bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Quantitative Lipid Profiles: Identification of CarnitineC18:1-OH, CarnitineC18:2-OH and FFA (20:1) as Novel Biomarkers for Pre-warning and Prognosis in Acute Myocardial Infarction
Authors: Liu Jun , Tang Liangqiu , Lu Qiqi , Yu Yi , Xu Qiu-Gui , Zhang Shanqiang , Chen Yun-Xian , Dai Wen-Jie , Li Ji-Cheng
Published: April 2022

This study was aimed to determine the association between potential plasma lipid biomarkers and early screening and prognosis of Acute myocardial infarction (AMI). In the present study, a total of 795 differentially expressed lipid metabolites were detected based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Out of these metabolites, 25 lipid metabolites were identified which showed specifical expression in the AMI group compared with the healthy control (HC) group and unstable angina (UA) group. Then, we applied the least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) methods to obtain three lipid molecules, including CarnitineC18:1-OH, CarnitineC18:2-OH and FFA (20:1). The three lipid metabolites and the diagnostic model exhibited well predictive ability in discriminating between AMI patients and UA patients in both the discovery and validation sets with an area under the curve (AUC) of 0.9. Univariate and multivariate logistic regression analyses indicated that the three lipid metabolites may serve as potential biomarkers for diagnosing AMI. A subsequent 1-year follow-up analysis indicated that the three lipid biomarkers also had prominent performance in predicting re-admission of patients with AMI due to cardiovascular events. In summary, we used quantitative lipid technology to delineate the characteristics of lipid metabolism in patients with AMI, and identified potential early diagnosis biomarkers of AMI via machine learning approach.
Cost-effectiveness of Direct Oral Anticoagulant vs. Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk
Authors: Choi Ju Hee , Kim Woojin , Kim Yun Tae , Cho Jaelim , Shin Seung Yong , Kim Changsoo , Kim Jin-Bae
Published: April 2022

Background

Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data.

Methods

We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained.

Results

The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis.

Conclusion

Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.
Recent Evolution of Glaciers in the Manaslu Region of Nepal From Satellite Imagery and UAV Data (1970–2019)
Authors: Racoviteanu Adina E. , Glasser Neil F. , Robson Benjamin A. , Harrison Stephan , Millan Romain , Kayastha Rijan B. , Kayastha Rakesh
Published: April 2022

Glacierized mountain ranges such as the Himalaya comprise a variety of glacier types, including clean and debris-covered glaciers. Monitoring their behaviour over time requires an assessment of changes in area and elevation along with surface features and geomorphology. In this paper we quantify the surface evolution of glacier systems in the Manaslu region of Nepal over the last five decades using 2013/2019 multi-sensor imagery and elevation data constructed from 1970 declassified Corona imagery and 1970 declassified Corona imagery. We investigate area changes, glacier thickness, geodetic glacier mass balance and surface velocity changes at regional scales and focus on the Ponkar Glacier and Thulagi Glacier and Lake for an in-depth assessment of surface geomorphology and surface feature dynamics (ponds, vegetation and ice cliffs). The time series of surface elevation changes for the lower ablation area of Ponkar Glacier is extended using 2019 UAV-based imagery and field-based ablation rates measured over the period 2016–2019. Glaciers in the Manaslu region experienced a mean area loss of −0.26 ± 0.0001% a−1 between 1970 and 2019. The mean surface lowering was −0.20 ± 0.02 ma−1 over the period 1970 to 2013, corresponding to a regional geodetic mass balance of −0.17 ± 0.03 m w. e.a−1. Overall, debris-covered glaciers had slightly higher thinning rates compared to clean ice glaciers; lake-terminating glaciers had double thinning rates compared to land-terminating glaciers. Individual glacier mass balance was negatively controlled by glacier slope and mean glacier elevation. During the period 1970 to 2013, Ponkar Glacier had a geodetic mass balance of −0.06 ± 0.01 m w. e.a−1, inversely correlated with parts of the central trunk thickening. Between 2013 and 2019 there was a nine-fold increase in the thinning rates over the lower parts of the glacier tongue relative to the period 1970–2013. Ice-surface morphology changes between 1970 and 2019 on Ponkar Glacier include a decrease in ogives and open crevasses, an increase in ice cliffs and ponds and the expansion of the supraglacial debris and ice-surface vegetation. These changes point to reduced ice-dynamic activity and are commensurate with the observed recession and negative glacier mass balance over the last five decades.
Holocene Environmental Dynamics of the Lago Cochrane/Pueyrredón Valley, Central West Patagonia (47°S)
Authors: Maldonado Antonio , de Porras María Eugenia , Martel-Cea Alejandra , Reyes Omar , Nuevo-Delaunay Amalia , Méndez César
Published: April 2022

