bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Fracture Opening Pressure in a Reservoir Based on Finite Element Numerical Simulation: A Case Study of the Second Member of the Lower Triassic Jialingjiang Formation in Puguang Area, Sichuan Basin, China
Authors: Li Jian , Zu Kewei , Li Qi , Zeng Daqian , Li Zhongchao , Zhang Jixi , Luo Zhouliang , Yin Nanxin , Zhu Zhenjun , Ding Xiaojun
Published: February 2022

All stages of oil and gas exploration and development involve the study of in-situ stress. Since the traditional two-dimensional and three-dimensional homogeneous models can no longer fulfil the requirements of research and production, numerical simulation of the stress field has become an effective study method. In this study, we took the Jia 2 member in Puguang area as a case to establish a geological model and a mechanical model based on the tectonic framework and the distribution characteristics of the rock mechanical parameters, respectively, and loaded the model with the present-day in-situ stress state calculated from the logging data as the boundary conditions. The simulation results show that 1) the orientation of the maximum horizontal principal stress in the study area is near E-W, and the in-situ stress orientation is locally deflected due to the influence of faults; and 2) the magnitude of in-situ stress is predominantly affected by the burial depth and lithology, and the minimum horizontal principal stress, maximum horizontal principal stress, and differential stress are mainly concentrated in the ranges of 30–60, 50–80, and 10–40 MPa, respectively. We also analysed the opening sequence of the multiple fracture systems during development, using the present-day stress field model. The analysis revealed that the E-W fractures will open first, and the continuously increasing operating pressure will lead to formation breakdown, producing a fracture network.
Biomarker Value of miR-221 and miR-222 as Potential Substrates in the Differential Diagnosis of Papillary Thyroid Cancer Based on Data Synthesis and Bioinformatics Approach
Authors: Cai Shang , Ma Jiayan , Wang Yong , Cai Yuxing , Xie Liwei , Chen Xiangying , Yang Yingying , Peng Qiliang
Published: February 2022

Background

MicroRNA (miRNA) has been reported to play a critical regulatory role in papillary thyroid carcinomas (PTC). However, the role of miR-221/222 in PTC remains unclear. Here, we performed this study to explore the diagnostic potentials and mechanisms of miR-221/222 in PTC.

Methods

First, we systematically analyzed the diagnostic value of miR-221/222 in the diagnosis PTC by pooling the published studies. Afterwards, we performed comprehensive bioinformatics analysis including gene ontology analysis, pathway enrichment analysis and protein-protein interaction analysis to explore the potential mechanisms of miR-221/222 involved in PTC.

Results

The overall sensitivity and specificity of miR-221/222 for PTC were 0.75 (95% CI: 0.70–0.80) and 0.80 (95% CI: 0.76–0.84) respectively with the AUC of 0.85 (95% CI: 0.81-0.88). The diagnostic performance varied among different subgroups including geographical locations, sample sources and sample sizes. Meanwhile, we found that a combination of miR-221/222 and other miRNAs when used in a diagnostic panel could improve the diagnostic accuracy than individual miR-221/222. Moreover, through the bioinformatics analysis, we confirmed that miR-221/222 targets were highly related to the molecular pathogenesis of PTC. The results revealed that miR-221/222 may exert important functions in PTC through thyroid hormone signaling pathway and some other key pathways by regulating some key genes.

Conclusion

These findings indicated that miR-221/222 have the potential to serve as auxiliary tools for diagnosing PTC. Further prospective clinical trials should be performed to assess the accuracy of these findings in a larger cohort and determine the clinical uses.
[177Lu]Lu-DOTA-TATE and [131I]MIBG Phenotypic Imaging-Based Therapy in Metastatic/Inoperable Pheochromocytomas and Paragangliomas: Comparative Results in a Single Center
Authors: Prado-Wohlwend Stefan , del Olmo-García María Isabel , Bello-Arques Pilar , Merino-Torres Juan Francisco
Published: February 2022

Purpose

The aim of the study is to assess phenotypic imaging patterns and the response to treatment with [177Lu]Lu-DOTA-TATE and/or [131I]MIBG in paragangliomas (PGLs) and pheochromocytomas (PHEOs), globally and according to the primary location.

Methods

This is a 17-patient retrospective observational study, with 9 cases treated with [177Lu]Lu-DOTA-TATE and 8 with [131I]MIBG (37 total treatments). Functional imaging scans and treatment responses were studied in order to choose the best therapeutic option and to define the progression-free survival (PFS) and disease control rate (DCR) according to treatment modality and primary location.

