bluuebunny/crossref_metadata_2025 huggingface dataset:
A Heterozygous LMF1 Gene Mutation (c.1523C>T), Combined With an LPL Gene Mutation (c.590G>A), Aggravates the Clinical Symptoms in Hypertriglyceridemia
Authors: Guo Danxia , Zheng Yingchun , Gan Zhongzhi , Guo Yingying , Jiang Sijie , Yang Fang , Xiong Fu , Zheng Hua
Published: March 2022

Hypertriglyceridemia is an important contributor to atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis. Familial hypertriglyceridemia is often caused by mutations in genes involved in triglyceride metabolism. Here, we investigated the disease-causing gene mutations in a Chinese family with hypertriglyceridemia and assessed the functional significance in vitro. Whole-exome sequencing (WES) was performed revealing that the severe hypertriglyceridemic proband carried a missense mutation (c.590G > A) in exon 5 of the LPL gene, as well as a missense mutation (c.1523C > T) in exon 10 of the LMF1 gene. Conservation analysis by Polyphen-2 showed that the 508 locus in the LMF1 protein and 197 locus in the LPL protein were highly conserved between different species. I-TASSER analysis indicated that the LMF1 c.1523C > T mutation and the LPL c.590G > A mutation changed the tertiary structure of the protein. A decrease in mRNA and protein expression was observed in 293T cells transfected with plasmids carrying the LMF1 c.1523C > T mutation. Subcellular localization showed that both wild-type (WT) and mutant LMF1 protein were localized at the cell cytoplasm. In the cell medium and cell lysates, these LMF1 and LPL gene mutations both caused a decreased LPL mass. Moreover, the combination of LMF1 and LPL gene mutations significantly decreased LPL levels compared to their individual effects on the LPL concentration. Both the clinical and in vitro data suggest that severe hypertriglyceridemia was of digenic origin caused by LMF1 and LPL mutation double heterozygosity in this patient.
Comparative Analysis of Differentially Expressed Circular RNAs in Polarized Macrophages
Authors: Zhou Rong-mei , Shi Ze-hui , Shan Kun , Zhang Shu-jie , Zhang Yi-han , Liang Yu , Yan Biao , Zhao Chen
Published: March 2022

Macrophage polarization is a process that macrophages exert different functions according to surrounding micro-environment. Macrophages commonly exist in two distinct subsets: classically activated M1 macrophages and alternatively activated M2 macrophages. Circular RNAs (circRNAs) are a novel class of non-coding RNAs generated by back-splicing. Thousands of circRNAs were identified in different cells and tissues. Recent studies have revealed that circRNAs play a crucial role in regulating transcriptional and post-transcriptional gene expression. However, the effects and roles of circRNAs in macrophage polarization have not been well elucidated. Here, circRNAs expression profiles were determined in human THP-1 macrophages incubated in conditions causing activation toward M1 (interferon-γ + LPS) or M2 (interleukin-4) phenotypes. Overall, 9,720 circular RNA were detected from RNA sequencing data. Compared with M2 macrophages, a total of 140 circRNAs were aberrantly expressed in M1 macrophages, including 71 up-regulated circRNAs and 69 down-regulated circRNAs. Quantitative real-time PCR (qRT-PCR) results were generally consistent with the selected differentially expressed circRNAs. Gene Ontology (GO) and KEGG pathway analyses were used to predict biological functions and potential mechanisms of the host linear transcripts of these up-regulated and down-regulated circRNAs. Furthermore, we found that the expression level of circRNA-RNF19B (circRNF19B) in M1 macrophages was significantly higher than that in THP-1 macrophages and M2 macrophages. circRNF19B expression was increased when M2 converted to M1 whereas decreased when M1 converted to M2. Knockdown of circRNF19B following the activation of THP-1 cells using interferon-γ + LPS diminished the expression of M1 macrophages markers and elevated the expression of M2 macrophages markers. In conclusion, these data suggest the involvement of altered circRNAs expression patterns in macrophages exposure to different activating conditions. Circular RNAs may play important roles in regulating macrophage polarization.
Novel SEPN1 Mutations in Exon 1 Are Common in Rigid Spine With Muscular Dystrophy Type 1 in Chinese Patients
Authors: Fan Yanbin , Xu Zhifei , Li Xing , Gao Feng , Guo Enyu , Chang Xingzhi , Wei Cuijie , Zhang Cheng , Yu Qing , Que Chengli , Xiao Jiangxi , Yan Chuanzhu , Wang Zhaoxia , Yuan Yun , Xiong Hui
Published: March 2022

