bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning methods for predicting major types of rheumatic heart diseases in children of Southern Punjab, Pakistan
Authors: Shahid Sana , Khurram Haris , Billah Baki , Akbar Atif , Shehzad Muhammad Ahmed , Shabbir Muhammad Farhan
Published: October 2022

Objective

Rheumatic heart disease (RHD) is a major health problem in the world, particularly in developing countries. This study aimed to predict mitral regurgitation (MR) and mitral stenosis (MS) RHD among children with RHD.

Methodology

Data was collected from the Pediatric Cardiology Department at Chaudhry Pervaiz Elahi Institute of Cardiology Multan, Pakistan from March to October 2019. A sample of 561 children aged 4–14 years, who were diagnosed with RHD of either MR or MS, were recruited from the hospital’s outpatient department. The presence of multivariate outliers was detected, and different machine learning methods, including subset logistic regression, subset logistic regression after deletion, stepwise winsorized logistic regression, robust logistic regression, subset deep neural network, and random forest models were compared using the area under receiver operating characteristics (ROC) curve, sensitivity, and specificity. Parsimony was also considered in model selection.

Results

Out of 561 patients in this study, 75.94% had RHD MR and 24.06% had RHD MS. The average age of study participants was 9.19 ± 2.45 years and of them 55.43% were male. Among the male participants, 58.6 and 45.2% had MR and MS, respectively; and among female participants, those were 70.4 and 29.6%, respectively. Subset logistic regression after deletion appeared as competitive with a discrimination power of 90.1% [95% CI 0.818–0.983]. The sensitivity and specificity of this model were 85.1 and 70.6%.

Conclusion

The best predictive model was subset logistic regression after deletion. The predicted method will be used in the decision-making process, which helps early diagnosis of the disease and leads to prevention. The study findings provide the proper guideline for earlier diagnosis of the RHD MR and MS cases among children with RHD in Pakistan.
Micron- to atomic-scale investigation of rare earth elements in iron oxides
Authors: Cook Nigel J. , Ciobanu Cristiana L. , Ehrig Kathy , Slattery Ashley D. , Gilbert Sarah E.
Published: October 2022

Hematite (α-Fe2O3) and magnetite (Fe3O4) readily accommodate a wide range of minor and trace elements from across the periodic table at up to wt.% concentrations. This prompts the question of whether these common minerals can also host rare earth elements (lanthanides, Y and Sc; REEs)? If so, what is the chemical and physical nature of the elements: are they incorporated into the oxide crystal structures, or do they occur as nanometer-to micron-sized inclusions of discrete REE-minerals? By combining micron-scale petrography and analysis by LA-ICP-MS with nanoscale imaging and energy-dispersive spectroscopy, the relationships between REEs and iron-oxides are addressed in samples from the world-class Olympic Dam Cu-U-Au-Ag deposit, South Australia. Spatially co-existing silician magnetite and hematite from the outer shell at Olympic Dam show stages of interconversion during which REEs are redistributed. REEs are shown to be preferentially incorporated into the magnetite structure, whereas hematite concentrates U, W, and Sn, and contains negligible structurally bound REEs. Abundant, <20 nm-sized uraninite nanoparticles (NPs) are a key host for REEs in hematite. In contrast, hematite from mineralized breccias displays co-precipitation of Fe-oxides and REE-minerals facilitated by discharge of high-volatile fluids. Variation in the shape of chondrite-normalized REE fractionation trends, ranging from concave (hematite containing uraninite NPs) to steeply downwards-sloping (included LREE-dominant phases such as monazite, florencite, fluocerite and cerianite), reflect these differences. Evolving NP mineralogy in the breccias, from in-situ NP formation to an abundance of monazite reflects successive overprinting events and remobilization of elements from solid-solution and subsequent trapping as NPs via coupled dissolution replacement reaction. REE-minerals such as florencite can host nanoinclusions of hematite. Atomic-scale observations, including defects in magnetite and an O-deficient, two-fold hematite superstructure show crystal structural accommodation during Fe-oxide interconversion and inclusion nucleation. Both silician magnetite and hematite show nanoscale muscovite forming along planar defects. Understanding the mineralogical deportment of REEs at Olympic Dam carries potential implications for investigating the viability of REE extraction opportunities from any resource in which Fe-oxides are the dominant component.
Application and prospect of trabecular bone score in differentiated thyroid cancer patients receiving thyrotropin suppression therapy
Authors: Ran Bingyu , Wei Feng , Gong Jian , Xu Hao
Published: October 2022