Results

All patients were studied with phenotypic nuclear medicine images. Twelve of 17 patients were tested with both [123I]MIBG and somatostatin receptor images, and 6/12 showed appropriate expression of both targets to treatment in the phenotypic images. The rest of the patients were tested with one of the image modalities or only showed suitable uptake of a single radiotracer and were treated with the corresponding therapeutic option. [177Lu]Lu-DOTA-TATE PFS was 29 months with a DCR of 88.8%. [131I]MIBG PFS was 18.5 months with a 62.5% DCR. According to the primary location, the best PFS was in PHEOs treated with [177Lu]Lu-DOTA-TATE. Although the series are small due to the low disease prevalence and do not allow to yield statistically significant differences, this first study comparing [177Lu]Lu-DOTA-TATE and [131I]MIBG displays a trend to an overall longer PFS with [177Lu]Lu-DOTA-TATE, especially in the adrenal primary location. When both radionuclide targets are expressed, the patients’ comorbidity and treatment effectiveness should be valued together with the intensity uptake in the phenotypic image in order to choose the best therapeutic option. These preliminary retrospective results reinforce the need for a prospective, multicentric trial to be confirmed.
Circulating α-Klotho Levels in Relation to Cardiovascular Diseases: A Mendelian Randomization Study
Authors: Sun Xingang , Chen Lu , He Yuxian , Zheng Liangrong
Published: February 2022

Background

Several studies have reported a protective role of circulating α-Klotho on cardiovascular diseases (CVD); however, the causality remains unclear. We aim to elucidate whether genetically predicted circulating α-Klotho levels were causally associated with the risk of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, ischemic stroke (IS), and IS subtypes.

Methods

A two-sample Mendelian randomization (MR) study was designed, with 5 single-nucleotide polymorphisms associated with circulating α-Klotho levels utilized as instrumental variables. MR estimates on each CVD outcome derived from the fixed-effects inverse-variance weighted (IVW) approach in different data sources were combined by the fixed-effects meta-analysis approach, complemented by several sensitivity analyses including the simple median, the weighed median, MR-Egger regression, and MR-pleiotropy residual sum and outlier.

Results

In the meta-analysis combining different data sources, suggestive inverse causal association of circulating α-Klotho concentrations with CAD [Odds ratio (OR), 0.97; 95% confidence interval (CI), 0.94, 1.00; P = 0.044] and significant inverse association of circulating α-Klotho concentrations with AF (OR, 0.96; 95% CI, 0.93, 0.99; P = 0.005) was observed. However, there was no causal association of α-Klotho with HF, any stroke, IS, or IS subtypes neither in different data sources nor in the meta-analysis. Complementary sensitivity analyses showed consistent and robust results in general.

Conclusion

Evidence was found for a protective effect of circulating α-Klotho on the prevention of AF risk. However, no significant causal association between genetically predicted circulating α-Klotho levels and risk of CAD, HF, stroke, IS, or IS subtypes was found.
Study on Dynamic Process Characteristics of CHP Unit With Variable Load Based on Working Point Linearization Modeling
Authors: Huang Yuehua , Chen Qing , Ye Jing , Lu Tianlin
Published: February 2022

In view of the difficulty of applying the refine modeling of combined heat and power (CHP) units to the optimization scenario of integrated energy system, a CHP unit model based on working point linearization modeling is proposed, and its variable load characteristics are analyzed. Firstly, the dynamic coupling relationship of CHP unit is analyzed, and the nonlinear dynamic model of the unit is constructed. Then, under the pure condensation and heating conditions, the linearized Laplace transform model of the working point is established, and the variable load capacity under the independent action of control variables is analyzed to test the availability of the Laplace model. On this basis, the dynamic adaptive particle swarm optimization algorithm is used for multivariable cooperative control to test the open-loop characteristics of the variable load capacity of the unit. At the same time, the control strategy of electrothermal cooperation and safety self-test is designed to adjust the control variables, and test the closed-loop characteristics of the unit’s regulation ability. Finally, a 300-MW steam extraction CHP unit is taken as an example to verify the applicability of the unit model and the effectiveness of the control strategy.
Assessment of Beta-2 Microglobulin Gene Edited Airway Epithelial Stem Cells as a treatment for Sulfur Mustard Inhalation
Authors: Naeimi Kararoudi Meisam , Alsudayri Alfahdah , Hill Cynthia L. , Elmas Ezgi , Sezgin Yasemin , Thakkar Aarohi , Hester Mark E. , Malleske Daniel T. , Lee Dean A. , Neal Matthew L. , Perry Mark R. , Harvilchuck Jill A. , Reynolds Susan D.
Published: February 2022