Congenital muscular dystrophy with early rigid spine, also known as the rigid spine with muscular dystrophy type 1 (RSMD1), is caused by SEPN1 mutation. We investigated the clinical manifestations, pathological features, and genetic characteristics of 8 Chinese RSMD1 patients in order to improve diagnosis and management of the disease. Eight patients presented with delayed motor development, muscle weakness, hypotonia, and a myopathic face with high palatine arches. All patients could walk independently, though with poor running and jumping, and most had a rigid spine, lordosis, or scoliosis. The symptoms of respiratory involvement were present early, and upper respiratory tract infections and pneumonia often occurred. Five patients had severe pneumonia, pulmonary hypertension, and respiratory failure. Lung function tests showed variable restrictive ventilation dysfunction. Polysomnography suggested hypoxia and hypoventilation. The serum creatine kinase (CK) level was normal or mildly increased. Muscle biopsy indicated chronic myopathic changes and minicores. Muscle magnetic resonance imaging (MRI) showed diffuse fatty infiltration of the gluteus maximus and thigh muscle. SEPN1 gene analysis revealed 16 compound heterozygous variants, 81.3% of which are unreported, including 7 exon 1 variants. Our study expands the spectrum of clinical and genetic findings in RSMD1 to improve diagnosis, management, and standards of care. SEPN1 mutations in exon 1 are common and easily missed, and exon 1 should be carefully analyzed when RSMD1 is suspected, which will provide valuable genetic counseling for the family and useful information for future natural history studies and clinical trials.
Comparative Analysis of Chloroplast Genome Structure and Phylogenetic Relationships Among Six Taxa Within the Genus Catalpa (Bignoniaceae)
Authors: Li Feng , Liu Ying , Wang Junhui , Xin Peiyao , Zhang Jiangtao , Zhao Kun , Zhang Minggang , Yun Huiling , Ma Wenjun
Published: March 2022

Species within the Genus Catalpa are mostly semievergreen or deciduous trees with opposite or whorled leaves. C. bungei, C. fargesii f. duclouxii and C. fargesii are sources of traditional precious wood in China, known as the “kings of wood”. Due to a lack of phenotypic and molecular studies and insufficient sequence information, intraspecific morphological differences, common DNA barcodes and partial sequence fragments cannot clearly reveal the phylogenetic or intraspecific relationships within Catalpa. Therefore, we sequenced the complete chloroplast genomes of six taxa of the genus Catalpa and analyzed their basic structure and evolutionary relationships. The chloroplast genome of Catalpa shows a typical tetrad structure with a total length ranging from 157,765 bp (C. fargesii) to 158,355 bp (C. ovata). The length of the large single-copy (LSC) region ranges from 84,599 bp (C. fargesii) to 85,004 bp (C. ovata), that of the small single-copy (SSC) region ranges from 12,662 bp (C. fargesii) to 12,675 bp (C. ovata), and that of the inverted repeat (IR) regions ranges from 30,252 bp (C. fargesii) to 30,338 bp (C. ovata). The GC content of the six chloroplast genomes were 38.1%. In total, 113 unique genes were detected, and there were 19 genes in IR regions. The 113 genes included 79 protein-coding genes, 30 tRNA genes and four rRNA genes. Five hypervariable regions (trnH-psbA, rps2-rpoC2, rpl22, ycf15-trnl-CAA and rps15) were identified by analyzing chloroplast nucleotide polymorphisms, which might be serve as potential DNA barcodes for the species. Comparative analysis showed that single nucleotide polymorphisms (SNPs) and simple sequence repeats (SSRs) were highly diverse in the six species. Codon usage patterns were highly similar among the taxa included in the present study. In addition to the stop codons, all codons showed a preference for ending in A or T. Phylogenetic analysis of the entire chloroplast genome showed that all taxa within the genus Catalpa formed a monophyletic group, clearly reflecting the relationships within the genus. This study provides information on the chloroplast genome sequence, structural variation, codon bias and phylogeny of Catalpa, which will facilitate future research efforts.
Dietary L-Carnitine Affects Leukocyte Count and Function in Dairy Cows Around Parturition
Authors: Kononov Susanne Ursula , Meyer Jennifer , Frahm Jana , Kersten Susanne , Kluess Jeannette , Bühler Susanne , Wegerich Anja , Rehage Jürgen , Meyer Ulrich , Huber Korinna , Dänicke Sven
Published: March 2022

