bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant Hysteromyoma After Vaginoplasty in a Woman With Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome: Case Report and Review of the Literature
Authors: Qiu Shikang , Xie Yunkai , Zou Yonghui , Wang Fei
Published: September 2021

Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder characterized by congenital absence of both the uterus and vagina. Some patients may need an operation to create a neovagina. However, the preservation of nonfunctional rudimentary uteri after surgery usually leads to some long-term complications. Case presentation: We report a rare case of a giant hysteromyoma after vaginoplasty in a woman with MRKH syndrome. A 31-year-old Chinese woman who was diagnosed with MRKH syndrome and received vaginal reconstruction 4 years ago presented with abdominal distension for half a month. Transabdominal ultrasonography showed a firm mass of approximately 10 x 10 cm in the lower abdomen. She then received an exploratory laparotomy, and a leiomyoma from her rudimentary uterus was removed.Conclusions: Gynecologists should pay attention to the risks of pelvic complications in women with MRKH syndrome who have undergone previous surgery and then choose suitable therapeutic methods.
A Proteome-Wide Association Study Identified Candidate Human Brain Proteins Associated with Coffee Consumption
Authors: Li Chun'e , Liang Xiao , Jia Yumeng , Wen Yan , Zhang Huijie , Cheng Shiqiang , Pan Chuyu , Zhang Jingxi , Zhang Zhen , Chen Yujing , Yang Xuena , Meng Peilin , Yao Yao , Zhang Feng , Wu Cuiyan , Wang Sen , Ning Yujie , Wang Xi
Published: September 2021

Background
Increasing evidence suggests the association between caffeine and the brain and nervous system. However, there is limited research on the genetic associations between coffee consumption subtypes and brain proteome, plasma proteomes, and peripheral metabolites.
Methods
First, proteome-wide association study (PWAS) of coffee consumption subtypes was performed by integrating two independent genome-wide association study (GWAS) datasets (91,462–502,650 subjects) with two reference human brain proteomes (ROS/MAP and Banner), by using the FUSION pipeline. Second, transcriptome-wide association study (TWAS) analysis of coffee consumption subtypes was conducted by integrating the two gene expression weight references (RNAseq and splicing) of brain RNA-seq and the two GWAS datasets (91,462–502,650 subjects) of coffee consumption subtypes. Finally, we used the LD Score Regression (LDSC) analysis to evaluate the genetic correlations of coffee consumption subtypes with plasma proteomes and peripheral metabolites.
Results
For the traits related to coffee consumption, we identified 3 common PWAS proteins, such as MADD (P PWAS−Banner−dis=0.0114, P PWAS−ROS/MAP−rep =0.0489). In addition, 11 common TWAS genes were found in two cohorts, such as ARPC2 (P TWAS−splicing−dis =2063×10− 12, P TWAS−splicing−dis =1.25×10− 10, P TWAS−splicing−dis =1.24e-08, P TWAS−splicing−rep =3.25×10− 9 and P TWAS−splicing−rep =3.42×10− 13). Importantly, we have identified 8 common genes between PWAS and TWAS, such as ALDH2 (P PWAS−banner−rep =1.22×10− 22, PTWAS− splicing−dis = 4.54×10− 92). For the LDSC analysis of human plasma proteome, we identified 11 plasma proteins, such as CHL1 (P dis = 0.0151, P rep =0.0438). For the LDSC analysis of blood metabolites, 5 metabolites have been found, such as myo-inositol (P dis = 0.0073, P dis = 0.0152, P dis =0.0414, P rep =0.0216).
Conclusions
We identified several brain proteins and genes associated with coffee consumption subtypes. In addition, we also detected several candidate plasma proteins and metabolites related to these subtypes.
The association between handgrip strength and depression in cancer survivors: a cross-section study
Authors: Zhang Xiao-Ming , Zhang Zhi-Biao , Chen Wei , Wu Xinjuan
Published: September 2021

BackgroundThe association between handgrip strength and depression in cancer survivors was unknown. We aim to examine the associations of handgrip strength and depression in cancer survivors by using public data (National Health and Nutrition Examination Survey). MethodsWe combined two waves of the data of the National Health and Nutrition Examination Survey during 2011-2014 to explore this important issue. The variable of handgrip strength was extracted by the maximum value of each hand. The depressive symptom was assessed by the Patient Health Questionnaire (PHQ-9) with the cut-off >=10 points indicating depressive symptoms. Other characteristics and health-related variables were evaluated. Multivariable logistic regression models were adopted to explore the associations between handgrip strength or low handgrip strength and depressive symptoms by adjusting for potential confounding factors. ResultsThere were 992 cancer survivors in our final analysis, with 456 (45.97%) male and the mean (SD) age of this whole group being 64.75 (14.02) years. The prevalence of low handgrip strength and depression was 20.36% and 13.31%, respectively. The results showed that handgrip strength was negatively associated with depression (OR=0.97,95%CI:0.96-0.99; P=0.01). In addition, after adjusting age, race, education, marital status, sleep disorder, history of stroke, polypharmacy and BMI, cancer survivors with low handgrip strength had a 2.11-fold risk of depression, compared to those with normal handgrip strength (OR=2.11,95%CI:1.19-3.73; P=0.01). ConclusionsLow handgrip strength, simple and modifiable parameter, is associated with a higher risk of depression in cancer survivors. Prospective cohort studies are warranted to confirm this association in the future.
Identification and Validation of a Seven m6A-related lncRNAs Signature Predicting Prognosis of Ovarian Cancer
Authors: Li Yan , Wang Xiaoying , Han Yue , Li Xun
Published: September 2021