Deglaciation modeling of the Patagonian Ice Field since the Last Glacial Maximum has been a topic of intensive research in Central West Patagonia (44°–49°S). However, the chronology of deglaciation onset, acceleration, and the subsequent thinning and recession of the different ice lobes as well as the timing and extension of large proglacial systems are still a matter of discussion. The maximum eastward extension the Lago Cochrane/Pueyrredón ice lobe was around ∼20,000–27,000 cal yrs BP; its associated proglacial lake drained toward the Pacific between 12,600 and 8,000 cal yrs BP. This study presents the first two pollen and charcoal records from the Lago Cochrane/Pueyrredón valley, spanning the last 11,650 cal yrs BP. The Laguna Maldonado record spans between 11,650 and 8,500 cal yrs BP, while the Laguna Anónima record the last 8,500 cal yrs BP, thereby overlapping chronologically. The lithological record of Laguna Maldonado shows that organic sedimentation began at the onset of the Holocene (11,650 cal yrs BP), once the site was free of glacio-lacustrine influence. Between 11,650 and 10,500 cal yrs BP, an open Nothofagus forest developed associated with high fire occurrence/frequency, followed by a transitional phase to a closer forest associated with a shift from low to high fire activity up to 9,400 cal yrs BP. Between 9,400 and 8,500 cal yrs BP, the Laguna Maldonado record suggests the development of an open forest or probably scattered patches of forest of variable size in a steppe matrix, probably related to geomorphological and paraglacial dynamics as well as climatic forcings, while the Laguna Anónima record indicates the development of a closed Nothofagus forest and high to low fire occurrence/frequency from 8,200 to 3,800 cal yrs BP. Since 3,800 cal yrs BP, a highly dynamic open forest or forest patches scattered in a grass/shrub–grass steppe matrix occurred around Laguna Anónima associated with high fire occurrence/frequency synchronous with an important increase in the presence of hunter-gatherers during the last 3,000 years. The results from the Lago Cochrane/Pueyrredón valley are integrated and discussed at the regional scale alongside other records from Central West Patagonia.
Experimental Study of Dynamic Characteristics of Tailings With Different Reconsolidation Degrees After Liquefaction
Authors: Wang Wensong , Cao Guansen , Li Ye , Zhou Yuxi , Lu Ting , Wang Ya , Zheng Binbin
Published: April 2022

The construction period of most tailing ponds generally lasts for more than 10 years or even decades. During this period, it may be affected by more than one earthquake and is often subjected to vibrations generated by mining activities. The tailings liquefied by earthquakes or vibrations may experience dynamic loads again. Due to the low permeability of tailings, the reconsolidation process of tailings after liquefaction is prolonged. Therefore, changes in the nature of the tailings caused by previous earthquakes will affect the performance of the tailing dam in the subsequent earthquakes. Dynamic triaxial tests and bending element tests were conducted on two kinds of tailings from a copper mine in Southwest China to study this process. The tailing specimens will undergo two consolidation processes and subsequent cyclic loads during the test. The influence of reconsolidation degree, confining pressure, and particle size on the dynamic characteristics and wave velocity of the tailings after liquefaction under cyclic loading was measured. The results show that the reconsolidation degree significantly affects the trend of the excess pore water pressure ratio changing with the increase in the cycle number of loads. The reconsolidation process after liquefaction of tailings will improve its liquefaction resistance. The relationship between the ratio of the cycle number of liquefaction after reconsolidation to the cycle number of first liquefaction and the reconsolidation degree is proposed. In the entire experimental process, the shear wave velocity of the tailings gradually decreases when applying the cyclic load and gradually increases during the consolidation process, including the first consolidation before cyclic loading and reconsolidation after liquefaction. The research results are of great significance to the safe disposal of tailings, especially those in earthquake-prone areas.
A Geospatial Cost Comparison of CO2 Plume Geothermal (CPG) Power and Geologic CO2 Storage
Authors: Ogland-Hand Jonathan D. , Adams Benjamin M. , Bennett Jeffrey A. , Middleton Richard S.
Published: April 2022

CO2 Plume Geothermal (CPG) power plants can use gigatonne-levels of CO2 sequestration to generate electricity, but it is unknown if the resources that support low-cost CPG power align with the resources that support low-cost CO2 sequestration. Here, we estimate and compare the geospatially-distributed cost of CPG and CO2 storage across a portion of North America. We find that the locations with lowest-cost CO2 storage are different than the locations with lowest-cost CPG. There are also locations with low-cost CO2 storage (<$5/tCO2) that do not support CPG power generation due to insufficient reservoir transmissivity or temperature. Thus, CPG development may require electricity prices that are greater than the levelized cost of electricity (LCOE) to offset the increased cost of sequestration. We introduce the “Additional Cost of Electricity (ACOE)” metric to account for this cost and add it to the LCOE to calculate breakeven electricity prices that are required for CPG development. We find that breakeven prices are lower when new CO2 injection wells are drilled specifically for CPG (i.e., “greenfield” CPG development) compared to if only existing CO2 sequestration injection wells are used (i.e., “brownfield” CPG development). This is because comparatively few wells are needed for sequestration-only, and the increased power capacity from having more CPG wells outweighs the increased costs from more drilling. We also find that sequestered CO2 could be used to approximately triple the United States geothermal electricity power capacity via a single CPG “sweet spot” in South Dakota, but that breakeven electricity price for this development is on the order of $200/MWeh.
Optimization of Re-Fracturing Method and Fracture Parameters for Horizontal Well in Mahu Conglomerate Oil Reservoir
Authors: Yi Yonggang , Wang Lei , Li Jie , Chen Sen , Tian Hui , Tian Gang
Published: April 2022

