bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of different load during eccentric training with blood flow restriction on muscle size, strength, and motor performance: a randomized controlled trial
Authors: Biral Taíse Mendes , Lemos Leonardo Kesrouani , Cavina Allysiê Priscilla de Souza , Cordeiro Anne Jhuly Cardoso , Junior Eduardo Pizzo , Filho Carlos Alberto Toledo Teixeira , Vendrame Julia Waszczuk , Pastre Carlos Marcelo , Vanderlei Franciele Marques
Published: October 2022

Background
studies on eccentric training with blood flow restriction (BFR) still has gaps, especially in strength and muscle hypertrophy. Therefore, the objective of the study was analyzed and compare the effects of six weeks of eccentric training of knee extensors at different load associated or not with BFR on strength, hypertrophy, and motor performance of knee extensors.
Methods
61 men performed six weeks of quadriceps muscle eccentric training in isokinetic dynamometer were randomized into four groups: high-load eccentric training with BFR (HLET-BFR), low-load eccentric training with BFR (LLET-BFR), high-load eccentric training (HLET) and low-load eccentric training (LLET). The strength, muscle structure and motor performance outcomes were evaluated at baseline, after 3 and 6 weeks of training.
Results
for eccentric peak torque in the first three weeks, HLET was superior to LLET, but similar to LLET-BFR. In the final three weeks, superiority was observed in relation to LLET-BFR; however, there was no difference in relation to HIET-BFR. For the outcomes isometric and concentric peak torque, muscle structure and motor performance, there were no differences between groups.
Conclusion
eccentric training led to strengthening of knee extensors and improved motor performance, but without altering the muscle structure. LLET-BFR promoted gains similar to HLET in the first three weeks of training.
Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis
Authors: Peng Cheng , Zhang Yanxiu , Lang Xueyan , Zhang Yao
Published: October 2022

Background
Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications of diabetes and a leading cause of death in diabetic patients. Mitochondrial metabolism and immune-inflammation are key for DCM pathogenesis, but their crosstalk in DCM remains an open issue. This study explored the separate roles of mitochondrial metabolism and immune microenvironment and their crosstalk in DCM with bioinformatics.
Methods
DCM chip data (GSE4745, GSE5606, and GSE6880) were obtained from NCBI GEO, while mitochondrial gene data were downloaded from MitoCarta3.0 database. Differentially expressed genes (DEGs) were screened by GEO2R and processed for GSEA, GO and KEGG pathway analyses. Mitochondria-related DEGs (MitoDEGs) were obtained. A PPI network was constructed, and the hub MitoDEGs closely linked to DCM or heart failure(HF) were identified with CytoHubba, MCODE and CTD scores. Transcription factors and target miRNAs of the hub MitoDEGs were predicted with Cytoscape and miRWalk database, respectively, and a regulatory network was established. The immune infiltration pattern in DCM was analyzed with ImmuCellAI, while the relationship between MitoDEGs and immune infiltration abundance was investigated using Spearman method. A rat model of DCM was established to validate the expression of hub MitoDEGs and their relationship with cardiac function.
Results
MitoDEGs in DCM were significantly enriched in pathways involved in mitochondrial metabolism, immunoregulation, and collagen synthesis. Nine hub MitoDEGs closely linked to DCM or HF were obtained. Immune analysis revealed significantly increased infiltration of B cells while decreased infiltration of DCs in immune microenvironment of DCM. Spearman analysis demonstrated that the hub MitoDEGs were positively associated with the infiltration of pro-inflammatory immune cells, but negatively associated with the infiltration of anti-inflammatory or regulatory immune cells. In the animal experiment, 4 hub MitoDEGs (Pdk4, Hmgcs2, Decr1, and Ivd) showed an expression trend consistent with bioinformatics analysis result. Additionally, the up-regulation of Pdk4, Hmgcs2, Decr1 and the down-regulation of Ivd were distinctly linked to reduced cardiac function.
Conclusions
This study unraveled the interaction between mitochondrial metabolism and immune microenvironment in DCM, providing new insights into the research on potential pathogenesis of DCM and the exploration of novel targets for medical interventions.
Terminal Digit Preference and Blood Pressure Control in VA Medical Centers
Authors: O'Halloran Meghan , Hughes Ashley , Weaver Frances , Huo Zhiping , Stroupe Kevin , Tarlov Elizabeth , Kramer Holly
Published: October 2022

Background
Few studies have examined terminal digit preference (TDP) and blood pressure (BP) measurement in Veterans Affairs (VA) medical centers.
Methods
This mixed methods study examined TDP for BP measured in Veterans age 18 to 85 years with a hypertension diagnosis during a primary care visit within 8 Midwest VA medical centers from January 1, 2019, through March 1, 2020. TDP for both systolic (SBP) and diastolic blood pressures (DBP) was examined using a goodness of fit test assuming10% frequency for digits 0 through 9. Interviews were conducted with primary care clinicians from 3 VA centers to assess perceptions of BP measurement protocols.
Results
The mean age of the 98,433 Veterans (93% male) was 68.5 years (SD 12.7). Frequency of terminal digits 0 through 9 differed significantly from 10% for both SBP and DBP overall and within each VA center (P < 0.001). The most common terminal digits recorded were 0 and 8 for SBP (14.9% and 14.3%, respectively) and for DBP (17.5% and 14.3%, respectively). Interviews were conducted with 6 LPNs, 1 nurse manager and 6 primary care physicians. Most interviewees reported their clinic BP measurements were performed using semi-automated oscillometric devices but elevated readings were often confirmed by auscultatory methods. Only 5 of the 13 interviewees were aware of a clinic policy for BP measurement for their VA center.
Conclusions
Significant TDP exists for BP measurement in these eight VA centers indicating measurement bias. Future studies should examine strategies for improving BP measurement accuracyto optimize diagnosis and treatment.
Cyclic phosphatidic acid is produced by GDE7 in the ER lumen as a lysophospholipid mediator
Authors: Kitakaze Keisuke , Ali Hanif , Kimoto Raiki , Takenouchi Yasuhiro , Ishimaru Hironobu , Yamashita Atsushi , Ueda Natsuo , Tanaka Tamotsu , Okamoto Yasuo , Tsuboi Kazuhito
Published: October 2022