In early lactation, an energy deficit leading to a negative energy balance (NEB) is associated with increased susceptibility to disease and has been shown to be an important factor during transition in dairy cows. L-carnitine as a key factor in the mitochondrial transport of fatty acids and subsequently for β-oxidation and energy release is known to modulate mitochondrial biogenesis and thus influence metabolism and immune system. In the current study, we characterized hematological changes around parturition and investigated the potential effects of dietary L-carnitine supplementation on immune cell functions. For this approach, dairy cows were assigned either to a control (CON, n = 30) or an L-carnitine group [CAR, n = 29, 25 g rumen-protected L-carnitine per cow and day (d)]. Blood samples were taken from d 42ante partum(ap) until d 110post-partum(pp), with special focus and frequent sampling from 0.5 to72 h post-calving to clarify the impact of L-carnitine supplementation on leukocyte count, formation of reactive oxygen species (ROS) in polymorphonuclear cells (PMN) and peripheral mononuclear cells (PBMC) and their phagocytosis activity. Blood cortisol concentration and the capacity of PBMC proliferation was also investigated. All populations of leukocytes were changed during the peripartal period, especially granulocytes showed a characteristic increase up to 4 hpp. L-carnitine supplementation resulted in increased levels of eosinophils which was particularly pronounced one day before to 4 hpp, indicating a possible enhanced support for tissue repair and recovery. Non-supplemented cows showed a higher phagocytic activity in PBMC as well as a higher phagocytic capacity of PMN during the most demanding period around parturition, which may relate to a decrease in plasma levels of non-esterified fatty acids reported previously. L-carnitine, on the other hand, led to an increased efficiency to form ROS in stimulated PMN. Finally, a short period around calving proved to be a sensitive period in which L-carnitine administration was effective.
Comparison of Lung-Homing Receptor Expression and Activation Profiles on NK Cell and T Cell Subsets in COVID-19 and Influenza
Authors: Brownlie Demi , Rødahl Inga , Varnaite Renata , Asgeirsson Hilmir , Glans Hedvig , Falck-Jones Sara , Vangeti Sindhu , Buggert Marcus , Ljunggren Hans-Gustaf , Michaëlsson Jakob , Gredmark-Russ Sara , Smed-Sörensen Anna , Marquardt Nicole
Published: March 2022

Respiratory viral infections with SARS-CoV-2 and influenza viruses commonly induce a strong infiltration of immune cells into the human lung, with potential detrimental effects on the integrity of the lung tissue. Despite comprising the largest fractions of circulating lymphocytes in the lung, rather little is known about how peripheral blood natural killer (NK) cell and T cell subsets are equipped for lung-homing in COVID-19 and influenza. Here, we provide a detailed comparative analysis of NK cells and T cells in patients infected with SARS-CoV-2 or influenza virus, focusing on the protein and gene expression of chemokine receptors known to be involved in recruitment to the lung. For this, we used 28-colour flow cytometry as well as re-analysis of a publicly available single-cell RNA-seq dataset from bronchoalveolar lavage (BAL) fluid. Frequencies of NK cells and T cells expressing CXCR3, CXCR6, and CCR5 were altered in peripheral blood of COVID-19 and influenza patients, in line with increased transcript expression of CXCR3, CXCR6, and CCR5 and their respective ligands in BAL fluid. NK cells and T cells expressing lung-homing receptors displayed stronger phenotypic signs of activation compared to cells lacking lung-homing receptors, and activation was overall stronger in influenza compared to COVID-19. Together, our results indicate a role for CXCR3+, CXCR6+, and/or CCR5+ NK cells and T cells that potentially migrate to the lungs in moderate COVID-19 and influenza patients, identifying common targets for future therapeutic interventions in respiratory viral infections.
Public Health Policy Pillars for the Sustainable Elimination of Zoonotic Schistosomiasis
Authors: Janoušková Eva , Clark Jessica , Kajero Olumayowa , Alonso Sergi , Lamberton Poppy H. L. , Betson Martha , Prada Joaquín M.
Published: March 2022