Background: Long non-coding RNAs (lncRNAs) play an important role in angiogenesis, immune response, inflammatory response and tumor development and metastasis. m6 A (N6 - methyladenosine) is one of the most common RNA modifications in eukaryotes. The aim of our research was to investigate the potential prognostic value of m6A-related lncRNAs in ovarian cancer (OC).Methods: The data we need for our research was downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Pearson correlation analysis between 21 m6A regulators and lncRNAs was performed to identify m6A-related lncRNAs. Univariate Cox regression analysis was implemented to screen for lncRNAs with prognostic value. A least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analyses was used to further reduct the lncRNAs with prognostic value and construct a m6A-related lncRNAs signature for predicting the prognosis of OC patients. Results: 275 m6A-related lncRNAs were obtained using pearson correlation analysis. 29 m6A-related lncRNAs with prognostic value was selected through univariate Cox regression analysis. Then, a seven m6A-related lncRNAs signature was identified by LASSO Cox regression. Each patient obtained a riskscore through multivariate Cox regression analyses and the patients were classified into high-and low-risk group using the median riskscore as a cutoff. Kaplan-Meier curve revealed that the patients in high-risk group have poor outcome. The receiver operating characteristic curve revealed that the predictive potential of the m6A-related lncRNAs signature for OC was powerful. The predictive potential of the m6A-related lncRNAs signature was successfully validated in the GSE9891, GSE26193 datasets and our clinical specimens. Multivariate analyses suggested that the m6A-related lncRNAs signature was an independent prognostic factor for OC patients. Moreover, a nomogram based on the expression level of the seven m6A-related lncRNAs was established to predict survival rate of patients with OC. Finally, a competing endogenous RNA (ceRNA) network associated with the seven m6A-related lncRNAs was constructed to understand the possible mechanisms of the m6A-related lncRNAs involed in the progression of OC.Conclusions: In conclusion, our research revealed that the m6A-related lncRNAs may affect the prognosis of OC patients and identified a seven m6A-related lncRNAs signature to predict the prognosis of OC patients.
Biomimetic Nanoparticles Blocking Autophagy for Enhanced Chemotherapy and Metastasis Inhibition via Reversing Focal Adhesion Disassembly
Authors: Shi Yesi , Lin Gan , Zheng Huili , Mu Dan , Chen Hu , Lu Zhixiang , He Pan , Zhang Yang , Liu Chao , Lin Zhongning , Liu Gang
Published: September 2021

BackgroundAutophagy is a conserved catabolic process, which plays an important role in regulating tumor cell motility and degrading protein aggregates. Chemotherapy-induced autophagy may lead to tumor distant metastasis and even chemo-insensitivity in the therapy of hepatocellular carcinoma (HCC). However, a vast majority of HCC cases do not produce a significant response to monotherapy with autophagy inhibitors. ResultsIn this work, we develop a biomimetic co-delivery nanoformulation (TH-NP) co-encapsulating Oxaliplatin (OXA)/HCQ (hydroxychloroquine, an autophagy inhibitor) to execute targeted autophagy inhibition, reduce tumor cell migration and invasion in vitro and attenuate metastasis in vivo. Especially, TH-NPs can significantly improve OXA and HCQ concentration with approximately 21 and 13-fold increment in tumor tissues compared to the free mixture of HCQ/OXA. Moreover, the tumor-targeting TH-NPs release HCQ can alkalize the acidic lysosomes and thus inhibit the fusion of autophagosomes and lysosomes, leading to most effective blockade of autophagic flux compared to various controls. This largely improves chemotherapeutic performance of OXA in subcutaneous and orthotopic HCC mouse models. Importantly, TH-NPs also exhibit the most effective inhibition of tumor metastasis in orthotopic HCCLM3 models, and in the HepG2, Huh-7 or HCCLM3 metastatic mouse models. Then, we illustrate the enhanced metastasis inhibition is attributed to the blockade or reverse of the autophagy-mediated degradation of focal adhesions (FAs) including E-cadherin and paxillin. ConclusionsTH-NPs can perform an enhanced chemotherapy and antimetastatic effect, and may represent a promising strategy for HCC therapy in clinics.
Analysis of Membrane Deploying Process Based on Miura Origami
Authors: Zhang Jing , Shen Youqing , Guo Hongwei , Liu Rongqiang , Kou Ziming
Published: September 2021

Aiming at a series of characteristics of the membrane structure in the folded configuration during the deploying process, the initial defect of the membrane crease is introduced by proxy model, and to realize the study of the deploying process of the membrane. Based on the finite element method, the deploying process of the multi-element Miura membrane is simulated. And the stretch ratio, maximum mises stress, deployment rate, wrinkle deformation, etc. of membrane structure are discussed. The existence of creases can cause damage to the membrane surface, so the total length of the creases should be within an appropriate size range. By changing the number of elements and the longitudinal crease angle of the same size membrane respectively, the influence of the above two factors on the total crease length, storage volume and deploying process of the folded membrane is studied. The results show that when the longitudinal crease angle is 15°, the transverse and longitudinal displacements of the Miura folded membrane with different element numbers are not synchronized during the deploying process. By keeping the number of elements constant and increasing the angle of the longitudinal creases from 15° to 45°, the synchronization of the transverse and longitudinal displacements during the membrane deploying process is gradually enhanced. In addition, the experiment on the membrane deploying process verifies the reliability of the finite element simulation results.
Silencing of LINC01279 is activated apoptosis and autophagy in lung cancer by regulating FAK/ERK via SIN3A
Authors: Su Wenmei , Wu Jiancong , Huang Xiaobi , Li Xiaofang , Zhou Honglian , Chen Xiaorao , Chen Yongyang , Huang Jian , Huang Hanqing , Huang Zhong , Chen Guoan , Zhang Jian , Yang Zhixiong
Published: September 2021

