bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanobodies: COVID-19 and Future Perspectives
Authors: Valenzuela-Nieto Guillermo , Miranda-Chacon Zaray , Salinas-Rebolledo Constanza , Jara Ronald , Cuevas Alexei , Berking Anne , Rojas-Fernandez Alejandro 
Published: July 2022

The COVID-19 pandemic has driven biotechnological developments to provide new and more effective tools for prophylaxis, diagnosis, and therapy. Historically, monoclonal antibodies have been valuable tools; however, the pandemic has shown some weaknesses, such as production limitations at a global scale. An alternative to conventional monoclonal antibodies are nanobodies, recombinant fragments of the variable region of single-domain antibodies derived mainly from the Camelidae family. Nanobodies have multiple characteristic benefits: they are small (15 KDa) and have remarkable refolding capability and unlimited possibilities for modifications due to their recombinant nature. Here, we review the application of nanobodies in diagnosis and treatment of SARS-CoV-2 infection.
Combining river replenishment and restrictions on groundwater pumping to achieve groundwater balance in the Juma River Plain, North China Plain
Authors: Cui Weizhe , Hao Qichen , Xiao Yong , Zhu Yuchen , Li Jianfeng , Yuanjing Zhang  
Published: July 2022

In recent years, to alleviate the decline in groundwater levels, extensive restrictions on groundwater pumping have been implemented in the North China Plain (NCP). In September 2018, a large-scale ecological water replenishment project was executed involving 22 rivers and lakes. How to adjust the layout of reduction on groundwater pumping within the context of ecological water replenishment is a key issue to be addressed in the study of groundwater level recovery in the NCP. This study adopted the Juma River Plain in Baoding city as a case study, established a numerical model of river replenishment of groundwater, predicted groundwater level changes over the next 15 years (2021–2035) and quantitatively calculated the impact of river replenishment on groundwater levels. To achieve the goal of an overall groundwater balance by 2035, a suitable groundwater pumping restriction scenario was defined based on the impact of river replenishment on groundwater levels. The results indicated that by 2035, the relative rise in groundwater levels attributed to river replenishment and restrictions on groundwater pumping could reach 3.51 and 2.28 m, respectively. River replenishment significantly impacts groundwater levels, especially those near the river. Under the current groundwater exploitation conditions, river replenishment could ensure groundwater level recovery near the river, which accounts for 15% of the total study area. The goal of an overall groundwater balance by 2035 could be achieved if restrictions on groundwater pumping were superimposed, with an average annual reduction of 56 million m3. This study provides valuable insights into groundwater management across the NCP. The proposed methods are useful for the management of other depleted aquifers recharged via ecological water replenishment.
Latent Autoimmune Diabetes in Adults: Background, Safety and Feasibility of an Ongoing Pilot Study With Intra-Lymphatic Injections of GAD-Alum and Oral Vitamin D
Authors: Björklund Anneli , Hals Ingrid K. , Grill Valdemar , Ludvigsson Johnny 
Published: July 2022

BackgroundLatent Autoimmune Diabetes in Adults (LADA) constitutes around 10% of all diabetes. Many LADA patients gradually lose their insulin secretion and progress to insulin dependency. In a recent trial BALAD (Behandling Av LADa) early insulin treatment compared with sitagliptin failed to preserve insulin secretion, which deteriorated in individuals displaying high levels of antibodies to GAD (GADA). These findings prompted us to evaluate a treatment that directly affects autoimmunity. Intra-lymphatic GAD-alum treatment has shown encouraging results in Type 1 diabetes patients. We therefore tested the feasibility of such therapy in LADA-patients (the GADinLADA pilot study).Material and MethodsFourteen GADA-positive (&gt;190 RU/ml), insulin-independent patients 30-70 years old, with LADA diagnosed within &lt; 36 months were included in an open-label feasibility trial. They received an intra-nodal injection of 4 μg GAD-alum at Day 1, 30 and 60 plus oral Vitamin D 2000 U/d from screening 30 days before (Day -30) for 4 months if the vitamin D serum levels were below 100 nmol/L (40 ng/ml). Primary objective is to evaluate safety and feasibility. Mixed Meal Tolerance Test and i.v. Glucagon Stimulation Test at baseline and after 5 and 12 months are used for estimation of beta cell function. Results will be compared with those of the recent BALAD study with comparable patient population. Immunological response is followed.ResultsPreliminary results show feasibility and safety, with almost stable beta cell function and metabolic control during follow-up so far (5 months).ConclusionsIntra-lymphatic GAD-alum treatment is an option to preserve beta cell function in LADA-patients. An ongoing trial in 14 LADA-patients show feasibility and safety. Clinical and immunological responses will determine how to proceed with future trials.
HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study
Authors: Ji Xiaoxiao , Hong Jianqiao , Qu Zihao , Yang Weinan , Wang Yibo , Lin Jiyan , Li Congsun , Wang Jie , Mou Haochen , Shi Mingmin , Zhou Chenhe , Wang Wei , Lin Changjian , Yan Shigui , Wu Haobo 
Published: July 2022