Respiratory system damage is the primary cause of mortality in individuals who are exposed to vesicating agents including sulfur mustard (SM). Despite these devastating health complications, there are no fielded therapeutics that are specific for such injuries. Previous studies reported that SM inhalation depleted the tracheobronchial airway epithelial stem cell (TSC) pool and supported the hypothesis, TSC replacement will restore airway epithelial integrity and improve health outcomes for SM-exposed individuals. TSC express Major Histocompatibility Complex (MHC-I) transplantation antigens which increases the chance that allogeneic TSC will be rejected by the patient’s immune system. However, previous studies reported that Beta-2 microglobulin (B2M) knockout cells lacked cell surface MHC-I and suggested that B2M knockout TSC would be tolerated as an allogeneic graft. This study used a Cas9 ribonucleoprotein (RNP) to generate B2M-knockout TSC, which are termed Universal Donor Stem Cells (UDSC). Whole genome sequencing identified few off-target modifications and demonstrated the specificity of the RNP approach. Functional assays demonstrated that UDSC retained their ability to self-renew and undergo multilineage differentiation. A preclinical model of SM inhalation was used to test UDSC efficacy and identify any treatment-associated adverse events. Adult male Sprague-Dawley rats were administered an inhaled dose of 0.8 mg/kg SM vapor which is the inhaled LD50 on day 28 post-challenge. On recovery day 2, vehicle or allogeneic Fisher rat UDSC were delivered intravenously (n = 30/group). Clinical parameters were recorded daily, and planned euthanasia occurred on post-challenge days 7, 14, and 28. The vehicle and UDSC treatment groups exhibited similar outcomes including survival and a lack of adverse events. These studies establish a baseline which can be used to further develop UDSC as a treatment for SM-induced airway disease.
Prenatal Diagnosis of Fetus With Transaldolase Deficiency Identifies Compound Heterozygous Variants: A Case Report
Authors: Xue Jiaxin , Han Jin , Zhao Xiaopeng , Zhen Li , Mei Shanshan , Hu Zhiyang , Li Xiuzhen
Published: February 2022

Transaldolase (TALDO) deficiency is a rare autosomal recessive disorder caused by variants in the TALDO1 gene that commonly results in multisystem dysfunction. Herein, we reported compound heterozygous variants in a Chinese prenatal case with TALDO deficiency using whole-exome sequencing (WES) for trios and Sanger sequencing. The heterozygous variants were located on the TALDO1 gene: NM_006755.2:c.574C > T(Chr11:g.763456C > T), a missense variant in exon 5 paternally inherited; NM_006755.2:c.462-2A > G(Chr11:g.763342A > G), a splicing aberration in intron 4 maternally inherited. The qualitative analysis of urinary polyols in neonatal urine indicated that xylitol + arabitol and ribitol in the proband’s urine were significantly increased. These findings expand the variation spectrum of the TALDO1 gene, provide solid evidence for the counseling of the family in regard to future pregnancies, strongly support the application of WES in prenatal diagnosis, and further prove that effective postpartum treatments could improve prognosis.
Single Nucleotide Polymorphisms in the Human Leukocyte Antigen Region Are Associated With Hemagglutination Inhibition Antibody Response to Influenza Vaccine
Authors: Zhong Shuyi , Wei Hejiang , Li Mao , Cheng Yanhui , Wen Simin , Wang Dayan , Shu Yuelong
Published: February 2022

Background: The annual death associated with seasonal influenza is 290,000–650,000 globally, which can be effectively reduced by influenza vaccination. However, the protective hemagglutination inhibition (HAI) antibody response to influenza vaccine is affected by many factors, among which single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can alter the antigen-presenting function of the HLA molecule, thus influencing the process of antibody mounting against vaccine antigen.

Methods: Healthy subjects of the Han nationality were recruited and received seasonal trivalent influenza vaccine. Paired serum samples collected on and approximately 28 days after vaccination were tested in parallel by HAI assays. HLA alleles related to the immune response to influenza vaccine reported in the previous literature were summarized, and six corresponding tag SNPs were selected and genotyped using the MassARRAY technology platform.

Results: The effects of HLA SNPs on HAI antibody response to influenza vaccine varied with different vaccine antigens. The AA genotype of rs41547618 was correlated with low A/H1N1-specific antibody titer compared with the GG + GA genotype (p = .007). The TT genotype of rs17885382 was correlated with low A/H3N2-specific antibody titer compared with the CC + CT genotype (p = .003). In addition, haplotype consisting of rs41542812—rs17885382—rs2068205—rs41547618—rs6905837—rs9270299—CCTGCA was correlated with non-responsiveness to influenza vaccine (OR = 2.39, 95% CI = 1.02–5.62).

Conclusion: HLA SNPs were associated with HAI antibody response to influenza vaccine, which can help in a better understanding of the varied responsiveness to influenza vaccine in the population.
Circular RNA as a Potential Biomarker for Forensic Age Prediction
Authors: Wang Junyan , Wang Chunyan , Wei Yangyan , Zhao Yanhao , Wang Can , Lu Chaolong , Feng Jin , Li Shujin , Cong Bin
Published: February 2022

