bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic field filtering of the hinge supercurrent in unconventional metal NiTe2-based Josephson junctions
Authors: Qu Fanming , Le Tian , Zhang Ruihan , Li Changcun , Jiang Ruiyang , Sheng Haohao , Tu Linfeng , Cao Xuewei , Lyu Zhaozheng , Shen Jie , Liu Guangtong , Liu Fucai , Wang Zhijun , Lu Li
Published: April 2023

Topological materials with boundary (surface/edge/hinge) states have attracted tremendous research interest. Besides, unconventional (obstructed atomic) materials have recently drawn lots of attention owing to their obstructed boundary states. Experimentally, Josephson junctions (JJs) constructed on materials with boundary states produce the peculiar boundary supercurrent, which was utilized as a powerful diagnostic approach. Here, we report the observations of conspicuous hinge supercurrent in NiTe2-based JJs. Particularly, applying an in-plane magnetic field along the Josephson current could rapidly suppress the bulk supercurrent and retain the nearly pure hinge supercurrent, namely the magnetic field filtering of supercurrent. Further systematic comparative analysis and theoretical calculations demonstrate the existence of unconventional nature and obstructed hinge states in NiTe2. Our results revealed the unique hinge states in unconventional metal NiTe2, and demonstrated in-plane magnetic field as an efficient method to filter out the futile bulk contributions and thereby to highlight the hinge states hidden in topological/unconventional materials.
Exploring Differentially Expressed Genes of Staphylococcus Aureus Exposed to Human Tonsillar Cells Using Rna Sequencing
Authors: Bastakoti Srijana , Ajayi Clement , Julin Kjersti , Johannessen Mona , Hanssen Anne-Merethe
Published: April 2023

Background: The nose and the throat are the most predominant colonizing sites of Staphylococcus aureus, and colonization is a risk factor for infection. Nasal colonization is well described; however, we have limited knowledge about S. aureus throat colonization. The main objective of this study was to explore differentially expressed genes (DEGs) in S. aureus throat isolate TR145 exposed to human tonsil epithelial cells (HTEpiC) by using RNA sequencing (RNA-seq) and pathway analysis. DEGs in S. aureus at 1 h and 3 h interaction with its host were explored.
Results: All samples after 3 h of exposure showed more than 65 % of RNA reads uniquely mapped with its reference genome. Mapping efficacy at 1 h of exposure condition was identified to range from 20 % to 93 %. Downstream analysis of the obtained gene read counts, revealed putative transcripts expressed upon S. aureus exposure to tonsillar cells. A total of 508 DEGs were identified including unique (1 h, 160 DEGs and 3 h, 78 DEGs) and commonly shared genes (1h and 3h, 270 DEGs). Among the DEGs, were genes encoding proteins involved in adhesion and immune evasion, as well as iron acquisition and transport. Reverse transcription qPCR was done on selected genes, and the results correlated with the RNA-seq data.
Conclusion: We have shown the suitability of using HTEpiC as an in vitro model for investigating key determinants in S. aureus during co-incubation with host cells. Several DEGs were unique after 1 or 3 h exposure to host cells, while others were commonly expressed at both time points. As their expression is induced upon meeting with host, they might be explored further for future targets for intervention to prevent either colonization or infection in the throat.
Cost-effectiveness analysis of prophylactic laser peripheral iridotomy for primary angle-closure suspect in Japan
Authors: Fujita Asahi , Konishi Takaaki , Sakata Rei , Hashimoto Yohei , Yasunaga Hideo , Aiahra Makoto
Published: April 2023

Background/Objectives:
This study aimed to compare the cost-effectiveness of prophylactic laser peripheral iridotomy (LPI) with that of observation for primary angle-closure suspect (PACS) in Japan.
Subjects/Methods:
A Markov model was developed to compare the costs and utilities of prophylactic LPI with those of observation of 40-year-old patients with PACS. In the model with a yearly cycle over a 20-year time horizon, the disease was postulated to irreversibly progress from PACS to primary angle closure, followed by primary angle-closure glaucoma, unilateral blindness, and bilateral blindness. The parameters were estimated based on a recent randomised controlled trial and analyses of Japanese claims data. The incremental cost-effectiveness ratio was estimated from the healthcare payer’s perspective and evaluated as the willingness-to-pay 5 million Japanese Yen per quality-adjusted life-year. The observation period was shortened, and the age at entry into the cohort was changed to 50 years in the sensitivity analyses. We conducted one-way deterministic sensitivity analysis and probabilistic sensitivity analysis with Monte Carlo simulations with 10 000 iterations.
Results
The incremental cost-effectiveness ratio of LPI was 2 270 224 Japanese Yen (14 189 pounds sterling) per quality-adjusted life-year, which was below the willingness-to-pay threshold. The ratios were approximately 4 and 8 million in the 15-year and 10-year time horizons, respectively. Increasing the age at entry had little influence on the incremental cost-effectiveness ratio. The deterministic and probabilistic sensitivity analyses indicated that the results were robust.
Conclusions
Our results indicate that prophylactic LPI for middle-aged patients with PACS is cost-effective in Japan.
Protective effect of Allium jesdianum in an Alzheimer's disease induced rat model
Authors: Kamranfar Farzaneh , Jaktaji Razieh Pourahmad , Shirani Kobra , Jamshidi Amirhossein , Samiei Fatemeh , Arjmand Abdollah , Khoramjouy Mona , Faizi Mehrdad , Pourahmad Jalal
Published: April 2023

