, material and MSCs groups. The alveolar process cleft model was established by removing the bone of equal volume at the left maxillary. Bone collagen matrix combined with HUC-MSCs that were then implanted in the defect area. X-ray analysis and blood analysis were analyzed 3 months after surgery. Skull tissues were collected for micro-focus computerized tomography (micro-CT) analysis and histochemical staining. The above experiment was repeated 6 months after surgery.Results: the main findingsResults: It was found that bone collagen matrix and HUC-MSCs showed good biocompatibility. Heterogeneous bone collagen matrix combined with HUC-MSCs significantly enhanced osteoinduction and osteoconduction. Conclusions: This experiment provides a new method for repairing alveolar process cleft.Trial registration: Not applicable.
Modeling the occurrence of unsafe behaviors based on dimensions of safety climate and organizational leadership style in oil platforms using fuzzy logic approach
Authors: Yarandi Mohsen Sadeghi , Rastegarzadeh Ehsan , Soltanzadeh Ahmad , Karimi Ali , Panahi Sevda
Published: March 2021

Background: Offshore oil and gas platforms have a high potential for major accidents due to sensitive operational conditions. Safety climate and leadership style have been identified as two key factors in the occurrence of unsafe behaviors. This study aimed to modeling the occurrence of unsafe behaviors based on dimensions of safety climate and organizational leadership style in oil platforms using fuzzy logic approach.Methods: This cross-sectional and modeling study was conducted in 2019 among five oil platforms located in the Persian Gulf. The sample size was 291 employees. To measure organizational leadership style and safety climate, multifactor leadership and standard occupational safety climate questionnaires were used, respectively. To determine unsafe behaviors, a checklist of unsafe acts was used. Data analysis was performed using one-way ANOVA and Pearson correlation coefficients in SPSS version 25. Fuzzy logarithmic model and MATLAB software were used for modeling.Results: There was a significant inverse relationship between transformational and transactional leadership style and the occurrence of unsafe behaviors. Moreover, finding revealed that there was a significant correlation between the dimensions of safety of workplace and the neglecting dangers and the occurrence of unsafe behaviors (P-value< 0.05). The results of the fuzzy logarithmic model also showed that mentioned parameters are important risk factors for predicting the occurrence of unsafe behaviors in oil platforms.Conclusion: Findings revealed that transformational and transactional leadership styles, safety of workplace and neglecting dangers in oil platforms are among important factors in the occurrence of unsafe behaviors. Using fuzzy logarithmic models can also be an effective way to predict and control the occurrence of unsafe behaviors in oil platforms.
Effectiveness of prospective audit-and-feedback intervention in promoting appropriate third-generation cephalosporin use at a tertiary public hospital in Malaysia
Authors: Tan Rou Wei , Thong Kah Shuen , Chang Chee Tao , Cheng Joo Thye , Chan Huan Keat , Cheah Meng Fei
Published: March 2021

Background: Inappropriate use of broad-spectrum antibiotics accelerates the development of drug resistance in nosocomial pathogens. In Malaysia, the National Antimicrobial Guidelines (NAG), along with the feedback from antimicrobial stewardship (AMS) teams, serves as an important guide for antibiotic use in hospitals. Objectives: This study aimed to determine the effectiveness of a prospective audit-and-feedback intervention in promoting the appropriate prescribing of third-generation cephalosporins and timely culture and sensitivity (C&S) testing in patients admitted to a neurosurgical ward. Method: In the pre-intervention phase, a ward pharmacist examined medical records of the patients receiving treatment with third-generation cephalosporins. The use of a cephalosporin was deemed to be appropriate only if it was in line with either the NAG or the recommendations made by the AMS team. The laboratory reports were also checked to see if the C&S testing was performed right before the first dose of a cephalosporin was given. The findings were subsequently presented and discussed in a 2-hour feedback session. The post-intervention audit was performed in the same manner as in the pre-intervention phase. Results: Seventy cases were studied in the pre- and post-intervention phases each. The proportion of cases with appropriate use of third-generation cephalosporin increased significantly from 77.1% (54/70) to 95.8% (67/70) following the intervention (p=0.001). The proportion of cases with a C&S test performed timely also increased significantly from 38.6% (27/70) to 58.6% (41/70) (p=0.018). Conclusion: The prospective audit-and-feedback intervention was effective in improving the appropriateness of the prescribing of third-generation cephalosporins and timely culture and sensitivity testing, indicating the antimicrobial stewardship strategy had produced a positive outcome.
CRISPR/Cas9 mediated T7 RNA polymerase gene knock-in in E. coli BW25113 makes T7 expression system work efficiently
Authors: Ye Changchuan , Chen Xi , Yang Mengjie , Zeng Xiangfang , Qiao Shiyan
Published: March 2021