Thyroid-stimulating hormone (TSH) suppression therapy is one of the common treatments for most patients with differentiated thyroid cancer (DTC). Unfortunately, its detrimental effects on bone health are receiving increasing attention. It may increase the risk of osteoporosis and osteoporotic fractures. The trabecular bone score (TBS) is a relatively new gray-scale texture measurement parameter that reflects bone microarchitecture and bone strength and has been shown to independently predict fracture risk. We reviewed for the first time the scientific literature on the use of TBS in DTC patients on TSH suppression therapy and aim to analyze and compare the utility of TBS with bone mass strength (BMD) in the management of skeletal health and prediction of fracture risk. We screened a total of seven relevant publications, four of which were for postmenopausal female patients and three for all female patients. Overall, postmenopausal female patients with DTC had lower TBS and a significant reduction in TBS after receiving TSH suppression therapy, but their BMD did not appear to change significantly. In addition, TBS was also found to be an independent predictor of osteoporotic fracture risk in postmenopausal women with DTC receiving TSH suppression therapy. However, due to limitations in the number of studies and study populations, this evidence is not sufficient to fully demonstrate the adverse effects of TSH suppression therapy on patients’ TBS or BMD and the efficacy of TBS, and subsequent larger and more case-cohort studies are needed to further investigate the relationship and application of TBS to TSH suppression therapy in terms of skeletal health impairment and fracture risk in DTC patients.
Investigation of anti-diabetic potential and molecular simulation studies of dihydropyrimidinone derivatives
Authors: Ilyas Umair , Nazir Bisma , Altaf Reem , Muhammad Syed Aun , Zafar Hajra , Paiva-Santos Ana Cláudia , Abbas Muhammad , Duan Yongtao
Published: October 2022

In an attempt to find new targets for α-amylase and α-glucosidase for the treatment of type 2 diabetes mellitus, the present study aims in determining the anti-diabetic potential of synthesized dihydropyrimidinone derivatives. The in vitro α-glucosidase and α-amylase inhibitory activity was performed and the molecular docking analysis of the ligand in the active binding site of target protein was determined. The results revealed significant percent inhibition of α-glucosidase by the compound 6-benzyl-4-(4-hydroxyphenyl)-3,4,6,7-tetrahydro-1H-pyrrolo[3,4-d]pyrimidine-2,5-dione (compound A). The active compound showed 81.99% inhibition when compared to standard ascorbic acid having percent inhibition 81.18%. The IC50 of active compound (A) showed to be 1.02 µg/ml. The molecular docking analysis revealed that the ligand bound to the active binding site of protein with the lowest binding energy of -7.9 kcal/mol that was also significantly similar to standard having -7.8 kcal/mol binding energy. The molecular dynamic simulation studies also revealed stable binding of ligand in the active binding site of protein with low RMSD of 1.7 Å similar to the protein RMSD 1.6Å In conclusion, the study revealed a potential new target against α-glucosidase to treat type 2 diabetes mellitus.
A review on unidirectional converters for on-board chargers in electric vehicle
Authors: Vijayakumar S. , Sudhakar N.
Published: October 2022

Transport is a vital sector for achieving sustainable development. The evolution of the electric vehicle is subject to the charging time, accessibility, and facility. On-board chargers are broadly used in the battery-electric and plug-in-electric fleets due to their easy installation and low cost. Also, it must be powerful and extremely efficient because of the constrained interior area and quick charging times. The minimization of hardware requirements and ease of interconnection problems are benefits of unidirectional charging. This review article presents an overview of charging levels, standards of chargers, and various topologies. On-board chargers pose a higher-power rating that reduces the anxiety of charging time and improves the charging facility on level-1 and level-2 grid supply. Unidirectional chargers reduce the charger size while other two-stage chargers pose a higher charging rate with various topologies. Finally, emerging charging trends in off-board charging, inductive charging, technology about vehicle-to-grid, wide-bandgap devices, and application of renewable energy uses are addressed.
Electron-phonon interaction and structural changes in the electronically excited state of WO3 photocatalyst
Authors: Kaneko Masanori , Nozawa Shunsuke , Yamashita Koichi
Published: October 2022

The structural changes in the electronically excited state of tungsten oxide (WO3), a promising visible-light-responsive photocatalyst, are discussed from the viewpoint of carrier-phonon interactions using first-principles calculations. The increase in the pre-edge peak observed immediately after photoexcitation by high-speed time-resolved X-ray absorption spectroscopy is attributed to the local lattice distortion due to Fröhlich-Polaron generation by the interaction with optical longitudinal phonons. Bimolecular recombination could be suppressed by the formation of bipolaron states, and high internal quantum yields in photocatalysis are expected. The bipolaron states are unstable states in the electronically excited state, and relax to stable structures in the electronically excited state by phonon-phonon interaction. In the stable structure, the transition dipole moment is found to be nearly zero, suggesting a non-radiative transition to the electronic ground state and a long lifetime in the electronically excited state.
The impact of the anti-corruption campaign on energy efficiency: Evidence from prefecture-level cities in China
Authors: Ji Hongkun
Published: October 2022