Schistosomiasis is a parasitic disease acquired through contact with contaminated freshwater. The definitive hosts are terrestrial mammals, including humans, with some Schistosoma species crossing the animal-human boundary through zoonotic transmission. An estimated 12 million people live at risk of zoonotic schistosomiasis caused by Schistosoma japonicum and Schistosoma mekongi, largely in the World Health Organization’s Western Pacific Region and in Indonesia. Mathematical models have played a vital role in our understanding of the biology, transmission, and impact of intervention strategies, however, these have mostly focused on non-zoonotic Schistosoma species. Whilst these non-zoonotic-based models capture some aspects of zoonotic schistosomiasis transmission dynamics, the commonly-used frameworks are yet to adequately capture the complex epi-ecology of multi-host zoonotic transmission. However, overcoming these knowledge gaps goes beyond transmission dynamics modelling. To improve model utility and enhance zoonotic schistosomiasis control programmes, we highlight three pillars that we believe are vital to sustainable interventions at the implementation (community) and policy-level, and discuss the pillars in the context of a One-Health approach, recognising the interconnection between humans, animals and their shared environment. These pillars are: (1) human and animal epi-ecological understanding; (2) economic considerations (such as treatment costs and animal losses); and (3) sociological understanding, including inter- and intra-human and animal interactions. These pillars must be built on a strong foundation of trust, support and commitment of stakeholders and involved institutions.
Diversity of Pacific Agathotanais (Peracarida: Tanaidacea)
Authors: Stępień Anna , Jóźwiak Piotr , Jakiel Aleksandra , Pełczyńska Alicja , Błażewicz Magdalena
Published: March 2022

Agathotanaisis one of the seven genera classified into the family Agathotanaidae. So far, 12 species have been described for the genus, seven of which are known from the Pacific. However, considering the present poor state of knowledge on deep-sea environments, a much higher number ofAgathotanaisspecies than currently known can be suspected. Among the studied material, collected from below 1,000 m during five deep-sea expeditions in different parts of the Pacific Ocean, we identified eight species: two of them were already known to the science and five species were identified as new to knowledge and their formal description is presented in the paper: two from the North West Pacific (the Sea of Okhotsk and Kuril-Kamchatka Trench), two from the Central Pacific (Clarion-Clipperton Fracture Zone), and one from the Australian slope. The eighthAgathotanaisspecies in our material was determined using a molecular approach, but it was represented by only one partially destroyed individual and could therefore not be formally described. The proportion ofAgathotanaiscollected at the Sea of Okhotsk was the highest (22%), whereas the numbers were substantially lower for the Kuril-Kamchatka Trench, and the Central and the Southern Pacific. Molecular analyses confirmed the monophyly ofAgathotanaisandParagathotanaisand a close relationship between both genera. Moreover, a close relationship between the two Australian species was revealed. As a result of our findings, the number of species known from the Pacific increased from 5 to 11, with the total number of species in this genus increasing from 12 to 17. An updated identification key forAgathotanaisspecies is given.
A Preliminary Study on Humpback Whales Lunge Feeding in the New York Bight, United States
Authors: Smith Samantha E. , Brown Danielle M. , Oliveras Jelisa R. , Sieswerda Paul L. , Ahearn Sean , Reiss Diana
Published: March 2022

Humpback whales (Megaptera novaeangliae) have recently been observed feeding in the New York Bight (NYB), the section of ocean from Montauk, New York to Cape May, New Jersey, United States (US). This feeding technique brings humpback whales to the surface of the water which puts them at a greater risk of vessel strike. The NYB is already an area of concern due to shipping traffic leading to the Ports of New York and New Jersey (PNYNJ). In this study, data collected by Gotham Whale from 2011 to 2019 were analyzed on humpback whales lunge feeding in the NYB apex, near the entrance to the PNYNJ. Clusters of lunge feeding were investigated, along with the water depths of lunge feeding locations. Using ArcGISPro, six significant hot spot clusters were identified, and water depth of lunge feeding locations ranged from 4.50 to 35.00 m with a mean of 14.83 m. The results of this study provide the first documentation on potential lunge feeding hot spot clusters in the NYB apex. Future studies should obtain comprehensive data looking at the amount of time humpback whales in the NYB are spending on the surface and time they are spending feeding in shipping lanes. This information will be important for the management of marine mammals in this area and may help to mitigate and reduce the incidence of boat strikes to humpback whales in this region.
A Road Map for the Development of the Bleached Coral Phenotype
Authors: Gómez-Campo Kelly , Enríquez Susana , Iglesias-Prieto Roberto
Published: March 2022