T7 Expression System is a common method of ensuring tight control and high-level induced expression. However, this system can only work in some bacterial strains in which the T7 RNA Polymerase gene resides in the chromosome. In this study, we successfully introduced a chromosomal copy of the T7 RNA Polymerase gene under control of the lacUV5 promoter into Escherichia coli BW25113. The T7 Expression System worked efficiently in this mutant strain named BW25113-T7. We demonstrated that this mutant strain could satisfactorily produce 5-Aminolevulinic Acid via C5 pathway. A final study was designed to enhance the controllability of T7 Expression System in this mutant strain by constructing a T7 Promoter Variants Library. These efforts advanced E. coli BW25113-T7 to be a practical host for future metabolic engineering efforts.
Piezoelectric Properties of Zinc Oxide/Iron Oxide filled Polyvinylidene fluoride Nanocomposite Fibers
Authors: AlAhzm Abdulrahman Mohmmed , Alejli Maan Omar , Ponnamma Deepalekshmi , Elgawady Yara , Al-Maadeed Mariam Al Ali
Published: March 2021

Piezoelectric nanogenerators (PENG) with flexible and simple design have pronounced significance in fabricating sustainable devices for self-powering electronics. This study demonstrates the fabrication of electrospun nanocomposite fibers from polyvinylidene fluoride (PVDF) filled Zinc Oxide (ZnO)/Iron Oxide (FeO) nanomaterials. The nanocomposite fiber based flexible PENG showed piezoelectric output voltage of 5.9 V when 3 wt.% of ZnO/FeO hybrid nanomaterial was introduced, which was 29.5 times higher than the neat PVDF. No apparent decline in output voltage was observed for almost 2000 seconds attributed to the outstanding durability. This higher piezoelectric output performance is correlated with the β-phase transformation studies from the Fourier transformation infrared spectroscopy and the crystallinity studies from the differential scanning calorimetry. Both these studies show respective enhancement of 3.79 and 2.16 % in the β-phase crystallinity values of PVDF-ZnO/FeO 3 wt.% composite. Higher dielectric constant value obtained for the same composite (3 times higher than the neat PVDF) confirms the increased energy storage efficiency as well. Thus the proposed soft and flexible PENG is a promising mechanical energy harvester, and its good dielectric properties reveals the ability to use this material as good power sources for wearable and flexible electronic devices.
Focal Unspecific Bone Uptake on [18F]-psma-1007 Pet: A Multicenter Retrospective Evaluation of the Distribution, Frequency, and Quantitative Parameters of a Potential Pitfall in Prostate Cancer Imaging
Authors: Grünig Hannes , Maurer Alexander , Thali Yannick , Kovacs Zsofia , Strobel Klaus , Burger Irene A. , Müller Joachim
Published: March 2021