Cyclic phosphatidic acid (cPA) is a lipid mediator, which regulates adipogenesis and glucose homeostasis by suppressing nuclear peroxisome proliferator-activated receptor γ (PPARγ). Glycerophosphodiesterase 7 (GDE7) is a Ca2+-dependent lysophospholipase D that localizes in the endoplasmic reticulum. Although mouse GDE7 catalyzes cPA production in a cell-free system, it is unknown whether GDE7 generates cPA in living cells. Here, we demonstrate that human GDE7 possesses cPA-producing activity in living cells as well as in a cell-free system. Furthermore, the active site of human GDE7 is directed towards the luminal side of the endoplasmic reticulum. Mutagenesis revealed that amino acid residues F227 and Y238 are important for catalytic activity. GDE7 deficiency derepresses the PPARγ pathway in human mammary MCF-7 cells, suggesting that cPA functions as an intracellular lipid mediator. These findings lead to a better understanding of the biological role of GDE7 and its product, cPA.
A hybrid WSN localization algorithm based on Range-free and TOA positioning method
Authors: Farzadi Maryam , Mohitpour Maryam
Published: October 2022

In most applications of wireless sensor networks, the location of every node within the network is needed for network function. Hence, the plan of node location systems for sensor networks ought to be based on sensor network utilization scenarios so these components make node’s localization in wireless sensor networks a challenging problem. Node’s localization in wireless sensor networks can be partitioned into two common categories of Range-free and Range-based strategies. Distance or Range-based positioning strategies precisely measure distance, while Range-free algorithms utilize communication information between nodes. Range-based procedures generally have two major downsides. First, distance information is easily affected by fading, multipath fading, noise, and environmental changes. Secondly, additional range-finding equipment is usually needed, which increases energy consumption and increases overall cost. One of the advantages of Range-free methods is that they can be implemented at a low cost and its other advantage is its strength because the interconnection information between nodes is not easily affected by environmental conditions, but its major disadvantage is the low accuracy of these methods as compared with Range-based methods. This study can be used to design and implement a WSN localization algorithm to detect abnormalities in a harsh environment such as the Nuclear Power Plant. Given that GPS performs well in outdoor environments and the equipped-GPS sensors would not be working properly in indoor environments such as inside a reactor, the WSN localization algorithm used in such applications must have at least some dependence on GPS technology. We proposed a two-stage localizing algorithm with acceptable accuracy and taking advantage of both Range-free and Range-based methods. In this way, first using the Range-free localization algorithms, the nodes with unknown locations (normal nodes) and with at least three neighboring anchors (which have a known position) will estimate their location. Then, these nodes are considered as anchor nodes for their neighbors. This approach can increase the accuracy of localizing the normal nodes and significantly reduce the number of anchor nodes (equipped-GPS sensors) needed for localization. The results show that the proposed localization algorithm's error as a tool for fault diagnostics is remarkably decreased.
Prediction and validation of melt pool dimensions and geometric distortions of additively manufactured AlSi10Mg
Authors: Ullah Rizwan , Lian Junhe , Akmal Jan , Jiaojiao Wu , Niemi Esko
Published: October 2022

A finite-element (FE) based thermomechanical modeling approach is developed in this study to provide a prediction of the mesoscale melt-pool behavior and part-scale properties for AlSi10Mg alloy. On the mesoscale, the widely adopted Goldak heat source model is used to predict melt pool formed by laser during powder bed fusion process (PBF), which, however, requires the determination of certain parameters as they control temperature distribution and hence melt pool boundaries. An approach based on a systematic parametric study is proposed in the study to determine these parameters, such as absorption coefficient and transient temperature evolution compared with the morphology of melt pool from experiments. Focusing on the part-scale domain, there is increasing demand for predicting geometric distortions and analyzing underlying residual stresses, which are highly influenced by the mesh size and initial temperature (Tinitial) setup. This study aims to propose a strategy for the correlation between the mesh size and the initial temperature to provide correct residual stresses when scaling up the model for efficiency. Results revealed that the predicted melt pool (MP) error produced by optimal Goldak function parameters is between 5–12%. On the part scale, according to the findings, the FE model is less sensitive to mesh size for distortion prediction and layer-lumping can be used to speed up simulation. The effect of large time increments, and layer lumping can be compensated by appropriate Tinitial value for AlSi10Mg.
Protective immunity against Eimeria necatrix infection in Chickens induced by immunization with the recombinant gametocyte antigen EnGAM22
Authors: Liu Dandan , Wang Feiyan , Ye Zhuang , Liu Yue , Wang Lele , Su Shijie , Hou Zhaofeng , Xu Jinjun , Tao Jianping
Published: October 2022