Aims: Alzheimer is a multifactorial disease that is caused by several different etiopathogenic mechanisms. The aim of this study is to evaluate the protective effects of Allium jesdianum extract on cognitive dysfunction, mitochondrial/cellular, and genetic parameters in Streptozotocin-induced Alzheimer's disease (AD) Rat Model.
Main methods: A single dose of STZ (3 mg/kg, i.c.v.) was injected to male Wistar rats in order to establish a model of sporadic AD. A. jesdianum extract (100,200, 400 mg/kg/day) and donepezil (5 mg/kg/day) were administered through oral gavage as treatment for 14 days after model induction. Cognitive function (radial arm water maze test), mitochondrial toxicity parameters consisting succinate dehydrogenase (SDH) activity, mitochondrial ROS formation, MMP decline, mitochondrial swelling and efflux of cytochrome c in various parts of the rat brain (whole brain, frontal cortex, hippocampus and cerebellum), and miR-330, miR-132, Bax and Bcl-2 genes expression in isolated rat brain neurons through RT-qPCR analysis were evaluated.
Key findings: A.jesdianum extract significantly attenuated i.c.v-STZ-induced cognitive dysfunction and mitochondrial upstream toxic events. As a result of STZ injection, Bax gene was highly expressed, whereas miR-330, miR-132 and Bcl-2 gene were poorly expressed and A. jesdianumreverses the expression of the above miRNAs and genes in favor of improving AD and reducing neuronal apoptosis.
Significance: A. jesdianum showed the neuroprotective capability against oxidative stress and cognitive impairment induced by STZ in rats shows its helpful therapeutic worth in AD.
Investigating the potential role of USP18 in atherosclerosis based on bioinformatics analysis
Authors: An Yang , Zhang Qiaojun , Liu Jiangjin , Zhou Hongmei , Xia Bing , Wan Chanwu , Lu Yanlin , Yu Yanni , Wang Jie , Dai Jialin
Published: April 2023

Background: Ubiquitin-specific protease 18 (USP18), is a member of the ubiquitin-specific protease family. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we aimed to investigate the expression pattern of USP18 in atherosclerosis and its relationship between the extent of atherosclerotic and the cholesterol transporter protein ABCG1.
Methods: GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ATP-binding cassette transporter protein G1 (ABCG1). Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescencewas performed for co-localization analysis of USP18 and ABCG1
Results: Bioinformatics analysis identified 462 DEGs including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). USP18 expression is upregulated in patients with coronary artery disease and negatively correlates with the extent of atherosclerosis. At the same time, The expression of ABCG1 is downregulated in CHD and SCD patients and is more pronounced in SCD patients. In atherosclerotic tissues, USP18 and ABCG1 expression were positively correlated. In addition, double immunofluorescence assay showed co-localization of USP18 and ABCG1.
Conclusions: USP18 is a differentially expressed gene of FH, and its expression in atherosclerosis is closely related to the extent of atherosclerosis.
Integrative proteomics and metabolomics data analysis exploring the mechanism of brain injury after cardiac surgery in chronic stress rats
Authors: Yan Haoqi , Wang Hongbai , Chen Wenlin , Jia Yuan , Yan Fuxia , Yuan Su
Published: April 2023

Objective
Preoperative chronic stress (CS) is associated with postoperative brain injury in patients undergoing open heart cardiac surgery. This research is to explore the potential molecular biological mechanisms of brain damage following cardiac surgery in preoperative CS rats by the analyses combining proteomics and metabolomics.
Methods
We constructed the chronic unpredictable stress (CUS) and cardiac surgery models in adult rats. We proved the brain injury in CUS cardiac surgery rats by Hematoxylin-Eosin(H&E) staining, followed by separating the hippocampal tissue and investigating the potential mechanisms of brain injury by the methods of data-independent acquisition proteomics and untargeted metabolomics.
Results
The signaling pathways of glycoproteins and metabolism of amino acids were the main possible mechanisms of brain injury in CUS rats following cardiac surgery according to the proteomics and metabolomics alone. The association analysis of proteomics and metabolomics demonstrated the pathways of lysine degradation and β-alanine metabolism may be the main mechanism of cardiac surgery related brain injury in preoperative CUS rats.
Conclusions
The pathways of lysine degradation and β-alanine metabolism may be the potential mechanisms of brain injury in CUS rats following cardiac surgery. We should focus on the varieties of bioproteins and metabolites in these pathways, and related changes in other signaling pathways induced by the two pathways.
Effects of remimazolam combined with sufentanil on hemodynamics during anesthetic induction in advanced-age patients with hypertension undergoing orthopedic surgery of the lower limbs：a randomized,controlled trial
Authors: xu qiaomin , WU Jimin , SHAN Weifeng , DUAN Gongchen , LAN Haiyan
Published: April 2023

