bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients
Authors: Wang Junyi , Xu Zihui , Lv Kang , Ye Yingchun , Luo Deng , Wan Li , Zhou Fen , Yu Ailin , Wang Shuo , Liu Jingcheng , Gao Ling 
Published: April 2022

BackgroundCardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences.MethodsIn this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN &lt;100 ms). All patients’ clinical data were collected and the correlation of clinical variables with HRV were analyzed by correlation and logistic regression analysis. The area below the ROC curve was used to evaluate the predictive performance of serum calcium on HRV.ResultsIn this study, declines in HRV were present in 37.0% of T2DM patients. Significant differences in albumin-adjusted serum calcium levels (CaA) (8.86 ± 0.27 vs. 9.13 ± 0.39 mg/dl, p &lt;0.001) and E/A (0.78 ± 0.22 vs. 0.83 ± 0.26, p = 0.029) were observed between declined HRV and normal HRV groups. Bivariate linear correlation analysis showed that CaA and E/A were positively correlated with HRV parameters including SDNN (p &lt; 0.001), SDNN index (p &lt; 0.001), and Triangle index (p &lt; 0.05). The AUC in the ROC curve for the prediction of CaA on HRV was 0.730 (95% CI (0.750–0.815), p &lt; 0.001). The cutoff value of CaA was 8.87 mg/dl (sensitivity 0.644, specificity 0.814). The T2DM patients with CaA &lt;8.87 mg/dl had significantly lower HRV parameters (SDNN, SDNN index, rMSSD, and triangle index) than those with CaA ≥8.87 mg/dl (p &lt; 0.01, respectively). Multivariate logistic regression analysis showed a significantly increased risk of declined HRV in subjects with CaA level &lt;8.87 mg/dl [OR (95% CI), 0.049 (0.024–0.099), p &lt; 0.001].ConclusionsDeclined HRV is associated with a lower CaA level and worse cardiac function. The serum calcium level can be used for risk evaluation of declined HRV in T2DM patients even within the normocalcemic range.
Microbial Fuel Cell for Wastewater Treatment as Power Plant in Smart Grids: Utopia or Reality?
Authors: Tsekouras George J. , Deligianni Panagiota M. , Kanellos Fotis D. , Kontargyri Vassiliki T. , Kontaxis Panagiotis A. , Manousakis Nikolaos M. , Elias Charalambos N. 
Published: April 2022

Microbial fuel cells (MFCs) have undergone great technological development in the last 20 years, but very little has been done to commercialize them. The simultaneous power production and wastewater treatment are features those greatly increase the interest in the use of MFCs. This kind of distributed power generation is renewable and friendly and can be easily integrated into a smart grid. However, there are some key issues with their commercialization: high construction costs, difficulty in developing high power structures, MFC lifespan, and maintaining a high level of efficiency. The objective of this article is to explore the possibilities of using MFCs in urban wastewater not only regarding the technical criteria of their application, but also mainly from an economic point of view, to determine the conditions through which the viability of the investment is ensured and the possibilities of their integration in a smart grid are identified. Initially, this article explores the implementation/configuration of a power plant with MFCs within an urban wastewater treatment plant on a theoretical basis. In addition, based on the corresponding physical quantities for urban wastewater treatment, the construction and operational costs are determined and the viability of the investment is examined based on classic economic criteria such as net present value, benefit–cost ratio, internal rate of return, and discounted payback period. Furthermore, sensitivity analysis is carried out, concerning both technical parameters, such as the percentage of organic matter removal, power density, sewage residence time, MFC efficiency, etc., and economical parameters, such as the reduction of construction costs due to change of materials, change of interest rate, and lifetime. The advantages and disadvantages of their use in smart grids is also analyzed. The results show that the use of MFCs for power generation cannot be utopian as long as they are integrated into the structure of a central wastewater treatment plant on the condition that the scale-up technical issues of MFCs are successfully addressed.
Microbial Residual Nitrogen Distribution in Brown Earth’s Aggregates as Affected by Different Maize Residues and Soil Fertility Levels
Authors: Xue Pingluo , Pei Jiubo , Ma Nan , Wang Jingkuan 
Published: April 2022