Macrogametocyte stage antigens reportedly provide protective immunity against coccidiosis in poultry. This study was designed to evaluate the ability of a purified recombinant protein from Eimeria necatrix gametocytes (rEnGAM22) to stimulate immunity against experimental infection with sporulated E. necatrix oocysts. The immunogenicity of the recombinant protein was studied in chickens by subcutaneous injection of 25, 50, or 75 µg of the protein with Freund’s adjuvant. Vaccine efficacy was assessed after oral parasite challenge by fecal oocyst output, lesion scores, body weight gain, serum antibodies, and cytokine responses. Chickens vaccinated with 50 µg of rEnGAM22 and challenged with sporulated E. necatrix oocysts showed reduced fecal oocyst shedding and lesion scores compared with other immunized groups and the infected control group, with the exception of the live oocyst group. There was no difference in body weight between the immunized groups and the infected control group. Furthermore, rEnGAM22 also stimulated higher production of anti-rEnGAM22 serum antibodies 7 days after secondary immunization, especially with 50 µg of rEnGAM22. Serum levels of interleukin (IL)-2, IL-4, IL10, and interferon (IFN)-γ also showed the greatest immune response from 50 µg of rEnGAM22, and IL-2 and IL-4 responses were greater than those of IL-10 and IFN-γ. These results indicated that rEnGAM22 protected against E. necatrix infection to some degree and may potentially be used to develop a recombinant subunit vaccine against coccidiosis.
Wire arc additive manufacturing of nanomodified 2024 alloy
Authors: Lopez Maider Arana , Ukar Eneko , Agirretxe Iñaki , Alvarez Pedro
Published: October 2022

Wire arc additive manufacturing (WAAM) has the objective of reducing the fabrication cost and time, as well as the material waste. This technology enables the manufacturing of complex parts near to net shape and as a result, allows greater design freedom. The use of Cold Metal Transfer (CMT) technology facilitates the welding of aluminium alloys susceptible to hot cracking due to the low heat input. One variant of this process, CMT pulsed advance (CMT-PADV), reduces this heat input even more in addition to using alternate polarity, which helps reducing porosity. In this study, nanomodified 2024 alloy is investigated for WAAM applications. Al-Cu aluminium alloys are usually considered non weldable and are highly susceptible to hot cracking. Addition of TiC nanoparticles to the wire enhances nucleation during liquid solid transformation, reducing the size of grains and segregation obtaining as a result a fine equiaxed microstructure. This completely avoids hot cracking of walls and contributed to achieve high isotropic strength after precipitation hardening treatment above 370 MPa yield stress, 450 MPa tensile strength and 4% elongation.
Design of VHF micro-EDM discharge state detection method based on energy coupling detection
Authors: Liao Lu , Zhang Yongbin , Dai Yue
Published: October 2022

Because the pulse frequency of VHF micro-EDM power supply (30MHz-300MHz) is higher than that of traditional EDM power supply and the pulse has two characteristics of positive and negative bipolar, it is impossible to use traditional discharge state detection technology to meet the requirements of VHF discharge state detection. And during the experiment, it was found that the resonant frequency of VHF pulse would migrate with the change of circuit impedance, leading to the change of pulse voltage amplitude. In order to breakthrough the limitations of traditional detection method, this paper combined the technology of EDM discharge state recognition and microwave detecting technology, based on the principle of electrode impedance change, put forward a discharge condition detection method of VHF pulse source based on energy principle of coupling detection, the method using double directional coupler and rf receiver device for detecting pulse energy, It can detect the interelectrode power of VHF pulse source with frequency range from 30MHz to 300MHz and power range below 100W, and realize accurate discharge status identification of VHF micro-EDM.
Dual inhibition of IDO1/TDO2 enhances anti-tumor immunity in platinum-resistant non-small cell lung cancer
Authors: Wu Chunjing , Spector Sydney , Theodoropoulos George , Nguyen Dan JM , Kim Emily , Garcia Ashley , Savaraj Niramol , Lim Diane C. , Paul Ankita , Feun Lynn G. , Bickerdike Michael , Wangpaichitr Medhi
Published: October 2022