Purpose
This study was performed to observe the effect of remimazolam combined with sufentanil on hemodynamics during anesthetic induction in advanced-age patients with hypertension undergoing orthopedic surgery of the lower limbs.
Methods
This randomized controlled trial included 60 advanced-age patients with hypertension who were undergoing orthopedic surgery of the lower limbs. The patients were randomly assigned to undergo general anesthesia with either remimazolam (group R) or propofol (group P, n = 30, each group).The MAP,HR,CO,CI,SVR and pulse oxygen saturation were recorded. The disappearance time of the eyelash reflex, injection pain, hypotension, bradycardia, hiccuping, nausea and vomiting, and other adverse events were observed.
Results
The MAP, HR, CO, CI, and SVR were significantly higher in Group R than P at T1, T2, T3, and T4 (P < 0.05). In Group P, the MAP, HR, CO, and CI were significantly lower and the SVR was significantly higher at T1, T2, T3, and T4 than at T0 (P < 0.05). The disappearance time of the eyelash reflex was significantly longer in Group R than P, and the injection pain, hypotension, and bradycardia were significantly lower in Group R than P (P < 0.05). There was no significant difference in hiccupping or nausea and vomiting between the two groups (P > 0.05).
Conclusion
The combination of remimazolam and sufentanil for induction of general anesthesia produces only small hemodynamic fluctuation, maintains stability of the circulation, and has few adverse effects, making it more suitable for advanced-age patients with hypertension.
Haploinsufficiency of ZNF251 causes DNA-PKcs-dependent resistance to PARP inhibitors in BRCA1-mutated cancer cells
Authors: Li Huan , Chatla Srinivas , Liu Xiaolei , Vekariya Umeshkumar , Kim Dongwook , Walt Matthew , Lian Zhaorui , Morton George , Feng Zijie , Yang Dan , Liu Hongjun , Reed Katherine , Childers Wayne , Yu Xiang , Madzo Jozef , Chitrala Kumaraswamy Naidu , Skorski Tomasz , Huang Jian
Published: April 2023

Poly (ADP-ribose) polymerase (PARP) inhibitors represent a promising new class of agents that have demonstrated efficacy in treating various cancers, particularly those that carry BRCA1/2 mutations. The cancer associated BRCA1/2 mutations disrupt DNA double strand break (DSB) repair by homologous recombination (HR). PARP inhibitors (PARPis) have been applied to trigger synthetic lethality in BRCA1/2-mutated cancer cells by promoting the accumulation of toxic DSBs. Unfortunately, resistance to PARPis is common and can occur through multiple mechanisms, including the restoration of HR and/or the stabilization of replication forks. To gain a better understanding of the mechanisms underlying PARPi resistance, we conducted an unbiased CRISPR-pooled genome-wide library screen to identify new genes whose deficiency confers resistance to the PARPi olaparib. Our study revealed that ZNF251, a transcription factor, is a novel gene whose haploinsufficiency confers PARPi resistance in multiple breast and ovarian cancer lines harboring BRCA1 mutations. Mechanistically, we discovered that ZNF251 haploinsufficiency leads to constitutive stimulation of DNA-PKcs-dependent non-homologous end joining (NHEJ) repair of DSBs and DNA-PKcs-mediated fork protection in BRCA1-mutated cancer cells (BRCA1mut + ZNF251KD). Moreover, we demonstrated that DNA-PKcs inhibitors can restore PARPi sensitivity in BRCA1mut + ZNF251KD cells ex vivo and in vivo. Our findings provide important insights into the mechanisms underlying PARPi resistance and highlight the unexpected role of DNA-PKcs in this phenomenon.
Flipped Learning as an Educational Model in a Cardiology Residency Program
Authors: Sierra-Fernández Carlos Rafael , Huipe-Dimas Alejandra , Garnica-Geronimo Luis Rodrigo , Trevethan-Cravioto Sergio Arnulfo , López-Meneses Mauricio , Azar-Manzur Francisco Javier
Published: April 2023

Introduction: Flipped learning (FL) is a model which allows students to adjust their study rhythm by taking advantage of class time to apply their knowledge. Although FL meets many of the needs of the traditional lecture-based model and the exclusively virtual model, its effectiveness in medical residency programs has not been thoroughly studied. Our study evaluates the efficacy of an FL model in a cardiology residency program based on the satisfaction and academic performance of the participants. Method: A prospective, observational, and descriptive study was conducted at Ignacio Chávez National Institute of Cardiology in Mexico City to evaluate the satisfaction and effectiveness of an FL model for acquiring competencies in electrocardiographic diagnosis among thirty-one first-year cardiology residents. The Advanced Electrocardiography Workshop and a virtual classroom were designed for the intervention. Four teachers taught the workshop and video classes, and ten medical specialists from the participants’ areas of work performed evaluations of practical skills before and after the intervention.
Results: 75% of the participants rated the intervention as very favorable compared to the traditional and virtual models. The main advantages offered by the FL model were identified. An improvement of high statistical significance was observed in participants’ academic performance after the intervention (P value <0.001).
Conclusion:The FL model has a high degree of acceptance among participants and teachers. Our study shows an improvement in academic performance after the intervention. Considering that the FL model is flexible and reproducible in other areas of medicine, it represents an excellent educational alternative that meets current needs.
Cardiology specialists versus other specialty physicians in the quality of anticoagulant therapy management for nonvalvular atrial fibrillation (NVAF) patients: A retrospective observational study
Authors: Liu Puqing , Yuan Fang , Zhang Yi , Chen Jingwen
Published: April 2023