China’s development has been accompanied by serious corruption and environmental pollution. Corruption is particularly prevalent in the energy sector, where it can bring very substantial benefits. However, corruption in the energy sector can lead to serious misallocation of energy, resulting in wasteful and inefficient use of energy. With the rise of the anti-corruption campaign, there is an urgent need to explore the impact of the anti-corruption campaign (ACC) on energy efficiency (EE). This paper investigates whether and how the ACC affects EE in China. Leveraging a staggered difference-in-differences (DID) model, we estimate the causal effect of the ACC in China on EE. Our results indicate that the ACC significantly improves EE, which is robust to a battery of robustness tests, such as parallel trend test, placebo test, excluding other policies, and substituting the explained variable. The positive relationship is correlated to reducing rent-seeking behavior, promoting innovation capacities, and upgrading industrial structure within a city. The heterogeneous results suggest that the effect of the ACC on EE improvement is more pronounced in big cities, cities located in the central, cities with high fiscal expenditures and low R&D expenditures. The results of this paper show that we must be tenacious in the anti-corruption campaign to establish a clean government and increase energy efficiency in order to achieve sustainable development.
Landslide susceptibility mapping (LSM) of Swat District, Hindu Kush Himalayan region of Pakistan, using GIS-based bivariate modeling
Authors: Islam Fakhrul , Riaz Salma , Ghaffar Bushra , Tariq Aqil , Shah Safeer Ullah , Nawaz Muhammad , Hussain Mian Luqman , Amin Naz Ul , Li Qingting , Lu Linlin , Shah Munawar , Aslam Muhammad
Published: October 2022

Landslides are a recurrent environmental hazard in hilly regions and affect the socioeconomic development in Pakistan. The current study area is the tourism and hydro energy hub of Pakistan and is affected by environmental hazard. A landslide susceptibility mapping (LSM) of the Hindu Kush Himalayan, Swat District, Pakistan, can be created to reduce demographic losses due to landslides. This current study is conducted to apply three bivariate models, including weights of evidence (WOE), frequency ratio (FR), and information value (IV) for an LSM that has not been explored or applied in the current study area. For this purpose, first, an inventory map of 495 landslides was constructed from both ground and satellite data and randomly divided into training (70%) and testing (30%) datasets. Furthermore, 10 conditioning factors (elevation, slope, aspect, curvature, fault, rainfall, land use land cover (LULC), lithology, road, and drainage) used for the mapping of landslides were prepared in ArcGIS 10.8. Finally, LSM is generated based on WOE, FR, and IV models and validated the performance of LSM models using the area under receiver operating characteristic curve (AUROC). The findings of success rate curve (SRC) of the WOE, FR, and IV models were 67%, 93%, and 64%, respectively, while the prediction rate curves (PRCs) of the three models were 87%, 95%, and 73%, respectively. The validation results for WOE, FR, and IV justified that the FR model is the most reliable technique of all three of these models to produce the highest accuracy LSM for the present study area. Policymakers can use the findings of current research work to mitigate the loss due to landslide hazard.
Root exudate glycine synergistically promotes phytoremediation of petroleum-contaminated soil
Authors: He Mengfan , Li Zhongbao , Mei Ping
Published: October 2022

The exploitation of petroleum, the production and use of petroleum products causes pollution that is harmful to the ecology and environment. At present, petroleum hydrocarbon pollution has become a universal concern in the world. As one of the bioremediation methods, plant root exudate repair has the effect of eliminating toxic substances in the environment. To explore the role of root exudates glycine in phytoremediation of petroleum-contaminated soil, seed germination and pot experiments were carried out to study the effects of glycine on the degradation of petroleum hydrocarbons in different plants and soil types. The results showed that when the concentration of petroleum pollutants was constant, the order of seed germination rate of the eight plants was ryegrass > sudan grass > white clover > tall fescue > alfalfa > pennisetum > canine root > maize grass.1000 mg L−1 of glycine could effectively promote plant biomass and the petroleum hydrocarbons degradation rate. The degradation effect was ryegrass + glycine > ryegrass > sudan grass + glycine > sudan grass > white clover + glycine > white clover. The degradation rate of ryegrass + glycine in 18,000 mg kg−1 petroleum-contaminated soil reached 55.7%. All plants had the highest biomass and plant height in loamy soil, while the highest degradation rate of petroleum hydrocarbons was observed in sandy soil, ranging from 50.36% to 59.36%. Among them, ryegrass combined with 1000 mg L−1 of glycine reached the highest petroleum hydrocarbons degradation rate of 59.36% in sandy soil. Ryegrass, sudan grass and white clover had the potential to remediate petroleum-contaminated soils. In the three types of soil, ryegrass had a strong remediation efficiency, and the degradation effect to petroleum hydrocarbons was more significant after the addition of glycine. Therefore, ryegrass can be planted with glycine as a priority for remediation in oil field areas contaminated by petroleum hydrocarbons.
Can socialized services reduce agricultural carbon emissions in the context of appropriate scale land management?
Authors: Chen Zhongwei , Tang Can , Liu Bo , Liu Pei , Zhang Xueyan
Published: October 2022