Background: In human lung adenocarcinoma (LUAD) tissues, Long noncoding RNA LINC01279 is significantly upregulated. However, the functions of LINC01279 in LUAD is yet to be clarified.Methods: In situ hybridization was employed to investigate the difference between expression of LINC01279 in LUAD and in normal tissues. The result of in situ hybridization is verified by qRT-PCR. Cytoplasmic and nuclear experiments showed that LINC01279 was mainly located in the cytoplasm of lung cancer cells. The loss of function experiment showed that LINC01279 could inhibit the proliferation, colony formation, invasion and migration of lung cancer cells. The interaction between SIN3A and LINC01279 was confirmed by RIP test. At the same time, through western bolt, we found that LINC01279 plays a key role in the regulation of apoptosis and autophagy in lung adenocarcinoma.Results: Our study confirmed that LINC01279 was upregulated in LUAD tissues, the knocking-down of which significantly inhibited the growth of LUAD cancer cells both in vitro and in vivo. Mechanistic investigations revealed that LINC01279 could directly interact with SIN3A and modulate the FAK and ERK protein expression in the cytoplasm. Moreover, the proteins of PARP and LC3B, P62, Beclin-1, respectively related with apoptosis and autophagy, were changed after LINC01279 siRNA. Conclusions: Taken together, our research found that LINC01279 which is significantly up-regulated in LUAD tissues and cell lines, and promotes the changes of FAK and ERK proteins in downstream pathways by combining with SIN3A, promotes the proliferation of LUAD cells, and inhibits apoptosis and autophagy. The results of this work illustrated how LINC01279 is part of a regulatory network that contributes to the oncogenesis of LUAD and proposed LINC01279 could be a potential target for LUAD diagnosis and treatment.
ThermomiR-377-3p-induced Suppression of Cirbp Expression Is Required for Effective Elimination of Cancer Cells and Cancer Stem-like Cells by Hyperthermia
Authors: Lin Tao-Yan , Jia Jun-Shuang , Luo Wei-Ren , Xiao Sheng-Jun , Lin Xiao-Lin , Yang Jie , Xia Jia-Wei , Zhou Chen , Zhou Zhi-Hao , Lin Shu-Jun , Li Qi-Wen , Shen Hong-Fen , Le Yei , Yang Zhi-Zhi , Yang Wen-Qing , Chen Lin-Bei , Xue Shu-Wen , Li Yong-Long , Wei Fang , Xiao-Xiang Rong , Luo Xiao-Jun , Zhao Bing-Xia , Huang Wen-Hua , Sun Yan , Xiao Dong
Published: September 2021

In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold-inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Our results firstly revealed that hyperthermia significantly attenuated the stemness property of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)-like population. Moreover, hyperthermia substantially improved the sensitivity of radiation-resistant NPC cells and CSC-like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti-tumor-killing activity of hyperthermia against NPC cells and CSC-like cells, whereas ectopic expression of Cirbp compromised tumor-killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377–3p improved the sensitivity of NPC cells and cancer stem-like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp nearly completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377–3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.
Impact of Exogenous Application of Salicylic Acid and Hydrogen Peroxide on Essential Nutrients and Silymarin in Silybum Marianum (L.) Gaertn Grown at Two Different Altitudes of Balochistan Under Cadmium Stress
Authors: Nizar Mereen , Shaukat Kanval , Zahra Noreen , Samad Abdul , Hafeez Mohammad Bilal , Gul Shamim
Published: September 2021

Cadmium (Cd+2) is a potentially toxic element that inhibits growth and development of several species of plants along with Silybum marianum (L.) Gaertn which is an essential medicinal plant belonging to family Asteraceae. The exogenous application with 0.25µM Salicylic acid (SA) and 10µM hydrogen peroxide (H2O2) to ameliorate harmful effects of cadmium (500 µM) on milk thistle were studied that were grown at two different ecological zones of Balochistan province of Pakistan i.e. Quetta (Qta) and Turbat (Tbt). The design of experiment was Randomized Complete Block Design (RCBD) with three replicates. Application of SA and H2O2, priming (P), Foliar spray (FS) and combinational treatments (P+FS) were highly helpful in alleviating the negative role of cadmium toxicity. The essential nutrients i.e. nitrate (NO3-), calcium (Ca2+) and potassium (K) were affected by Cd+2 induced toxicity however, the substantial role of SA and H2O2 widely helped to reduce the cadmium stress and boosted up the plant nutrients content. In a nutshell, exogenous treatments of SA and H2O2 enhanced the yield potential along with highest silymarin contents in milk thistle seeds which is of prime significance for its medicinal importance in treatment of liver diseases. The data obtained in this study highly recommend the priming and foliar spray of SA and H2O2 on milk thistle plants, as the best solution to alleviative the cadmium toxicity which will ultimately leads to better growth and yield of the plants.
Thioacetamide promotes osteoclast transformation of bone marrow macrophages by influencing PI3K/AKT pathways
Authors: Jin Xiaoli , Li Yang , Yang Yayang , Shen Hao , Chen Jin , Xu Bin , Xu Jian
Published: September 2021