Objective: Nonvalvular atrial fibrillation (NVAF) patients are increasingly being admitted in hospital and distributed both in the cardiology department and other departments. The perception and experience on anticoagulant therapy of clinical physicians are related to the quality of anticoagulation in NVAF patients. Our study aimed to explore the difference of anticoagulation quality between cardiology specialists and other specialty physicians.
Methods: A retrospective investigation was conducted in a Chinese tertiary hospital to collect patients with NVAF who were classified in the cardiology specialists managed anticoagulation care group (CMAC) group or other specialty physicians’ managed anticoagulation care (OMAC) group according to admission departments. The primary outcomes included emergency visiting events, bleeding events and thrombotic events. The secondary outcomes were practice of thrombotic and bleeding risk assessment, qualified warfarin TTR, appropriate medication of DOACs, patients’ follow-up rate and doctors’ knowledge on anticoagulant therapy.
Results: A total of 687 NVAF patients were enrolled, including 216 warfarin patients, 342 patients on rivaroxaban and 129 dabigatran patients. Between CMAC group and OMAC group: there was no difference in baseline characters; anticoagulation related emergency visiting event occurred 2.7% vs 9.4% (p=0.038) in warfarin subgroup; bleeding events occurred 4.5% vs 14.2% (p=0.015) in warfarin subgroup and 0.8% vs 14.3% (p=0.007) in dabigatran subgroup; thrombotic events incidence was not different in each anticoagulant subgroup (p>0.05); assessment of thrombotic risk or bleeding risk in each anticoagulant subgroup was apparently different (p=0.000); qualified TTR rate in warfarin subgroup was 36.4% vs 21.6% (p=0.011); appropriateness of rivaroxaban dosage was 28.1% vs 18.7% (p=0.019), appropriateness of dabigatran dosage was 54.5% vs 36.5%, (p=0.040); for follow-up of anticoagulation clinics the warfarin subgroup was 62.7% vs 48.1% (p=0.031), rivaroxaban subgroup was 58.4% vs 45.7%(p=0.019) and dabigatran subgroup was 71.2% vs 37.1 (p=0.000).
Conclusion: The study identified that the anticoagulation quality for NVAF patients in the CMAC group is better than in the OMAC group. And compared with other specialty physicians, cardiology specialists are much more acquainted with anticoagulant therapy. It is necessary to establish a cardiology specialists integrated multidisciplinary team to carry out anticoagulation management for all NVAF inpatients, so as to improve the quality of anticoagulant therapy.
Effects of Different Soil Amendments on Soil Physical and Chemical Properties, Rice Yield, and Economic Benefits in Low-lying Saline Alkali Land in Northern Shaanxi
Authors: Zhe Pang , Li Juan , Wang Qilong , Shen Jianglong
Published: April 2023

To explore the effects of different soil modifiers on the improvement of low-lying saline alkali land in Northern Shaanxi, the effects of three soil modifiers (desulfurization gypsum, “Jinfufeng” soil conditioner, and humic acid) on the physical and chemical properties soil, rice yield, and economic benefits were studied and compared through field experiment and indoor analysis. Results show that compared with the blank control, the three soil modifiers could effectively reduce the soil bulk density, improve the physical properties of soil, and reduce the soil pH, and humic acid could also significantly reduce the salt content of surface soil. In addition, the “Jinfufeng” soil conditioner and humic acid had a significant effect on the soil organic matter and total nitrogen contents but no significant effect on the available potassium and phosphorus. Desulfurized gypsum had a significant effect on the soil’s available potassium content but no significant effect on the organic matter and total nitrogen contents and the available phosphorus. The application of soil conditioner could significantly improve the 1000 grain weight and yield of rice, which respectively increased by 10.19–13.59% and 13.54–27.95% compared with the control. The 1000 grain weight and yield of the humic acid modifier treatment were the highest, reaching 23.4 g and 7380 kg•hm− 2, respectively. The analysis of economic benefits revealed that the application of a modifier could significantly improve the output value and net profit of rice. Among the modifiers, the application of a humic acid modifier could obtain the maximum output value, net profit, and yield investment ratio. Considering the rice quality, the rice yield, and the economic benefits, priority should be given to the application of a humic acid soil modifier to improve the low-lying saline alkali land in Northern Shaanxi.
Slit2-Robo4 Signal Pathway and Tight Junction in Intestine Mediate LPS-Induced Inflammation in Mice
Authors: Wang Lv , Chen Yingtai , Wu Hao , Qu Jin-long , Ma Linhao
Published: April 2023

Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated up to now. Here we reported that C57BL/6J mice injected with LPS (5 mg/kg, i.p.) for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1β, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 (10 mg/kg, i.p.), an inhibitor of NLRP3 inflammasome, could reverse these effects induced by LPS. The further experiment results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. These results indicated that the increased level of IL-1β and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. Altogether, our findings revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.
Age and Maternal Mortality in Japan: Increased Maternal Mortality in Advanced Maternal Age
Authors: Tanaka Hiroaki , Hasegawa Junichi , Katsuragi Shinji , Tanaka Kayo , Arakaki Tatsuya , Nakamura Masamitsu , Hayata Eijiro , Nakata Masahiko , Murakoshi Takeshi , Sekizawa Akihiko , Ishiwata Isamu , Ikeda Tomoaki
Published: April 2023