Background
The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production.
Methods
Co-Culture, syngeneic, and humanize mice models were utilized. C57BL/6 mice were inoculated with either Lewis lung carcinoma mouse cells (LLC) or its platinum-resistant counterpart (LLC-CR) cells. Humanize mice were inoculated with either A (human CS cells) or ALC (human CR cells). Mice were treated with either IDO1 inhibitor or TDO2 (tryptophan 2,3-dioxygenase-2) inhibitor at 200 mg/kg P.O. once a day for 15 days; or with a new-in-class IDO1/TDO2 dual inhibitor AT-0174 at 170mg/kg P.O. once a day for 15 days with and without anti-PD1 antibody (10 mg/kg, every 3 days). Immune profiles as well as KYN and tryptophan (TRP) productions were evaluated.
Results
CR tumors exhibited a more highly immunosuppressive environment and blocked the anti-tumor immune response. IDO1-mediated KYN production from CR cells suppressed NKG2D on immune effector natural killer (NK) and CD8+ T cells and enhanced immunosuppressive regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Importantly, while the selective IDO1 inhibitor attenuated CR tumor growth, it concomitantly upregulated the TDO2 enzyme. To overcome the compensatory induction of TDO2 activity, we employed IDO1/TDO2 dual inhibitor, AT-0174. Dual inhibition of IDO1/TDO2 in CR mice suppressed tumor growth to a greater degree than IDO1 inhibition alone. Significant enhancement in NKG2D frequency on NK and CD8+ T cells and a reduction in Tregs and MDSCs were observed following AT-1074 treatment. Additionally, CR cells possessed an increased expression of PD-L1 (programmed death-ligand-1); therefore, we assessed the dual inhibition + PD1 (programmed cell death protein-1) blocking and report a profound anti-tumor growth and immunity in CR tumors which in turn extended overall survival in mice.
Conclusion
Our study reports the presence of platinum-resistant lung tumors that utilize both IDO1/TDO2 enzymes for survival and to escape immune surveillance as a consequence of KYN metabolites. We also report early in vivo data in support of the potential therapeutic efficacy of the dual IDO1/TDO2 inhibitor AT-0174 as a part of immuno-therapeutic treatment that disrupts tumor metabolism and enhances anti-tumor immunity.
Prenatal phthalate exposure and cord blood DNA methylation
Authors: Lee Jooah , Kim Jeeyoung , Zinia Sabrina Shafi , Park Jaehyun , Won Sungho , Kim Woo Jin
Published: October 2022

The indiscriminate use of phthalate-containing products in daily life can adversely affect pregnant women and their children. Phthalate can modify DNA methylation in the cord blood of infants. Therefore, we examined the association between prenatal phthalate exposure and cord blood DNA methylation in a Korean birth cohort. Phthalate levels in maternal blood during late pregnancy and cord blood were measured and DNA methylation of cord blood was measured using the Illumina HumanMethylationEPIC BeadChip kit. The association between CpG methylation and phthalate levels was analyzed using the ‘limma’ package in R, adjusting for infant sex, maternal body mass index, current maternal smoking status, and estimated leukocyte composition. We used data from 274 samples for estimating mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhxyl) phthalate (MEHHP) levels and 273 samples for estimating mono-n-butyl phthalate (MnBP) levels to determine maternal phthalate concentrations during late pregnancy. Additionally, 102 samples were analyzed for all three types of phthalates in the cord blood. The meta-analysis revealed significant associations between the CpG sites near the CHN2 and CUL3 genes and cord blood MEOHP and MnBP concentrations, respectively. However, the three maternal phthalate concentrations during late pregnancy showed no significant association with CpG sites. In conclusion, prenatal phthalate exposure is significantly associated with DNA methylation at several CpG sites.
The maximal and current accuracy of rigorous protein-ligand binding free energy calculations
Authors: Ross Gregory , Lu Chao , Scarabelli Guido , Albanese Steven , Houang Evelyne , Abel Robert , Harder Edward , Wang Lingle
Published: October 2022

It is well recognized that computational techniques can speed up the identification of hits and accelerate the optimization of such hits to lead series and development candidate molecules. A class of rigorous physics-based methods known as free energy perturbation (FEP) have emerged as the most consistently accurate relative affinity prediction tool available to support such efforts. Yet, there remains uncertainty about how accurate these techniques are and how accurate they can ever be. Here, we assemble what we believe to be the largest publicly available dataset of proteins and congeneric series of small molecules and assess the accuracy of the leading FEP workflow in predicting relative binding affinities. To ascertain the limit of achievable accuracy, we survey the reproducibility of experimental relative affinity measurements by comparing chemical series that have been assayed by two or more different techniques. We find a wide variability in experimental accuracy and a general correspondence between binding and functional assays. When the protein and ligand structures are prepared with care, we find that FEP can achieve a level of accuracy close to what we find in our experimental survey. Throughout, we highlight reliable protocols that can help maximize the accuracy of FEP in prospective studies.
Emergence of a new variant of dengue virus serotype 2 in Jazan region, southwestern Saudi Arabia
Authors: Dafalla Ommer , Abdulhaq Ahmed A. , Almutairi Hatim , Noureldin Elsiddig , Ghzwani Jaber , Mashi Omar , Shrwani Khalid J. , Hobani Yahya , Sufyani Ohood , Ayed Reem , Alamri Abdullah , Al-Mekhlafi Hesham M. , Eisa Zaki
Published: October 2022

Background: Dengue virus (DENV) infection is a global economic and public health concern, particularly in tropical and subtropical countries where it is endemic. Saudi Arabia has seen an increase in DENV infections, especially in the western and southwestern regions. This study aims to investigate the genetic variants of DENV-2 that were circulating during a serious outbreak in Jazan region in 2019.
Methods: A total of 482 serum samples collected during 2019 from Jazan region were tested with reverse transcription-polymerase chain reaction (RT-PCR) to detect and classify DENV; positive samples underwent sequencing and bioinformatics analyses.
Results: Out of 294 positive samples, type-specific RT-PCR identified 58.8% as DENV-2 but could not identify 41.2%. Based on sequencing and bioinformatics analyses, the samples tested PCR positive in the first round but PCR negative in the second round were found to be a new genetic variant of DENV-2. The newly identified DENV-2 variant showed similarities to DENV-2 sequences reported in Malaysia, Singapore, Korea and China. The results revealed a new genetic variant of DENV-2 was circulating in Jazan region that was highly prevalent and drove the serious regional outbreak in 2019.
Conclusions: The emergence of new DENV variants is a serious challenge for the dengue fever surveillance and control programmes in endemic areas. Therefore, further investigations and continuous surveillance of existing and new viral strains in the region are warranted.
Analysis of The Effect of Atmosphere-Ocean Interaction on Winter Rainfall in Iran
Authors: Ebrahimi Atefe , Rahimi Dariush , Gushchina Daria
Published: October 2022