Background
Osteoclast cell increase is a major risk factor for osteoporosis and degenerative bone and joint diseases. Thioacetamide (TAA) can lead to many types of liver and kidney damage, but less attention has been paid to the association of TAA with bone damage. In this work, we investigated the effects of TAA on the osteoclastogenesis and differentiation of bone marrow macrophages (BMMs).
Methods
Bone marrow mononuclear macrophages of SD rat suckling mice were taken for primary culture. CCK-8 was used to detect the toxic effects of TAA on BMMs, and flow cytometry was used to detect the effects of TAA on the cell cycle, cell viability, apoptosis and intracytoplasmic Ca2+ concentration of BMMs. TRAP immunohistochemistry and fluorescence staining were used to detect the effect of TAA on osteoclast differentiation of BMMs. Western Blot was used to detect the expression level of PI3K/AKT pathway and osteoclast-specific proteins (TRAP and Cts-K).
Results
The results suggested that TAA inhibited the proliferation of BMMs, while enhancing osteoclastogenesis at 0.5 mg/mL and 1 mg/mL as assayed by TRAP staining, and BMMs could differentiate into osteoclast-like cells with overexpression of cathepsin K and TRAP proteins after TAA treatment. Western blot results showed that TAA can activate the expression levels of P-PI3K, P-AKT, P-P38, and P-JNK, accompanied by apoptosis of BMM cells and increase of intracellular Ca2+.
Conclusion
TAA may induce osteoclast formation in BMMs by activating the expression of PI3K/AKT pathway proteins, which is comparable to the classic osteoclast differentiation inducer RANKL. This suggests that we may find a cheap osteoclast inducer.
Cross-talk of different dimensional methylation modification patterns alters tumor microenvironment infiltration and immunotherapy response in renal cancer
Authors: Qin Xin , Pan Ling , Yan Lei , Fang Zhiqing , Fan Yidong
Published: September 2021

Background

Different dimensional methylation modifications, including DNA, RNA and histone methylation, are mediated by different functional regulators and play an indispensable role in tumor progression. However, the cross-talk and underlying mechanisms of these modification patterns in tumorigenesis, tumor microenvironment (TME) disorder and aberrant immune response are still unknown.
Methods

We summarized the 9 most common types of modifications from different dimensions and revealed transcriptional and genetic alterations of 104 modification regulators in clean cell renal cell carcinoma (ccRCC) patients. Next, we constructed a prognosis-correlation network to further explore their interactions and identified distinct methylation modification patterns by using unsupervised clustering algorithm. Lastly, we constructed a methylation modification regulator score (MMR Score) model to quantify the characterizations of different modification patterns for individual patients, and validated its predictive value to immunotherapy response.
Results

We investigated the interactions between different dimensional modifications and identified critical negative regulated nodes in the prognosis-correlation network. Our clustering results revealed that, different from other cancers, immune activity in ccRCC not only depended on the abundance of immune cells, but also the infiltration of stromal cells. The MMR Score for the quantification of each patient can act as an effective biomarker to predict clinical outcomes. Patients with high MMR Score were more likely to experience a therapeutic advantage and clinical benefits from immunotherapy.
Conclusions

This work revealed that cross-talk of different modifications could lead to the complexity and heterogeneity of individual TME. The integrated quantification of individual modification patterns can better guide clinical personalized cancer treatments.
Evaluation of Anti-Malaria Potency of Wild and Genetically Modified Enterobacter Cloacae Expressing Effector Proteins in Anopheles Stephensi
Authors: Dehghan Hossein , Mosa-Kazemi Seyed Hassan , Yakhchali Bagher , Maleki-Ravasan Naseh , Vatandoost Hassan , Oshaghi Mohammad
Published: September 2021

Background: Malaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. To fight the disease, paratransgenesis using symbiotic bacteria offers a sustainable and environmentally-friendly strategy. Here we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage, using wild and modified insect gut bacterium, Enterobacter cloacae.Methods: The assay was carried out using E. cloacae dissolvens wild-type (WT) and its three engineered strains expressing GFP-defensin (GFP-D), scorpine-HasA (S-HasA), and HasA, The 3-5 day-old female mosquitoes were supplemented overnight with the studied bacteria [1×109cells/mL of 5% (wt/vol), fructose and red dye (1/50 ml)] soaked on cotton-wool. Each group of sugar-fed mosquitoes was then starved for 4-6 hours and fed on a P. berghei–infected mouse for 20 min in the dark at 17-20°C. The blood-fed mosquitoes were kept at 19±1°C and RH 80±5, and parasite infection was measured by midgut dissection and oocyst counting 10 days post-infection (dpi). Results: Both wild-type and genetically modified bacterial strains significantly (P< 0.0001) disrupted the P. berghei development in the An. stephensi midgut, in comparison with the control group. The mean parasite inhibition of E. cloacaeWT, E. cloacaeHasA, E. cloacaeS-HasA, and E. cloacaeGFP-D was measured as 72, 86, 92.5 and 92.8 respectively. Conclusions: The wild and modified E. cloacae might abolish oocyst development by providing a physical barrier or by excretion of intrinsic effector molecules. These findings reinforce the case for the use of either wild or genetically modified E. cloacae bacteria as a powerful tool to combat malaria.
Not All Dual Users of Cigarettes and E-vapor Products Are the Same: Biomarkers and Tobacco Use Behavior in Subpopulations of Dual Users From the PATH Wave 1 Data
Authors: Lizhnyak Pavel N. , Noggle Richard B. , Wei Lai , Edmiston Jeffery , Becker Elizabeth , Black Ryan A. , Sarkar Mohamadi
Published: September 2021