Objectives: This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management.
Methods: Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause of death, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated.
Results: The maternal mortality rates were 0.8 (95% confidence interval [CI], 0.3-4.7) for <20 years of age, 2.6 (95% CI, 1.7-3.8) for 20-24 years, 2.9 (95% CI, 2.3-3.6) for 25-29 years, 3.9 (95% CI, 3.3-4.5) for 30-34 years, 6.8 (95% CI, 5.9-7.9) for 35-39 years, and 11.2 (95% CI, 8.8-14.3) for ≥40 years. Patients who were ≥40 years of age had a significantly higher mortality rate compared to other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54 %]) was the most common cause of hemorrhagic stroke.
Conclusion: Maternal mortality is significantly higher in older pregnant women than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women >40 years of age. More than half of hemorrhagic strokes are associated with gestational hypertensive nephropathy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care.
Heparin Dose in Non-valvular Atrial Fibrillation Patients Undergoing Left Atrial Appendage Closure Under Different Antithrombotic Management
Authors: Liu Yan , Li HuaKang , Liu Feng , Wang XingPeng , Wei Xin , Wen Ling , Dong ShuYuan , Wan Chen , Xu Xiang , Zhang ZhiHui , Song ZhiYuan
Published: April 2023

Objective
To investigate the correlation between the heparin dose and activated clotting time (ACT) during left atrial appendage occlusion (LAAC) in patients with non-valvular atrial fibrillation (NVAF) under different antithrombotic management backgrounds and to provide evidence for the rational use of heparin in LAAC.
Methods
Patients with NVAF who underwent LAAC in our hospital from February 2017 to March 2021 were evaluated. The patients were grouped according to the type of antithrombotic therapy they received before LAAC and the international normalised ratio (INR) into the following groups: patients on antiplatelet drugs, patients on non-vitamin K antagonist oral anticoagulants, patients with a warfarin INR < 1.8, and patients with a warfarin INR ≥ 1.8. The heparin doses were 100, 100, 100, and 80 U/kg, respectively. To measure ACT, venous blood samples were collected at 15 minutes after administering the drug.
Results
The study enrolled 435 patients, comprising 135, 155, 107, and 78 in the antiplatelet drug, non-vitamin K antagonist oral anticoagulant, warfarin INR < 1.8, and, warfarin INR ≥ 1.8 groups, respectively. At baseline, the proportion of patients with coronary heart disease was significantly lower in the warfarin INR < 1.8 group than in the other three groups (p < 0.01), while there were no significant differences in other parameters among the groups (p > 0.05). The heparin dose was significantly lower in the warfarin INR ≥ 1.8 group (80.25 ± 2.84 U/kg) than in the other three groups (p < 0.001). There was no significant difference in the ACT among the four groups (p > 0.05). LAAC was completed in all 435 patients without perioperative bleeding or thromboembolic complications.
Conclusions
For patients not taking warfarin or with an INR < 1.8 on warfarin before LAAC, it is reasonable to use heparin at a dose of 100 U/kg. It is safe and effective to reduce the heparin dose by 20% in patients with an INR ≥ 1.8.
Analysis on epidemiological characters and HIV care continuum of HIV-infected students: a retrospective cohort study in Shandong province, China
Authors: Yang Xingguang , Li Ling , Zhang Na , Hao Lianzheng , Zhu Xiaoyan , Yu Haiying , Wang Guoyong , Kang Dianmin
Published: April 2023

Backgroud The proportion of HIV-infected students in China showed an increasing trend. This study aimed to identify the epidemiological characteristics and the status of HIV care continuum for HIV-infected students in Shandong Province, China.
Methods Case report data and follow-up data of HIV-infected students were obtained from the National HIV/AIDS comprehensive response information management system. Cochran-Armitage trend test was used to analyze the temporal trend of HIV-infected students over these years, Logistic regression analyses were used to analyze the influencing factors of HIV-infected students accepting CD4 + T cells (CD4) test and antiviral therapy (ART) in 30 days, and ArcGIS software was used for the spatial distribution map of student cases.
Results From 2017 to 2019, 403 HIV-infected students were reported in Shandong Province, 99.5% was male (401 cases) and 92.1% were homosexual transmitted. They distributed in 96 counties (96/139, 69.1%) of Shandong Province, mainly in Jinan city and Qingdao city. 99.3% (400 cases) received follow-up within 2 weeks, 99.0% (399 cases) acceptted CD4 test, 68.5% (276 cases) acceptted CD4 test in 30 days, 93.8% (378 cases) acceptted ART, and 48.6% (196 cases) started ART in 30 days. Binary Logistic regression analysis showed that the heterosexual transmitted cases (AOR = 0.458, 95%CI: 0.210–0.998), patients accepting HIV care in western Shandong (AOR = 0.266,95%CI: 0.147–0.481) were less likely to detecte CD4 within 30 days; patients aged 23–25 (AOR = 2.316, 95%CI: 1.009–5.316) and patients tested CD4 within 30 days (AOR = 4.377; 95%CI: 2.572–7.447) prefered to receive ART within 30 days; patients accepted HIV care in Central Shandong (AOR = 0.407; 95%CI: 0.251–0.657) and Western Shandong (AOR = 0.508; 95%CI: 0.261–0.989) and patients diagnosed by voluntary blood donation (AOR = 0.352; 95%CI: 0.144–0.864) were less willing to receive ART in 30 days.
Conclusions The HIV care continuum of HIV-infected students in Shandong Province still needed strenghthing. More health education and case management should be done for cases transmitted through heterosexual behavior, accepted HIV care in central and western Shandong, and diagnosed by voluntary blood donation.
Effects of Bacterial Inoculation on Osmolyte Production and morphological traits in Three Generations of alfalfa (Medicago sativa) populations selected for salt tolerance
Authors: Lundell Seth , Biligetu Bill
Published: April 2023