Mahu Oilfield, the largest conglomerate oilfield around the world, is facing the severe problems of rapid production decline and low recovery ratio. Re-fracturing of horizontal wells is an effective method to improve this situation. The study of horizontal well re-fracturing has increased popularity recently, but the optimization of re-fracturing parameters has not been thoroughly investigated, especially for the conglomerate reservoir. The optimal selection of re-fracturing parameters such as length and conductivity is unclear, which significantly influences re-fracturing treatment and economic cost. In order to fill this gap, a series of numerical models are established based on filed data to predict horizontal well production after re-fracturing. The parameters of primary hydraulic fractures are calculated by net pressure matching and are imported into the numerical models. A production matching is conducted to confirm the reliability of numerical models. The cumulative productions of different re-fracturing stimulation methods, including lengthening old fractures and perforating new fractures, are simulated, and the corresponding re-fracturing parameters are optimized. The results have shown that the length of primary fractures is smaller than designed, which means lengthening old fractures is necessary. Lengthening old fractures and perforating new fractures between primary clusters can increase production. On the condition of the same fracture length, the increasing ranges of production corresponding to perforating new fractures are larger than that of lengthening old fractures. Lengthening old fractures is particularly suitable to the situation that the length of primary fractures is smaller than designed, and the optimal value in lengthening half-length of old fractures is 160 m. By contrast, perforating new fractures between old clusters applies to the case that the cluster spacing of primary hydraulic fracturing is larger than 35 m, and the optimal fracture half-length is 140 m.
Environmental Flows Assessment for Macroinvertebrates at the River Reach Scale in Different Degrees of Hydromorphological Alteration
Authors: Szałkiewicz Ewelina , Kałuża Tomasz , Grygoruk Mateusz
Published: April 2022

One of the most commonly used methods of environmental flows assessment is the approach based on Habitat Suitability Modeling (HSM) and habitat preferences curves (HPCs). Relationships between organisms and physical parameters describing the habitat remain strongly nonlinear and vary depending on several factors. The most common comparisons concern analyses between natural and regulated rivers, where the degree of river channel alterations is undefined and usually refers to all forms of hydromorphological degradation. Additionally, spatial scale and computational range of such a research mostly focus on longer river reaches and statistical analysis of HPC transferability, without detailed estimation of environmental flows values. The main aim of our research was assessment and comparison of environmental flows’ values for macroinvertebrates at two reaches of one river with different degrees of hydromorphological alteration. Two research hypotheses were verified: 1) morphological conditions impact on values of environmental flows and weighted usable area; 2) the mean value of environmental flows at the regulated river reach is higher compared to the natural reach. In order to put the obtained values of environmental flows into a broader context, the analyses of hydrological data and calculation of hydrology-based environmental flows were performed. Additionally, before determination of environmental flows, the transferability of habitat suitability criteria between reaches was verified. The obtained results confirmed research hypotheses, revealing strong dependence of environmental flows values to morphological conditions. Additionally, for both studied sections the lower limits of environmental flows were greater than hydrology-based values.
Genetic Diversity and Population Differentiation of Naked Carp (Gymnocypris przewalskii) Revealed by Cytochrome Oxidase Subunit I and D-Loop
Authors: Fang Di-an , Luo Hui , He Miao , Mao Chengcheng , Kuang Zhen , Qi Hongfang , Xu Dongpo , Tan Longfei , Li Yuandong
Published: April 2022

The genetic diversity in the naked carp (Gymnocypris przewalskii) of China is threatened by climate change, human activities, as well as natural factors, eliciting conservation concerns. To explore the genetic aspects ofG. przewalskii, the genetic diversity, genetic structure, population differentiation, and historical demography of 566 representative individuals from seven geographically distinct ranges of Qinghai Lake were evaluated by mitochondrial DNA cytochrome oxidase subunit I (COI) and D-loop sequences. Estimates of genetic parameters showed that the seven populations ofG. przewalskiihad high levels of haplotype diversity (0.50243–0.94620) and low levels of nucleotide diversity (0.00079–0.00624). Haplotype genealogy indicated there was no obvious phylogenetic pattern between haplotypes. Both markers denoted the absence of population genetic structure [the genetic differentiation coefficient F-statistics (Fst) < 0] and the presence of high genetic flow (COI: 0.9731–1.0441; D-loop: 0.9480–1.0398). The mismatch between the distribution and neutrality tests supported the evidence of population expansion, which occurred during the late middle Pleistocene [COI: 0.36–0.108 MYA (Million Years Ago); D-loop: 0.497–0.165 MYA]. Furthermore, this work illustrated two simple, reliable, and inexpensive molecular markers for analysis of genetic diversity, while the sensitivity of the mitochondrial D-loop region as a reflection of genetic diversity inG. przewalskiiis higher than that of theCOIgene.
Resilient Eggs: Highly Successful Loggerhead Sea Turtle Nesting Sites Vary in Their Characteristics
Authors: Gravelle Jessica , Wyneken Jeanette
Published: April 2022