Decades of drought and heavy rainfall are the most important climatic hazards in Iran. Anomalies and concentration of winter rainfall are effective in the challenge and water shortage. Iran's rainfall is strongly influenced by teleconnection. So that changes in SLP[1],SST[2] and changes in the level of 500 hPa have an effective role in the temporal distribution and volume of rainfall. The effect of three factors of sea level pressure, 2.5°*2.5° were evaluated from 1984 to 2018.The results indicated that decreased pressure on the Red Sea (Sudan Low) and the Pacific Ocean and increased pressure on the Atlantic and Indian oceans increase Iran's winter precipitation. In 500hpa, the results indicated that increased winter precipitation in Iran is associated with an increase in altitude of 500hPa on the Baltic Sea and the Indian Ocean and a decrease in altitude of 500hPa on the Caspian Sea, the Mediterranean Sea, the Arabian Sea and the Red Sea. In SST, the results indicated that the linkage between SST and precipitation of Iran is positive in regions such as the Arabian and Red sea, Madagascar, and north Atlantic Ocean. Therefore, any change in sea level pressure, 500hPa level and sea surface temperature leads to positive and negative anomalies on Iran's rainfall. Therefore, global warming, which leads to changes in SLP, atmospheric thickness (1000-500) and SST, has a greater impact on Iran's rainfall and leads to challenges in water resources and climate risks.

[1] -Sea level pressure
[2] -Sea surface temperature
Bioremediation of Cu with the Endophytic Bacteria Bacillus sp. and Streptomyces griseus
Authors: Özkoç Hülya Böke , Aliustaoğlu Miraç Tansu , Şentürk İlknur
Published: October 2022

In this study, the acute toxic effect of copper on organisms was determined with the use of two bacterial species Bacillus sp. and Streptomyces griseus. After 4 days of acute toxicity test, changes in metal and bacteria concentration in water, inhibition (%), bioaccumulation rate and bioconcentration factor were evaluated in terms of toxicology. Cell weights decreased and inhibition rates (%) increased with increasing metal concentrations after a certain level (10 mg L-1 Cu). With increasing metal concentrations from 5 to 25 mg L-1, % biosorption decreased from 35.94 to 20.73 for S. griseus and from 56.36 to 34.47 for Bacillus sp. The bioaccumulation quantities increased with increasing metal concentrations for both species. Bacillus sp. and S. griseus are suitable candidates for bioremediation of copper ions from the contaminated environment.
MDK Promotes Lymph Node Metastasis of Cervical Squamous Cell Carcinoma by Activating the PI3K/AKT and p38 MAPK Pathway
Authors: Fei He , Lin Qiwang , Wang Shu , Shen Min , Yu Huihui , Jin Yunfeng , Chen Tong , Jiang Hua
Published: October 2022

Purpose
The mechanism of lymph node metastasis (LNM) of cervical squamous cell carcinoma (CSCC) remains unconfirmed. Here we investigate the effects and mechanisms of midkine (MDK) on CSCC LNM.
Methods
The expression of MDK in CSCC and normal cervical tissue was analyzed. In vivo and in vitro experiments explored the effects of MDK on LNM. A retrospective study of 134 CSCC and 53 healthy controls on the relationship of serum-MDK(s-MDK) and clinicopathological characteristics was performed to evaluate the clinical value of s-MDK in CSCC LNM.
Results
MDK was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM.MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells. MDK exerted these biological effects by interacting with syndecan-1 and activating PI3K/AKT and p38 MAPK pathway. s-MDK was related to LNM, stage, tumor size, vascular invasion and muscle invasion. s-MDK combined with serum-squamous cell carcinoma antigen improved the diagnostic accuracy of CSCC LNM.
Conclusions
These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.
Frequency-specific brain network architecture in resting-state fMRI
Authors: Kajimura Shogo , Margulies Daniel , Smallwood Jonathan
Published: October 2022

The analysis of brain function in resting-state network (RSN) models, which has been found in the functional connectivity pattern of resting-state functional magnetic resonance imaging (rs-fMRI), is sufficiently powerful for studying large-scale functional integration of the brain. Although there has been an increasing interest in the relatively higher frequency of rs-fMRI data, the network architecture has been regarded as the same through different frequency bands in RSN-based research. This study examined whether the network architecture changes with frequency. The blood-oxygen-level-dependent (BOLD) signal was decomposed into four frequency bands (ranging from 0.007 Hz to 0.438 Hz), for each of which the clustering algorithm was applied. The best clustering number was selected for each frequency-band based on the overlap ratio with task activation maps provided by Neurosynth. The results demonstrate that (1) resting-state BOLD signals have frequency-specific network architecture, that is, the networks finely subdivided in the lower frequency bands are integrated into fewer networks in higher frequency bands rather than reconfigured, and (2) the default mode network(DMN) is the only associative network that has a strong enough architecture to survive the increasing noise in higher frequency bands. These findings provide a novel framework that enables a better understanding of brain function through the multiband frequency analysis of ultra-slow rs-fMRI data.
Synthesis and Characterization of NiS and Zn doped NiS Quantum Dots and their application in methylene blue degradation in aqueous solution
Authors: Qayoom Azad , Ashraf Irtiqa , Jan saima , Rashid Adfar , Ayoub Mehnaz , Kumar Deepak
Published: October 2022