Mass coral bleaching compromises the long-term persistence of coral reefs, yet our current understanding of the different cellular mechanisms leading to the development of a bleached coral is still limited. In this perspective, we mapped the cascade of cellular events and physiological responses of symbiotic corals triggered by thermal stress. Based on existing knowledge, we created an integrated model that describes phenotypic changes induced by sensing mechanisms. Cellular responses are mapped in the context of reactive oxygen species (ROS) production in the algal symbiont chloroplast, followed by signaling to the nucleus and subsequent “leak” to the coral host cell. The starting point is set by ROS production and signaling, which is a day-to-day mechanism by which symbiotic corals maintain homeostasis and acclimate to environmental variation. As stress and acclimation are intimately linked, our model maps coral responses from the initial stimulus in the chloroplast to the complex cascade of events leading to seasonal phenotypic changes (i.e., seasonal acclimation), and if stress progresses, to the downstream coral bleached phenotype (i.e., when the coral’s capacity to acclimate is overwhelmed by heat stress). Placing acclimation, heat stress and bleaching responses in a common ground is a critical step to reduce the source of uncertainty in understanding the coral response to climate change, fundamental for the development of predictive climate models.
Wind-Controlled Transport of Saltwater in the Southeastern Baltic Sea: A Model Study
Authors: Zhurbas Victor , Väli Germo
Published: March 2022

We hypothesized that the saltwater transport in a system of the southeastern Baltic basins including the Gdańsk and Gotland deeps connected by the Hoburg Channel, is greatly controlled by wind forcing, which has a clear physical explanation. Namely, the westerly winds develop the Ekman transport in the upper layer to the south from the Gotland Deep to the Gdańsk Deep which causes a compensatory saltwater countercurrent in the deep layer to the north from the Gdańsk Deep toward the Gotland Deep, and, vice versa, the easterly winds develop the Ekman transport to the north from the Gdańsk Deep toward the Gotland Deep causing a compensatory saltwater countercurrent in the deep layer to the south from the Gotland Deep to the Gdańsk Deep. To confirm the hypothesis, results of numerical modeling of the Baltic Sea circulation for a 10-year period (2010–2019) are applied. The daily saltwater transport to the northeast through a cross-section of the Hoburg Channel is found to be highly correlated with the wind stress component toward southeast (the correlation coefficient is 0.812) which can be considered as a straightforward confirmation of the hypothesis indicating the strong wind-driven circulation also in the deep layers of the Baltic Sea. Estimates of the daily saltwater transport through the above-mentioned and several other cross-sections of the southeastern Baltic Sea basins confirm a rule stating that the maximum correlation takes place between the saltwater transport and a wind stress component directed perpendicularly to the right relative to the direction of saltwater transport.
Magnetically Reconfigurable Unidirectional Propagation of Electromagnetic Waves by Zero-Index–Based Heterostructured Metamaterials
Authors: Luo Qilin , Zhao Lingzhong , Zhou Jialin , Zhang Lin , Wen Guangfeng , Ba Qingtao , Wu Huabing , Lin Zhifang , Liu Shiyang
Published: March 2022

We present a zero-index–based heterostructured magnetic metamaterial (HSMM) composed of two arrays of ferrite rods with different radii and lattice separations, which exhibits unidirectional propagation of electromagnetic (EM) waves, and the unidirectionality is reconfigurable dependent on the bias magnetic field (BMF). By calculating the photonic band diagrams and the effective constitutive parameters, it is shown that, for the MMs with two groups of lattice separations and ferrite rod radii, the effective refractive index is switched either from effective zero index (EZI) to effective positive index (EPI) by decreasing the BMF for one MM or from EZI to effective negative index (ENI) for the other MM by increasing the BMF. As a result, two kinds of HSMMs can be constructed with the combination of either EZI and ENI or EZI and EPI, both of which can be used to implement the unidirectional transport of EM waves and exhibit reconfigurable unidirectionality by either decreasing or increasing the BMF, thus providing us with more degrees of freedom. The concept put forward in the present work can be possibly extended to the heterostructured metamaterials made of phase-change materials and realize reconfigurable EM properties in optical frequency by tuning the temperature.
Case Report: Herpes Simplex Virus Type 2 Acute Retinal Necrosis With Viral Encephalitis in Children
Authors: He Luyao , Duan Jialiang , Shang Qingli
Published: March 2022