In order to achieve low carbon transformation and green development in agriculture, we analyzed the effects of different types of socialized services on agricultural carbon emissions based on provincial panel data from 2010 to 2020 in China. We further analyzed the possible ways for agricultural social services to reduce the intensity of agricultural carbon emissions with the help of mediating effect model. The results show that socialized services can provide basic services, production and operation services, financial services, and circulation services for the agricultural production chain, which can significantly reduce the agricultural carbon emissions intensity. The results of the intermediation effect suggest that socialized services can break the labor constraint by promoting the scale effect, and thus reduce the agricultural carbon emissions intensity. However, the mediation effect of technology diffusion is not significant. The reason is that although the diffusion of agricultural technology can improve the efficiency of resource utilization, the diffusion of technology also leads to the use of elements such as high concentrations of chemicals and heavy agricultural tools which may increase carbon emissions. In addition, the effect of socialized services on reducing agricultural carbon emissions intensity shows obvious spatial heterogeneity, with the reduction gradually increasing from coastal to inland provinces and from eastern to western regions.
SPH modeling of substance transport in flows with large deformation
Authors: Liu Wanying , Hou Qingzhi , Lei Xiaohui , Lian Jijian , Dang Jianwu
Published: October 2022

The velocity field in coastal and oceanic currents is mostly non-uniform, which will result in irregular particle distribution when the fluid is represented by an amount of moving discrete particles as in smoothed particle hydrodynamics (SPH). When the non-uniformity of the flow is big, i.e., with large deformation, the conventional SPH method can hardly solve the associated advection-diffusion process (e.g., substance transport). To accurately simulate the substance transport in flows with large deformation, two types of particle shifting techniques (PSTs) are incorporated into the conventional SPH in this paper. One is based on current particle distance, and the other is based on Fick’s law. In the second type, the repulsive force (RF) term for suppressing the paring instability that occurs in particle shifting technique (PST) is studied and the effect of the kernel function is examined. By introducing a particle disorder measurement, the simulated results of SPH with the two types of PSTs and their modifications are evaluated and the influence of the shifting magnitude is analyzed. The suggestions for how to set reasonable parameters in PSTs are provided by a systematic parametric study. For further illustration, the simulation of the anisotropic diffusion is also examined. To give reliable reference solutions, the high-resolution modified total variation diminishing Lax Friedrichs scheme with Superbee limiter (MTVDLF-Superbee) with fine mesh is also implemented. The validated Lagrangian particle model with optimized PST is applied to a practical application.
Carbon-isotope composition of artiodactyl tooth enamel and its implications for paleodiets
Authors: Wang Bian , Badgley Catherine
Published: October 2022

The stable carbon-isotope composition of mammalian tooth enamel is a powerful tool for reconstructing paleodiet and paleoenvironment. Its application in the fossil record relies on a thorough understanding of the isotopic composition of mammalian diets in modern ecosystems. We compiled and evaluated a global dataset of the carbon-isotope values of artiodactyl tooth enamel, supplemented by new samples, for 79 extant species. After correcting for differences in atmospheric carbon-isotope composition, body mass, and digestive physiology, we compared the inferred carbon-isotope values of ingested forage (δ13Cdiet) among seven feeding categories. The artiodactyl herbivore dietary spectrum is expressed through a wide range of δ13Cdiet values, with the most depleted mean value in frugivores and the most enriched in obligate grazers. In general, grazing species have a broader range of isotope values than browsing species, suggesting a wider dietary niche breadth. Notably, variable grazers exhibit a bimodal distribution of δ13Cdiet values, with North American and Asian taxa consuming C3 diets and African taxa consuming C4 diets, reflecting the amount of C4 vegetation in the environment. Variation in δ13Cdiet values also occurs among terrestrial ecoregions and artiodactyl clades. Grassland ecoregions differ significantly from forest ecoregions. We detected a low but significant phylogenetic signal in the mean δ13Cdiet values of extant species, with some of the oldest ruminant lineages having maintained C3 feeding and pure C4 diets being restricted to two bovid clades. Determining variation in δ13Cdiet values in different feeding categories and lineages will help refine paleoecological and paleoenvironmental reconstructions from the rich fossil record of artiodactyls.
Varying cultivation strategies in eastern Tianshan corresponded to growing pastoral lifeways between 1300 BCE and 300 CE
Authors: Tian Duo , Sun Yufeng , Ritchey Melissa M. , Xi Tongyuan , Ren Meng , Ma Jian , Wang Jianxin , Zhao Zhijun , Ling Xue , Liu Xinyi
Published: October 2022