The authors have requested that this preprint be removed from Research Square.
The livestock sector can overshoot planetary boundaries and threaten Paris Agreement
Authors: Li Chaohui , Wu Xudong , Pradhan Prajal , Liu Jingyu , Li Zhi , Chen Guoqian
Published: April 2023

The livestock sector represents major challenges to safeguarding environmental integrity. Therefore, we comprehensively analyze twelve environmental impacts of the livestock sector from 1995 to 2016 and project them until 2030. Our findings show livestock production impacts land resources, freshwater use, energy demand, climate change, nitrogen and phosphorus flows, and atmospheric aerosol loading. The livestock sector alone will likely exceed the planetary boundary of GHG emissions by 2030 and pose threats to other boundaries. Continuation of the current patterns of livestock production will also preclude limiting global warming well below 2°C, as the Paris Agreement aims. The impacts from the livestock sector are unevenly distributed worldwide, with spillover effects from developed to developing regions. Livestock footprints, i.e., environmental impacts of the livestock sector, are concentrated in emerging economies of Asia & the Pacific and South America. In contrast, per-capita livestock footprints are highest in developed economies such as the US and the EU. The livestock sector represents targeted opportunities for climate change mitigation and global environmental change. Adopting a less meat-based diet can reduce livestock footprints.
LncRNA SNHG1 promotes colorectal cancer cells invasion and migration by upregulating SERPINA3
Authors: Xiao Yu-Feng , Yang Huan , Gong Chun-Li , Chen Yang , Li Zhi-Bin , Shi Qiuyue , Liu Jiao , Gao Nannan , He Bing , Wang Chao , wu yu , Liao Qiushi , Bai Jianying
Published: April 2023

Colorectal cancer metastasis (CRC) is the main reason for patients’ death and remains a crucial clinical challenge. LncRNAs play kinds of important roles in the progression of CRC metastasis, but the implied mechanisms are still unclear. In our research, we studied the lncRNA small nucleolus host gene 1 (SNHG1) which was up-regulated in CRC tissues, and the high expression of lncRNA SNHG1 was correlated with poor prognosis of patients. Functionally, lncRNA SNHG1 acted as an oncogene and promoted CRC cells invasion and migration. Mechanistically, lncRNA SNHG1 mainly located in cell cytoplasm, in which it recruited heterogeneous nuclear ribonucleoprotein D (HNRNPD) and increased the mRNA stability of serpin family A member 3 (SERPINA3), and then subsequently upregulated SERPINA3 expression to facilitated CRC cells invasion and migration. Our finding demonstrated a different role of lncRNA SNHG1 in the cytoplasm and lncRNA SNHG1/HNRNPD-SERPINA3 might serve as a potential therapy for CRC.
Functional Connectivity and Disability in Multiple Sclerosis: a Cross-sectional Study
Authors: Scheffer Morgana , Esper Nathalia Bianchini , Soares Nayron Medeiros , Becker Jefferson , Almeida Rosa Maria Martins
Published: April 2023

Multiple Sclerosis (MS) is characterized by an inflammatory demyelinating disease that affects the Central Nervous System (CNS). This disease results in lesions in the white and gray matter of the brain network architecture and can play an important role in the clinical symptoms. The objective of this study was to verify the connectivity of brain networks through RSfMRI in two different groups of MS when compared to mild (n = 26) and moderate (n = 25) EDSS. The results showed statistically significant differences -*between the groups. The moderate EDSS showed increased rsFC in the Right Posterior Cingulate Cortex, Left and Right Precuneus, Left Superior Temporal Gyrus, and Left Middle Cingulate Cortex compared to mild EDSS. We suggest studies that examine the combination of structural and functional changes in disability in MS
LncRNA018392 promotes proliferation of Liaoning cashmere goat skin fibroblasts through up-regulation of CSF1R by binding to SPI1
Authors: Jin Mei , Lyu Suhe , Liu Xinyang , Cui Lixin , Fan Weiyu
Published: April 2023