In forensic science, accurate estimation of the age of a victim or suspect can facilitate the investigators to narrow a search and aid in solving a crime. Aging is a complex process associated with various molecular regulations on DNA or RNA levels. Recent studies have shown that circular RNAs (circRNAs) upregulate globally during aging in multiple organisms such as mice and C.elegans because of their ability to resist degradation by exoribonucleases. In the current study, we attempted to investigate circRNAs’ potential capability of age prediction. Here, we identified more than 40,000 circRNAs in the blood of thirteen Chinese unrelated healthy individuals with ages of 20–62 years according to their circRNA-seq profiles. Three methods were applied to select age-related circRNA candidates including the false discovery rate, lasso regression, and support vector machine. The analysis uncovered a strong bias for circRNA upregulation during aging in human blood. A total of 28 circRNAs were chosen for further validation in 30 healthy unrelated subjects by RT-qPCR, and finally, 5 age-related circRNAs were chosen for final age prediction models using 100 samples of 19–73 years old. Several different algorithms including multivariate linear regression (MLR), regression tree, bagging regression, random forest regression (RFR), and support vector regression (SVR) were compared based on root mean square error (RMSE) and mean average error (MAE) values. Among five modeling methods, regression tree and RFR performed better than the others with MAE values of 8.767 years (S.rho = 0.6983) and 9.126 years (S.rho = 0.660), respectively. Sex effect analysis showed age prediction models significantly yielded smaller prediction MAE values for males than females (MAE = 6.133 years for males, while 10.923 years for females in the regression tree model). In the current study, we first used circRNAs as additional novel age-related biomarkers for developing forensic age estimation models. We propose that the use of circRNAs to obtain additional clues for forensic investigations and serve as aging indicators for age prediction would become a promising field of interest.
Prevalence of Hyperuricemia Among Chinese Adults: Findings From Two Nationally Representative Cross-Sectional Surveys in 2015–16 and 2018–19
Authors: Zhang Mei , Zhu Xiaoxia , Wu Jing , Huang Zhengjing , Zhao Zhenping , Zhang Xiao , Xue Yu , Wan Weiguo , Li Chun , Zhang Wenrong , Wang Linhong , Zhou Maigeng , Zou Hejian , Wang Limin
Published: February 2022

Objective

To determine the nationwide prevalence of hyperuricemia in China and evaluate its trends and associated risk factors.

Methods

Using a multi-stage, stratified, cluster-randomized sampling design, two cross-sectional surveys (representative of national and provincial information) were conducted in 31 provinces (autonomous regions and municipalities) in mainland China, with 166, 861 Chinese adults in 2015–16 and 168, 351 in 2018–19. Serum uric acid (SUA) levels of all participants were measured after a >10-hour overnight fast. Hyperuricemia (HUA) was defined when SUA was >420 μmol/L. Prevalence estimates were weighted to represent the total population considering the complex sampling design. Multivariable logistic regression models was used to estimate factors associated with HUA.

Results

The overall hyperuricemia prevalence in the Chinese adult population was 11.1% (95% confidence interval 10.3% to 11.8%) in 2015–16 and 14.0% (13.1% to 14.8%) in 2018–19; an alarming rise was observed in the three years. Hyperuricemia was more common in men with 19.3% (17.9% to 20.7%) in 2015–16 and 24.4% (23.0% to 25.8%) in 2018–19, although the prevalence also escalated from 2.8% (2.5% to 3.0%) in 2015–16 to 3.6% (3.2% to 4.0%) in 2018–19 in women. The hyperuricemia risk factors include the urban culture, settlement in the East, Zhuang descent, high education, heavy or frequent beer drinking, high red meat intake, physical inactivity, high body mass index, central obesity, hypertension, hyperlipidemia, and low glomerular filtration rate.

Conclusion

The estimated hyperuricemia prevalence among Chinese adults was 14.0% in 2018-19; significant escalating trends were observed between 2015-16 and 2018-19.
Alteration of Gut Microbiome and Correlated Amino Acid Metabolism Contribute to Hyperuricemia and Th17-Driven Inflammation in Uox-KO Mice
Authors: Song Siyue , Lou Yu , Mao Yingying , Wen Xianghui , Fan Moqi , He Zhixing , Shen Yang , Wen Chengping , Shao Tiejuan
Published: February 2022

Although gut dysbiosis had been demonstrated to be an important factor affecting hyperuricemia (HUA) and gout, little is known for its potential mechanistic connections. In this study, Uox-KO mice model that with spontaneously developed pronounced HUA and urate nephropathy was used to explore the pathophysiologic mechanism of microbiota alterations in HUA and gout with integrated multi-omics analysis. 16S rRNA gene sequencing was performed to characterize the characteristic bacteria, and untargeted LC/MS analysis was applied to reveal the featured metabolites. Our results showed there was a significant shift in gut microbiota composition and function in Uox-KO mice compared to WT mice and apparent metabolomics differences between the two groups. Among them, amino acids metabolism appears to play a critical role. Correlation analysis further revealed that the characteristic metabolites were strongly influenced by the discrepant bacterial genera. Furthermore, impairment of intestinal integrity and profound alterations in the profile of solute carrier family resulted in dysregulation of amino acids transportation, which subsequently impacted serum uric acid level and CD4+ Th17 driven inflammation. Together, these data indicate that gut dysbiosis promotes purine metabolism disorder and inflammation in Uox-KO mice. Remodeling the gut microbiota is a promising strategy to combat HUA and gout.
Convalescent Plasma Treatment in Patients with Covid-19: A Systematic Review and Meta-Analysis
Authors: Jorda Anselm , Kussmann Manuel , Kolenchery Nebu , Siller-Matula Jolanta M. , Zeitlinger Markus , Jilma Bernd , Gelbenegger Georg
Published: February 2022

Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17th, 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma and 24.4% (1903 of 7769) with standard of care (risk ratio (RR) 0.97, 95% CI 0.90-1.04) (high-certainty evidence). All-cause mortality did not differ in the subgroups of noncritically ill (21.7% [1288 of 5929] vs. 22.4% [1320 of 5882]) and critically ill (36.9% [518 of 1404] vs. 36.4% [455 of 1247]) patients with Covid-19. The use of convalescent plasma in patients who tested negative for anti-SARS-CoV-2 antibodies at baseline was not associated with significantly improved survival (RR 0.94, 95% CI 0.87-1.02). In the overall study population, initiation of mechanical ventilation (RR 0.97, 95% CI 0.88-1.07), time to clinical improvement (HR 1.09, 95% CI 0.91-1.30), and time to discharge (HR 0.95, 95% CI 0.89-1.02) were similar between the two groups. In patients with Covid-19, treatment with convalescent plasma, as compared with control, was not associated with lower all-cause mortality or improved disease progression, irrespective of disease severity and baseline antibody status.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).
The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats
Authors: Wang Lu , Deng Zihui , Sun Yan , Zhao Yan , Li Yun , Yang Mengmeng , Yuan Rui , Liu Yuyan , Qian Zhirong , Zhou Feihu , Kang Hongjun
Published: February 2022

Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.
Microstructure and Mechanical Properties of Aluminum Matrix Composites Reinforced With In-Situ TiB2 Particles
Authors: Wu Weiguo , Zeng Tiancheng , Hao Wenfeng , Jiang Shiping
Published: February 2022

The present article investigates the microstructure and mechanical properties of A356 matrix composite reinforced with TiB2 particles synthesized by the salt metal reaction of as-cast and T6 state. Microscopic observations of the prepared composites reveal that in-situ grown TiB2 particles are characterized with regular shapes and nearly uniform distributed in the A356 matrix. A clear interface between the A356 matrix and TiB2 particles was observed. The detailed analysis of mechanical properties of synthesized composites of as-cast and T6 state show that the ultimate tensile strength and Young’s modulus of the synthesized composites increased with the increasing weight percentage (wt%) of in-situ TiB2 particles in the A356 matrix, but the Poisson’s ratio of the synthesized composites decreased with the increase of TiB2 particles wt%. The Young’s modulus of the composites increased by up to 10.8% and the Poisson’s ratio decreased by up to 3.2% with the increase of TiB2 particles wt%, compared to A356 alloy. With the increase of TiB2 particle wt%, the yield strength of the composites decreased at first (when the TiB2 particle wt% is less than 1%) then increased, while elongation and percent reduction in area increased at first and then decreased. Furthermore, T6 heat treatment can refine grain and effectively improve the mechanical properties of composites.
Efficacy and Safety of Ultrasound Guided-Deep Serratus Anterior Plane Blockade With Different Doses of Dexmedetomidine for Women Undergoing Modified Radical Mastectomy: A Randomized Controlled Trial
Authors: Xu Xia , Chen Xingfang , Zhu Wenchao , Zhao Jing , Liu Yanchao , Duan Caiping , Qi Yingying
Published: February 2022

Background

Ultrasound guided-deep serratus anterior plane block (USG-DSAPB) has been used for pain management of patients undergoing modified radical mastectomy (MRM), but evidence supporting their adjuvant analgesic benefits is limited. We explored the efficacy and safety of preemptive use of ropivacaine combined with different doses of dexmedetomidine (DEX) in USG-DSAPB for patients undergoing MRM.

Methods

Ninety-five female patients undergoing unilateral MRM were allocated randomly to two groups. Group RD1 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 0.5 μg·kg−1 DEX in USG-DSAPB. Group RD2 had 20 mL of 0.5% ropivacaine with 5 mg of dexamethasone and 1 μg·kg−1 DEX in USG-DSAPB. The primary outcome was sufentanil consumption 72 h after USG-DSAPB. Secondary outcomes were: postoperative pain scores and level of sedation; intraoperative hemodynamics; duration of post-anesthesia care unit (PACU) stay; prevalence of moderate-to-severe pain; one-time puncture success; procedure time of blockade; time to first rescue analgesia; requirement of rescue analgesia; satisfaction scores of patients and surgeons; duration of hospital stay; adverse events; prevalence of chronic pain; quality of postoperative functional recovery.

Results

Compared with the RD1 group, the visual analog scale score for coughing was significantly lower at 4, 8, 12 h and sufentanil consumption was significantly lower at 4, 8, 12, 24, and 48 h after surgery in the RD2 group (P < 0.05). The time to first rescue analgesia was significantly longer in the RD2 group (P < 0.05). The requirement for rescue analgesia was significantly higher in the RD1 group (P < 0.05). The prevalence of moderate-to-severe pain, number of patients using vasoactive agents, duration of PACU stay, as well as consumption of propofol, remifentanil, and DEX were significantly lower in the RD2 group (P < 0.05). There were no significant differences between the two groups with respect to one-time puncture success, procedure time of blockade, total dermatomal spread, satisfaction scores of patients and surgeons, postoperative complications, duration of hospital stay, 40-item Quality of Recovery questionnaire (QoR-40) score, or prevalence of chronic pain (P > 0.05).

