bluuebunny/crossref_metadata_2025 huggingface dataset:
Obese mammary tumour-bearing mice are highly sensitive to doxorubicin-induced hepatotoxicity
Authors: Sedeman Megan , Christowitz Claudia , de Jager Louis , Engelbrecht Anna-Mart
Published: March 2022

Background: Breast cancer is a major health burden for women, worldwide. Lifestyle-related risk factors, such as obesity and being overweight, have reached epidemic proportions and contributes to the development of breast cancer. Doxorubicin (DXR) is a chemotherapeutic drug commonly used to treat breast cancer, and although effective, may cause toxicity to other organs. The mechanisms and effects of DXR on hepatic tissue, and the contributing role of obesity, in breast cancer patients are poorly understood. The aim of this study was therefore to investigate the effects of doxorubicin on hepatic tissue in an obese tumour-bearing mouse model. Methods: A diet-induced obesity (DIO) mouse model was established, where seventy-four three-week-old female C57BL/6 mice were divided into two main groups, namely the high fat diet (containing 60% kcal fat) and standard diet (containing 10% kcal fat) groups. After eight weeks on their respective diets, the DIO phenotype was established, and the mice were further divided into tumour and non-tumour groups. Mice were subcutaneously inoculated with E0771 triple negative breast cancer cells in the fourth mammary gland and received three doses of 4 mg/kg DXR (cumulative dosage of 12 mg/kg) or vehicle treatments via intraperitoneal injection. The expression levels of markers involved in apoptosis and alanine aminotransferase (ALT) were compared by means of western blotting. To assess the pathology and morphology of hepatic tissue, haematoxylin and eosin staining was performed. The presence of fibrosis and lipid accumulation in hepatic tissues were assessed with Masson’s trichrome and Oil Red O staining, respectively. Results: Our western blot results indicated that a significant increase in the ratio of cleaved caspase-8 and caspase-8 protein expression was observed in the standard diet tumour-bearing mice treated with DXR compared to the high fat diet tumour-bearing mice treated with DXR. Microscopic examination of liver tissue showed significant changes in the high fat diet tumour-bearing mice treated with DXR, consisting of macrovesicular steatosis, hepatocyte ballooning and lobular inflammation, compared to the standard diet tumour-bearing mice treated with DXR and the control group (standard diet mice). These changes are the hallmarks of non-alcoholic fatty liver disease, associated with obesity.Conclusion: Our results suggest that DXR activated the extrinsic apoptotic pathway in tumour-bearing mice on the standard diet. The histopathological findings indicated that DXR caused significant hepatic parenchymal injury in the obese tumour-bearing mouse model. Hepatotoxicity is aggravated in obesity as an underlying co-morbidity. It has been shown that obesity is associated with poor clinical outcomes in patients receiving neo-adjuvant chemotherapy treatment regimens.
Intraventricular hemorrhage prediction in premature neonates in the era of hemodynamics monitoring:a prospective cohort study
Authors: Farag Marwa , Gouda Mohamed Hazem , Almohsen Ali Mohamed Abd , Khalifa Mohammed Attia
Published: March 2022

Purpose Unstable hemodynamics and prematurity are the main players in IVH development. Our objective was the use of SVCF, LVO and RVO, and ACA Doppler measures in prediction of IVH in the first week of life in preterm infant ≤ 32 weeks.Method Prospective cohort Study in NICU of the Maternity university hospital is presented. Of 147 patients, 132 infants born ≤32 weeks GA were enrolled in the study. 127 completed the study till 7th day of life. Infants were scanned for ACA-RI using transfontanellar ultrasound, and SVC flow, LVO, and RVO using FE in the first 24 hours after birth. Patients had another two scans on DOL3 and7 to detect IVH development. Results Low SVCF and high ACA-RI significantly increased the risk of IVH using logistic regression models with (OR, 3.16; 95%Cl, 1.19 – 8.39; P0.02) and (OR, 1.64; 95%Cl, 1.10 – 2.44;P0.02),respectively. Low SVCF and high ACA-RI significantly increased risk of catastrophic IVH P 0.025 and 0.023, respectively. Combined use Low SVCF < 55 ml/kg/min and ACA-RI > 0.75 is predictor of IVH with sensitivity 40.8% and 82.1% specificity. This work was registered in clinical trial.gv no NCT05050032ConclusionsThere are strong relations between both low SVC flow and high ACA-RI and IVH development in premature neonates ≤32 weeks, with more significance towards catastrophic IVH. Admission RSS and LVO are the strongest factors affecting SVC flow. PDA size (mm/kg) and CRT were significantly associated with high ACA-RI. Theses finding helps in more understanding of pathophysiological factors affecting central perfusion that might affect the longer term neurodeveopmental outcome.
The prevalence and risk factors for anxiety/depression in patients with connective tissue disease (CTD) associated interstitial lung diseases (ILDs)
Authors: Liao Jun-Zhe , qi Min , Zhu Min , Luo Feng-Ming
Published: March 2022