Brown earth is one of the typical soils in the dryland areas of Northeast China, and its degradation is closely related to food security in the local. Effectively preventing soil nitrogen (N) loss can promote the soil fertility supply. As the hub of nitrogen cycling, microorganisms play an important role in N transformation and accumulation. Soil aggregates are important in improving soil fertility and preventing soil degradation because they are an important index to maintain soil fertility. However, the allocation of microbial residual N and its contribution to total N in brown earth’s aggregates are still limited, especially the effects of different maize residue types’ return and soil fertility levels. Focusing on this, a 360-day laboratory incubation experiment at 25°C was carried out induced by adding maize roots and shoots into brown earth with low (L) and high (H) fertility, respectively. Randomized soil samples were taken on the incubation day of 0, 30, 60, 180, and 360, and then, they were divided into macroaggregates (&gt;250 μm) and microaggregates (&lt;250 μm) using a dry-sieved method. The relative contributions of fungal and bacterial residual N to soil total N were calculated by the amino sugar content to examine the accumulated differences of microbial residual N in brown earth’s aggregates with the addition of different parts of maize residues and fertility levels. The results showed that maize residue types had different effects on the fungal and bacterial residual N enrichment in soil aggregates. In macroaggregates, maize roots promoted the accumulation of fungal residual N. The fungal residual N contributions to total nitrogen with root treatments were 1.03 times more than those with shoot treatments. However, in microaggregates, the bacterial residual N contributions to total nitrogen with shoot treatments were 1.01 times more than those with root treatments. These indicated that maize roots should be more beneficial to the accumulation of bacterial residual N in microaggregates. Moreover, the high fertility soil could sequester more microbial residual N than the low fertility soil, showing the content of microbial residual N in high fertility was 1.12–1.18 times more than that in low fertility. Furthermore, the fungal residual N was more beneficially accumulated in low fertility soil. Regardless of the level of fertility, the proportion of N in total N with shoot treatment was higher than that with root treatment, indicating that the above ground maize residues could better promote the metabolic process of microorganisms than the below ground ones. These could provide a theoretical basis for studying the microbial transformation mechanism of nitrogen after maize straw returning to the field, which could be of great significance to main soil fertility.
Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review
Authors: Zhu Jun , Wan Shuisen , Zhao Xueqi , Zhu Binlu , Lv Yuan , Jiang Hongkun 
Published: April 2022

Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A &gt; G (p.Gln27Arg) and c.609G &gt; A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved.Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA.Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.
Lymphoplasma Exchange Improves Myasthenia Gravis Exacerbations: A Retrospective Study in a Chinese Center
Authors: Ouyang Song , Yin Weifan , Zeng Qiuming , Li Bijuan , Zhang Jian , Duan Weiwei , Li Yi , Liang Yong , Wang Jiaqi , Tan Hong , Yang Huan 
Published: April 2022