PurposeImproved logistics and availability led to a rapid increase in the use of [18F]-PSMA-1007 for prostate cancer PET imaging. Initial data suggests increased uptake in benign lesions compared to [68Ga]-PSMA-11, and clinical observations found increased unspecific bone uptake (UBU). We therefore investigate the frequency and characteristics of UBU in [18F]-PSMA-1007 PET.MethodsWe retrospectively analyzed [18F]-PSMA-1007 PET scans from four centers for the presence of UBU, defined as a focal mild-to-moderate uptake (SUVmax < 10.0) not obviously related to a benign or malignant cause. If present, up to three leading UBUs were quantified (SUVmax), localized, and correlated to clinical parameters, such as age, PSA, injected dose, Gleason-score, tumor size (T1–T4), and type of PET scanner (analog vs. digital). Additionally, clinical and imaging follow-up results and therapeutic impact were evaluated.ResultsUBUs were identified in 179 out of 348 patients (65.2%). The most frequent localizations were ribs (57.5%) and pelvis (24.8%). The frequency of UBUs was not associated with PSA, Gleason-score, tumor size, age, or the injected [18F]-PSMA-1007 dose. UBUs were significantly more frequent in images obtained with digital scanners (70.1%) than analog scanners (p=.0001). In 80 out of 179 patients (44.7%), the interpretation of UBUs was critical for therapeutic management and therefore considered clinically relevant. For 65 UBUs, follow-ups were available: three biopsies, three radiotherapies with PSA follow-up, and 59 cases with imaging. After follow-up UBUs were still considered unclear in 28 of 65 patients (43.1%), benign in 28 (43.1%), and malignant in nine (13.8%) patients.ConclusionUBUs occur in two-thirds of patients imaged with [18F]-PSMA-1007 PET/CT and are significantly more frequent on digital PET scanners than analog scanners. UBUs should be interpreted carefully to avoid over-staging.
The influence of exocyclic lone pairs on the bonding and geometry of type A mesoionic rings
Authors: Ramsden Christopher Antony , Oziminski Wojciech Piotr
Published: March 2021

Based on structures determined by X-ray crystallography, ab initio MP2 calculations on type A mesoionic rings give geometries in good agreement with observed values. A study of four mesoionic ring systems, each with exocyclic oxygen, nitrogen or carbon groups, shows that the presence and configuration of exocyclic lone pairs significantly influences the geometry and configurational preference. Using a localised bond model, these effects are rationalised in terms of an anomeric interaction of lone pairs with the antibonding orbitals of adjacent σ bonds. In agreement with experiment, similar effects are calculated for pyran-2-imines.
Predictive Evaluation of Quantitative Spatial Profiling of the Tumor Microenvironment by Multiplex Immunofluorescence in Recurrent Glioblastoma Treated with PD-1 Inhibitors
Authors: Cieremans David Alexander , Kim Ju Young , Valencia Ariana , Santos Justin , Bordeaux Jennifer , Tran Thai , Vaupel Christine , Dakappagari Naveen , Tangri Shabnam , Iwamoto Fabio
Published: March 2021

Introduction: PD-1 inhibitors have shown limited efficacy in glioblastoma due to microenvironment immunosuppression and low tumor mutational burden. In GBM, PD-L1 expression is not a predictive marker for response to PD-1 or PD-L1 inhibitors. Multiplex immunostaining panel technology allows for detailed analyses of tumor microenvironment cells and their interaction. Methods: Pre-treatment tumor tissue was collected retrospectively from 27 patients at Columbia University Irving Medical Center with primary glioblastoma who were diagnosed within the past three years, had surgery here, and were either treated with SOC therapy (n= 8) or PD-1 inhibitors at recurrence (n= 19). Multiplex immunofluorescence panels included 1) CD11b/IDO1/HLADR/GFAP, 2) PD1/PD-L1/GFAP, and 3) CD4/CD8/CD25/FoxP3/Ki67/GFAP. Results: Multiplex immunofluorescence panels did not show any correlation with outcomes in patients treated with SOC therapy. Among the 19 patients treated with PD-1 inhibitors, those with more HLA-DR positive cells had worse outcomes (p= 0.02). PD-L1 expression on tumor cells was not predictive of outcomes. There was a correlation trend between PD-1/PD-L1 interaction score (p= 0.08) and outcomes. PTEN loss was correlated with higher Ki67 expression in both tumor cells (p= 0.05) and non-tumors cells (p= 0.03); however, this was not found in Ki67 in CD4+ cells, CD8+ cells, or CD4+CD8+ cells combined. Tumor-associated macrophages, myeloid-derived suppressor cells, CD8+ cells, and CD4+ cells were not significant predictive markers for outcome. Conclusion: Quantitative spatial profiling by multiplex immunofluorescence is feasible in FFPE glioblastoma tissue. More refined and extensive quantitative and spatial microenvironment analyses may allow for the development of biomarkers for immunotherapy in GBM.
Highly pleiotropic variants of human traits are enriched in genomic regions with strong background selection
Authors: Novo Irene , López-Cortegano Eugenio , Caballero Armando
Published: March 2021