Background
Connective tissue disease(CTD) associated interstitial lung diseases (ILDs) is a common chronic disease. Given that anxiety and depression are prevalent in patients with chronic diseases, this study aimed to explore the prevalence of anxiety/depression in CTD-ILD patients, and identify its associated risk factors.
Methods
This study is based on the ICE study (Interstitial lung disease in West China Hospital: a 24-month prospective Cohort in the real world). The anxiety and depression symptoms were evaluated in CTD-ILD patients using Hamilton Anxiety/Depression Rating Scale (HAM-A/D), respectively. Demographic data, clinical symptoms, pulmonary function, and radiological data were collected. Multivariate analysis was performed to identify the independent risk factors of anxiety/depression in CTD-ILD patients.
Result
A total of 118 patients with CTD-ILD were enrolled. Among them, 66 patients (55.93%) with anxiety symptoms (HAM-A > 7), 55 patients (46.61%) with depression symptoms (HAM-D > 8), while 51patients (43.22%) with both anxiety and depression symptoms. Muscle soreness (OR = 3.451, 95% CI: 1.147–10.384, P = 0.028) is significantly associated with anxiety. And muscle soreness (OR = 4.337, 95% CI: 1.43–13.154, P = 0.01), Raynaud's phenomenon (OR = 4.264, 95% CI: 1.355–13.424, P = 0.013), and lower FVC% predicted (OR = 1.768, 95% CI: 1.152–2.714, P = 0.018) are significantly associated with depression. Besides, muscle soreness (OR = 4.737, 95% CI: 1.451–15.463, P = 0.010), lower FVC% predicted (OR = 1.649, 95% CI: 1.067–2.549, P = 0.024) and more severe dyspnea scaled by mMRC score (OR = 1.725, 95% CI: 1.075–2.769, P = 0.024) were associated with comorbid depression and anxiety.
Conclusion
Anxiety and depression were common in CTD-ILD patients. Impaired respiratory physiology (reduced FVC% predicted, dyspnea) and CTD related symptoms (Raynaud's phenomenon and muscle soreness) were risk factors for anxiety and depression in CTD-ILD patients, which emphasize the importance of focusing on the management of psychological disorders in CTD-ILD patients.
Evaluating the effects of CMIP6 model uncertainty on extreme flows of the Caspian Hyrcanian forest watersheds by BMA method
Authors: Lotfirad Morteza , Adib Arash , Riyahi Mohammad Mehdi , Jafarpour Mohammad
Published: March 2022

This paper investigates the climate change effects on the hydrological and meteorological parameters of the Navrood Basin (a Caspian Hyrcanian forest watershed) in the north of Iran. Outputs of seven CMIP6 GCMs (Tmin, Tmax, and precipitation) under two scenarios, SSP2-4.5 and SSP5-8.5, were utilized. This study considered the historical period (1994 to 2014), the near future (2025 to 2049), the middle future (2050 to 2074), and the far future (2075 to 2099). The EDCDFm and MBA methods were used for bias correction of the outputs of GCMs and combine GCMs, respectively. The LARS-WG model was used for statistical downscaling. The IHACRES model calculated the runoff. The annual Tmin under SSP2-4.5 and SSP5-8.5 will increase 1.04 °C and 1.25 °C in the near future, 1.55 °C and 2.48 °C in the middle future and, 2.09 °C and 4.11 °C in the far future, respectively. The annual Tmax under SSP2-4.5 and SSP5-8.5 will increase 1.59 °C and 1.38 °C in the near future, 1.98 °C and 3.02 °C in the middle future and, 2.58 °C and 4.94 °C in the far future, respectively. The annual precipitation (PCP) under SSP2-4.5 and SSP5-8.5 will increase 6.81% and 7.11% in the near future, 6.15% and 4.43% in the middle future, 8.63% and 6.58% in the far future, respectively. Finally, the annual runoff under SSP2-4.5 and SSP5-8.5 will increase 16.3% and 15.4% in the near future, 14.8% and 10.6% in the middle future and, 19.2% and 15.1% in the far future, respectively.
Development and Characterization of Novel Hybrid Materials Formed from ZnO-SiO2-Modified and Polyaniline for Organic Dyes Adsorption and Electrochemical Supercapacitor Applications
Authors: Benchikh Imen , Lahreche Saadia , Benmimoun Youcef , Benyoucef Abdelghani
Published: March 2022

Polyaniline (PANI) coated ZnO-SiO2 based hybrid material was prepared successfully by in-situ polymerization method and the product was analyzed by XPS, XRD, TEM, UV-vis, TGA, FTIR and BET techniques. According to these characterization results, ZnO were successfully incorporated with SiO2 and PANI matrix was also supported on ZnO–SiO2. The optical band gap was calculated from the Tauc’s plot it has been found 2.89 eV. The development of a PANI@ZnO–SiO2 is a new way to achieve better adsorption efficacy for Congo Red (CR) and Methylene Blue (MB) dyes in aqueous solutions due to the engineered excellent porous structure, which was 83.82 and 71.19 mg.g− 1, respectively. Moreover, this work reports also an extensive study of the effect of the SiO2 on the electrochemical performance of hybrid material based on ZnO and PANI employing cyclic voltammetry. It was found that the perfect stability, which can be sustained during a longtime of the galvanostatic charge-discharge (GCD) operation. The results reveal a superior cycling stability, with 90.1% capacitance retention after 1500 cycles.
MicroRNA-140-5p was involved in osteonecrosis of the femoral head by inhibiting osteogenic diffentiation and migration of hBMSCs
Authors: Hui Pu-Sheng , Qi Jia-Yi , Cao Chun-hao , Rong Xiao-Feng
Published: March 2022