This study combines plant stable isotope and archaeobotanical analyses to explore how ancient pastoral communities in varying landscapes of eastern Tianshan managed their barley fields. The question is less archaeologically investigated, as recent discussions have focused on pastoral and nomadic activities. Results show that diversified cultivation strategies were employed in barley cultivation at different locations in eastern Tianshan. We also observed a diachronic transition toward less labour-intensive crop management corresponding to a growing pastoral lifeway from the late Bronze Age (1300–800 BCE) to historical periods (400 BCE–300 CE). These results inform us about the mechanism by which southwest Asian originated domesticates were adapted to the Inner Asian environments in the context of the early food globalisation.
Molecular subtypes based on cuproptosis-related genes and immune profiles in lung adenocarcinoma
Authors: Wang Yufei , Zhang Chen , Ji Chengyue , Jin Wenli , He Xin , Yu Shunzhi , Guo Renhua
Published: October 2022

Background: Recent studies have identified several molecular subtypes of lung adenocarcinoma (LUAD) that have different prognoses to help predict the efficacy of immunotherapy. However, the prognostic prediction is less than satisfactory. Alterations in intracellular copper levels may affect the tumor immune microenvironment and are linked to cancer progression. Previous studies have identified some genes related to cuproptosis. The characteristics of the cuproptosis molecular subtypes have not been thoroughly studied in LUAD.

Methods: The transcriptomic data and clinical information of 632 LUAD patients were used to investigate the LUAD molecular subtypes that are associated with the cuproptosis-related genes (CRGs), the tumor immune microenvironment, and stemness. The cuproptosis score was constructed using univariate Cox regression and the minor absolute shrinkage and selection operator (LASSO) to quantify the prognostic characteristics.

Results: Three different molecular subtypes related to cuproptosis, with different prognoses, were identified in LUAD. Cluster A had the highest cuproptosis score and the worst prognosis. Patients in the high cuproptosis score group had a higher somatic mutation frequency and stemness scores. Patients in the low cuproptosis score group had more immune infiltration and better prognosis.

Conclusion: Molecular subtypes of LUAD based on CRGs reflect the differences in LUAD patients. The cuproptosis score can be used as a promising biomarker, which is of great significance to distinguish the relationship between cuproptosis and the immune microenvironment. The cuproptosis signature based on the cuproptosis score and clinical characteristics of individual patients will be useful for guiding immunotherapy in LUAD.
Characterization of WOX genes revealed drought tolerance, callus induction, and tissue regeneration in Gossypium hirsutum
Authors: Muhammad Tajo Sani , Pan Zhaoe , He Shoupu , Chen Baojun , KM Yusuf , Mahmood Tahir , Bello Sadau Salisu , Shahid Iqbal Muhammad , Gereziher Teame , Suleiman Abubakar Umar , Joseph Masha , Sammani Tajo , Geng Xiaoli , Du Xiongming
Published: October 2022

Cotton is an important natural fiber crop; its seeds are the main oil source. Abiotic stresses cause a significant decline in its production. The WUSCHEL-related Homeobox (WOX) genes have been involved in plant growth, development, and stress responses. However, the functions of WOX genes are less known in cotton. This study identified 39, 40, 21, and 20 WOX genes in Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum, and Gossypium raimondii, respectively. All the WOX genes in four cotton species could be classified into three clades, which is consistent with previous research. The gene structure and conserved domain of all WOX genes were analyzed. The expressions of WOX genes in germinating hypocotyls and callus were characterized, and it was found that most genes were up-regulated. One candidate gene Gh_ A01G127500 was selected to perform the virus-induced gene silencing (VIGS) experiment, and it was found that the growth of the silenced plant (pCLCrVA: GhWOX4_A01) was significantly inhibited compared with the wild type. In the silenced plant, there is an increase in antioxidant activities and a decrease in oxidant activities compared with the control plant. In physiological analysis, the relative electrolyte leakage level and the excised leaf water loss of the infected plant were increased. Still, both the relative leaf water content and the chlorophyll content were decreased. This study proved that WOX genes play important roles in drought stress and callus induction, but more work must be performed to address the molecular functions of WOX genes.
Role of cytokinins in seed development in pulses and oilseed crops: Current status and future perspective
Authors: Sharma Sandhya , Kaur Parampreet , Gaikwad Kishor
Published: October 2022