Sea turtle nest success, defined as the number of eggs in a nest that successfully hatch and emerge, is closely linked to environmental conditions. Interacting biotic and abiotic factors influence hatching and hatchling emergence success. To date, combinations of multiple factors interacting together, which result in highly successful sea turtle nests are not well understood. Using 25 years of historic nest data and local expert experience, we identified five historically successful loggerhead (Caretta caretta) nesting beaches (hotspots) along the Florida (United States) Atlantic coast and measured nest environments along with the nest success. Principal component analysis was used to reduce 12 environmental variables so that the relative contributions of sand characteristics, nest temperatures, sand moisture, and nest location were considered. The nest environments differed among nesting beaches and were broadly segregated into two distinct climates: subtropical (hot and humid) and warm-temperate (warm and dry). We found that nests at subtropical sites, compared with warm-temperate sites, were characterized by environmental gradients in contrasting ways. Nest locations were predominantly mid-beach in subtropical sites but clustered at higher elevations and closer to the base of the dune at warm-temperate climate sites. Collectively, highly successful nest hotspots represent a mosaic of abiotic factors providing conditions that promote successful hatching and emergence. This new perspective on consistently successful loggerhead nesting beach traits demonstrate that the key traits of sea turtle nesting habitat vary with prevailing climate type and should be managed accordingly.
Prevalence of Hemoglobin-S and Baseline Level of Knowledge on Sickle Cell Disease Among Pregnant Women Attending Antenatal Clinics in Dar-Es-Salaam, Tanzania
Authors: Tutuba Hilda J. , Jonathan Agnes , Lloyd William , Luoga Fredrick , Marco Emanuela , Ndunguru Joyce , Kidenya Benson R. , Makani Julie , Ruggajo Paschal , Minja Irene K. , Balandya Emmanuel
Published: April 2022

Background: Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Newborn screening (NBS) is the recommended intervention aimed at early identification of babies with SCD and their linkage to care. To ensure success of NBS, pregnant women need to have the required knowledge on SCD and therefore motivation to screen their babies.

Objective: The aim of this study was to determine the prevalence of hemoglobin-S and assess the baseline level of knowledge on SCD among pregnant women attending antenatal clinics in urban settings in Dar-es-Salaam, Tanzania.

Methods: This cross-sectional study was conducted between August 2020 and February 2021, involving 600 pregnant women at 20–28 weeks of gestation attending antenatal clinics at Buguruni Health Center, Mbagala Hospital, and Sinza Hospital in Dar-es-Salaam, Tanzania. We administered a structured questionnaire to all participants to assess socio-demographic characteristics and baseline level of knowledge on SCD, where those scoring 7 or higher out of 10 questions were considered to have good knowledge. We screened for SCD a total of 300 participants from two centers (Buguruni Health Center and Mbagala Hospital) by using Sickle SCAN point-of-care test (BioMedomics Inc., United States). We used SPSS version 23 to analyze the data. On determining the association between level of knowledge and socio-demographic factors, we used Pearson’s Chi-square and multivariate logistic regression in ascertaining the strength of associations.

Results: Of the 600 participants, the majority were of the age between 26 and 35 years (51%), with the parity of 1-3 children (55.8%) and secondary level of education (43%), while 56% were self-employed. Only 14.7% had good knowledge on SCD. The majority of the participants had ever heard of SCD (81.3%), most of them heard from the streets (42.4%), and only 2.4% heard from hospitals. Of all 600 study participants, only 2 (0.3%) knew their SCD status while 7.7% declared having a family history of SCD. A proficient level of knowledge on SCD is associated with a high level of education, occupation, and knowing personal status of SCD. Among 300 participants who were screened for SCD, 252 were Hb-AA (84%), 47 were Hb-AS (15.7%), and 1 (0.3%) was Hb-SS.

Conclusion: Despite the high prevalence of hemoglobin-S among pregnant women attending antenatal clinics in urban settings in Tanzania, there is a poor level of knowledge on SCD and personal knowledge of SCD status. Maternal screening and health education on SCD should be included as part of the comprehensive package for health promotion at antenatal clinics.
Global Gene Expression and Docking Profiling of COVID-19 Infection
Authors: Jabeen Almas , Ahmad Nadeem , Raza Khalid
Published: April 2022

Coronavirus is an enclosed positive-sense RNA virus with club-like spikes protruding from its surface that causes acute respiratory infections in humans. Because it is considered a member of the complex pathogen group, it has been found to infect different host species and cause a variety of diseases. So far, it has been discovered that it may affect the immune, infection, and inflammatory systems, leading to the hypothesis that the immune and inflammatory systems (signaling pathways and components) fail to control infection, opening the door to look for potential targets primarily in these systems. The study’s main purpose is to identify highly overexpressed genes and their functional implications as a result of COVID-19 infection, as well as to investigate probable infections, inflammation, and immune systems to better understand the impact of coronavirus infection. We explored the genes and pathways mostly linked with infection, inflammation, and the immune systems using the datasets available for COVID-19 infection gene expression compendium. NFKBIA, FN1, FAP, KANK4, COMP, FAM101B, COL1A2, ANKRD1, TAGLN, SPARC, ADAM19, OLFM4, CXCL10/11, OASL, FOS, APOBEC3A, IFI44L, IFI27, IFIT1, RSAD2, NDUFS1, SRSF6, HECTD1, CBX3, and DDX17 are among the genes that may be impacted by infection, according to our findings. The functional changes are mainly associated with these pathways TNF, cytokine, NF—kB, TLR, TCR, BCR, Foxo, and TGF signaling pathways are among them and there are additional pathways such as hippo signaling, apoptosis, estrogen signaling, regulating pluropotency of stem cells, ErbB, Wnt, p53, cAMP, MAPK, PI3K—AKT, oxidative phosphorylation, protein processing in endoplasmic reticulum, prolactin signaling, adipocytokine, neurotrophine signaling, and longevity regulating pathways. Moreover, we have also explored the potential herbal drug (apigenin, quercetin, and resveratrol) targets for the top-rated genes based on the overall analysis where we observe that quercetin and resveratrol as most effective.
Case Report: Atypical Manifestations Associated With FOXP3 Mutations. The “Fil Rouge” of Treg Between IPEX Features and Other Clinical Entities?
Authors: Gentile Micaela , Miano Maurizio , Terranova Paola , Giardino Stefano , Faraci Maura , Pierri Filomena , Drago Enrico , Verzola Daniela , Ghiggeri Gianmarco , Verrina Enrico , Angeletti Andrea , Cafferata Barbara , Grossi Alice , Ceccherini Isabella , Caridi Gianluca , Lugani Francesca , Nescis Lorenzo , Fiaccadori Enrico , Lanino Luca , Fenoglio Daniela , La Porta Edoardo
Published: April 2022