Background

Few cases concerning acute retinal necrosis with viral encephalitis in children have been reported, especially cases where the fundus cannot be identified due to severe vitreous opacity in the early stage that makes diagnosis difficult.

Methods

We conducted a retrospective review of an unusual case of herpes simplex virus-2 (HSV-2) acute retinal necrosis with viral encephalitis in an immunocompetent child, along with a review of relevant literature published up to September 2021.

Result

An 11-year-old girl presented with an approximate 20-day history of ocular redness and decreased visual acuity in the left eye. Examination revealed anterior uveitis and vitreous opacity in the left eye. An anterior chamber tap was performed because the fundus could not be observed clearly, and the aqueous humor was positive for HSV-2 DNA. Cerebrospinal fluid also tested positive for HSV-2. She was diagnosed with acute retinal necrosis syndrome and viral encephalitis. The condition was controlled with timely antiviral and steroid therapy. She was also treated with prophylactic laser therapy to prevent retinal detachment during subsequent follow-up. The pathogenesis, diagnosis, and treatment of HSV-2 acute retinal necrosis in children and the association between acute retinal necrosis and viral encephalitis are further discussed, based on published literature.

Conclusion

HSV-2-related pediatric acute retinal necrosis may be due to the acquisition of subclinical infection with HSV-2 during parturition, followed by reactivation of the virus latent in the body on account of certain factors. Moreover, it may be complicated with viral encephalitis. For suspected cases with invisible fundus, early intraocular fluid examination is especially helpful for differential diagnosis. Early diagnosis, early treatment, and timely prophylactic laser treatment to prevent retinal detachment are key to a better prognosis. Physicians need to pay attention to such suspected cases during diagnosis and treatment.
Transfusional Approach in Multi-Ethnic Sickle Cell Patients: Real-World Practice Data From a Multicenter Survey in Italy
Authors: Graziadei Giovanna , De Franceschi Lucia , Sainati Laura , Venturelli Donatella , Masera Nicoletta , Bonomo Piero , Vassanelli Aurora , Casale Maddalena , Lodi Gianluca , Voi Vincenzo , Rigano Paolo , Pinto Valeria Maria , Quota Alessandra , Notarangelo Lucia D. , Russo Giovanna , Allò Massimo , Rosso Rosamaria , D'Ascola Domenico , Facchini Elena , Macchi Silvia , Arcioni Francesco , Bonetti Federico , Rossi Enza , Sau Antonella , Campisi Saveria , Colarusso Gloria , Giona Fiorina , Lisi Roberto , Giordano Paola , Boscarol Gianluca , Filosa Aldo , Marktel Sarah , Maroni Paola , Murgia Mauro , Origa Raffaella , Longo Filomena , Bortolotti Marta , Colombatti Raffaella , Di Maggio Rosario , Mariani Raffaella , Piperno Alberto , Corti Paola , Fidone Carmelo , Palazzi Giovanni , Badalamenti Luca , Gianesin Barbara , Piel Frédéric B. , Forni Gian Luca
Published: March 2022

Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT03397017.
Exploring the Change of Host and Microorganism in Chronic Obstructive Pulmonary Disease Patients Based on Metagenomic and Metatranscriptomic Sequencing
Authors: Yang Jing , Zhang Qiang , Zhang Jun , Ouyang Yan , Sun Zepeng , Liu Xinlong , Qaio Feng , Xu Li-Qun , Niu Yunfei , Li Jian
Published: March 2022

Background

Chronic obstructive pulmonary disease (COPD) is a universal respiratory disease resulting from the complex interactions between genes and environmental conditions. The process of COPD is deteriorated by repeated episodes of exacerbations, which are the primary reason for COPD-related morbidity and mortality. Bacterial pathogens are commonly identified in patients’ respiratory tracts both in the stable state and during acute exacerbations, with significant changes in the prevalence of airway bacteria occurring during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Therefore, the changes in microbial composition and host inflammatory responses will be necessary to investigate the mechanistic link between the airway microbiome and chronic pulmonary inflammation in COPD patients.