Background: Osteonecrosis of the femoral head (ONFH) is a common but intractable disease and usually leads to disability. The unclear mechanism caused the trouble in diagnosis and early therapy of ONFH. Methods: We downloaded and analyzed the traumatic ONFH miRNA expression profile GSE89587. Then western blotting, PCR, alkaline phosphatase staining, wound healing assay and alizarin red S staining was used to investigate the effect of the selected miR-140-5p on human bone marrow-derived stem cells (hBMSCs). Furthermore, the relationship between miR-140-5p and BMP2 was detected by WB and we also used a siRNA of BMP2 to study whether silencing miR-140-5p could mitigate the damage caused by BMP2 interference.Results: 6 up-regulated miRNAs and 12 down-regulated miRNAs were identified and an upregulated miR-140-5p was selected for the downstream experiments. The further experiments showed that miR-140-5p upregulation in hBMSCs inhibited the expression of collagen type 1, OCN, and BMP2, reduced the ALP activity, mineralization, and migration ability of hBMSCs. In addition, inhibition of BMP2 inhibited osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis, while silencing miR-140-5p promoted osteogenesis of hBMSCs by regulating the BMP2-SMAD1/5/9-RUNX2 axis. Our study showed that miR-140-5p may be an emerging and valuable target for studying the mechanism of ONFH.
Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing
Authors: Diricks Margo , Merker Matthias , Wetzstein Nils , Kohl Thomas , Niemann Stefan , Maurer Florian
Published: March 2022

Mycobacterium abscessus (Mab) is an emerging multidrug-resistant nontuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Over 2000 isolates of Mab, covering all subspecies and main dominant circulating clones as well as extra-pulmonary outbreak strains and sequential isolates of chronically infected cystic fibrosis patients, were used to validate the scheme and set genetic distance thresholds to delineate transmission events and global population structure. Most global clonal complexes previously classified using cgSNP were confirmed by our cgMLST approach, and also correlated well with traditional 7-loci MLST sequence types. 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used for initial cluster analysis and to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.
Insilco Analysis of Anti-malarial drug resistant genes of Plasmodium falciparum 3D7 to understand its expression
Authors: Waktole Gemechis , Donghee Cho
Published: March 2022

Malaria is one amongst the foremost necessary infectious diseases that threaten 1/2 the world’s population. Federal Democratic Republic of Ethiopia is among countries with a high protozoan infection burden. Plasmodium falciparum is that the commonest (64%) reason for Malaria infection in Federal Democratic Republic of Ethiopia whereas P. vivax accounts for the remaining cases (34%). Despite various advances in malaria infection management methods, the disease still kills innumerable kids worldwide, principally in desert African countries and protozoan infection still remains a serious public pathological state in Federal Democratic Republic of Ethiopia. Analyzing parasite biology has monumental potential to help each effort at elimination additionally as international efforts toward wipeout. Therefore, this study is aimed to in atomic number 14 analysis of regulative parts like CpG islands, transcription factors (TFs) and their corresponding binding sites (TFBSs) concerned within the regulation of organic phenomenon of Plasmodium falciparum 3D7 isolates drug-resistant genes. during this analysis, 9 drug resistance touching cistron secret writing sequences, on the market within the NCBI information with the beginning sequence at the start of the sequence and solely useful genes (protein-coding) were deliberated. consequently, the promoter prediction by neural network promoter prediction result showed Plasmodium falciparum 3D7 drug resistance touching genes have 1–6 toxic shock syndrome and 5 common candidate motifs (MPfI, MPfII, MPfIII, MPfIV, and MPfV) were known. The study indicates the poor incidence of CpG islands in each cistron body and promoter regions which can have an effect on the access of the promoter region of genes to their transcription factors, therefore touching their expression. In general, this in silico analysis of cistrons secret writing for Plasmodium falciparum drug resistance touching genes can be useful to feature data concerning the molecular knowledge and collateral to spot gene regulative parts within the promoter regions.
CarpeDiem: Exploring health pillars to define a holistic recommender system to accomplish a sutainable change in lifestlye habits
Authors: Migliorelli Carolina , Ros-Freixedes Laura , Gómez-Martínez Meritxell , Orte Silvia
Published: March 2022

To live longer, healthier, and more active, people at any age have to follow simple and clear suggestions that cover the 3 main pillars of health: physical activity, nutrition, and sleeping. Unfortunately, due to the intrinsic (e.g., daily-life habits) and extrinsic (e.g., environmental change) factors, people are far to have a healthy life and, thus, there is an increase of chronic diseases, mental disorders, and premature death. This paper presents the approach followed in CarpeDiem, an IoT-based system focused on self-management as a way to engage and empower citizens in order to improve their quality of life and to allow a better follow-up of their own health. The CarpeDiem self-management system is intelligent and autonomous, and it is aimed at monitoring physical-and sleeping-activity, nutrition, as well as environmental data and lifestyle habits, with the final goal of providing personalized recommendations and nudges to foster behaviour change towards healthier behaviours. CarpeDiem system currently designed to provide individual recommendations in each one of the domains. However, there is increasing evidence that these three pillars influence each other. Subsequently, the final goal of the application is to assemble the information provided by the three pillars together and supply holistic recommendations to the users to induce a meaningful and enduring change in their behaviours. The purpose of this study is to analyze the existing associations between the three mentioned pillars, by using data from a previous pilot and current state of the art, to later design intelligent recommendations capable of producing lasting behavioural changes in the user’s community.
Towards robust in vivo quantification of oscillating biomagnetic fields using Rotary Excitation based MRI
Authors: Gram Maximilian , Albertova Petra , Schirmer Verena , Blaimer Martin , Gamer Matthias , Herrmann Martin J. , Nordbeck Peter , Jakob Peter
Published: March 2022