Introduction

The Forkhead box protein P3 (FOXP3) is a transcription factor central to the function of regulatory T cells (Treg). Mutations in the FOXP3 gene lead to a systemic disease called immune dysregulation, polyendocrinopathy, and enteropathy, an X-linked syndrome (IPEX) characterized by the triad of early-onset intractable diarrhea, type 1 diabetes, and eczema. An atypical presentation of IPEX has been reported.

Method

We report rare cases with equivocal clinical associations that included inflammatory, kidney, and hematologic involvements screened with massively parallel sequencing techniques.

Results

Two patients with hemizygous mutations of FOXP3 [c.779T>A (p.L260Q)] and [c.1087A>G (p.I363V)] presented clinical manifestations not included in typical cases of IPEX: one was a 16-year-old male patient with an initial clinical diagnosis of autoimmune lymphoproliferative syndrome (ALPS) and who developed proteinuria and decreased kidney function due to membranous nephropathy, an autoimmune renal condition characterized by glomerular sub-epithelial antibodies. The second patient was a 2-year-old child with bone marrow failure who developed the same glomerular lesions of membranous nephropathy and received a bone marrow transplantation. High levels of IgG4 in serum, bone marrow, and kidney led to the definition of IgG4-related kidney disease (IgG4 RKD) in this young boy. The circulating Treg levels were normal in the former case and very low in the second.

Conclusion

Two atypical associations of functional mutations of FOXP3 that include ALPS and IgG4 RKD are described. Membranous nephropathy leading to renal failure completed in both cases the clinical phenotypes that should be included in the clinical panorama of FOXP3 failure.
The Th17 Pathway in Vascular Inflammation: Culprit or Consort?
Authors: Robert Marie , Miossec Pierre , Hot Arnaud
Published: April 2022

The involvement of IL-17A in autoimmune and inflammatory diseases has prompted the development of therapeutic strategies to block the Th17 pathway. Promising results came from their use in psoriasis and in ankylosing spondylitis. IL-17A acts on various cell types and has both local and systemic effects. Considering the premature mortality observed during chronic inflammatory diseases, IL-17A action on vascular cells was studied. Bothin vitroandin vivoresults suggest that this cytokine favors inflammation, coagulation and thrombosis and promotes the occurrence of cardiovascular events. These observations led to study the role of IL-17A in diseases characterized by vascular inflammation, namely allograft rejection and vasculitis. Increased circulating levels of IL-17A and histological staining reveal that the Th17 pathway is involved in the pathogenesis of these diseases. Vasculitis treatment faces challenges while the use of steroids has many side effects. Regarding results obtained in giant cell arteritis with IL-6 inhibitors, a cytokine involved in Th17 differentiation, the use of anti-IL-17 is a promising strategy. However, lessons from rheumatoid arthritis and multiple sclerosis must be learnt before targeting IL-17 in vasculitis, which may be culprit, consort or both of them.
A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization
Authors: Harwardt Julia , Bogen Jan P. , Carrara Stefania C. , Ulitzka Michael , Grzeschik Julius , Hock Björn , Kolmar Harald
Published: April 2022

Various formats of bispecific antibodies exist, among them Two-in-One antibodies in which each Fab arm can bind to two different antigens. Their IgG-like architecture accounts for low immunogenicity and also circumvents laborious engineering and purification steps to facilitate correct chain pairing. Here we report for the first time the identification of a Two‐in‐One antibody by yeast surface display (YSD) screening of chicken-derived immune libraries. The resulting antibody simultaneously targets the epidermal growth factor receptor (EGFR) and programmed death‐ligand 1 (PD-L1) at the same Fv fragment with two non-overlapping paratopes. The dual action Fab is capable of inhibiting EGFR signaling by binding to dimerization domain II as well as blocking the PD-1/PD-L1 interaction. Furthermore, the Two-in-One antibody demonstrates specific cellular binding properties on EGFR/PD-L1 double positive tumor cells. The presented strategy relies solely on screening of combinational immune-libraries and obviates the need for any additional CDR engineering as described in previous reports. Therefore, this study paves the way for further development of therapeutic antibodies derived from avian immunization with novel and tailor-made binding properties.
Salinity Acclimation Strategies in Nitrifying Bioreactors
Authors: Navada Sharada , Vadstein Olav
Published: April 2022