BackgroundAs a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors.MethodsTake HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices.ResultsGenetically increased HbA1C was associated with the lower heel eBMD [odds ratio (OR) 0.91 (95% CI 0.87, 0.96) per %-unit, P = 3 × 10−4(IVW)]. Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants [OR 0.87 (0.82, 0.93), P=2× 10−5(IVW)]; However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we test the association of erythrocytic traits with heel eBMD.ConclusionOur study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices).
A Comparison of Biophysical Conditions Between Sundanese Migrant and Non-Migrant Pekarangans in Indonesia
Authors: Ali Muhammad Saddam , Arifin Hadi Susilo , Arifin Nurhayati , Astawan Made 
Published: July 2022

Pekarangan is a typical Indonesian home garden. This article aimed to look at biophysical conditions of pekarangan between Sundanese migrants and non-migrants. A total of 40 pekarangans in Selajambe and Ciomas Rahayu villages, West Java, were chosen as representative locations for the Sundanese non-migrant population (native Sundanese), and 40 pekarangans in Tegal Yoso and Tanjung Kesuma villages, Lampung, were chosen as representatives of the Sundanese migrant population. Research has been carried out in the period 2019–2021. To measure the biophysical conditions of pekarangans, we analyzed the pekarangan area, pekarangan size, number of species and individual of pekarangan plants, vertical diversity and horizontal diversity of plants, and the relationship between the pekarangan area and number of species and individual plants. The results showed that the difference in conditions of the pekarangan was indicated by the difference in the area and size but not by the diversity of the plants. Both types of pekarangans have the same level of diversity, as indicated by the number of individual plants that are almost the same in number per 100 m2. In addition, a strong and positive correlation (0.69–0.88) between the area of pekarangan and the number of individual plants indicated that the small to medium size or large pekarangan sizes had almost the same diversity of plants. The difference lied in the type of plant that is cultivated. Migrant pekarangans are dominant in cultivating food crops, while non-migrant pekarangans are dominant in cultivating ornamental plants. The selection of plants that have important and valuable functions can be a solution in maintaining the area of the pekarangan. Choosing plants with a variety of functions can be an option for a small to medium pekarangan size. To improve the biophysical conditions of the pekarangan was also inseparable from the involvement of economic, social, and cultural aspects in the pekarangan.
Characteristics and Pollution Contribution of the Internal Nitrogen Release From the Sediments in the Dahekou Reservoir in Inner Mongolia
Authors: Lu Junping , Liu Tingxi , Shi Xiao Hong , Sun Biao , Zhao Shengnan 
Published: July 2022

To clarify the influence of the changes in the overlying water environment on the internal nitrogen release from reservoir sediments in different seasons, the quantitative linear relationship between the intensity of the nitrogen release from the sediment and the environmental factors of the overlying water was established, and their contribution rate to the nitrogen pollution of the reservoir during different storage periods was investigated. In this study, the sediment samples were collected from the Dahekou Reservoir in the Xilingol League, and the orthogonal simulation experiments were conducted in the laboratory. The mathematical model, which was established using multiple linear regression methods, revealed the following. The order of the significance of the influences of the environmental factors on the nitrogen release from the sediments in the Dahekou Reservoir is water temperature (T) &gt; dissolved oxygen (DO) &gt; pH value &gt; hydrodynamic force (K). The total nitrogen release flux from the sediments in the Dahekou Reservoir was 14.278 t/a in 2018, accounting for 27.91% of the total nitrogen (TN) pollution load input during the same period. In particular, in winter, the contribution rate of the nitrogen released from the sediments reached the highest level (57.06–63.26%), which was significantly higher than the river’s contribution to the total nitrogen pollution load of the reservoir. The nitrogen released from the sediments became the main source of nitrogen nutrients in the reservoir in the ice-sealed period.
Characteristic analysis of lightning activities on the Yungui Plateau using ground-based remote sensing
Authors: Liu Yinping , Jiang Yuhui , Gao Qisen , Shi Zheng , Jiang Zhuyi , Hu Jiarui 
Published: July 2022