Abstract
The NiS and Zn-doped NiS Quantum dots were synthesized using the solvothermal approach. The nanomaterial prepared was investigated with FESEM, EDS and XRD to determine morphology and size of the compound. The presence of functional groups present in our molecule was analysed with FTIR spectroscopy. The elemental composition of NiS and Zn doped NiS QDs was examined by EDS analysis. The results indicate that crystalline samples of NiS and Zn-doped NiS QDs with specific surface area were synthesized. The band gap energy of NiS and Zn doped NiS was calculated using Tauc plot. The photodegradation efficiency of NiS and Zn doped NiS nanomaterial was examined in this article. The results obtained indicate that Zn doping enhance the photocatalytic activity of NiS Quantum Dots (QDs). Thus, Zn doped NiS could be employed as an effective photocatalyst against environmental contaminant Methylene Blue dye.
Genetic insights into cholesteryl ester transfer protein as a novel therapeutic target for sepsis and severe pneumonia
Authors: Li Quan , Wang Yang , Sun Mingwei , Wang Ruiyu , Wang Minggui , Zeng Jun , Zhu Huadong , Lv Chuanzhu
Published: October 2022

Background
Lipoproteins were associated with sepsis related mortality because of their critical role in immune-inflammatory modulation and pathogen sequestration. Cholesteryl ester transfer protein (CETP), a lipid-modifying drug target, was reported to be associated with sepsis in recent animal models. However, whether there was a causal effect of inhibition of CETP on reducing the risk of sepsis and severe pneumonia for patients in critical care being still unknown. Therefore, we estimated the causal association of genetically proxied inhibition of CETP, along with high-density and low-density lipoprotein cholesterol directly, with the risk of sepsis, pneumonia and 28-day mortality in critical care.
Methods
The genotype of sepsis and pneumonia cohorts (N 431,365) were obtained from multi-center biobanks throughout the United Kingdom between 2006 and 2010. Single-nucleotide polymorphisms (SNPs) in CETP associated with circulating high-density lipoprotein cholesterol in a genome-wide association study (GWAS) (N 188,577) were used to proxy inhibition of CETP. We also conducted genetically proxied other three commonly lipid-modifying drug targets (3-hydroxy-3-methylglutaryl coenzyme A reductase, proprotein convertase subtilisin/kexin type 9, and Niemann-Pick C1-Like 1) using a similar method. A drug-target Mendelian randomization framework with inverse-variance weighted method was used to assess the causal association.
Results
Genetically proxied inhibition of CETP was significantly associated with lower risk of sepsis (odds ratio [OR], 0.83 [95% CI, 0.73–0.95]; P = 0.005), pneumonia (OR, 0.78 [95% CI, 0.72–0.86]; P = 1.46e-07) and lower 28-day mortality from sepsis in critical care (OR, 0.68 [95% CI, 0.52–0.87]; P = 0.003). There was no significant evidence of direct association of genetically proxied high-density and low-density lipoprotein cholesterol levels, and other commonly lipid-modifying drug targets with sepsis, pneumonia and 28-day mortality in critical care.
Conclusion
Our findings support a causal effect of genetically proxied inhibition of CETP on lower risk of sepsis, severe pneumonia, and sepsis related mortality in critical care. This effect seems to be mechanism-specific, independent of circulating high-density lipoprotein cholesterol levels. However, whether pharmaceutical CETP inhibitors could be a promising strategy for sepsis prevention and treatment remained further clinical trials.
Photodegradation of Carbofuran in Paddy Water Samples
Authors: Baharudin Nurul Syuhada Haji , Ahmad Harlina
Published: October 2022

Rice fields are one of the agricultural sectors in Malaysia that are heavily pesticide-treated. This study aimed to determine how carbofuran degrades in paddy water and what happens to its metabolite products, carbofuran phenol, and 3-ketocarbofuran. The experiment was conducted in two distinct ways, with one water sample being exposed to sunshine and the other remaining in the dark. Within 56 days of observation, the study discovered that carbofuran decomposed very slowly in all conditions. The water sample exposed to sunlight showed a faster degradation rate, 0.04 day-1, compared to the water kept in the dark at 0.0186 day-1. The results also demonstrated that photolysis and hydrolysis enhance the degradation of the carbofuran in the water. Both 3-ketocarbofuran and carbofuran–phenol was detected as metabolites with low concentration levels, ranging from 0.03 to 0.23 ppm. These metabolites are considered 'emerging pollutants' as they can be detected in the environment and may post-treat as much as the parent compounds themselves. Hence, this study is trying to fill in the research gap to assess the route and rate of carbofuran and its transformation products.
Continue or quit? -- Recommendations for repeated controlled ovarian stimulation therapy
Authors: Qi Lin , Wang Shiming , Liu Yaping , Chen Xiaoli , Wang Ningning , Su Yingchun
Published: October 2022