Recent studies have shown the ubiquity of pleiotropy for variants affecting human complex traits. These studies also show that rare variants tend to be less pleiotropic than common ones, suggesting that purifying natural selection acts against highly pleiotropic variants of large effect. Here we investigate the mean frequency, effect size and recombination rate associated with pleiotropic variants, and focus particularly on whether highly pleiotropic variants are enriched in regions with putative strong background selection. We evaluate variants for 41 human traits using data from the NHGRI-EBI GWAS Catalog, as well as data from other three studies. Our results show that variants involving a higher degree of pleiotropy tend to be more common, have larger mean effect sizes, and contribute more to heritability than variants with a lower degree of pleiotropy. Using data from four different studies, we show that more pleiotropic variants are enriched in genome regions with stronger background selection than less pleiotropic variants. Thus, we conclude that even though highly pleiotropic variants found so far have larger average effect sizes and frequencies than less pleiotropic ones, they are likely to be subjected to stronger background selection.
How Epithelial Cells Reorient in Response to Cyclic Stretching
Authors: Lien Jui-Chien , Wang Yu-Li
Published: March 2021

Many types of adherent cells are known to reorient upon uniaxial cyclic stretching perpendicularly to the direction of stretching to facilitate such important events as wound healing, angiogenesis, and morphogenesis. While this phenomenon has been documented for decades, the underlying mechanism remains poorly understood. Using an on-stage stretching device that allowed programmable stretching with synchronized imaging, we found that the reorientation of NRK epithelial cells took place primarily during the relaxation phase when cells underwent rapid global retraction followed by extension transverse to the direction of stretching. Inhibition of myosin II caused cells to orient along the direction of stretching, whereas disassembly of microtubules enhanced transverse reorientation. Our results indicate distinct roles of stretching and relaxation in cell reorientation and implicate a role of myosin II-dependent contraction via a microtubule-modulated mechanism. The importance of relaxation phase also explains the difference between the responses to cyclic and static stretching.
Philosophical foundations of research, and the case of the epistemic well, in a least developed nation.
Authors: Chakravartty Avaniendra
Published: March 2021

Inspired by an ancient tale of kupamanduka (Well Frog) that never ventures out of the well and lives to think the well as the world and see nothing beyond it. This article conceptualises the ‘Epistemic Well’ and the native epistemic community that dwells in it remains within the confines of the epistemic well. Philosophical foundations are the core of each individual researcher and all research questions, hypothesis, methodologies, recommendations are shaped by it. Particular modes of governance instil particular modes of philosophies. Under neoliberalism the prevailing philosophical foundations have been identified as, detached, decontextualized, depoliticized, dehistoricized, dissocialized, deproblematized, reductionist/individualist, instrumentalization, separation, marketisation, positivist and objectivist. The combination of these attributes builds the epistemic well. The epistemic well of research is not absolute and is not meant to provide quantification data. The epistemic well is a reflexive tool that can be used to evaluate a research especially for a nation like Nepal. The research funds or the benefits that ensues a researcher are important criteria for research. When thinking of a research topic, the primary determining factor becomes the amount of fund available the gaze of a native researcher can overlook various conditions and processes. The epistemic community that is formed by these researchers maintain and sustain particular epistemes. The NCD’s were selected primarily to stick to a cohort but this does not limit the scope and purpose of the epistemic well.
Electrically Controllable Active Plasmonic Directional Coupler of Terahertz Signal based on a Periodical Dual Grating Gate Graphene Structure
Authors: Morozov Mikhail Yu. , Popov Vyacheslav V. , Fateev Denis V.
Published: March 2021