The spatiotemporal distribution of cloud-to-ground (CG) lightning activities on the Yungui Plateau is investigated in this study by using a 5-year dataset (2016–2020) from the ground-based National Lightning Detection Network (CNLDN). The correlations between the lightning activities and different meteorological factors in the region are also analyzed. The results show that there is an obvious difference in the spatial distribution of lightning activities on the Yungui Plateau during the 5 years, with high lightning density in the east and low lightning density in the west. The lightning activities shift and gather more towards the eastern plateau especially after 2019. Affected by the quasi-stationary front in Kunming, the spatial distributions of lightning flashes in cold and warm seasons are different. On the other hand, the frequency of the lightning activities varies from year to year, such as the surge in 2019. But in general, 62% of the lightning activities are produced in summer and the lightning flashes occur more often in the afternoon and evening on the Yungui Plateau. Additionally, it is found that lightning activities in the 5 years are closely related to precipitation and temperature, while there is a weak correlation with relative humidity and almost no correlation with sensible heat flux. The analysis also indicates that the CAPE×P (convective available potential energy times precipitation rate) proxy can be effectively used to describe and predict lightning activities on the Yungui Plateau as the lightning flashes corresponds well to CAPE×P, especially of the spatial distribution.
Variable Clinical Features in a Large Family With Diamond Blackfan Anemia Caused by a Pathogenic Missense Mutation in RPS19
Authors: Cole Sarah , Giri Neelam , Alter Blanche P. , Gianferante D. Matthew 
Published: July 2022

Introduction:Diamond Blackfan anemia (DBA) is an autosomal dominant ribosomopathy caused predominantly by pathogenic germline variants in ribosomal protein genes. It is characterized by failure of red blood cell production, and common features include congenital malformations and cancer predisposition. Mainstays of treatment are corticosteroids, red blood cell transfusions, and hematologic stem cell transplantation (HSCT). Despite a better understanding of the genotype of DBA, the biological mechanism resulting in the clinical phenotype remains poorly understood, and wide heterogeneity can be seen even within a single family as depicted here.Case Description:Thirty family members enrolled in the National Cancer Institute inherited bone marrow failure syndromes study were evaluated with detailed medical questionnaires and physical examinations, including 22 in the family bloodline and eight unrelated partners. Eight participants had been previously told they had DBA by clinical criteria. Targeted germlineRPS19testing was done on all family members. A pathogenic heterozygous missense mutation inRPS19(p.R62Q, c.185G &gt; A) was detected in ten family members, including one person previously presumed unaffected. Eight family members presented with macrocytic anemia in infancy; all of whom were responsive to prednisone. Four family members became treatment independent; however, one individual became transfusion-dependent 36 years later following an episode of pneumonia. One prednisone responsive individual electively discontinued steroid treatment, and lives with severe anemia. One prednisone responsive individual died at age 28 from a stroke. Two family members developed colorectal cancer in their fifties; one had never required treatment for anemia. None had major congenital anomalies.Discussion:This large family with DBA demonstrates the heterogeneity of phenotypes that can be seen within the same genotype. Most family members presented with steroid-responsive anemia in infancy and subtle congenital malformations, findings consistent with recent genotype-phenotype studies ofRPSDBA. However, two family members were relatively unaffected, underscoring the importance of further studies to assess modifier genes, and epigenetic and/or environmental factors which may result in normal erythropoiesis despite underlying ribosome dysfunction. This large, multigenerational family highlights the need for individualized treatment, the importance of early cancer surveillance even in individuals with clinically mild phenotypes, and the benefit of long-term follow-up to identify late complications.
Genome-wide identification, characterization and expression analysis of the BMP family associated with beak-like teeth in Oplegnathus
Authors: Ma Yuting , Xiao Yongshuang , Xiao Zhizhong , Wu Yanduo , Zhao Haixia , Gao Guang , Wu Lele , Wang Tao , Zhao Ning , Li Jun 
Published: July 2022