Background: It is ambiguous whether the multiple COS with supraphysiologic hormonal doses impact ovarian reserve functions or pregnancy outcomes. Furthermore, relevant retrospective studies are relatively scarce, chiefly in the last century, and ART techniques have seen innovation and improvement in the previous 20 years.
Methods: The retrospective study included 45,555 IVF/ICSI fresh cycles enrolled between January 2015 and March 2021 were segregated into 5 different cycle cohorts. The participants were retrospectively grouped according to the number of repeated cycles. The primary observables symbolizing ovarian reserve function were antral follicle count (AFC) and anti-Müllerian hormone (AMH). We analyzed clinical pregnancy rate (CPR), live birth rates (LBR), and early miscarriage rate (EMR) to explore clinical pregnancy outcomes. Statistical methods were used for intra-group self-control comparisons, between-group comparisons, and logistic regression analysis.
Result(s): Among the ovarian reserve function indicators, the AMH, AFC, basal FSH and basal LH exhibit no difference between groups (P> 0.05). In different populations, there was a natural dropout trend for CPR (r = - 0.922, P = 0.026) and LBR (r = - 0.920, P = 0.027) with increasing number of population repetitions, while EMR displayed an increasing trend (r = 0.957, P = 0.011). All differences between groups were statistically significant after logistic regression analysis. Intra-group analysis within same population revealed that, Cycle 2 in Group B (aOR = 8.29; 95% CI, 6.80-10.12; P = 0.000), Cycle 3 in Group C (aOR = 6.05; 95% CI, 3.28-11.15; P = 0.000) and Cycle 4 in Group D (aOR = 20.46; 95% CI, 3.05-137.24; P = 0.002) had the highest CPR within each group; Cycle 2 in Group B and Cycle 3 in Group C had the highest LBR and lowest EMR within each group, and the differences did not reached statistical significance in the remaining groups.
Conclusion(s): Repeated COS ( ≤ 5 times) does not disrupt ovarian reserve function. A raise in cycle number significantly increases CPR in the cohort of ≤ 4 repeated cycles, improves LBR, and reduces EMR in cohorts with ≤ 3 repeated cycles. Hence, patients are not advised to undergo ≥ 5 COS cycles.
Comparison of different Gaussian fitting and phase contrast retrieval methods
Authors: Djurabekova Nargiza , Buchanan Ian , Doherty Adam , Endrizzi Marco , Enwald Joel , Munro Peter , Olivo Alessandro , Savvidis Savvas , Arridge Simon
Published: October 2022

Edge illumination is an X-ray phase contrast imaging technique that allows for the recovery of differential phase and dark-field (also known as scattering) contrast, in addition to conventional attenuation based contrast. These signals are retrieved by analysing the illumination profile of a series of beamlets across a detector. This can provide a wealth of information about the sample, especially biological tissues which produce little contrast using conventional attenuation radiography. To perform signal retrieval, Gaussian curves can be fit to the illumination profiles using a variety of methods. In this work, we compare the most prominent of these methods in terms of their contrast to noise ratio as well as computational times to investigate their effect on the retrieved projection data as well as the final reconstructions.
UX Debt in an Agile Development Process: Evidence and Characterization
Authors: Rodriguez Andres , Gardey Juan Cruz , Grigera Julián , Rossi Gustavo , Garrido Alejandra
Published: October 2022

The metaphor of Technical Debt (TD) has generated a conceptual framework on factors that weaken the quality of software and accumulate a repair cost. However, user-related aspects like user experience (UX) receive little consideration among TD types, for reasons like the substantial focus on code TD, some dynamics inherent to agile processes, and an apparent lack of cumulative cost over time. This article has two main goals: first, to present evidence of the existence of UXDebt as a type of TD, with a cumulative cost for the development team as well as stakeholders; second, to propose a definition and characterization of UXDebt that may serve as a frame for further research on methods and tools for continuous management within agile processes. For the first goal, we have compiled evidence on the current state of UXDebt from three sources: a literature review, a survey among software engineering professionals in agile teams, and the analysis of UX issues in GitHub. All sources have evidenced some form of UXDebt; surveyed practitioners have recognized its poor management with a cost for the entire team that accumulates over time. Moreover, issue-tracking systems allow to visualize and measure a technical form of UXDebt. For the second goal, we have defined a conceptual model that characterizes UXDebt in terms of both technical and non-technical aspects. On the technical side, we propose the notion of UX smells which allows us to discuss concrete management activities.
Relationship of cognition and Alzheimer’s disease with gastrointestinal tract disorders: a large-scale genetic overlap and Mendelian randomisation analysis
Authors: Adewuyi Emmanuel O , O’Brien Eleanor K. , Porter Tenielle , Laws Simon M
Published: October 2022