Conclusions

We discovered that 1 μg·kg−1 (not 0.5 μg·kg−1) DEX combined with 20 mL of 0.5% ropivacaine and 5 mg of dexamethasone in USG-DSAPB could provide superior postoperative analgesia for patients undergoing MRM. However, the quality of postoperative functional recovery and prevalence of chronic pain were similar.

Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=54929, identifier: ChiCTR2000033685.
Association Between the Surrogate Markers of Insulin Resistance and Chronic Kidney Disease in Chinese Hypertensive Patients
Authors: Shi Yumeng , Hu Lihua , Li Minghui , Zhou Wei , Wang Tao , Zhu Lingjuan , Bao Huihui , Cheng Xiaoshu , Li Ping
Published: February 2022

Background

We aim to evaluate the four surrogate markers of insulin resistance (IR), including triglyceride-glucose index (TyG), lipid accumulation product index (LAP), visceral adiposity index (VAI), triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL), on prevalence of chronic kidney disease (CKD) and to examine any possible effect modifiers in Chinese hypertensive patients.

Methods

A total of 13,055 hypertensive participants were included in this cross-sectional study. In addition, average age of the study population was 63.81 ± 9.46 years, and 47.66% of them are men. The primary outcome was CKD, defined as eGFR <60 ml/min/1.73 m2. Multivariate logistic regression analysis and the generalized additive model and a fitted smoothing curve (penalized spline method) were used to examine the association between the surrogate markers of IR and CKD.

Results

Four surrogate markers of IR were independently and positively associated with CKD in a dose-response fashion. The association between four surrogate markers of IR and the prevalence of CKD was examined as a continuous variable per one unit increment and also as a categorical variable using tertiles with the tertiles (T1) as the reference group. In the fully adjusted model, multivariate logistic analyses showed that the per one unit increments of the TyG, LAP, VAI, and TG/HDL ratios were all significantly associated with 42, 31, 67, and 78% higher risk for CKD, respectively. Consistently, the adjusted ORs (95% CI) for CKD were 1.48 (1.21, 1.81), 1.34 (1.06, 1.69), 1.26 (1.03, 1.53), 1.35 (1.12, 1.63) when comparing the highest tertile to the lowest tertile of the TyG, LAP, VAI, and TG/HDL ratios, respectively. The stratification analysis showed that a significant positive correlation between TyG, VAI, and TG/HDL and CKD in patients over 65 years old.

Conclusion

Four surrogate markers of IR were independently and positively correlated with CKD, and LAP was better than the other surrogate markers of IR for predicting CKD. Only among participants aged over 65 years were higher levels of TyG, VAI and TG/HDL found to be closely related to the increased prevalence of CKD.
Incidence of Sindbis Virus in Hospitalized Patients With Acute Fevers of Unknown Cause in South Africa, 2019–2020
Authors: Meno Kgothatso , Yah Clarence , Mendes Adriano , Venter Marietjie
Published: February 2022

Background

Sindbis virus (SINV) is a mosquito-borne alphavirus that is widely distributed worldwide. Little is known about the febrile and neurological disease burden due to SINV in South Africa.

Patients and Methods

Clinical samples of patients with acute febrile disease of unknown cause (AFDUC) were collected through the African Network for Improved Diagnostics, Epidemiology and Management of Common Infectious Agents at three sentinel hospital surveillance sites in South Africa. In total, 639 patients were screened using a PCR-based macroarray that can simultaneously detect nucleic acids of 30 pathogens, including SINV, from January 2019 to December 2020. Serum samples were randomly selected from the arbovirus season (January–June) and also screened with a commercial indirect immunofluorescence assay for anti-SINV IgM. In addition, 31 paired cerebrospinal fluid (CSF) specimens from the same patients were screened for IgM. Micro-neutralization assays were performed on all IgM-positive samples.

Results

None of the specimens tested positive for SINV by molecular screening; however, 38/197 (19.0%) samples were positive for SINV-specific IgM. A total of 25/38 (65.8%) IgM-positive samples tested positive for SINV-neutralizing antibodies, giving an overall incidence of 12.7%. Furthermore, 2/31 (6.5%) CSF specimens tested positive for IgM but were negative for neutralizing antibodies. There was a higher incidence of SINV-positive cases in Mpumalanga (26.0%) than Gauteng province (15.0%). The most significant months for IgM-positive cases were April 2019 (OR = 2.9, p < 0.05), and May 2020 (OR = 7.7, p < 0.05).