The Liaoning cashmere goat has been confirmed as a valuable genetic resource breed that is prohibited from genetic outflow in China, and it achieves the highest single fleece production. Hair follicle development in the cashmere goat is regulated by melatonin and long non-coding RNAs (lnRNAs). However, the role played by lncRNAs in mediating melatonin-promoted cash-mere growth remains unclear. A novel lncRNA-lncRNA018392 with significant overexpression, which played a certain role in the melatonin-promoted proliferation of cashmere skin fibroblasts, was screened in previous research. The flow cytometry and CCK-8 results confirmed that the knockdown of lncRNA018392 reversed the effect of melatonin on cell proliferation, and the prolif-eration of cashmere skin fibroblasts was inhibited after the cells were interfered with the gene CSF1R near lncRNA018392. The dual-luciferase reporter assay further demonstrated that lncRNA018392 can positively regulate the promoter of CSF1R. Moreover, as indicated by the results of RNA-binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation sequencing (ChIP-Seq), lncRNA018392 formed a complex with transcription factor SPI1, and CSF1R served as a downstream target gene regulated by SPI1. As revealed by the results of this study, melatonin-mediated novel lncRNA018392 accelerated the cell cycle, facilitated cell proliferation, and inhibited apoptosis by recruiting SPI1 to up-regulate the expression of nearby gene CSF1R. This study lays a theoretical basis for clarifying the molecular mechanism of cashmere growth and molecular breeding of cashmere goats.
Transition From Depression to Mental Health: Toward an Operationalization of Plasticity
Authors: Branchi Igor , Colli Claudia Delli , Chiarotti Flavia , Campolongo Patrizia , Giuliani Alessandro
Published: April 2023

Plasticity is the ability to modify brain and behavior and allows the transition from psychopathology to mental wellbeing. High plasticity has been associated to high susceptibility to contextual factors, e.g., living conditions, which ultimately drive plasticity outcome. Here, we exploited network analysis to show that plasticity – i.e., the susceptibility to modify depression score – can be assessed by measuring the symptom network connectivity: the weaker the connectivity, the higher the plasticity, resulting in a greater modification in mood symptoms. We analyzed the STAR*D dataset and proved that connectivity strength at baseline is weaker in responder compared to non-responder patients. Moreover, connectivity strength at baseline was inversely correlated with improvement in depression score (Pearson's r=-0.87) and susceptibility to change mood according to context (Pearson's r=-0.77). This operationalization of plasticity provides a mathematical tool to investigate and predict resilience, vulnerability and recovery, and to develop novel approaches for the prevention and treatment of depression.
A systematic review of clinical psychological guidance for perinatal mental health
Authors: O’Brien Jayne , Gregg Lynsey , Wittkowski Anja
Published: April 2023

Background
Guidelines on psychological and/or psychosocial assessment and intervention in the perinatal period can provide beneficial practice guidance for healthcare professions to reduce maternal distress and potential mortality. As little is known about the similarities in recommendations across guidelines, which could impact the quality of therapeutic intervention women receive, this systematic review was conducted to draw out the consistent guidance for perinatal psychological and/or psychosocial therapeutic input.
Method
Eight literature and two guideline databases were searched alongside guideline development institutions, and organisations of maternity or perinatal mental health care. All relevant guidance was searched for and extracted before guideline quality was assessed using the AGREE-II instrument. Included guidelines had a primary or secondary focus on psychological assessment and therapeutic intervention for perinatal mental health difficulties. Using a narrative synthesis approach, recommendation consistencies and inconsistencies were outlined.
Results
From the 92 records screened, seven guidelines met the inclusion criteria. Only two guidelines were rated high (> 80%) across all assessed domains, with the other guidelines scoring between poor and excellent across domains. Highest rated domains across all seven guidelines were clarity of presentation (75%) and scope and purpose (70%). Recommendations for structured psychological assessment and intervention were most commonly reported in the guidelines; however, the level of detail and depth of information varied across guidelines. Whilst assessment and intervention recommendations for mother-infant dyad and partners were considered, research into working therapeutically with these client groups in perinatal mental health services is only just emerging. Hence, guideline recommendations for working with the mother-infant dyad and partners were based on consensus of expert opinion.
Conclusion
Perinatal mental health guidelines were consistent in scope but showed considerable variability in quality and depth of recommendations, which could have implications for standards of clinical practice. However, there is still a need to improve the evidence underpinning recommendations in perinatal mental health guidelines to advance the implementation of psychological and/or psychosocial interventions. High quality interventions in the perinatal period could improve outcomes for women and their families.
Spatiotemporal Adaptive Attention Graph Convolution Network for city-level Air Quality Prediction
Authors: Liu Hexiang , Han Qilong , Sun Hui , Sheng Jingyu , Yang Ziyu
Published: April 2023

Air pollution is the leading cause of human diseases. Accurate air quality predictions are critical to human health. However, it is difficult to extract spatiotemporal features among complex spatiotemporal dependencies effectively. Most existing methods focus on constructing multiple spatial dependencies and ignore the systematic analysis of spatial dependencies. We found that besides spatial proximity stations, functional similarity stations, and temporal pattern similarity stations, the shared spatial dependencies also exist in the complete spatial dependencies. In this paper, we propose a novel deep learning model, the spatiotemporal adaptive attention graph convolution model (STAA-GCN), for city-level air quality prediction. Specifically, we encode multiple spatiotemporal dependencies and construct complete spatiotemporal interactions between stations using station-level attention. Among them, we design a Bi-level sharing strategy to extract shared inter-station relationship features between certain stations efficiently. Then we extract multiple spatiotemporal features with multiple decoders, which it is extracted from the complete spatial dependencies between stations. Finally, we fuse multiple spatiotemporal features with a gating mechanism for multi-step predictions. Our model achieves state-of-the-art experimental results in several real-world datasets.
Washed microbiota transplantation improves symptoms and intestinal barrier function in patients with functional bowel disorders: a propensity-score matching analysis
Authors: Ye Xiao-Yan , Chen Jun-Yi , Wu Li-Hao , Luo Dan-Ping , Ye Xiao-Huo , Wu Li-Quan , He Xing-Xiang
Published: April 2023