We propose a concept of an electrically controllable plasmonic directional coupler of terahertz signal based on a periodical structure with an active (with inversion of the population of free charge carriers) graphene with a dual grating gate and numerically calculate its characteristics. Proposed concept of plasmon excitation by using the grating gate offers highly effective coupling of incident electromagnetic wave to plasmons as compared with the excitation of plasmons by a single diffraction element. The coefficient which characterizes the efficiency of transformation of the electromagnetic wave into the propagating plasmon has been calculated. This transformation coefficient substantially exceeds the unity (exceeding 6 in value) due to amplification of plasmons in the studied structure by using pumped active graphene. We have shown that applying different dc voltages to different subgratings of the dual grating gate allows for exciting the surface plasmon in graphene, which can propagate along or opposite the direction of the structure periodicity, or can be a standing plasma wave for the same frequency of the incident terahertz wave. The coefficient of unidirectionality, which is the ratio of the plasmon power flux propagating along (opposite) the direction of the structure periodicity to the sum of the absolute values of plasmon power fluxes propagating in both directions, could reach up to 80 percent. Two different methods of the plasmon propagation direction switching are studied and possible application of the found effects are suggested.
­­Duloxetine for the prevention of oxaliplatin induced peripheral neuropathy: a randomized, placebo-controlled, double-blind clinical trial
Authors: Aghili Mahdi , Darzikolaee Nima Mousavi , Babaei Mohammad , Ghalehtaki Reza , Farhan Farshid , Razavi Seyede Zahra Emami , Rezaei Saeed , Esmati Ebrahim , Samiei Farhad , Azadvari Mohadese , Farazmand Borna , Amiri Ardavan
Published: March 2021

IntroductionPeripheral neuropathy is a dose-limiting adverse effect of oxaliplatin. The aim of this study was to evaluate the efficacy and safety of duloxetine in the prevention of oxaliplatin-induced peripheral neuropathy (OIPN).MethodCancer patients receiving oxaliplatin chemotherapy were randomized into two arms. Duloxetine 60 mg capsule was given in the first 14 days of each chemotherapy cycle to one arm and placebo was similarly given to another arm. We compared the two arms based on the incidence of neuropathy and the results of the nerve conduction study.ResultsThirty two patients were randomized to duloxetine and placebo arms. Most of the patients had rectal cancer (90.6%). Compared with the placebo arm, patients in the duloxetine arm had a lower percentage of chemotherapy cycles (mean) in which they reported distal paresthesia (84% vs. 51%, P = 0.01) and throat discomfort (69% vs. 37%, P = 0.01). There was no difference in the percentage of cycles in which patients reported cold-induced dysesthesia. Highest grade of neuropathy in each cycle was not significantly different between the two arms. Six weeks after the last cycle of chemotherapy, nerve conduction velocity was significantly higher in duloxetine arm compared to the placebo arm in the deep peroneal nerve and tibial nerve. Duloxetine was safe and well-tolerated.ConclusionIn spite of small sample size, results of this study suggests potential efficacy of duloxetine in the prevention of OIPN, as indicated by objective measures of neurotoxicity and some patient-reported symptoms.
A Study of Arabidopsis Cold Stress Tolerance Improvement via AthHOS1-Targeting HOS1-AmiRNA Approach
Authors: Karimi Marzieh , Shiran Behrouz , Rabei Mohammad , Fallahi Hossein , Đeri Bojana Banović
Published: March 2021