Background
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, mechanisms underlying their relationships remain unclear. Leveraging several large-scale genome-wide association studies summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with GIT disorders.
Method
We assessed the global and local genetic correlation of ten cognitive traits (sample size [n] = 68,065–766,345) and AD (n = 455,258) with six GIT disorders (n = 332,601–456,327), using the linkage disequilibrium score regression (LDSC) and the Local Analysis of [co]Variant Association (LAVA) methods, respectively. We utilised the bidirectional two-sample Mendelian randomisation (MR) analysis method to investigate the potential causality between cognitive traits and GIT disorders. Also, we performed gene-based analyses and assessed the gene-level genetic overlap between cognitive traits and GIT disorders.
Results
LDSC reveals a strong and highly significant inverse global genetic correlation between all cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). LAVA detects 35 significant (P < 4.37 × 10− 5) bivariate local genetic correlations, across 14 loci, between cognitive traits, AD and GIT disorders (including IBD). MR analysis suggests a risk-decreasing causality of educational attainment, intelligence, cognitive performance and other cognitive traits on PUD, and GERD but not IBD. Also, we found a putative causal association of GERD with cognitive function decline. These findings were supported by other MR models and sensitivity analyses. Genes with nominal association (Pgene < 0.05) were significantly enriched (Pbinomial−test = 1.18 × 10− 3 – 2.20 × 10− 16), across GIT disorders (IBD inclusive), AD, and cognitive traits—evidence of gene-level genetic overlap.
Conclusion
Our study reveals highly significant negative global and local genetic correlations of all cognitive traits with all GIT disorders, except IBD. Findings highlights causally protective roles of cognitive traits on PUD, and GERD, and a putative causal association of GERD with cognitive function decline. Identified local genetic correlations enhance novel insights, especially, into IBD’s relationship with cognitive traits and AD, characterising important targets for further investigations.
Design and development of Recirculating Aquaculture System (RAS) for sustainable production and water quality research
Authors: Potnis Atharva , Ghanekar Kshitij , Sinnarkar Atharva
Published: October 2022

Fisheries are the primary source of livelihood for several communities. Fishing in India is a primary industry, employing 14.5 million people and contributing to 1.07% of the total GDP of India (2020, “Fishing in India - Wikipedia). Currently, most aquaculture systems are biofloc systems or pond farming setups. While wild fishing is slowly becoming unsustainable, aquaculture faces the problem of people using incorrect filtration methods, which leads to a high mortality rate. A 3-stage filtration system for freshwater aquaculture or recirculating aquaculture system (RAS) was built to tackle this problem. The RAS prototype was designed to satisfy compactness, efficiency, longevity, and financial requirements. The culture tank (main fish tank) has a capacity of 1000 L and is stocked with 100 fish. The stocking density comes out to be almost double as compared to bio floc systems. The three stages of filtration are mechanical filtration, biological filtration, and ultraviolet (UV) filtration. The fish used to test this prototype are mono-sex tilapia(200g) (GIFT)(2019, “An Excellent Candidate Species for World Aquaculture: A Review).
Policy Reinvention in Diffusion: Evidence from Municipal Solid Waste Classification Policy in China
Authors: Zhang Qingzhi , Luo Dan , Xie Aiwen
Published: October 2022

While research on policy diffusion has attracted the attention of many scholars, little attention has been given to policy reinvention in diffusion. With the aim to explore the influencing factors and combination paths of policy reinvention in the Municipal Solid Waste Classification Policy (MSWCP), this study constructs a theoretical framework concerning internal factors, intergovernmental relations and external influence, and carries out an empirical analysis on the MSWCP of 31 large and medium-sized cities in China using the Qualitative Comparative Analysis. Based on the empirical results, this study identifies the different combination paths that induced local governments to reinvent policies and clarifies the various roles of financial resources, government attention, policy experience, peer competition, learning, and social demand in achieving policy reinvention, which is expected to provide new theoretical and practical enlightenment for policy reinvention research.
FTO attenuates the cytotoxicity of cisplatin on KGN cells by regulating the Hippo/YAP1 signaling pathway Short title：FTO disrupts the Hippo/YAP1 signaling pathway
Authors: Wang Rongli , Yang Xinyuan
Published: October 2022

Premature ovarian failure (POF) is a devastating condition for women under 40 years old, which causes serious health consequences, especially the cessation of ovarian function. They will be confronted with infertility, osteoporosis, increased cardiovascular incidence, and so on. However, its pathogenesis is not yet fully clarified. The increase in granulosa cell apoptosis is an essential pathophysiological process for POF. Our previous studies have demonstrated that FTO plays an essential role in protecting granulosa cells from cisplatin-induced cytotoxicity and down-regulation of FTO aggravated the cisplatin-induced granulosa cells apoptosis and the ovarian injury of C57BL/6 mice. Various studies have suggested that the Hippo/YAP signaling pathway plays a significant role in regulating cell apoptosis and proliferation. However, whether the Hippo/YAP signaling pathway is involved in the protective effect of FTO on granulosa cells remains to be further studied. In this study, we found that granulosa cells apoptosis increased in a concentration-dependent manner after cisplatin-treated, accompanied by the downregulation of FTO and the activation of the Hippo/YAP signaling pathway. Western blotting and qRT-PCR results indicated that overexpression of FTO promoted the expression of MST1, LATS1, YAP1, and Bcl − 2, and decreased the expression of pMST1/MST1, p-LATS1/LATS, pYAP1/YAP1, BAX, and caspase3, and the downstream targets of YAP1 (CTGF, CYR61, and ANKRD1). Immunofluorescence staining results clarified that the expression of YAP1 in the nucleus increased significantly. However, these effects were completely reversed by the small molecule inhibitor of YAP1-verteporfin (VP). Downregulation of FTO got the opposite results. Taken together, FTO may decrease injured granulosa cell apoptosis and promote its proliferation by increasing the expression of multiple genes in the Hippo/YAP signaling pathway, especially the YAP1, which serves as a significant downstream effector.