Cytokinins constitutes a vital group of plant hormones regulating several developmental processes, including growth and cell division, and have a strong influence on grain yield. Chemically, they are the derivatives of adenine and are the most complex and diverse group of hormones affecting plant physiology. In this review, we have provided a molecular understanding of the role of cytokinins in developing seeds, with special emphasis on pulses and oilseed crops. The importance of cytokinin-responsive genes including cytokinin oxidases and dehydrogenases (CKX), isopentenyl transferase (IPT), and cytokinin-mediated genetic regulation of seed size are described in detail. In addition, cytokinin expression in germinating seeds, its biosynthesis, source-sink dynamics, cytokinin signaling, and spatial expression of cytokinin family genes in oilseeds and pulses have been discussed in context to its impact on increasing economy yields. Recently, it has been shown that manipulation of the cytokinin-responsive genes by mutation, RNA interference, or genome editing has a significant effect on seed number and/or weight in several crops. Nevertheless, the usage of cytokinins in improving crop quality and yield remains significantly underutilized. This is primarily due to the multigene control of cytokinin expression. The information summarized in this review will help the researchers in innovating newer and more efficient ways of manipulating cytokinin expression including CKX genes with the aim to improve crop production, specifically of pulses and oilseed crops.
Genetic polymorphisms of toll-like receptors in leprosy patients from southern Brazil
Authors: Masin Priscila Saamara , Visentin Hugo Alves , Elpidio Laíse Nayana Sala , Sell Ana Maria , Visentainer Lorena , Lima Neto Quirino Alves De , Zacarias Joana Maira Valentini , Couceiro Patrícia , Higa Shinzato Andressa , Santos Rosa Manuel , Rodrigues-Santos Paulo , Visentainer Jeane Eliete Laguila
Published: October 2022

Leprosy is a chronic disease and also a global health issue, with a high number of new cases per year. Toll-like receptors can respond to mycobacterial molecules in the early stage of infection. As important components of the innate immune response, alterations in genes coding for these receptors may contribute to susceptibility/protection against diseases. In this context, we used a case-control study model (183 leprosy cases vs. 185 controls) to investigate whether leprosy patients and the control group, in southern Brazil, have different frequencies in TLR1 (TLR1 G>T; rs5743618), TLR2 (TLR2 T>C, rs1816702 and rs4696483), and TLR4 (TLR4 A>G, rs1927911) polymorphisms. Analysis of the TLR1 1805G>T polymorphism presented the G/G genotype more frequently in the control group. TLR2 T>C rs1816702 and TLR2 T>C rs4696483, the T/T and C/T genotype, respectively, were more frequent in the control group than in leprosy patients, suggesting protection from leprosy when the T allele is present (rs4696483). Haplotype analyses between TLR1 (rs5743618) and TLR2 (rs1816702 and rs4696483) polymorphisms suggest risk for the presence of the TCC haplotype and protection in the presence of the TCT haplotype. This study suggests that polymorphisms in TLR1 and TLR2 are factors that may contribute to development/resistance of leprosy.
The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis
Authors: Littera Roberto , Perra Andrea , Miglianti Michela , Piras Ignazio S. , Mocci Stefano , Lai Sara , Melis Maurizio , Zolfino Teresa , Balestrieri Cinzia , Conti Maria , Serra Giancarlo , Figorilli Francesco , Firinu Davide , Onali Simona , Matta Laura , Porcu Carmen , Pes Francesco , Fanni Daniela , Manieli Cristina , Vacca Monica , Cusano Roberto , Trucas Marcello , Cipri Selene , Tranquilli Stefania , Rassu Stefania , Cannas Federica , Carta Mauro Giovanni , Kowalik Marta Anna , Giuressi Erika , Faa Gavino , Chessa Luchino , Giglio Sabrina
Published: October 2022

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH).

Method and materials

We analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy).

Results

Analysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D’ = 0.92 vs D’ = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 – 17.4) U/mL vs 21.3 (16.5 – 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 – 44.8) U/mL vs 8.8 (6.1 – 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies.

Conclusion

This study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.
Booster dose of mRNA vaccine augments waning T cell and antibody responses against SARS-CoV-2
Authors: Özbay Kurt Feyza Gül , Lepper Alisa , Gerhards Catharina , Roemer Mathis , Lasser Samantha , Arkhypov Ihor , Bitsch Rebekka , Bugert Peter , Altevogt Peter , Gouttefangeas Cécile , Neumaier Michael , Utikal Jochen , Umansky Viktor
Published: October 2022