The authors have requested that this preprint be removed from Research Square.
C-STICH: Cerclage Suture Type for an Insufficient Cervix and its Effect on Health Outcomes. A Multicentre Randomised Controlled Trial.
Authors: Israfil-Bayli Fidan , Morton Victoria Ann Hodgetts , Hewitt Catherine A , Ewer Andrew K , Grey Jim , Norman Jane , Lees Christoph , Simpson Nigel A B , Shennan Andrew , Hughes Max , Daniels Jane , Brocklehurst Peter , Morris R.Katie , Middleton Lee , Toozs-Hobson Philip
Published: March 2021

Background: Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage the procedure can be performed using either a monofilament (single-stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. Methods: A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either: a history of three or more previous mid trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women; who have taken part in C-STICH previously, aged less than 18 years old at the time of presentation, requiring a rescue cerclage, who are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life) and secondary outcomes include the core outcome set for preterm birth trials.Discussion: Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates.Trial registration: ISRCTN 15373349 registered before recruitment 03/12/2014 prior to first recruit.
CASP9 As a Prognostic Biomarker and Promising Drug Target Plays a Pivotal Role in Inflammatory Breast Cancer
Authors: Zhang Mingdi , Wu Kejin , Wang Maoli , Bai Fang , Chen Hongliang
Published: March 2021

Background : Inflammatory breast cancer (IBC) is one of the most rare and aggressive subtype of primary breast cancer (BC). Our study aimed to explore hub genes related to the pathogenesis of IBC, which could be considered as novel molecular biomarkers for IBC diagnosis and prognosis. Material and Methods: Two datasets from gene expression omnibus database (GEO) were selected. Enrichment analysis and protein-protein interaction (PPI) network for the DEGs were performed. We analyzed the prognostic values of hub genes in the Kaplan–Meier Plotter. Connectivity Map (CMap) and Comparative Toxicogenomics Database (CTD) was used to find candidate small molecules capable to reverse the gene status of IBC. Results : 157 DEGs were selected in total. We constructed the PPI network with 154 nodes interconnected by 128 interactions. KEGG pathway analysis indicated that the DEGs were enriched in apoptosis, pathways in cancer and insulin signaling pathway. PTEN, PSMF1, PSMC6, AURKB, FZR1, CASP9, CASP6, CASP8, BAD, AKR7A2, ZNF24, SSX2IP, SIGLEC1, MS4A4A and VSIG4 were selected as hub genes based on the high degree of connectivity. Six hub genes (PSMC6, AURKB, CASP9, BAD, ZNF24 and SSX2IP) that were significantly associated with the prognosis of breast cancer. The expression of CASP9 protein was associated with prognosis and immune cells infiltration of breast cance. CASP9- naringenin (NGE) is expected to be the most promising candidate gene-compound interaction for the treatment of IBC. Conclusion : Taken together, CASP9 can be used as a prognostic biomarker and a novel therapeutic target in IBC.
Essential norms and Schatten(-Herz) classes of integration operators from Bergman spaces to Hardy spaces
Authors: Chen Jiale , Pau Jordi , Wang Maofa
Published: March 2021

In this paper, we completely characterize the compactness of the Volterra type integration operators Jb acting from weighted Bergman spaces Apa to Hardy spaces Hq for all 0 < p; q < 1. Furthermore, we give some estimates for the essential norms of Jb : Apa -> Hq in the case 0 < p < q < 1. We finally describe the membership in the Schatten(-Herz) class of the Volterra type integration operators.
Solving the mystery of the walk-off soliton
Authors: Zitelli Mario , Mangini Fabio , Ferraro Mario , Sidelnikov Oleg , Wabnitz Stefan
Published: March 2021