Introduction: Dual users of cigarettes and e-vapor products (EVP) are often considered as a homogenous group even though multiple subgroups may exist. We examined biomarkers of exposure (BOE) and biomarkers of potential harm (BOPH) to differentiate between subgroups of dual users based on PATH Study Wave 1 (2013-2014) data.Methods: We segmented adult dual users (n=970) into four subgroups based on the number of days of product used in past 30 days – frequent dual users of both products (FreqDU, n=169), frequent smokers who vape infrequently (SMVP, n=678), frequent vapers who smoke infrequently (VPSM, n=57), and infrequent dual users of both products (InfreqDU, n=66). Eighteen BOEs (representing exposure to TSNAs, nicotine, heavy metals, PAHs, and volatile organic compounds), and four BOPHs (representing inflammation and oxidative stress) were analyzed within the subgroups, versus exclusive daily cigarette smokers (ESM, n=2,442) and exclusive daily e-cigarette users (EVP, n=169).Results: Levels of many BOEs and BOPHs were higher among SMVP relative to FreqDU, VPSM and InfreqDU. Compared to ESM, many BOEs were significantly lower in VPSM (15/18) and InfreqDU (17/18), and some BOEs were higher among SMVP (4/18). InfreqDU showed significantly lower levels of 2/18 BOEs than EVP, and lower levels of 2/4 BOPHs than ESM.Conclusions: Overall, the levels of BOEs and BOPHs in dual users are associated with frequency of cigarette smoking. Our findings indicate that not all dual users are the same, and tobacco product use frequency should be considered when categorizing dual users.
Comparison of the Diagnostic Efficacy of 68Ga-FAPI-04 PET/MRI and 18F-FDG PET/CT in Patients With Pancreatic Cancer
Authors: Zhang Zeyu , Jia Guorong , Pan Guixia , Cao Kai , Yang Qinqin , Meng Hongyu , Yang Jian , Zhang Lu , Wang Tao , Cheng Chao , Zuo Changjing
Published: September 2021

PurposeTo assess the diagnostic performance of 68Ga-FAPI-04 (68Ga-FAPI) PET/MR for primary as well as metastatic lesions in pancreatic cancer patients and to compare the results with those of 18F-FDG PET/CT.MethodsProspectively, we evaluated 31 patients suspected to have pancreatic malignancy. Within one week, each patient underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/MR. Comparisons of the detection abilities and the standardized uptake values (SUVs) for primary tumors, lymph nodes, as well as hepatic metastases were conducted for the two imaging approaches.ResultsTwenty-eight pancreatic cancer patients and three pancreatitis ones were enrolled. 68Ga-FAPI and 18F-FDG exhibited equivalent (100%) detection rates for primary tumors. The SUVs of primary tumors on 68Ga-FAPI PET were markedly higher than those on 18F-FDG (p < 0.05). Fifteen pancreatic cancer patients were accompanied by pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in 3 patients only (53.57% vs. 10.71%, p < 0.001). The number of positive lymph nodes detected was higher for 68Ga-FAPI than for 18F-FDG PET (31 vs. 26), led to N upstaging in 27.27% (3/11) of patients, however, the difference was not statistically significant (p = 0.053). 18F-FDG PET was able to detect more liver metastases than 68Ga-FAPI, and 68Ga-FAPI uptake of metastatic tumors was significantly lower than 18F-FDG (6.13 ± 1.63 vs. 8.09 ± 1.68, p < 0.001). In larger liver metastatic lesions, 68Ga-FAPI tended to distribute around the periphery of the lesions. In addition, multiple sequence MR imaging was helpful for finding more micrometastases.Conclusion68Ga-FAPI PET demonstrated equivalent detection rate with 18F-FDG for primary tumors of pancreatic cancer, and its percentage of pancreatic parenchymal uptake caused by inflammation was higher. It might be better in the detection of suspicious lymph node metastases. The MR multiple sequence imaging of integrated PET/MR was helpful for detecting tiny liver metastases.
Caffeine, Coffee, Tea and Risk of Rheumatoid Arthritis: Systematic Review and Dose- Response Meta-analysis of Prospective Cohort Studies
Authors: Asoudeh Farzaneh , Dashti Fatemeh , Jayedi Ahmad , Hemmati Amirhossein , Fadel Abdulmannan , Mohammadi Hamed
Published: September 2021