A gradual decay in humoral and cellular immune responses over time upon SAR1S-CoV-2 vaccination may cause a lack of protective immunity. We conducted a longitudinal analysis of antibodies, T cells, and monocytes in 25 participants vaccinated with mRNA or ChAdOx1-S up to 12 weeks after the 3rd (booster) dose with mRNA vaccine. We observed a substantial increase in antibodies and CD8 T cells specific for the spike protein of SARS-CoV-2 after vaccination. Moreover, vaccination induced activated T cells expressing CD69, CD137 and producing IFN-γ and TNF-α. Virus-specific CD8 T cells showed predominantly memory phenotype. Although the level of antibodies and frequency of virus-specific T cells reduced 4-6 months after the 2nd dose, they were augmented after the 3rd dose followed by a decrease later. Importantly, T cells generated after the 3rd vaccination were also reactive against Omicron variant, indicated by a similar level of IFN-γ production after stimulation with Omicron peptides. Breakthrough infection in participants vaccinated with two doses induced more SARS-CoV-2-specific T cells than the booster vaccination. We found an upregulation of PD-L1 expression on monocytes but no accumulation of myeloid cells with MDSC-like immunosuppressive phenotype after the vaccination. Our results indicate that the 3rd vaccination fosters antibody and T cell immune response independently from vaccine type used for the first two injections. However, such immune response is attenuated over time, suggesting thereby the need for further vaccinations.
Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis
Authors: Nemeth Dora , Vago Hajnalka , Tothfalusi Laszlo , Ulakcsai Zsuzsanna , Becker David , Szabo Zsofia , Rojkovich Bernadett , Merkely Bela , Nagy Gyorgy
Published: October 2022

Background

To investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA).

Methods

Serological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains.

Results

We prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken (“sampling interval”) was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055).

Conclusion

Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.
Humoral response and neutralising capacity at 6 months post-vaccination against COVID-19 among institutionalised older adults in Argentina
Authors: Rodriguez Pamela E. , Silva Andrea P. , Miglietta Esteban A. , Rall Pablo , Pascuale Carla A. , Ballejo Christian , López Miranda Lucía , Ríos Antonella S. , Ramis Lila , Marro Jimena , Poncet Verónica , Mazzitelli Bianca , Salvatori Melina , Ceballos Ana , Gonzalez Lopez Ledesma María M. , Ojeda Diego S. , Aguirre María F. , Miragaya Yanina , Gamarnik Andrea V. , Rossi Andrés H. ,   Laboratorio SeVa Group,   PAMI Group
Published: October 2022

The COVID-19 pandemic has particularly affected older adults residing in nursing homes, resulting in high rates of hospitalisation and death. Here, we evaluated the longitudinal humoral response and neutralising capacity in plasma samples of volunteers vaccinated with different platforms (Sputnik V, BBIBP-CorV, and AZD1222). A cohort of 851 participants, mean age 83 (60-103 years), from the province of Buenos Aires, Argentina were included. Sequential plasma samples were taken at different time points after vaccination. After completing the vaccination schedule, infection-naïve volunteers who received either Sputnik V or AZD1222 exhibited significantly higher specific anti-Spike IgG titers than those who received BBIBP-CorV. Strong correlation between anti-Spike IgG titers and neutralising activity levels was evidenced at all times studied (rho=0.7 a 0.9). Previous exposure to SARS-CoV-2 and age <80 years were both associated with higher specific antibody levels. No differences in neutralising capacity were observed for the infection-naïve participants in either gender or age group. Similar to anti-Spike IgG titers, neutralising capacity decreased 3 to 9-fold at 6 months after initial vaccination for all platforms. Neutralising capacity against Omicron was between 10-58 fold lower compared to ancestral B.1 for all vaccine platforms at 21 days post dose 2 and 180 days post dose 1. This work provides evidence about the humoral response and neutralising capacity elicited by vaccination of a vulnerable elderly population. This data could be useful for pandemic management in defining public health policies, highlighting the need to apply reinforcements after a complete vaccination schedule.
Extreme heat loss in the Northern Red Sea and associated atmospheric forcing
Authors: Papadopoulos Vassilis P. , Krokos George , Dasari Hari Prasad , Abualnaja Yasser , Hoteit Ibrahim
Published: October 2022

A regional, high-resolution reanalysis was analyzed to explore extreme heat loss events in the Northern Red Sea (NRS) and their links to specific regional atmospheric circulation patterns. Such events are determinant for the overturning circulation of the Red Sea and occur frequently between November and March, with maximum frequency during December and January. During these events, the most intense heat loss, often with daily-averaged values lower than -1000 W/m2, is found over the southern half of the Gulf of Aqaba and along the western coastline of the open NRS. Analyses of the spatial modes of variability of these events suggest that the majority of them extend over the entire NRS in an almost uniform way; however, secondary, nonuniform patterns related to regional adjustment in the wind field are also identified. The uniform cold outbursts are associated with distinct atmospheric circulation patterns, which favor the transfer of cold air masses from higher latitudes over the eastern Mediterranean Seaviaa strong northwest wind field. Nonuniform events affect considerable parts of the NRS and occur when cold and dry air masses reach the NRS through the Middle East and the northern part of the Arabian Peninsula. The regional sea level pressure drives a clockwise rotation of the wind field that ultimately blows from the northeast/east direction. This rotation of the wind field favors local intensification and lee areas defined by the complex topography and characteristic gaps in the mountain chain along the eastern coastline of the NRS, reflecting the differentiations in the spatial distribution of the heat flux minima.
Inversion of thermal properties of lunar soil from penetration heat of projectile using a 2D axisymmetric model and optimized PSO algorithm
Authors: Li Fan , Li Honglang , Lu Zixiao , Cao Junhao , Zhang Weiwei , Tang Junyue , Tian Yahui , Chi Cheng , Jiang Shengyuan
Published: October 2022