Spin-lock based functional magnetic resonance imaging (fMRI) has the potential for direct spatially-resolved detection of neuronal activity and thus may represent an important step for basic research in neuroscience. In this work, the corresponding fundamental effect of Rotary EXcitation (REX) is investigated both in simulations as well as in phantom and in vivo experiments. An empirical law for predicting optimal spin-lock pulse durations for maximum magnetic field sensitivity was found. Experimental conditions were established that allow robust detection of ultra-weak magnetic field oscillations with simultaneous compensation of static field inhomogeneities. Furthermore, this work presents a novel concept for the emulation of brain activity utilizing the built-in MRI gradient system, which allows REX sequences to be validated in vivo under controlled and reproducible conditions. Via transmission of Rotary EXcitation (tREX), we successfully detected magnetic field oscillations in the lower nano-Tesla range in brain tissue. Moreover, tREX paves the way for the quantification of biomagnetic fields.
Development of multi-epitope chimeric antigens for scrub typhus diagnostics and vaccines: An in-silico investigation
Authors: Namsa Nima D , Dolley Anutee , Goswami Himanshu Ballav , Dowerah Dikshita , Dey Upalabdha , Kumar Aditya , Sharma Debashree Saikia , Hmuaka Vanlal , Mukhopadhyay Rupak , Kundu Debasree , Varghese George M. , Doley Robin , Deka Ramesh , Saharia Niruprabha
Published: March 2022

Scrub typhus is a zoonotic bacterial disease caused by Orientia tsutsugamushi and accounts for up to 20% of common febrile illnesses and hospitalizations. The main obstacle to vaccine development is the lack of identification of relevant immunodominant antigens that stimulate broad-spectrum immune responses, including antibody, CD4 + T cells, and CD8 + T cells production. We examined the 56-kDa type-specific cell membrane surface protein (TSA56) and ScaA as candidates for developing vaccine and diagnostic assays using an in-silico approach. We predicted 35 linear and 29 conformational immunogenic B-cell epitopes and 51 non-overlapping strong binders of MHC class I and 27 for MHC class II T-cell epitopes in the conserved and variable regions of TSA56. We used this information to design effective multi-epitope vaccine constructs that are predicted to stimulate cross-protective immunity. Furthermore, the epitope-based vaccine constructs showed antigenic, non-allergenic, and interferon gamma-inducing properties, as predicted by online servers. We cloned the chimeric gene into a pET-15b plasmid vector and successfully expressed the histidine-tagged recombinant antigen in an Escherichia coli expression system. The findings the present study provide a platform for validations of the predicted epitopes and chimeric antigens for designing effective epitope-based vaccine candidates and serological diagnostic assays against scrub typhus.
Does the Modality of Renal Replacement Therapy Affect Gastrointestinal Symptoms and Findings?
Authors: KARAHAN Doğu , ŞAHİN İdris
Published: March 2022

OBJECTİVE: Chronic kidney disease (CKD) affects gastrointestinal system (GIS) and causes histological, functional and mucosal changes. There are scarce data investigating GIS symptoms and findings in patients with CKD stage III-V, receiving hemodialysis (HD) and peritoneal dialysis (PD). In this study, we aimed to evaluate the frequency of gastrointestinal symptoms and findings and effect of renal replacement therapy on GIS.METHOD: A total of 300 patients (97 in CKD stage III-V, 92 PD, 101 HD) included to this study. Gastrointestinal complaints and diseases, background characteristics of patients, drugs they used were questioned by interviews, forms were filled and examinations of patients were performed. Results of upper GIS endoscopy, colonoscopy, abdominal ultrasonography and tomography of patients were evaluated.RESULTS: The most common complaints were dyspepsia (50%), nausea (45%), epigastric pain (44%) among all patients, generally. Gastrointestinal disorders like gastritis (62%), gastroesophageal reflux (39%) were frequent in patients. Ratio of patients with weight loss was 20% in predialysis and 8% in PD and the ratio was higher in predialysis group significantly (p=0,016). It is found that gastritis ratio 70% in PD, 55% in HD, hemorrhoids ratio 24% in PD, 12% in HD. Gastritis and hemorrhoids ratio was higher in the PD group than in the HD group significantly (p=0.043,p= 0.028), otherwise there wasn’t difference between PD and predialysis group, significantly.CONCLUSİON: This study showed that; gastrointestinal symptoms and disorders were very common in CKD, beside of this; while gastritis and hemorrhoids were more frequent in the PD, esophagitis and hiatal hernia were more frequent in the HD.
siRNA-mediated gene knockdown via electroporation in hydrozoan jellyfish embryos
Authors: Nakajima Yu-ichiro , Masuda-Ozawa Tokiha , Fujita Sosuke , Nakamura Ryotaro , Watanabe Hiroshi , Kuranaga Erina
Published: March 2022