Conclusion

SINV or a closely related virus contributed to 12.7% of AFDUC cases in hospitalized patients during the late summer and autumn months in South Africa and was significantly associated with arthralgia, meningitis, and headaches.
Habitats Show More Impacts Than Host Species in Shaping Gut Microbiota of Sympatric Rodent Species in a Fragmented Forest
Authors: Teng Yuwei , Yang Xifu , Li Guoliang , Zhu Yunlong , Zhang Zhibin
Published: February 2022

Gut microbiota play a significant role for animals to adapt to the changing environment. Host species and habitats are key drivers in shaping the diversity and composition of the microbiota, but the determinants of composition of the sympatric host gut microbiome remain poorly understood within an ecosystem. In this study, we examined the effects of habitats of different succession stages and host species on the diversity and composition of fecal gut microbiota in four sympatric rodent species (Apodemus draco, Leopoldamys edwardsi, Niviventer confucianus, and Niviventer fulvescens) in a subtropical forest. We found, as compared to the differences between species, habitat types showed a much larger effect on the gut microbiota of rodents. Alpha diversity of the microbial community of A. draco, N. fulvescens, and N. confucianus was highest in farmland, followed by primary forest and shrubland, and lowest in secondary forest. Beta diversity of the three rodent species showed significant different among habitats. The alpha diversity of gut microbiota of L. edwardsi was significantly higher than those of A. draco and N. confucianus, and its beta diversity showed significant difference from A. draco. Our results suggested that gut microbiota were important for animals in responding to diet changes in different habitats under human disturbances.
T Cell Receptor Repertoire Analysis Reveals Signatures of T Cell Responses to Human Mycobacterium tuberculosis
Authors: Shao Ming-Ming , Yi Feng-Shuang , Huang Zhong-Yin , Peng Peng , Wu Feng-Yao , Shi Huan-Zhong , Zhai Kan
Published: February 2022

Characterization of T cell receptor (TCR) repertoires is essential for understanding the mechanisms of Mycobacterium tuberculosis (Mtb) infection involving T cell adaptive immunity. The characteristics of TCR sequences and distinctive signatures of T cell subsets in tuberculous patients are still unclear. By combining single-cell TCR sequencing (sc-TCR seq) with single-cell RNA sequencing (sc-RNA seq) and flow cytometry to characterize T cells in tuberculous pleural effusions (TPEs), we identified 41,718 CD3+ T cells in TPEs and paired blood samples, including 30,515 CD4+ T cells and 11,203 CD8+ T cells. Compared with controls, no differences in length and profile of length distribution were observed in complementarity determining region 3 (CDR3) in both CD4+ and CD8+ T cells in TPE. Altered hydrophobicity was demonstrated in CDR3 in CD8+ T cells and a significant imbalance in the TCR usage pattern of T cells with preferential expression of TRBV4-1 in TPE. A significant increase in clonality was observed in TCR repertoires in CD4+ T cells, but not in CD8+ T cells, although both enriched CD4+ and CD8+ T cells showed TH1 and cytotoxic signatures. Furthermore, we identified a new subset of polyfunctional CD4+ T cells with CD1-restricted, TH1, and cytotoxic characteristics, and this subset might provide protective immunity against Mtb.
Metabolomics and its Applications in Cancer Cachexia
Authors: Cui Pengfei , Li Xiaoyi , Huang Caihua , Li Qinxi , Lin Donghai
Published: February 2022

Cancer cachexia (CC) is a complicated metabolic derangement and muscle wasting syndrome, affecting 50–80% cancer patients. So far, molecular mechanisms underlying CC remain elusive. Metabolomics techniques have been used to study metabolic shifts including changes of metabolite concentrations and disturbed metabolic pathways in the progression of CC, and expand further fundamental understanding of muscle loss. In this article, we aim to review the research progress and applications of metabolomics on CC in the past decade, and provide a theoretical basis for the study of prediction, early diagnosis, and therapy of CC.
The Impact of Disease Registries on Advancing Knowledge and Understanding of Dementia Globally
Authors: Heikal Shimaa A. , Salama Mohamed , Richard Yuliya , Moustafa Ahmed A. , Lawlor Brian
Published: February 2022

To help address the increasing challenges related to the provision of dementia care, dementia registries have emerged around the world as important tools to gain insights and a better understanding of the disease process. Dementia registries provide a valuable source of standardized data collected from a large number of patients. This review explores the published research relating to different dementia registries around the world and discusses how these registries have improved our knowledge and understanding of the incidence, prevalence, risk factors, mortality, diagnosis, and management of dementia. A number of the best-known dementia registries with high research output including SveDem, NACC, ReDeGi, CREDOS and PRODEM were selected to study the publication output based on their data, investigate the key findings of these registry-based studies. Registries data contributed to understanding many aspects of the disease including disease prevalence in specific areas, patient characteristics and how they differ in populations, mortality risks, as well as the disease risk factors. Registries data impacted the quality of patients’ lives through determining the best treatment strategy for a patient based on previous patient outcomes. In conclusion, registries have significantly advanced scientific knowledge and understanding of dementia and impacted policy, clinical practice care delivery.
Peripherical Electrical Stimulation for Parkinsonian Tremor: A Systematic Review
Authors: Meng Lin , Jin Mengyue , Zhu Xiaodong , Ming Dong
Published: February 2022