Methods

We performed metatranscriptomic and metagenomic sequencing on sputum samples for twelve AECOPD patients before treatment and for four of them stable COPD (stabilization of AECOPD patients after treatment). Sequencing reads were classified by Kraken2, and the host gene expression was analyzed by Hisat2 and HTseq. The correlation between genes was obtained by the Spearman correlation coefficient. Mann–Whitney U-test was applied to identify microbes that exhibit significantly different distribution in two groups.

Results

At the phyla level, the top 5 dominant phyla were Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, and Fusobacteria. The proportion of dominant gates in metagenomic data was similar in metatranscriptomic data. There were significant differences in the abundance of specific microorganisms at the class level between the two methods. No significant difference between AECOPD and stable COPD was found. However, the different expression levels of 5 host genes were significantly increased in stable COPD and were involved in immune response and inflammatory pathways, which were associated with macrophages.

Conclusion

Our study may provide a clue to investigate the mechanism of COPD and potential biomarkers in clinical diagnosis and treatment.
A New Way to Trace SARS-CoV-2 Variants Through Weighted Network Analysis of Frequency Trajectories of Mutations
Authors: Huang Qiang , Zhang Qiang , Bible Paul W. , Liang Qiaoxing , Zheng Fangfang , Wang Ying , Hao Yuantao , Liu Yu
Published: March 2022

Early detection of SARS-CoV-2 variants enables timely tracking of clinically important strains in order to inform the public health response. Current subtype-based variant surveillance depending on prior subtype assignment according to lag features and their continuous risk assessment may delay this process. We proposed a weighted network framework to model the frequency trajectories of mutations (FTMs) for SARS-CoV-2 variant tracing, without requiring prior subtype assignment. This framework modularizes the FTMs and conglomerates synchronous FTMs together to represent the variants. It also generates module clusters to unveil the epidemic stages and their contemporaneous variants. Eventually, the module-based variants are assessed by phylogenetic tree through sub-sampling to facilitate communication and control of the epidemic. This process was benchmarked using worldwide GISAID data, which not only demonstrated all the methodology features but also showed the module-based variant identification had highly specific and sensitive mapping with the global phylogenetic tree. When applying this process to regional data like India and South Africa for SARS-CoV-2 variant surveillance, the approach clearly elucidated the national dispersal history of the viral variants and their co-circulation pattern, and provided much earlier warning of Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). In summary, our work showed that the weighted network modeling of FTMs enables us to rapidly and easily track down SARS-CoV-2 variants overcoming prior viral subtyping with lag features, accelerating the understanding and surveillance of COVID-19.
Identification of a 3-Gene Prognostic Index for Papillary Thyroid Carcinoma
Authors: Zhong Lin-Kun , Deng Xing-Yan , Shen Fei , Cai Wen-Song , Feng Jian-Hua , Gan Xiao-Xiong , Jiang Shan , Liu Chi-Zhuai , Zhang Ming-Guang , Deng Jiang-Wei , Zheng Bing-Xing , Xie Xiao-Zhang , Ning Li-Qing , Huang Hui , Chen Shan-Shan , Miao Jian-Hang , Xu Bo
Published: March 2022

The accurate determination of the risk of cancer recurrence is a critical unmet need in managing thyroid cancer (TC). Although numerous studies have successfully demonstrated the use of high throughput molecular diagnostics in TC prediction, it has not been successfully applied in routine clinical use, particularly in Chinese patients. In our study, we objective to screen for characteristic genes specific to PTC and establish an accurate model for diagnosis and prognostic evaluation of PTC. We screen the differentially expressed genes by Python 3.6 in The Cancer Genome Atlas (TCGA) database. We discovered a three-gene signature Gap junction protein beta 4 (GJB4), Ripply transcriptional repressor 3 (RIPPLY3), and Adrenoceptor alpha 1B (ADRA1B) that had a statistically significant difference. Then we used Gene Expression Omnibus (GEO) database to establish a diagnostic and prognostic model to verify the three-gene signature. For experimental validation, immunohistochemistry in tissue microarrays showed that thyroid samples’ proteins expressed by this three-gene are differentially expressed. Our protocol discovered a robust three-gene signature that can distinguish prognosis, which will have daily clinical application.
In-Memory Computation Based Mapping of Keccak-f Hash Function
Authors: Kingra Sandeep Kaur , Parmar Vivek , Suri Manan
Published: March 2022