Objective: Prospective cohort studies on coffee, tea and caffeine in relation to the risk of rheumatoid arthritis (RA) have shown conflicting results. The aim of this study was to conduct a dose–response meta-analysis of cohort studies on the association between dietary caffeine, different types of coffee and tea consumption and the risk of RA.Methods: PubMed/Medline, Scopus and EMBASE were searched up to July 2021 to identify relevant studies that had considered different types of coffee (caffeinated or decaffeinated), tea or caffeine exposure with RA as the main, or one of the, outcome(s). Two authors independently screened 742 publications. Finally, 5 prospective cohort studies were included in our meta-analysis. Pooled relative risks (RRs) were calculated by using a fixed-effects model. We also performed linear and non-linear dose-response analyses to examine the dose-response relations. Results: Comparing extreme categories, we found a positive, significant association between coffee (RR: 1.30; 95% CI: 1.04-1.62; I2 = 0%, n = 5) and decaffeinated coffee (RR: 1.89; 95% CI: 1.35-2.65; I2 =38.1%, n =3) consumption and risk of RA. One additional cup of coffee consumed per day was associated with an increased risk of RA by 6% (95% CI: 1.02-1.10; I2 = 0%;). This increase in the risk of RA for one cup/d of decaffeinated coffee was 11% 95% CI: 1.05-1.18; I2 = 38). No significant association was observed between caffeinated coffee, tea or caffeine intake and the risk of RA.Conclusion: We found that a higher intake of coffee and decaffeinated coffee was associated with increased risk of RA. No significant association between caffeinated coffee, tea or caffeine intake and the risk of RA was observed.
Deubiquitinase USP9X loss Sensitizes Cancer Cells to mTOR Inhibitors through p62 Dysregulation
Authors: Roldán-Romero Juan M. , Santos Maria , Lanillos Javier , Maroto Pablo , Anguera Georgia , Calsina Bruna , Martinez-Montes Angel , Monteagudo María , Mellid Sara , Leandro-García Luis J. , Montero-Conde Cristina , Cascón Alberto , Roncador Giovanna , Coloma Javier , Robledo Mercedes , Rodriguez-Antona Cristina
Published: September 2021

BackgroundMutations in MTOR and TSC1/2 can only explain part of variability in mTOR inhibitor response. Here, we performed a comprehensive molecular characterization of tumors with high sensitivity to these drugs to uncover novel mechanisms of response.MethodsChromophobe renal cell carcinoma (chRCC) tumors were analyzed by whole-exome sequencing. Rapamycin sensitivity, expression of mTOR pathway effectors, ubiquitylome analyses to identify USP9X substrates, p62 immunoprecipitation and autophagy assessment through immunofluorescence assays for p62 and LC3 were performed in USP9X depleted HeLa and 786-O cells for mechanistic investigation. ResultsWhole-exome sequencing of chRCC patients with high mTOR inhibitor sensitivity, uncovered USP9X deubiquitinase as the only mutated gene shared by these tumors. The clonal characteristics of the mutations, revealed by studying multiple primary and metastatic samples, together with the low USP9X mutation rate in unselected chRCC series, implied a causal link between USP9X and mTOR inhibitor sensitivity. The high sensitivity was recapitulated in vitro, and while no direct effect on mTORC1 was detected, an unbiased ubiquitylome analysis revealed p62 as a direct USP9X target. Bortezomib treatment, which also led to p62 ubiquitination, increased rapamycin effect. Finally, immunofluorescence assays for p62 and LC3 confirmed dysregulated autophagy in USP9X depleted cells, supporting a synthetic lethal interaction between rapamycin-induced autophagy via mTOR-axis and USP9X loss.ConclusionsOur study uncovers USP9X as a potential novel marker of sensitivity to mTOR inhibitors and suggests the inhibition of this gene as a clinically exploitable strategy able to increase sensitivity to these drugs through a novel p62 regulatory mechanism.
Enhanced Simultaneous Photocatalytic Removal of SO2 and CO2 Using Powder and Coated Zeolites-Supported TiO2 Under Concentrated Sunlight Irradiation
Authors: Razavi Zahra , Mirghaffari Nourollah , Soleimani Mohsen
Published: September 2021

Single-step process for simultaneous removal of gaseous pollutants is more advantageous than multi-steps one. In this study, the efficiency of a novel synthetic zeolite (Ze) prepared from stone cutting sludge and a natural zeolite (clinoptilolite, Cp) as the supports of TiO2 photocatalyst were examined for the separate and simultaneous removal of SO2 and CO2 under solar irradiation using a parabolic trough collector (PTC). The composites exhibited a higher efficiency than raw zeolites and TiO2 for the removal of both gases. The maximum removal of SO2 by TiO2-Ze and TiO2-Cp under sunlight was 41.9 % and 56.2 % that enhanced to 53.4 % and 78.8 %, respectively in the presence of CO2. Correspondingly, it was 61.8 % and 68.7 % for single CO2 removal that increased to 74.2 % and 79.0 % in the binary gas stream. This behavior could be due to the enhanced simultaneous SO2 oxidation and CO2 reduction. The performance of coated composite for SO2 was higher than of powder one (54.3% vs. 41.9%) and for CO2 removal was almost close together (58.9% vs. 61.2%). This work promises the application of photocatalytic co-removal of SO2 and CO2 by using synthetic and natural zeolite under solar irradiation.
Association between dietary salt and plasma glucose, insulin and hemoglobin A1C levels among type 2 diabetes patients in Eastern China
Authors: Lin Yi , Kaushik  , Yang Xi , Li Jia-Lin , Chen Yan-Shu , Zhou Ye , Li Li
Published: September 2021