Several industries, including aquaculture, produce effluents with high or varying salt concentrations. The treatment of such effluents by the biological nitrification process can be challenging, as the microbes performing this process are sensitive to salinity. In certain cases, such as in recirculating aquaculture systems (RAS), it is essential to maintain high nitrification efficiency during salinity changes to prevent ammonia and nitrite toxicity. Therefore, suitable strategies are required to make nitrifying bioreactors tolerant to salinity variations. Although salinity changes can impact the nitrification performance, it has been shown that nitrifying bioreactors can acclimate to salinity variations over several days. This acclimation can be due to the physiological adaptation of the existing microorganisms or due to selection for microorganisms adapted to that salinity regime. Other factors, such as the biofilm matrix, can also play a role in salinity acclimation. Recent studies have shown that microbial management strategies can be applied to improve the salinity tolerance and reduce the recovery time of nitrifying bioreactors. Here, we discuss the existing knowledge on salinity acclimation in nitrifying systems, and recent advances in strategies to make nitrifying biofilms more tolerant to salinity variations. We also propose directions for future research to improve our understanding of the salinity acclimation mechanisms in nitrifying systems.
Impact of the Scatterer Type on Ultrasound Wave Propagation in Microstructure Composites: Calculation and Application
Authors: Yang Yuming , Duan Huilong , Zheng Yinfei
Published: April 2022

This study is motivated to quantitatively analyze the differences among various multiple scattering models to determine the role played by the scatterer type in ultrasonic wave propagation. By calculating the transmission and reflection coefficients of the composites, the results of multiple scattering theoretical models of different scatterer types have been evaluated. The problem of acoustic properties in a fluid matrix containing different types of micron-scale scatterers operating in the ultrasound frequency range is considered. Theoretical calculations are conducted for composites with different mechanical properties. Meanwhile, the theoretical results have been compared with numerical finite element method simulations, which can be regarded as a benchmark to verify the validity of different theoretical models. The results show that the composites can achieve negative acoustic properties by selecting appropriate resonant scatterers, paving the way for searching ultrasonic metamaterials with desired negative acoustic properties. We further explored the application of microstructure ultrasonic metamaterials by enhancing the ultrasound transmitted energy through the high-impendence skull layer, having the potential for non-invasive ultrasound brain imaging and therapy.
48V EGR Pump System Development and Fuel Benefit Evaluation
Authors: Bagal Nilesh L. , Bhardwaj Divyanshu
Published: April 2022

Upcoming global emission regulations include considerable reduction in emission of nitrogen oxides (NOx) and greenhouse gases (GHGs) for vehicles with heavy-duty (HD) diesel application. These regulations will phase between 2024 and 2030 in the United States and the European Union. CARB Regulations include up to 90% reduction in NOx levels along with ∼25% reduction in CO2. One of the primary technologies used to reduce engine out NOx emission is the use of cooled exhaust gas recirculation (EGR). Research studies carried out across multiple domains by engine/vehicle original equipment manufacturers (OEMs) and others have identified air handling as one of the technologies to help meet next-generation regulations (Joshi, 2020; Dreisbach et al. 2021). This includes more efficient turbomachinery which helps improve engine efficiency and thus reduce GHGs. This has an adverse effect on driving EGR which affects engine out NOx. In this study, the development and performance impact of the EGR pump is investigated, which allows improved engine fuel efficiency without the corresponding penalty to engine out NOx. Computational fluid dynamics (CFD) is used to optimize the EGR pump design, which leads to reduction in fluid-borne noise of the pump, which is then evaluated for fuel benefits using a calibrated GT-POWER engine model.
Impact of COVID-19 Outbreak on the Gynecological Outpatients HPV Infection Rate in Wuhan, China: A Retrospective Observational Study
Authors: Liu Hang , Yao Qian , Li Di , Zhao Zhiming , Li Yan
Published: April 2022

Background

The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has caused millions of deaths and greatly influenced the timely diagnosis and treatment of other diseases. Throughout the pandemic, there was a dramatic reduction in the prevalence of several sexually transmitted infections. However, the impact of the ongoing pandemic on human papillomavirus (HPV) infection rates has not been investigated thus far.

Materials and Methods

We retrospectively collected data regarding HPV and cervical cancer screening results of outpatients from gynecological clinics of a tertiary hospital from 1 December 2018 to 31 December 2020 in Wuhan. Based on the timeline of the SARS-CoV-2 pandemic in Wuhan, we divided this period into four relatively independent stages to compare the HPV screening visit numbers and infection rates.

Results

There was a 50% drop in HPV screening visits and a 10% drop in HPV infection rates throughout the pandemic when compared with the numbers collected before the pandemic. Strict lockdown measures greatly decreased the HPV infection rate (17.03 vs. 8.29, P = 0.003). During the pandemic, the most prevalent HPV genotypes were HPV 16, 52, 58, and 53. After the pandemic, the HPV infection rate recovered quickly, but it was still slightly lower than the infection rate found before the outbreak (23.3 vs. 21.2%).