As the sister group to bilaterians, cnidarians stand in a unique phylogenetic position that provides insights into evolutionary aspects of animal development, physiology, and behavior. While cnidarians are classified into two types, sessile polyps and free-swimming medusae, most studies at the cellular and molecular levels have been conducted on representative polyp-type cnidarians and have established techniques of genetic manipulation. Recently, gene knockdown by delivery of short hairpin RNAs into eggs via electroporation has been introduced to two polyp-type cnidarians, Nematostella vectensis and Hydractinia symbiolongicarpus, enabling systematic loss-of-function experiments. By contrast, current methods of genetic manipulation for medusa-type cnidarians, or jellyfish, are quite limited, and reliable techniques are required to interrogate function of specific genes. Here, we present a method to knockdown target genes by small interfering RNA (siRNA) delivery into fertilized eggs via electroporation, using the hydrozoan jellyfish, Clytia hemisphaerica and Cladonema paciificum. We show that siRNAs targeting endogenous GFP1 and Wnt3 in Clytia efficiently knockdown gene expression and result in known planula phenotypes: loss of green fluorescence and defects in axial patterning, respectively. We also successfully knock down endogenous Wnt3 in Cladonema by siRNAs electroporation, which circumvents the technical difficulty of microinjecting small eggs. Unexpectedly, Wnt3 knockdown in Cladonema does not induce morphological defects in planula, suggesting a distinct mechanism that operates during embryogenesis. Our method for electroporation of siRNAs targeting specific genes is applicable to other animals, including and beyond jellyfish species, and will facilitate the investigation and understanding of myriad aspects of animal development.
Antitumor effect of polyphyllin D on liver metastases of neuroblastoma
Authors: Kondo Yasuhiro , Watanabe Shunsuke , Naoe Atsuki , Takeuchi Toshiyuki , Niimi Atsuko , Suzuki Motoshi , Asai Naoya , Okada Seiji , Tsuchiya Tomonori , Murayama Mika , Yasui Toshihiro , Inoue Mikihiro , Suzuki Tatsuya
Published: March 2022

PurposeWe previously reported that polyphyllin D, a main component of the traditional Chinese medicinal herb Paris polyphylla, exhibited anticancer effects in vitro against human neuroblastoma cells. The aim of this investigation was to examine the presence or absence of in vivo anti-metastasis effects of polyphyllin D.MethodsSubcutaneous and intraperitoneal tumors, and metastasis models were established in immune-deficient BALB/c nude and BALB/c Rag-2/Jak3 double-deficient (BRJ) mice using the human neuroblastoma cell lines IMR-32, LA-N-2, or NB-69. For evaluating polyphyllin D activity, we used a mouse model of metastasis of the IMR-32 cell line and analyzed the livers of the phosphate buffer solution- and polyphyllin D- treated groups.ResultsLiver metastasis and intraperitoneal dissemination models were successfully established in immune-deficient BRJ mice using the three human neuroblastoma cell lines. In the liver metastasis model, we found that polyphyllin D suppressed both the number and total area of metastatic foci.ConclusionsWe developed a mouse model of neuroblastoma metastasis and demonstrated for the first time that polyphyllin D has an antitumor effect on neuroblastoma liver metastases.
Integrated Bioinformatics Analysis Reveals Marker Genes and Immune Infiltration for Pulmonary Arterial Hypertension
Authors: Tang Shengxin , Zeng Xiaojuan , Liu Yue , Liu Bin
Published: March 2022

Background
It is well known that Pulmonary arterial hypertension (PAH) is a chronic cardiopulmonary syndrome with high pulmonary vascular load and eventually causing RV heart failure even death. This research is aimed to detect the underlying key genes and potential mechanism of PAH using some kinds of bioinformatic tools.
Methods
The gene microarrays GSE22356, GSE131793 and GSE168905 were acquired from the GEO. Subsequently, a host of bioinformatics techniques, for instance, DAVID for GO annotation and KEGG enrichment analysis, STING for PPI, Cytoscape software etc. were utilized to investigate DEGs between PAH and healthy controls. Additionally, we also predicted the transcription factors regulating DEGs. And CIBERSORT was used to conduct immune infiltration analysis.
Results
we identified 403 up-regulated DEGs and 874 down-regulated DEGs in peripheral blood samples between 32 PAH patients and 29 controls. These functional changes of DEGs were mainly enriched in protein binding, extracellular exosome, extracellular space, extracellular region and integral component of plasma membrane. SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B were detected as hub genes. These key genes are chiefly enriched at extracellular exosome, hemoglobin complex, blood microparticle, oxygen transporter activity. Among TF-DEGs network, 42 target DEGs and 6 TFs were predicted with an NES > 4 (TEAD4, TGIF2LY, GATA5, GATA1, GATA2, FOS). Immune infiltration analysis showed that monocytes occupied the largest proportion of immune cells.
Conclusion
We detected SLC4A1, AHSP, ALAS2, CA1, HBD, SNCA, HBM, SELENBP1, SERPINE1 and ITGA2B as the most significant markers of PAH. The PAH patients had higher infiltration of NK cell activation, monocyte, T cell CD4 memory activation, and mast cell than healthy controls and lower infiltration of T cell CD4 naive. These identified genes and these immune cells probably have precise regulatory relationships in the development of PAH.
Heart Disease Prediction Using Scaled Conjugate Gradient Back Propagation of Artificial Neural Network
Authors: PAUL BANIBRATA , Karn Bhaskar
Published: March 2022

Heart disease is a deadly disease in human life. The mortality rate from any disease is the highest in the world. Therefore, before reaching the final stage of this heart disease, all precautionary measures must be taken. For this reason without the help of any kind of traditional methods, if we can scientifically diagnose heart disease at an early stage through various decision support systems, then surely death rate of this disease will decrease in the whole world. Many researchers investigate the diagnosis of heart disease by creating various intelligent medical decision support systems. Artificial neural network concepts represent the highest predictive accuracy over medical data compared to other decision support systems. In this paper we propose a better prediction method for the existence of heart disease through the scaled conjugate gradient back propagation of artificial neural networks using K-fold cross validation. For cardiac datasets, the University of California Irvine (UCI) Machine Learning Repository and IEEE data port have been used. For Cleveland processed heart dataset, the proposed system uses 13 input attributes and provides minimum 63.3803% & maximum 100% accurate results similarly for Cleveland Hungarian Statlog heart dataset the proposed system uses 11 input attributes and provides minimum 88.4754% & maximum 100% accurate results by estimating the presence and absence of heart disease during testing.
Interaction of Diabetes Mellitus and Chronic Kidney Disease on Outcome in Heart Failure with Reduced Ejection Fraction
Authors: Yang Yanfang , Huang Zhidong , Wu Bo , Lu Jin , Xiu Jiaming , Tu Jiabin , Pan Yuxiong , Bao Kunming , Wang Junjie , Chen Weihua , Liu Jin , Chen Shiqun , Chen Kaihong , Chen Liling
Published: March 2022