The thermophysical parameters of lunar soil can be inferred from the temperature field during the invasion process of reconnaissance projectile. This paper adopts a two-dimensional axisymmetric model to reconstruct the projectile invasion process. An optimized particle swarm optimization method is then used to retrieve the thermophysical parameters of lunar soil. When the reconnaissance projectile penetrates the lunar interior, it rubs against the lunar soil and generates heat, which diffuses between the projectile body and the lunar soil. The sensors inside the reconnaissance projectile measure the temperature variation of the projectile body to inverse the thermophysical parameters. This paper carried out physical modeling of the penetration process of reconnaissance projectile. A two-dimensional axisymmetric simulation model is constructed for the physical process, and the adaptive inertial weight particle swarm algorithm is adopted. The inversion experiment of lunar soil thermophysical parameters based on the simulation model shows that the inversion error is less than 10%, which verifies the feasibility of this method.
A mixed methods study of the awareness and management of familial hypercholesterolaemia in Irish general practice
Authors: Homeniuk Robyn , Gallagher Joseph , Collins Claire
Published: October 2022

Introduction

Familial Hypercholesterolemia (FH) is one of the most common genetic disorders, with an estimated global prevalence of 1:200-500, which leads to premature cardiovascular disease. Nevertheless, public and professional awareness of FH is often lacking, with an estimated 20,000 largely undiagnosed cases in Ireland.

Purpose

The overall aim of the project was to test the feasibility of a model of care that would include electronic record screening, clinical assessment, and coding of possible FH patients across a network of general practices in Ireland. In addition, a secondary aim was to gauge the awareness and knowledge of FH across the network.

Methods

This study took part in multiple phases, employing a mixed methods design. The study included a validated questionnaire, tailored online educational resources, a retrospective chart review of patients with a history of elevated LDL cholesterol (LDLc) and an active review with a selection of those patients. Results were analyzed using SPSS V27, where descriptive statistics and relevant correlation tests were employed.

Results

Eighteen general practices agreed to take part in the study. In the initial survey, respondents rated their personal and practice familiarity with FH as slightly below average. Around one-third of respondents were not aware of FH guidelines. Of over 55,000 adult patient records searched, only 0.2% had a recorded FH diagnosis and 3.9% had ever had an LDLc above 4.9 mmol/l. Eight practices completed 198 chart reviews. Among these, 29.8% of patients had a family history recorded, and 22.2% had a family history of CVD recorded. Female patients had higher averages for highest and recent LDLc. Seventy patients underwent a clinical review—with 27% of these patients identified as “probable” or “definite FH.” There was a statistically significant (p = 0.002) relationship between FH status and whether the patient had other CVD risk factors.

Conclusion

General practitioners in Ireland had similar levels of awareness of FH compared to findings from elsewhere. The activities discussed encouraged clinicians to consider FH when talking to their patients, especially those with elevated LDLc at an early age. Broader awareness of the condition could increase conversations about FH and benefit patient outcomes.
Design and analysis of umbrella trials: Where do we stand?
Authors: Ouma Luke O. , Wason James M. S. , Zheng Haiyan , Wilson Nina , Grayling Michael
Published: October 2022

Background

The efficiencies that master protocol designs can bring to modern drug development have seen their increased utilization in oncology. Growing interest has also resulted in their consideration in non-oncology settings. Umbrella trials are one class of master protocol design that evaluates multiple targeted therapies in a single disease setting. Despite the existence of several reviews of master protocols, the statistical considerations of umbrella trials have received more limited attention.

Methods

We conduct a systematic review of the literature on umbrella trials, examining both the statistical methods that are available for their design and analysis, and also their use in practice. We pay particular attention to considerations for umbrella designs applied outside of oncology.

Findings

We identified 38 umbrella trials. To date, most umbrella trials have been conducted in early phase settings (73.7%, 28/38) and in oncology (92.1%, 35/38). The quality of statistical information available about conducted umbrella trials to date is poor; for example, it was impossible to ascertain how sample size was determined in the majority of trials (55.3%, 21/38). The literature on statistical methods for umbrella trials is currently sparse.

Conclusions

Umbrella trials have potentially great utility to expedite drug development, including outside of oncology. However, to enable lessons to be effectively learned from early use of such designs, there is a need for higher-quality reporting of umbrella trials. Furthermore, if the potential of umbrella trials is to be realized, further methodological research is required.