Conclusion

During coronavirus disease 2019 (COVID-19) pandemic, cervical cancer screening visits and HPV infection rates have decreased dramatically. The HPV transmission has also decreased after strict lockdown. Effective HPV and cervical cancer screening programs should be strengthened immediately to reduce the transmission of HPV during and after the pandemic.
Multimodal Heartbeat and Compression Optical Coherence Elastography for Mapping Corneal Biomechanics
Authors: Nair Achuth , Singh Manmohan , Aglyamov Salavat R. , Larin Kirill V.
Published: April 2022

The biomechanical properties of the cornea have a profound influence on the health, structural integrity, and function of the eye. Understanding these properties may be critical for diagnosis and identifying disease pathogenesis. This work demonstrates how two different elastography techniques can be combined for a multimodal approach to measuring corneal biomechanical properties. Heartbeat optical coherence elastography (Hb-OCE) and compression OCE were performed simultaneously to measure the stiffness of the cornea in an in vivo rabbit model. Measurements were further performed after collagen crosslinking to demonstrate how the combined technique can be used to measure changes in corneal stiffness and map mechanical contrast. The results of this work further suggest that measurements from Hb-OCE and compression OCE are comparable, meaning that Hb-OCE and compression OCE may be used interchangeably despite distinct differences in both techniques.
Presbyopia-Correcting Intraocular Lenses Implantation in Eyes After Corneal Refractive Laser Surgery: A Meta-Analysis and Systematic Review
Authors: Sun Yang , Hong Yingying , Rong Xianfang , Ji Yinghong
Published: April 2022

Purpose

To assess the efficacy, safety, and predictability of presbyopia-correcting intraocular lenses (IOLs) in cataract patients with previous corneal refractive surgery.

Methods

A systematic literature search was performed to identify studies evaluating the clinical outcomes of presbyopia-correcting IOLs implantation in cataract surgery after laser refractive surgery. Outcomes were efficacy, safety and predictability parameters.

Results

The authors identified 13 studies, involving a total of 128 patients and 445 eyes. Presbyopia-correcting IOLs were effective at improving distance, intermediate and near visual acuity aftercataract surgery. The proportion of post-laser surgery eyes with uncorrected distance visual acuity (UDVA) ≥ 20/25 was 0.82 [95% confidence interval (CI), 0.74-0.90] and the pooled rates of spectacle independence at near, intermediate, and far distances were 0.98 (95% CI, 0.94-1.00), 0.99 (95% CI, 0.95-1.00) and 0.78 (95% CI, 0.65-0.94) respectively. The percentage of participants who suffered from halos and glare was 0.40 (95% CI, 0.25-0.64) and 0.31 (95% CI, 0.16-0.60), respectively. The predictability had a percentage of 0.66 (95% CI, 0.57-0.75) and 0.90 (95% CI, 0.85-0.96) of eyes within ±0.5 diopters (D) and ±1.0 D from the targeted spherical equivalent.

Conclusions

Presbyopia-correcting IOLs provide satisfactory results in terms of efficacy, safety and predictability in patients with previous corneal refractive surgery, but have a higher risk of photopic side effects such as halos and glare.
Maternal and Neonatal Outcomes After Assisted Reproductive Technology: A Retrospective Cohort Study in China
Authors: Tai Wen , Hu Lingmin , Wen Juan
Published: April 2022

Background

With the progress of assisted reproductive technology (ART) and the increasing number of ART pregnancy, its safety has become the focus of attention. The present study aimed to explore the associations of ART pregnancy with maternal and neonatal outcomes, as compared with naturally pregnancy.

Methods

This retrospective cohort study included all pregnant women who delivered at Women’s Hospital of Nanjing Medical University in 2011–2020. We compared maternal characteristics and pregnancy outcomes between group of ART pregnancy and group of naturally pregnancy using Logistic regression adjusted for confounders.

Results

A total of 13,604 ART pregnancies and 198,002 naturally pregnancies were included. The proportion of ART pregnancies has increased every year for the past 10 years, peaking in 2020 (9.0%). Multivariable logistic regression analysis showed that the risks of gestational diabetes, preeclampsia, moderate or severe anemia, liver-related diseases, thyroid-related diseases, preterm birth, placenta previa, postpartum hemorrhage, and cesarean section were significantly increased in ART pregnancy. For neonatal outcomes, women conceived by ART were more likely to have twins or multiples, and the risk of stillbirth or abnormal development was also significantly increased. When restriction to singletons, these risks were reduced. And the effects of ART on the risk of premature rupture of membrane, cord entanglement, intrapartum fever, cesarean section, and stillbirth or abnormal development were more pronounced in singletons pregnancies compared with that in pregnancies of twins or multiples.

Conclusion

Women conceived by ART were at increased risks of several adverse pregnancy outcomes compared with women conceived naturally. Multiple pregnancies could partly explain this phenomenon. For ART pregnancy, prenatal and intrapartum monitoring should be strengthened, and neonatal outcomes should be closely observed.
Anti-RNP Antibody: A Potential Novel Predictor for Osteonecrosis in Systemic Lupus Erythematosus
Authors: Xiong Jiangbiao , Wang Gang , Xu Tian , Liu Ren , Yu Shujiao , Wang Yan , Wu Rui
Published: April 2022

Objective

To explore risk factors for developing osteonecrosis in patients with systemic lupus erythematosus (SLE).