Parkinsonian tremor is one of the most common motor disorders in patients with Parkinson's disease (PD). Compared to oral medications and brain surgery, electrical stimulation approaches have emerged as effective and non-invasive methods for tremor reduction. The pathophysiology, detection and interventions of tremors have been introduced, however, a systematic review of peripherical electrical stimulation approaches, methodologies, experimental design and clinical outcomes for PD tremor suppression is still missing. Therefore, in this paper, we summarized recent studies on electrical stimulation for tremor suppression in PD patients and discussed stimulation protocols and effectiveness of different types of electrical stimulation approaches in detail. Twenty out of 528 papers published from 2010 to 2021 July were reviewed. The results show that electrical stimulation is an efficient intervention for tremor suppression. The methods fall into three main categories according to the mechanisms: namely functional electrical stimulation (FES), sensory electrical stimulation (SES) and transcutaneous electrical nerve stimulation (TENS). The outcomes of tremor suppression were varied due to various stimulation approaches, electrode locations and stimulation parameters. The FES method performed the best in tremor attenuation where the efficiency depends mainly by the control strategy and accuracy of tremor detection. However, the mechanism underlying tremor suppression with SES and TENS, is not well-known. Current electrical stimulation approaches may only work for a number of patients. The potential mechanism of tremor suppression still needs to be further explored.
Prostacyclin Promotes Degenerative Pathology in a Model of Alzheimer’s Disease
Authors: Womack Tasha R. , Vollert Craig T. , Ohia-Nwoko Odochi , Schmitt Monika , Montazari Saghi , Beckett Tina L. , Mayerich David , Murphy Michael Paul , Eriksen Jason L.
Published: February 2022

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression significantly worsened multiple measures associated with amyloid-β (Aβ) disease pathologies. Mice overexpressing both Aβ and PGI2 exhibited impaired learning and memory and increased anxiety-like behavior compared with non-transgenic and PGI2 control mice. PGI2 overexpression accelerated the development of Aβ accumulation in the brain and selectively increased the production of soluble Aβ42. PGI2 damaged the microvasculature through alterations in vascular length and branching; Aβ expression exacerbated these effects. Our findings demonstrate that chronic prostacyclin expression plays a novel and unexpected role that hastens the development of the AD phenotype.
Long-Term Cultures of Spinal Cord Interneurons
Authors: Vargova Ingrid , Kriska Jan , Kwok Jessica C. F. , Fawcett James W. , Jendelova Pavla
Published: February 2022

Spinal cord interneurons (SpINs) are highly diverse population of neurons that play a significant role in circuit reorganization and spontaneous recovery after spinal cord injury. Regeneration of SpIN axons across rodent spinal injuries has been demonstrated after modification of the environment and neurotrophin treatment, but development of methods to enhance the intrinsic regenerative ability of SpINs is needed. There is a lack of described in vitro models of spinal cord neurons in which to develop new regeneration treatments. For this reason, we developed a new model of mouse primary spinal cord neuronal culture in which to analyze maturation, morphology, physiology, connectivity and regeneration of identified interneurons. Isolated from E14 mice, the neurons mature over 15 days in vitro, demonstrated by expression of maturity markers, electrophysiological patch-clamp recordings, and formation of synapses. The neurons express markers of SpINs, including Tlx3, Lmx1b, Lbx1, Chx10, and Pax2. The neurons demonstrate distinct morphologies and some form perineuronal nets in long-term cultivation. Live neurons in various maturation stages were axotomized, using a 900 nm multiphoton laser and their fate was observed overnight. The percentage of axons that regenerated declined with neuronal maturity. This model of SpINs will be a valuable tool in future regenerative, developmental, and functional studies alongside existing models using cortical or hippocampal neurons.
The Impact of Preinjury Use of Antiplatelet Drugs on Outcomes of Traumatic Brain Injury: A Systematic Review and Meta-Analysis
Authors: Cheng Li , Cui Gaoliang , Yang Rong
Published: February 2022

Objective

The study aimed to compare outcomes of traumatic brain injury (TBI) in patients on pre-injury antiplatelet drugs vs. those, not on any antiplatelet or anticoagulant drugs.

Methods

PubMed, Embase, and Google Scholar databases were searched up to 15th May 2021. All cohort studies comparing outcomes of TBI between antiplatelet users vs. non-users were included.

Results

Twenty studies were included. On comparison of data of 2,447 patients on pre-injury antiplatelet drugs with 4,814 controls, our analysis revealed no statistically significant difference in early mortality between the two groups (OR: 1.30 95% CI: 0.85, 1.98 I2 = 80% p = 0.23). Meta-analysis of adjusted data also revealed no statistically significant difference in early mortality between antiplatelet users vs. controls (OR: 1.24 95% CI: 0.93, 1.65 I2 = 41% p = 0.14). Results were similar for subgroup analysis of aspirin users and clopidogrel users. Data on functional outcomes was scarce and only descriptive analysis could be carried out. For the need for surgical intervention, pooled analysis did not demonstrate any statistically significant difference between the two groups (OR: 1.11 95% CI: 0.83, 1.48 I2 = 55% p = 0.50). Length of hospital stay (LOS) was also not found to be significantly different between antiplatelet users vs. non-users (MD: −1.00 95% CI: −2.17, 0.17 I2 = 97% p = 0.09).

Conclusion

Our results demonstrate that patients on pre-injury antiplatelet drugs do not have worse early mortality rates as compared to patients, not on any antiplatelet or anticoagulant drugs. The use of antiplatelets is not associated with an increased need for neurosurgical intervention and prolonged LOS.