BackgroundLymphoplasma exchange (LPE), a technique combining plasma exchange with leukapheresis, is emerging as promising treatment for autoimmune diseases. Data on the efficacy and safety of LPE in myasthenia gravis (MG) therapy are scarce. In this study, we aimed to comprehensively review the clinical efficacy, safety, and immunological characteristics of LPE therapy in MG patients.Study Design and MethodsA Chinese cohort of 276 generalized MG patients in state of exacerbation, including impeding crisis, myasthenia crisis, and preparation for thoracic exsection between January 2014 and December 2020, were evaluated in this study.ResultsA total of 276 patients with a median age of 45.5 ± 16.7 years underwent a total of 635 LPE sessions. Clinical scales of Quantitative Myasthenia Gravis (QMG) scores, Myasthenia Gravis Specific Manual Muscle Testing (MMT) scores, activities of daily living (ADL) scores, and quality of life (QOL) scores were improved during 4 weeks’ follow-up. Adverse effects occurred in 20 out of 276 patients, with 14 patients having one adverse event each. Independent predictive factors for good response to LPE therapy were symptom onset before LPE therapy ≤3 days and age on LPE therapy &lt;50 years of age. LPE decreased the serum levels of antibodies, immunoglobulins, and complements 4 weeks after the first replacement, with decreased levels of interleukin (IL)-17A and interferon (IFN)-γ and increased level of IL-10.ConclusionLPE is an effective treatment for MG patients in state of exacerbation and preparation for thymectomy. Early use of LPE on early-onset MG may have good therapeutic effects. The potential mechanism for LPE is the polarization of cytokines from IL-17A, IFN-γ, into IL-10.
Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review
Authors: Cabezas Lara , Jouve Thomas , Malvezzi Paolo , Janbon Benedicte , Giovannini Diane , Rostaing Lionel , Noble Johan 
Published: April 2022

IntroductionChronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.Materials and MethodsWe systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.ResultsMost studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.ConclusionTCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors
Authors: Harding James J. , Garrido-Laguna Ignacio , Chen Xiaoying , Basu Cynthia , Dowlati Afshin , Forgie Alison , Hooper Andrea T. , Kamperschroer Cris , Max Steven I. , Moreau Allison , Shannon Megan , Wong Gilbert Y. , Hong David S. 
Published: April 2022

P-cadherin is a cell-cell adhesion molecule that is overexpressed in several solid tumors. PF-06671008 is a T-cell–redirecting bispecific antibody that engages both P-cadherin on tumors and CD3ϵ on T cells and induces antitumor activity in preclinical models. We conducted a phase 1, open-label, first-in-human, dose-escalation study to characterize the safety and tolerability of PF-06671008, towards determining the recommended phase 2 dose. Adult patients with treatment-refractory solid tumors received PF-06671008 (1.5–400 ng/kg) as a weekly intravenous (IV) infusion on a 21-day/3-week cycle. Parallel cohorts evaluated dosing via subcutaneous injection (SC) or an IV-prime dose. Of the 27 patients enrolled in the study, 24 received PF-06671008 IV in escalating doses, two received SC, and one IV-prime. A dose-limiting toxicity of cytokine release syndrome (CRS) occurred in the 400-ng/kg IV group, prompting evaluation of SC and IV-prime schedules. In all, 25/27 patients who received PF-06671008 reported at least one treatment-related adverse event (TRAE); the most common were CRS (21/27), decreased lymphocyte count (9/27), and hypophosphatemia (8/27). Seven patients permanently discontinued treatment due to adverse events and no treatment-related deaths occurred. Cytokine peak concentrations and CRS grade appeared to positively correlate with Cmax. Although the study was terminated due to limited antitumor activity, it provides important insights into understanding and managing immune-related adverse events resulting from this class of molecules.Clinical Trial RegistrationURL: https://clinicaltrials.gov/ct2/show/NCT02659631, ClinicalTrials.gov Identifier: NCT02659631.
Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Gene and Human Diseases and Phenotypes
Authors: Zhang Min , Bai Ye , Wang Yutong , Cui Huijie , Tang Mingshuang , Wang Lanbing , Wang Xin , Gu Dongqing 
Published: April 2022

BackgroundGenetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes.MethodsWe searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence.ResultsWe included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn’s disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions.ConclusionsOur study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases.
Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective
Authors: Escalante Gabriela M. , Mutsvunguma Lorraine Z. , Muniraju Murali , Rodriguez Esther , Ogembo Javier Gordon 
Published: April 2022