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor beta (TGF-β) family, are critical for the control of developmental processes such as dorsal-ventral axis formation, somite and tooth formation, skeletal development, and limb formation. Despite Oplegnathus having typical healing beak-like teeth and tooth development showing a trend from discrete to healing, the potential role of BMPs in the development of the beak-like teeth is incompletely understood. In the present study, 19 and 16 BMP genes were found in O. fasciatus and O. punctatus, respectively, and divided into the BMP2/4/16, BMP5/6/7/8, BMP9/10, BMP12/13/14, BMP3/15 and BMP11 subfamilies. Similar TGFb and TGF_β gene domains and conserved protein motifs were found in the same subfamily; furthermore, two common tandem repeat genes (BMP9 and BMP3a-1) were identified in both Oplegnathus fasciatus and Oplegnathus punctatus. Selection pressure analysis revealed 13 amino acid sites in the transmembrane region of BMP3, BMP7, and BMP9 proteins of O. fasciatus and O. punctatus, which may be related to the diversity and functional differentiation of genes within the BMP family. The qPCR-based developmental/temporal expression patterns of BMPs showed a trend of high expression at 30 days past hatching (dph), which exactly corresponds to the ossification period of the bones and beak-like teeth in Oplegnathus. Tissue-specific expression was found for the BMP4 gene, which was upregulated in the epithelial and mesenchymal tissues of the beak-like teeth, suggesting that it also plays a regulatory role in the development of the beak-like teeth in O. punctatus. Our investigation not only provides a scientific basis for comprehensively understanding the BMP gene family but also helps screen the key genes responsible for beak-like tooth healing in O. punctatus and sheds light on the developmental regulatory mechanism.
Development of a High-Density 665 K SNP Array for Rainbow Trout Genome-Wide Genotyping
Authors: Bernard Maria , Dehaullon Audrey , Gao Guangtu , Paul Katy , Lagarde Henri , Charles Mathieu , Prchal Martin , Danon Jeanne , Jaffrelo Lydia , Poncet Charles , Patrice Pierre , Haffray Pierrick , Quillet Edwige , Dupont-Nivet Mathilde , Palti Yniv , Lallias Delphine , Phocas Florence 
Published: July 2022

Single nucleotide polymorphism (SNP) arrays, also named « SNP chips », enable very large numbers of individuals to be genotyped at a targeted set of thousands of genome-wide identified markers. We used preexisting variant datasets from USDA, a French commercial line and 30X-coverage whole genome sequencing of INRAE isogenic lines to develop an Affymetrix 665 K SNP array (HD chip) for rainbow trout. In total, we identified 32,372,492 SNPs that were polymorphic in the USDA or INRAE databases. A subset of identified SNPs were selected for inclusion on the chip, prioritizing SNPs whose flanking sequence uniquely aligned to the Swanson reference genome, with homogenous repartition over the genome and the highest Minimum Allele Frequency in both USDA and French databases. Of the 664,531 SNPs which passed the Affymetrix quality filters and were manufactured on the HD chip, 65.3% and 60.9% passed filtering metrics and were polymorphic in two other distinct French commercial populations in which, respectively, 288 and 175 sampled fish were genotyped. Only 576,118 SNPs mapped uniquely on both Swanson and Arlee reference genomes, and 12,071 SNPs did not map at all on the Arlee reference genome. Among those 576,118 SNPs, 38,948 SNPs were kept from the commercially available medium-density 57 K SNP chip. We demonstrate the utility of the HD chip by describing the high rates of linkage disequilibrium at 2–10 kb in the rainbow trout genome in comparison to the linkage disequilibrium observed at 50–100 kb which are usual distances between markers of the medium-density chip.
The Application of DNA Barcoding in Crustacean Larvae Identification from the Zhongsha Islands, South China Sea
Authors: Xu Lei , Wang Xuehui , Huang Delian , Wang Lianggen , Ning Jiajia , Li Yafang , Liu Shuangshuang , Du Feiyan 
Published: July 2022

Marine crustaceans are known as a group with high morphological diversity and great economic value. Most species have planktonic larval stages that are difficult to identify to species level using traditional approaches because of insufficient morphological diagnostic characters or taxonomic descriptions. We used DNA barcoding and molecular species identification to investigate the species diversity and distribution of crustacean larvae in the Zhongsha Islands waters, South China Sea. In total, 108 sequences were obtained from crustacean larvae collected in the Zhongsha Islands waters in 2019 using vertical hauls between the depths of 5 and 200 m. The molecular classification approach confirmed that 108 sequences represented crustaceans typical to the South China Sea, with 70 species identified, representing 43 genera, 23 families, and 4 orders. However, the cytochrome c oxidase subunit I gene sequences of only 27 species identified from the larval samples matched with available sequences taken from adults in GenBank. The comparison of K2P distances yielded a notable gap of 3.5–10.7% between intraspecific and interspecific distances across the sequence dataset. More than 80% of the crustacean larvae species belonged to the order Decapoda, and they displayed marked differences in their distributionsin the Zhongshan Islands waters. The orders Calanoida and Amphipoda were represented by the fewest species, which were recorded only at the edge of the Zhongsha Atoll.
A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China
Authors: Wu Xiaoying , Du Qianqian , Li Dongfang , Yuan Lin , Meng Qinghong , Fu Zhou , Xu Hongmei , Yao Kaihu , Zhao Ruiqiu 
Published: July 2022

BackgroundPrevious limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.MethodsThe present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.ResultsA total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2–9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips.ConclusionThe present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.