Pioneering works on multimode fiber transmission [1,2], dated 40 years ago, predicted the existence of multimode solitons, providing conditions for the temporal trapping of the input optical modes to form a spatiotemporal soliton [3-5]. Only recently [6-8], multimode solitons were experimentally investigated in graded-index multimode fibers (GRIN), unveiling the complexity of a new, uncharted field. In our work, we experimentally and numerically investigated the propagation of ultrashort pulses over long distances of GRIN fiber. We discovered a new class of spatiotemporal solitons with surprising properties: basically single-mode, they cannot be described by the variational theory; their pulsewidth and energy are independent of the input pulse duration, and appear to depend only on the fiber dispersive parameters and, therefore, the wavelength. The new solitons are promising for the delivery of high-energy laser beams, for high-power spatiotemporal mode-locked multimode fiber lasers, and for high-bit rate
multimode fiber networks.
Long-Term Monitoring of SARS-COV-2 RNA in Wastewater in Brazil: A More Responsive and Economical Approach
Authors: Claro Ieda Carolina , Cabral Aline , Augusto Matheus , Duran Adriana , Graciosa Melissa Cristina , Fonseca Fernando Luiz , Speranca Marcia Aparecida , Bueno Rodrigo
Published: March 2021

SARS-CoV-2, the novel Coronavirus, was first detected in Wuhan, China, in December 2019, and has since spread rapidly, causing millions of deaths worldwide. As in most countries of the world, in Brazil, the consequences of the COVID-19 pandemic have been catastrophic. The increasing of deaths and the decrease of available beds in the hospitals, especially in 2021, have disturbed the health authorities. Several studies have reported the fecal shedding of SARS-CoV-2 RNA titers from infected symptomatic and asymptomatic individuals. Therefore, the quantification of SARS-CoV-2 in wastewater can be used to track the virus spread in a population via Wastewater-based Epidemiology (WBE). In this study, samples of untreated wastewater were collected weekly between June 9th, 2020 and March 17th, 2021 (41 weeks) at five sampling sites in the ABC Region, São Paulo, Brazil. This long-term monitoring was performed to evaluate the SARS-CoV-2 occurrence in the sewerage system. SARS-CoV-2 RNA titers were detected throughout the period. The viral RNA concentration ranged from 2.7 to 7.1 log10 genome copies.L− 1, with peaks in the last weeks of monitoring. Furthermore, we observed a positive correlation between the viral load in wastewater samples and the epidemiological/clinical data, with the former preceding the latter by approximately two weeks. The COVID-19 prevalence for each sampling site was estimated using the viral load observed in wastewater and other parameters, via Monte-Carlo simulation. The mean predicted prevalence ranged 0.05 to 0.38%, slightly higher than reported (0.016 ± 0.005%) in the ABC Region for the same period. These results highlight the viability of the WBE approach for COVID-19 infection monitoring in the largest urban agglomeration in South America. Environmental surveillance can be especially useful for health agencies and public decision-makers in predicting SARS-CoV-2 outbreaks, as well as in local tracing of infection clusters.
Controlling the pandemic during the SARS-CoV-2 vaccination rollout: a modeling study
Authors: Viana João , Dorp Christiaan van , Nunes Ana , Gomes Manuel , Boven Michiel van , Kretzschmar Mirjam , Veldhoen Marc , Rozhnova Ganna
Published: March 2021

There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevalence data, hospital admissions, and projected vaccination coverage for Portugal. Our analyses suggest that the pressing need to restart socioeconomic activities could lead to new pandemic waves, and that substantial control efforts prove necessary throughout 2021. Using knowledge on control measures introduced in 2020, we anticipate that relaxing measures completely or to the extent as in autumn 2020 could launch a wave starting in April 2021. Additional waves could be prevented altogether if measures are relaxed as in summer 2020 or in a step-wise manner throughout 2021. We discuss at which point control of COVID-19 would be achieved for each scenario.