Background
Alterations in the intestinal microbiota may have a role in functional bowel disorders (FBDs) pathogenesis. Probiotics are widely used to improve intestinal dysbacteriosis in patients suffering from FBDs. Compared with probiotics, washed microbiota transplantation (WMT) could be a promising treatment for FBDs. We conducted a retrospective evaluation of both treatments using a propensity-score matching analysis (PSMA).
Methods
A total of 103 patients with FBDs (irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB)) were divided into a WMT group or probiotics group (taking probiotics capsules). The following information was matched for PSMA: age, sex, disease course, body mass index, anxiety, insomnia, tobacco smoking, alcohol consumption, as well as levels of D-lactate, diamine oxidase (DAO), and lipopolysaccharide (LPS). IBF and symptoms were evaluated at the first and second hospitalizations. Prognostic factors were assessed by Cox proportional hazards regression analysis.
Results
PSMA resulted in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group). WMT was better for improving symptoms in FBD patients than probiotics (P = 0.002). Significantly fewer patients with intestinal barrier damage were in the WMT group than the probiotics group (38.2% vs. 67.6%, P = 0.041). D-lactate levels were reduced significantly after WMT (P = 0.031) and were selected as the prognostic factor for FBDs (HR = 0.248, 95%CI 0.093–0.666, P = 0.006) by univariate Cox regression analysis.
Conclusion
WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels may predict a strong efficacy of WMT in these patients.
Human Capital and Income Inequality in Sub-Saharan Africa: Does Reallocation of Resources Matter?
Authors: Ndjokou Itchoko Motande Mondjeli Mwa , Messy Martin Ambassa
Published: April 2023

In this paper, we analyze the effect of reallocating resources to human capital (education and health) on income inequality (II) in sub-Saharan Africa (SSA) by keeping the total level of public expenditure unchanged. Using a sample of 33 SSA countries, we estimate a panel data model using the fixed-effect ordinary least squares (OLS) technique with the Driscoll and Kraay estimator for standard errors and the Generalized Method of Moment (GMM) in system technique over the period 2004–2020. Our model is inspired by the work of Ormaecheas and Morozumi (2017) and Doumbia and Kinda (2019). Our results reveal that: (i) the reallocation of resources to education and health financed by cutting military and infrastructure spending does not contribute to a significant reduction of II in SSA. Security challenges and corruption problems are the main explanatory factors for this insignificant effect. (ii) The reallocation of resources to education and health financed by a cut in social protection spending significantly amplifies SSA's II. The vulnerability of the social strata and the profound precariousness of the population are the result of such an outcome in SSA. Our results suggest that the fight against II depends on the fight against corruption, the improvement of the quality of public spending and a better reallocation of resources.
Whole-genome bisulfite sequencing reveals the alteration of DNA methylation during malignant transformation of oral mucosal cells
Authors: Wang Peiyan , Yu Xiaofei , Sun Pei , Pan Keqing , Guo Yiqing , Liu Zhaochen , Jiao Mengyu , Deng Jing , Zhang Hui
Published: April 2023

Background
According to recent researches, the overall malignant transformation rate of oral potentially malignant disorders (OPMDs) is among 7.9%, and the probability of malignant transformation of OPMDs with severe epithelial dysplasia to oral squamous cell carcinoma (OSCC) is as high as 57%. In recent years, more and more studies have confirmed that abnormal DNA methylation, especially hypermethylation of the promoter CpG islands, is closely related to the occurrence and malignant transformation of OPMDs. Hypermethylation of certain tumor suppressor genes can be used as a key indicator for diagnosing early OSCC and judging the prognosis of OPMDs. There is an urgent need to expand the understanding of DNA methylation alterations occurred in OPMDs and OSCC at the cellular level.
Methods and results
We used the Illumina sequencing platform to perform the whole-genome bisulfite sequencing （WGBS）on dysplastic oral keratinocyte (DOK) and CAL-27 cell lines, which respectively represents epithelial dysplasia and carcinogenesis. Then we compared the results with trends in human gingival fibroblasts (HGFs) to identify differentially methylated regions (DMRs). Gene Oncology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to further explore the biological functions and signaling pathways related to the observed differences. Compared with those in HGFs, respectively 4,149 and 2,863 genes were abnormally hypermethylated in DOK and CAL-27 cells in the promoter CG context. GO and KEGG analyses showed that the identified differentially methylated genes were involved in system development, transcriptional regulation, cell differentiation, and other pathways (e.g., autophagy, mitophagy, and cAMP signaling).
Conclusions
Our results expand on the knowledge of DNA methylation alterations associated with OPMDs and OSCC at the cellular level. The key genes and pathways involved in the regulatory mechanisms of DNA methylation may provide a theoretical basis for research on the malignant transformation of OPMDs as well as for the early diagnosis and treatment of oral squamous cell carcinoma.