Methods

Twenty-six SLE patients with osteonecrosis from January 2018 to December 2019 were described. Fifty SLE patients without osteonecrosis were selected as controls from the SLE database (total 2,680) of our hospital during the same period. Clinical manifestations and laboratory tests were recorded and analyzed, especially antibodies. Univariate and multivariate analyses were used to evaluate possible associated risk factors.

Results

Twenty-six (3 male, 23 female) SLE patients with osteonecrosis were confirmed by X-ray and magnetic resonance imaging. The median course from SLE onset to osteonecrosis onset was 45 (range 2–302) months. Seven (27%) patients had a single joint involved and 19 (73%) patients had two or more joints involved. Besides, the incidence of femoral head osteonecrosis (FHON), knee ON, and humerus head ON were 85% (22/26), 27% (7/26), and 12%(3/26), respectively. The multivariate logistic regression analysis showed that the score of European Consensus Lupus Activity Measurement (ECLAM) at SLE onset [odds ratio (OR) 1.37; 95% confidence interval (CI) 1.07–1.75], a cumulative dose of prednisone above 10 g (OR 15.49; 95% CI 3.38–84.61), and positive of independent anti-RNP antibodies (OR 3.35; 95% CI 0.80–10.73) were significantly associated with osteonecrosis in SLE.

Conclusion

The score of ECLAM at SLE onset, a cumulative dose of prednisone above 10 g, and positive anti-RNP antibodies are associated with osteonecrosis in SLE. Herein, we reported for the first time that anti-RNP antibodies were associated with osteonecrosis in SLE patients and might be a novel predictor.
Three-Dimensional Analysis of Choroidal Vessels in the Eyes of Patients With Unilateral BRVO
Authors: Chen Lulu , Yuan Mingzhen , Sun Lu , Chen Youxin
Published: April 2022

Purpose

To investigate the three-dimensional analysis of choroidal vascular changes in eyes with monocular branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography (SS-OCT).

Methods

Twenty two unilateral BRVO patients with superior-temporal branch retinal vein occlusion and 27 healthy eyes were analyzed retrospectively. OCT and OCT angiography (OCTA) images of 12 * 12 mm centered on the foveal of each eye were analyzed. Three-dimensional choroidal vascularity index (CVI), choroidal thickness, and choriocapillaris density were compared among BRVO eyes, fellow eyes, and healthy control eyes. En face CVI maps in BRVO eyes were generated to analyze the dilatation pattern of choroidal vessels.

Results

CVI values in a few 1 * 1 mm grids in the non-affected hemi side were higher in BRVO eyes compared with the fellow eyes and control eyes (p< 0.05). Choriocapillaris density decreased in both BRVO eyes and fellow eyes compared with normal eyes while choriocapillaris density was higher in a few grids in the non-affected hemi side in BRVO eyes compared with fellow eyes (p< 0.05). Choroidal dilatation pattern was categorized into four types and inferior choroidal dilatation and posterior pole choroidal dilatation were the major types.

Conclusion

Three-dimensional CVI tended to increase in non-affected hemi side and choroidal vessels tended to dilate in adjacent areas in BRVO eyes. Choriocapillaris density decreased in both eyes of monocular BRVO patients. The choroidal changes suggested that choroidal redistribution occurred in BRVO.
Case Report: A Case of Acute T Lymphoblastic Leukemia With Mixed Infection of Lethal Invasive Mucormycosis and Multi-Drug Resistant Bacteria
Authors: Cui Qingya , Dai Haiping , Wu Depei , He Jun , Xu Yang , Tang Xiaowen , Xu Jie
Published: April 2022

Pulmonary mucormycosis (PM) is a rare and life-threatening fungal infection. Here, we report a case of an acute T lymphoblastic leukemia patient with mixed infections of lethal invasive Mucormycosis and multi-drug resistant (MDR) bacteria. After receiving anti-infection drugs to control the patient's fever, he was treated with induction chemotherapy. However, the malignant hematological disease was poorly controlled by the chemotherapy and the patient developed more symptoms of infection. Although the results of multiple β-D-Glucan (G) and Galactomannan (GM) tests remained negative, several pathogens were detected using metagenomic next-generation sequencing (mNGS). In particular, mNGS identified Malassezia pachydermum, Mucor racemosus, and Lauteria mirabilis in the peripheral blood and local secretion samples. The Mucor and bacterial infections were further confirmed via multi-site and repeated fungal and bacterial cultures, respectively. Despite adjusting the anti-infection therapy according to the diagnostic results, the patient's blood disease and symptoms of infection were not alleviated. Additionally, the MDR Acinetobacter baumannii infection/colonization was not confirmed until the seventh culture of the peripheral venous catheter tip. Due to the patient's deteriorating conditions, his family decided to withdraw him from further treatment. Overall, mNGS can facilitate a diagnosis of Mucormycosis by providing clinical and therapeutic information to support conventional diagnostic approaches. For the early and timely diagnosis and treatment of PM, it is also necessary to consider the malignant hematological conditions and repeated tests through multiple detection methods.