Purpose
Type 2 diabetes (T2D) is one of the major public health concerns in China. Studies on the association between dietary salt intake and the glycaemia response of T2D are lacking in China. The aim was to investigate the association between the levels of dietary salt intake and the plasma glucose, insulin and hemoglobin A1c (HbA1c) in T2D patients.
Methods
Patients with T2D, who accepted management and treatment by the National Standardized Metabolic Disease Management Center at Ningbo First Hospital from March 2018 to January 2020, were included in this study. Dietary salt was collected through a standardized food frequent questionnaire. Anthropometry, blood pressure and biomarkers were measured by well-trained endocrinology nurses. Generalized linear models (GLM) were used to examine the association.
Results
A total of 1145 eligible T2D patients with the mean age of 51.4 years were included in the study. Fasting plasma glucose (FPG), 2h postprandial plasma glucose and 2h postprandial insulin, were significantly increased across dietary salt categories. Generalized linear models further showed that dietary salt > 8g/d were positively associated with FPG and HbA1c.
Conclusion
Higher daily salt intake was found to be associated with FPG and HbA1c in T2D patients. Lifestyle education and promotion on salt reduction should be provided to T2D patients.
Association Between MUC1 rs4072037 Polymorphism and Helicobacter Pylori in Patients With Gastric Cancer
Authors: Shekarriz Ramin , jabbari hadi , Alikhani Reza , Navaei Reza Alizadeh , Hashemi‑Soteh Mohammad Bagher
Published: September 2021

The authors have requested that this preprint be removed from Research Square.
RAB20 Promotes Proliferation via G2/M Phase Through the Chk1/cdc25c/cdc2-cyclinB1 Pathway in Penile Squamous Cell Carcinoma
Authors: Tan Xingliang , Yuan Gangjun , Wang Yanjun , Chen Dong , Zou Yuantao , Luo Sihao , Han Hui , Qin Zike , Liu Zhuowei , Zhou Fangjian , Liu Yanling , Yao Kai
Published: September 2021

Background: RAB20, a member of the RAS GTPase oncogene family, promotes tumorigenesis in several cancers with poor survival outcomes but its role in penile squamous cell carcinoma (PSCC) remains unclear. Here, comprehensive genomic profiling was performed on eight PSCC and normal tissue pairs and revealed that RAB20 is upregulated in tumors, especially in metastatic lymph nodes. We aimed to explore the clinical significance and oncogenic effect of RAB20 on PSCC and to identify its specific mechanisms in tumor progression.Methods: RT-qPCR and Western blotting were performed on PSCC tissue pairs and our newly established PSCC cell lines to examine the RAB20 expression pattern. The clinical relevance and prognostic value of RAB20 were validated by immunohistochemistry in samples from 259 PSCC patients, the largest cohort to date. Cell proliferation, migration, colony formation, and cell cycle assays were performed along with analysis of a nude mouse tumorigenesis model to explore RAB20’s oncogenic functions. RAB20-mediated G2/M phase cell cycle arrest mechanisms were further demonstrated by bioinformatics analysis and Western blotting.Results: RAB20 expression was upregulated in PSCC tissues, especially in metastatic lymph nodes. High RAB20 expression in PSCC was associated with T, N, and M status, extranodal extension and clinical stage (P < 0.01). Survival analysis indicated that RAB20 was an unfavorable independent prognostic indicator (p = 0.011, HR = 2.090; 95% Cl: 1.183–4.692), and patients with high expression experienced shorter 5-year cancer‐specific survival (P < 0.001). Furthermore, knockdown of RAB20 inhibited cell growth and tumorigenesis in vitro and in vivo. Mechanistic studies indicated that RAB20 depletion arrested the PSCC cell cycle at G2/M via the Chk1/cdc25c/cdc2-cyclinB1 pathway.Conclusions: RAB20 promotes PSCC progression, predicting advanced disease with poor outcomes. RAB20 could be a promising prognostic biomarker and potential therapeutic target for PSCC.
Mental Health, Alcohol Consumption, and Partnerships After the Third Wave During the Corona Pandemic - A Comparison of German Psychology Students and Other Students
Authors: Supke Max , Schulz Prof. Dr. Wolfgang
Published: September 2021

Background.

At the end of winter and in spring 2021, Germany experienced the third wave of the corona pandemic leading to a strict lockdown. This study compares psychology students and students of other subjects in terms of their mental health, alcohol consumption, and partnerships after the third wave during the corona pandemic.
Methods.

The study sample consists of n = 127 (female: n = 108, male: n = 19) psychology students and n = 579 (female: n = 322, male: n = 257) students of other subjects from the TU Braunschweig in Germany. These students participated in an online survey in June and July 2021. The comparison was performed separately for women and men. The PHQ-9 and GAD-7 were used to assess depressive mood problems and worrying.
Results.

Significantly fewer female psychology students were above the cut-off for clinically relevant mood problems (31.5%), worrying (22.2%), and both simultaneously (19.4%) compared to other female students (mood: 66.1%; worrying: 41.9%; both: 39.8%). The small sample of male psychology students showed similar tendencies; however, the results were not significant. While female psychology students rated their general health and life satisfaction significantly higher, male psychology students had significantly fewer concerns about their professional future compared to their respective counterparts. No significant effects were found for alcohol consumption and partnerships.
Conclusion.