Background
Diabetes mellitus (DM) is common in patients with heart failure (HF). But the harmful effect of DM on mortality in patients with HF remains controversial. Furthermore, it seems that no consistent conclusion on whether chronic kidney disease (CKD) modifies the relationship of DM and poor prognosis in patients with HF.
Methods
We analyzed the individuals with heart failure with reduced ejection fraction (HFrEF) from the Cardiorenal ImprovemeNt (CIN) cohort between January 2007 to December 2018. The primary endpoint was all-cause mortality. The patients were divided into four groups (control vs. DM alone vs. CKD alone vs. DM and CKD). Multivariate Cox proportional hazards analysis was conducted to examine the association among DM, CKD and all-cause mortality.
Results
There were 3,273 patients included in this study (mean age: 62.7 ± 10.9 years, 20.4% were female). During a median follow-up of 5.0 years (interquartile range: 3.0 to 7.6 years), 740 (22.6%) patients died. Patients with DM have a higher risk of all-cause mortality (HR [95% confidence interval (CI)]:1.32[1.10–1.57]) than those without DM. In patients with CKD, DM had a 61% (HR [95% CI]:1.61[1.26–2.06]) increased adjusted risk of death relative to non-DM, while in patients with non-CKD, there was no significantly difference in risk of all-cause mortality (HR [95% CI]:1.01[0.77–1.32]) between DM and non-DM (p for interaction = 0.013).
Conclusions
Diabetes is a potent risk factor for mortality in patients with HFrEF. Furthermore, DM had a substantially different effect on all-cause mortality depending on CKD. The association between DM and all-cause mortality was only observed in patients with CKD.
WITHDRAWN: Factors Influencing Residents' Satisfaction Under Multiple Sources of Environmental Pollution: A Structural Equation Modelling Approach
Authors: Pham Thoa Thi Kim , Tran Phuong Thi Minh , Nguyen Teron
Published: March 2022

Residents living nearby multiple sources of environmental pollution are suffering from adverse health effects and many other factors. However, very few studies focus on the complex interaction between multiple effects on residents' satisfaction. This study reports a case study in Phuoc Tuong quarry and Khanh Son landfill in Danang city, Vietnam, the two environmental hotspots hindering city development toward sustainability. Using Structural Equation Modelling (SEM) approach and 420 valid questionnaires, the relationship between measured variables and latent constructs was analyzed and established. Due to the wider spread of influencing area, the effects of Phuoc Tuong quarry are higher than Khanh Son landfill (path coefficient |ß| = 0.265 > 0.161), whereas, living distance (ß = 0.165) and residents' demographics (|ß| = 0.134) are also contributing to residents' satisfaction with business, health and life in overall. Among them, living distance from the pollution sources is confirmed to have a positive influence while the rest constructs negatively influence residents' satisfaction. The satisfaction, in turn, has a direct negative influence on residents' moving intention, meaning residents desire to resettle their living locations when dissatisfied with the current living conditions. Based on the study findings, practical applications can be focused more efficiently on appropriate measures to reduce the harmful effects of the quarry as compared to the landfill. Also, urgent measures should also be focused on the resident group living within 1 km from both pollution sources.
HPV16 Status Predicts Differential Interactome in Head and Neck Squamous Cell Carcinoma: Potential Prognostic Biomarkers and Therapeutics in Framework of 3P Medicine
Authors: Kori Medi , Arga Kazim Yalcin
Published: March 2022

Human papillomavirus (HPV) infection is one of the causative factors in the development of head and neck squamous cell carcinoma (HNSC). One in four HNSC cases is positive for HPV infection, and HPV16 is the most common infection in HNSC cancer. HPV-positive and HPV-negative HNSC patients differ significantly in their molecular profiles and clinical features. Although the diagnosis and treatment strategies of HNSC patients should differ depending on the HPV status of the patient, there are no specific treatment regimens for these patients today. Given the enormous variation in HNSC cancers depending on HPV status, the 3P framework is of great importance specifically for these patients. In this study we present systemic biomarkers and treatment options tailored to the patient's HPV status. Gene expression levels of HPV16-positive and -negative cancer patients were used as proxies, and the differential interactome algorithm was employed to identify the differential interacting proteins (DIPs) around which significant changes occur at protein-protein interactome level. By assessing the prognostic capabilities and druggabilities of DIPs and their interacting partners (DIP-centered modules), we were able to introduce eight DIP-centered modules as potential systems biomarkers specialized for either HPV16-positive or HPV16-negative phenotype. The prognostic power of three modules specific for HPV16-positive phenotype was also validated by an independent cohort study. Finally, raloxifene was repositioned as a drug candidate for the treatment of HPV16-positive HNSC patients. With this study, we open new perspectives for the development of effective prognostic and treatment strategies for HNSC patients depending on their HPV16 status.
Consecutive transcutaneous tissue oxygen measurement for determining peripheral revascularization and correlation to ischemic diabetic ulcers outcome
Authors: Sun Haoyi , Wu Yichun , Sung Lichin , Lin Xinyi , Tsai Fengchou , Lin Yenkuang , Tam Kawai , Chang Shuncheng
Published: March 2022