BackgroundEpstein-Barr virus (EBV) is the causal agent of infectious mononucleosis and has been associated with various cancers and autoimmune diseases. Despite decades of research efforts to combat this major global health burden, there is no approved prophylactic vaccine against EBV. To facilitate the rational design and assessment of an effective vaccine, we systematically reviewed pre-clinical and clinical prophylactic EBV vaccine studies to determine the antigens, delivery platforms, and animal models used in these studies.MethodsWe searched Cochrane Library, ClinicalTrials.gov, Embase, PubMed, Scopus, Web of Science, WHO’s Global Index Medicus, and Google Scholar from inception to June 20, 2020, for EBV prophylactic vaccine studies focused on humoral immunity.ResultsThe search yielded 5,614 unique studies. 36 pre-clinical and 4 clinical studies were included in the analysis after screening against the exclusion criteria. In pre-clinical studies, gp350 was the most commonly used immunogen (33 studies), vaccines were most commonly delivered as monomeric proteins (12 studies), and mice were the most used animal model to test immunogenicity (15 studies). According to an adaptation of the CAMARADES checklist, 4 pre-clinical studies were rated as very high, 5 as high, 13 as moderate quality, 11 as poor, and 3 as very poor. In clinical studies, gp350 was the sole vaccine antigen, delivered in a vaccinia platform (1 study) or as a monomeric protein (3 studies). The present study was registered in PROSPERO (CRD42020198440).ConclusionsFour major obstacles have prevented the development of an effective prophylactic EBV vaccine: undefined correlates of immune protection, lack of knowledge regarding the ideal EBV antigen(s) for vaccination, lack of an appropriate animal model to test vaccine efficacy, and lack of knowledge regarding the ideal vaccine delivery platform. Our analysis supports a multivalent antigenic approach including two or more of the five main glycoproteins involved in viral entry (gp350, gB, gH/gL, gp42) and a multimeric approach to present these antigens. We anticipate that the application of two underused challenge models, rhesus macaques susceptible to rhesus lymphocryptovirus (an EBV homolog) and common marmosets, will permit the establishment ofin vivocorrelates of immune protection and attainment of more generalizable data.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=198440, identifier PROSPERO I.D. CRD4202019844.
Clinical Features and T Cell Immune Characteristics of Postpartum Hepatitis Flare in Pregnant Women With HBeAg-Positive Chronic HBV Infection
Authors: Song Aixin , Liu Yisi , Cao Zhenhuan , Lu Junfeng , Ren Shan , Zheng Sujun , Ma Lina , Hu Zhongjie , Lin Xiao , Li Hong , Zheng Yanhong , Chen Xinyue 
Published: April 2022

BackgroundThe extent of the increase in postpartum alanine transaminase (ALT) varies significantly among pregnant women in the immune tolerance stage of nucleoside analogue (NA) intervention, so this study is an attempt to analyze the clinical features of patients with and without postpartum hepatitis flare and preliminarily explore the differences in their immune functions.MethodsPregnant women with a gestational age of 24–28 w and in the immune tolerance stage of NA intervention for hepatitis B virus (HBV) infection were included and divided into a hepatitis group (Group 1) and a nonhepatitis group (Group 2) according to the ALT level at 6–12 w after childbirth. The clinical features were analyzed, and the phenotypes, functions, and cytokines of clusters of differentiation CD8+ T cells in the two groups of patients were detected using flow cytometry before and after childbirth.ResultsA total of 15 patients with postpartum hepatitis flare were enrolled in Group 1, and 10 matched patients were selected as controls for Group 2. Compared with the individuals in Group 2, the postpartum clinical features in Group 1 included a remarkable elevation of the ALT level on the basis of a relatively low HBV DNA level, usually accompanied by a decline in hepatitis B virus surface antigen levels as well as HBeAg levels. In addition, CD8+ T cell activation was enhanced after childbirth in Group 1. In particular, there was a notable difference in the activation of TEMRA subsets, and the frequency of CD8+ T cells expressing perforin and granzyme B increased.ConclusionThe changes in the immune characteristics of CD8+ T cells may play a certain role in breaking down immune tolerance in patients with postpartum hepatitis flare, and the indexes related to activating and killing functions may help to indicate the population with hepatitis flare after childbirth.