We found hints that psychology students, especially female students, appear to be less psychologically distressed in terms of depressive mood problems and worrying during the corona pandemic. Better mental health knowledge could be a possible explanation for these findings.
Feasibility And Safety of A CaO-SiO2-P2O5-B2O3 Bioactive Glass Ceramic Spacer In Posterior Lumbar Interbody Fusion: A Prospective Randomized Controlled Trial
Authors: Kwon Byung-Taek , Kim Ho-Joong , Park Sang-Min , Ham Dae-Woong , Kwon Ohsang , Yeom Jin S.
Published: September 2021

Study design: Prospective randomized controlled trial.Background: The CaO-SiO2-P2O5-B2O3 glass-ceramic (BGS-7) spacer is a recently developed spacer that shows chemical bonding to bone with high mechanical stability. Further, this spacer achieves similar results to those of titanium cages. However, evidence regarding the advantages of the BGS-7 spacer is weak compared to polyetheretherketone (PEEK) cage. A randomized controlled trial is therefore warranted. The purpose of this study was to compare the radiographic and clinical efficacies and safety of the BGS-7 spacer compared to those of the PEEK cage in patients who underwent posterior lumbar interbody fusion (PLIF). Methods: The 54 participants who required one- or two-level PLIF due to lumbar degenerative disorders were randomly assigned to receive a BGS-7 spacer or PEEK cage. Visual analog scale (VAS), Oswestry Disability Index (ODI), European Quality of Life-5 Dimensions (EQ-5D), painDETECT score were evaluated before surgery and at 3, 6, and 12 months after surgery. The fusion rate, degree of osteolysis, cage migration and subsidence around the cage (spacer) were evaluated on computer tomography (CT) images at 12 months after surgery. Results: The 12-month fusion rates were 75% in the BGS-7 spacer group and 79.3% in the PEEK cage group, with no significant difference (p=0.676). The result regarding the non-inferiority of BGS-7 spacer was inconclusive. The linear mixed model showed no significant intervention effect in VAS, ODI, EQ-5D, and painDETECT score at the 3-, 6-, or 12-month follow-up. In addition, we found no significant between-group differences in the extent of osteolysis, spacer migration. However, the subsidence around the cage was significantly lower in the BGS-7 spacer group. Conclusions: This trial found similar fusion rates, clinicoradiographic outcomes, and adverse events between the BGS-7 spacer and PEEK cage for PLIF. However, the non-inferiority was inconclusive, and thus, the BGS-7 spacer can be a feasible and safe alternative to PEEK cage in PLIF surgery after further studies.
Perceived Causes and Diagnosis of Febrile Convulsion in Selected Rural Contexts in Cape Coast Metropolis, Ghana
Authors: Owusu Bernard Afriyie
Published: September 2021

Background: Febrile convulsion (FC) in children under age five is a common childhood condition especially in deprived communities. In 2015, the Ghana Health Service (GHS) attributed about 30% of all under-five mortality cases to FC. Although, the perceived causes and diagnosis of FC are significant in determining treatment approaches, such evidence is limited in the literature. Objective: This study explored the perceived causes and diagnosis of FC in selected rural communities in the Cape Coast Metropolis, Ghana. Methods: A descriptive phenomenological study design underpinned the study at five selected communities located not more than 2 Kilometres from the University of Cape Coast Hospital. Purposive and snowball sampling techniques were used to interview 42 participants made up of 27 parents, two grandmothers, seven registered traditional health practitioners, four herbalists, and two faith healers in the communities. The data was analysed using QSR NVivo 12.Results: Three perceived causes of FC were identified – biological, social/behavioural, and spiritual. Biological causes include genetic abnormalities and other underlying health conditions. The behavioural factors include poor childcare practices and nutrition. Spiritual causes include harm caused by evil spirits. The diagnosis of FC entails pre-attack, attack and post-attack stages. The former is largely associated with high body temperature. The attack stage is often associated with extreme body jerking. Post-attack diagnosis of FC include deafness, dumbness and paralysis.Conclusion: The perceived causes of FC are interplay of complex natural, social and spiritual factors that are deep-rooted in local socio-cultural beliefs and FC experiences. Unlike the attack stage, pre-attack diagnosis were usually missed, or misconstrued to mean other health conditions.
QTL analysis in multiple sorghum mapping populations facilitates dissection of the genetic control of agronomic and yield-related traits in sorghum [Sorghum bicolor (Moench)]
Authors: Mekonnen Techale Birhan , Dong Hongxu , Getinet Mihrete , Gabizew Aregash , Paterson Andrew , Bantte Kassahun
Published: September 2021

The genetic architectures of agronomic and yield-related traits are expected to involve multiple loci that are unlikely all to segregate for alternative alleles in a single bi-parental population. Therefore, the identification of quantitative trait loci (QTL) that are expressed in diverse genetic backgrounds of multiple bi-parental populations provides evidence about both background-specific and common genetic variants. The purpose of this study was to map QTLs for agronomic and yield related traits using three connected mapping populations of different genetic backgrounds, to gain insight into the genomic landscape of these important traits in elite Ethiopian sorghum germplasm. The three bi-parental populations, each with 207 F 2:3 lines were evaluated using an alpha lattice design with two replications under two moisture stress environments. Data analysis was done separately for each population using composite interval mapping, finding a total of 105 QTLs. All the QTLs identified from individual populations were projected on a combined consensus map, comprising a total of 25 meta QTLs for seven traits. The consensus map allowed us to deduce locations of a larger number of markers than possible in any individual map, providing a reference for genetic studies in different genetic backgrounds. The meta QTLs identified in this study could be used for marker-assisted breeding programs in sorghum after validation. Only one trait reduced leaf senescence, showed a striking bias of allele distribution, indicating substantial standing variation among the lines that might be employed in improving drought tolerance of sorghum.