BACKGROUND
The ankle-brachial index (ABI) might underestimate the prevalence of peripheral vascular disease (PVD) in patients with diabetic foot ulcers (DFUs). This study manifested the effectiveness of transcutaneous oxygen pressure (TcPO2) in determining whether PVD should be treated with revascularization.
METHODS
100 patients with diabetic foot ulcers underwent ABI and TcPO2 measurement and were divided into the vascular or nonvascular reconstruction group. TcPO2 and ABI were consecutively measured 4 times within 6 months in patients with DFUs. Differences in TcPO2 values up to 6 months were compared between vascular reconstruction and non-reconstruction groups and patients with and without end-stage renal disease (ESRD).
RESULTS
Of 100 patients with diabetic foot ulcers, 51 who had abnormal transcutaneous oxygen pressure values underwent vascular reconstruction. TcPO2, but not the ABI, measured before treatment significantly differed between the 2 groups. TcPO2 values significantly increased after vascular reconstruction. TcPO2 values gradually decreased during the 6-month follow-up after vascular reconstruction; however, the ABI tended to increase. In patients with ESRD, transcutaneous oxygen pressure values declined significantly and rapidly within 3 months. TcPO2 values before vascular reconstruction were significantly lower in patients receiving amputation than those receiving limb salvage surgery.
CONCLUSIONS AND RELEVANCE:
Compared with ABI, TcPO2 measurement is a more accurate and appropriate method for evaluating ischemic limb perfusion and the necessity of revascularization. TcPO2 measurement should be used as the major follow-up tool, and patients with end-stage renal disease should undergo more follow-ups.
TRIAL REGISTRATION:
Joint Institutional Review Board of Taipei Medical University (N201701054 and N201805105).
The effect of Ethyl methanesulfonate and Methylsalicylate induced on physiological and biochemical characteristics of rice OMCS2000 in anaerobic germination and plant growth under waterlogging
Authors: Dat Luu Khai , Thong Le Minh , Hien Pham Thi Thu , Loi Tran Thuy , Ha Pham Thi Thu
Published: March 2022

Background
The use of direct seeding in lowland rice ecosystems brings many advantages for cultivators such as reducing labor costs, effective water management, early harvesting, and less dependence on herbicides, thus improving tolerance to submergence during germination in rice is the best suggestion. In this study, rice seeds of variety OMCS2000 were treated with different concentrations of Ethyl-methane sulphonate (EMS) (0.1% and 0.125%) and concentration of Methylsalicylate (MeSA) (0.1 mM and 0.125 mM) to examine the positive and negative impact on seed germination, plant height, root length, α-amylase activity, phenolic, and flavonoid content under various water levels for submerged conditions (0, 5, 10, and 15 cm) of plants at 14 days.
Results
Our data showed that 0.1% EMS significantly increased the germination rate, germination vigor index, morphological (root and shoot lengths), and alpha amylase of rice under waterlogging while MeSA significantly reduced them. But we also recognized that MeSA (0.1 mM) significantly improved in phenolic and flavonoid contents of rice under waterlogging.
Conclusion
The treatment with 0.1% EMS showed the highest tolerance to anaerobic conditions which could be recommended to apply in a breeding program new OMCS2000 line for waterlogging tolerance.
Intervention Efficacy of Off-Label use of Alprostadil Lipid Microsphere Injection on Neurosurgical Patients: A Retrospective Before-after Study
Authors: Luo Yuling , Fan Qingze , Yu Yongqi , Zhang Lunhui , Dong Limei , Luo Hongli
Published: March 2022

Background and purpose: As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE1) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE1 is very common. This study aimed to investigate the use of Lipo-PGE1 and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE1 in neurosurgical patients in a Chinese tertiary hospital. Methods: Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE1, judging the rationality of medical records, and establishing reward and punishment mechanism. Results: Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE1. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE1 use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE1 were also obviously decreased. Conclusions: The administrative intervention obviously reduced the off-label use of Lipo-PGE1. However, there still remains a number of inappropriate uses of Lipo-PGE1. To further improve rational use of Lipo-PGE1, the combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.
An early relapse-associated gene signature optimizes prognostic prediction for gastric cancer patients
Authors: Wang Pengchao , Song Qingyu , Xia Qingcheng , Qiu Shipei , Tang Xin , Lu Ming , Zhao Qinghong , Ma Xiang
Published: March 2022

Background: Gastric cancer (GC) is one of the most common cancers in the world. Patients with GC who experienced early relapse have poor prognosis. We aim to develop an early relapse-associated gene signature to optimize prognosis prediction in patients with replapsing GC. Methods: The GC cohorts including GSE62254 set (N=300) and GSE15459 set (N=192) were extracted from Gene Expression Omnibus (GEO) database. Propensity score matching (1:1) based on pathological stage was executed between patients with early relapse and long-term survival from GSE62254 set. Global transcriptome analysis was performed between the two groups to identify early relapse-associated gene. Based on the differentially expressed genes, we developed a classifier incorporating 5 genes that using LASSO Cox regression model. The signature’s prognostic value was internally validated in 210 GC patients and validated in GSE15459 set externally. The patients from GSE62254 set could be divided into high-risk or low-risk group.Results: In the train set, patients in high-risk group had poor prognosis as compared to those in low-risk group [hazard ratio (HR): 3.002, 95% confidence interval (CI): 2.132-4.226, P<0.001)]. Good reproducibility for the prognostic value of early relapse-associated gene signature was verified in the internal validation set (HR: 2.772, 95% CI: 1.836–4.184, P<0.001) and another external validation set (HR: 1.733, 95% CI: 1.149–2.614, P=0.009). Also, we developed a nomogram which integrated the five mRNA classifier, pathological stage and lymph node ratio (LNR) to evaluate prognosis based on GSE62254 set. Time-dependent receiver-operating characteristic at 1 year demonstrated that integrated signature had better prognostic accuracy [area under curve (AUC=0.849)] than the American Joint Commission on Cancer TNM staging system (AUC=0.773) and LNR (AUC=0.811) in GSE62254 set. Conclusions: This study suggest that an early relapse-associated gene signature that can robustly divide gastric cancer patients into two groups with distinctive prognosis. This classifier may contribute to select gastric cancer patients with poor prognosis who require more frequent follow-up and more aggressive therapeutic intervention.
New index using triglyceride-glucose-body mass index for predicting mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Park Pil Gyu , Pyo Jung Yoon , Ahn Sung Soo , Song Jason Jungsik , Park Yong-Beom , Huh Ji Hye , Lee Sang-Won
Published: March 2022

This study aimed to investigated whether triglyceride-glucose-body mass index (TyG-BMI) and a new index using TyG-BMI (NITGB) could predict all-cause mortality in nonobese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The medical records of 78 nonobese AAV patients (BMI < 23.0 kg/m2 for Asian) were retrospectively reviewed. TyG-BMI was calculated by the equation: Ln [triglyceride × fasting glucose/2] × BMI. To develop NITGB, we assigned a weight of a number close to an 0.1 decimal integer to each variable according to the slopes for independent variables with P-value < 0.1 in the multivariable Cox analysis. The median age was 54.3 years and five patients died. When nonobese AAV patients were divided into two groups based on TyG-BMI ≥ 187.74, those with TyG-BMI ≥ 187.74 exhibited a significantly higher risk for all-cause mortality than those without (RR 9.450). Since age (HR 1.324), Birmingham vasculitis activity score (BVAS; HR 1.212), and TyG-BMI ≥ 187.74 (HR 12.168) were independently associated with all-cause mortality, NITGB was developed as follow: age + 0.2 × BVAS + 2.5 × TyG-BMI ≥ 187.74. When nonobese AAV patients were divided into two groups based on NITGB ≥ 27.36, those with NITGB ≥ 27.36 showed a significantly higher risk for all-cause mortality than those without (RR 284.000). Both nonobese AAV patients with TyG-BMI ≥ 187.74 and those with NITGB ≥ 27.36 exhibited significantly higher cumulative rates of all-cause mortality than those without. NITGB along with TyG-BMI could predict all-cause mortality in nonobese AAV patients.
Efficacy and safety for combination of trephine with a new tool in foraminoplasty in percutaneous endoscopic transforaminal discectomy: a retrospective study
Authors: Zhu Guangye , Tang Jingjing , Lin Shaohao , He Jiahui , Ge Zhilin , Zhang Peng , Ren Hui , Cui Jianchao , Liang De , Jiang Xiaobing
Published: March 2022

Background: Foraminoplasty is a critical step in percutaneous endoscopic transforaminal discectomy (PETD) for the treatment of lumbar disc herniation (LDH). It is usually performed using trephine under fluoroscopy guidance and is especially suitable for beginners. However, foraminoplasty with trephine may sometimes leave the cut bone in the body and then even cause neural symptoms. We designed a new tool named anchor drill to assist trephine in performing foraminoplasty. The purpose of this study was to evaluate efficacy and safety for combination of trephine with anchor drill in foraminoplasty.Methods: A retrospective review was performed to identify patients with lumbar disc extrusion or sequestration between January 2018 to January 2021 who underwent PETD. Foraminoplasty using trephine alone or trephine combined with anchor drill under fluoroscopy guidance was performed in all surgeries. Duration of foraminoplasty, endoscopic operation time, fluoroscopy time, bone residual incidence after foraminoplasty and perioperative complications were reviewed. Visual analog scale (VAS) and Japanese Orthopedic Association (JOA) scores were assessed before, 1 day, 3 months and 12 months after surgery for all patients.Results: A total of 100 patients were included (55 in combination group, 45 in trephine group). Bone residual incidence after foraminoplasty of combination group was 9.09%, which was significantly lower than that of trephine group with 33.33% (P＜0.05). Mean endoscopic operation time of combination group was significantly shorter than that of trephine group (P＜0.05). Fluoroscopy time and duration of foraminoplasty showed no significant differences between two cohorts. Total perioperative complication incidence was lower in combination group, among which the neural irritation incidence showed significant difference (combination group: 3.64%, trephine group: 17.78%, P＜0.05). No severe vascular and neurological complications occurred in perioperative period. VAS and JOA scores were compared before and after surgery and differences were statistically significant for all patients (P＜0.001). At each follow-up visit, no significant differences were found in VAS and JOA scores between two cohorts. Conclusions: Combination of trephine with anchor drill was demonstrated to be safe and effective in foraminoplasty in PETD, improving success rate of foraminoplasty and reducing neurological complications relative to using trephine alone.