Cryptographic hash functions play a central role in data security for applications such as message authentication, data verification, and detecting malicious or illegal modification of data. However, such functions typically require intensive computations with high volume of memory accesses. Novel computing architectures such as logic-in-memory (LIM)/in-memory computing (IMC) have been investigated in the literature to address the limitations of intense compute and memory bottleneck. In this work, we present an implementation of Keccak-f (a state-of-the-art secure hash algorithm) using a variant of simultaneous logic-in-memory (SLIM) that utilizes emerging non-volatile memory (NVM) devices. Detailed operation and instruction mapping on SLIM-based digital gates is presented. Through simulations, we benchmark the proposed approach using LIM cells based on four different emerging NVM devices (OxRAM, CBRAM, PCM, and FeRAM). The proposed mapping strategy when used with state-of-the-art emerging NVM devices offers EDP savings of up to 300× compared to conventional methods.
A Cooperative Shared Control Scheme Based on Intention Recognition for Flexible Assembly Manufacturing
Authors: Zhou Guangbing , Luo Jing , Xu Shugong , Zhang Shunqing
Published: March 2022

Human–robot collaboration (HRC) has been widely utilized in industrial manufacturing and requires a human to cooperate with a robot at the same workspace. However, as HRC focuses on workspace sharing along with independent work, it is not a real collaboration between a human and a robot and, thus, cannot guarantee a smooth cooperation and synchronous operation. To this end, a cooperative shared control scheme based on intention recognition is proposed in this study by sharing workspace and time. In the proposed method, a classification algorithm based on three-dimensional (3D) point cloud is utilized to recognize the human operation intention. Then, the robot can select a suitable tool to match the human's operation. A robot motion control algorithm is developed to detect the obstacles in the HRC process. A cooperative control strategy is introduced to achieve synchronous operation. A simple assembly task is also performed to demonstrate the proposed scheme's effectiveness. The proposed HRC method with shared control can be extended to more complicated and delicate flexible tasks in assembly manufacturing.
Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy
Authors: Gao Yu-lei , Liu Yan-cun , Zhang Xiang , Shou Song-tao , Chai Yan-fen
Published: March 2022

Sepsis-associated encephalopathy (SAE) is a diffuse central nervous system (CNS) dysfunction during sepsis, and is associated with increased mortality and poor outcomes in septic patients. Despite the high incidence and clinical relevance, the exact mechanisms driving SAE pathogenesis are not yet fully understood, and no specific therapeutic strategies are available. Regulatory T cells (Tregs) have a role in SAE pathogenesis, thought to be related with alleviation of sepsis-induced hyper-inflammation and immune responses, promotion of T helper (Th) 2 cells functional shift, neuroinflammation resolution, improvement of the blood-brain barrier (BBB) function, among others. Moreover, in a clinical point of view, these cells have the potential value of improving neurological and psychiatric/mental symptoms in SAE patients. This review aims to provide a general overview of SAE from its initial clinical presentation to long-term cognitive impairment and summarizes the main features of its pathogenesis. Additionally, a detailed overview on the main mechanisms by which Tregs may impact SAE pathogenesis is given. Finally, and considering that Tregs may be a novel target for immunomodulatory intervention in SAE, different therapeutic options, aiming to boost peripheral and brain infiltration of Tregs, are discussed.
Case Report: The Imperfect Association Between Craniofacial Lesion Burden and Pain in Fibrous Dysplasia
Authors: Golden Emma , Zhang Fan , Selen Daryl J. , Ebb David , Romo Laura , Drubach Laura A. , Shah Nehal , O'Donnell Lauren J. , Lemme Jordan D. , Myers Rachel , Cay Mariesa , Kronenberg Henry M. , Westin Carl-Fredrik , Boyce Alison M. , Kaban Leonard B. , Upadhyay Jaymin
Published: March 2022

Patients with fibrous dysplasia (FD) often present with craniofacial lesions that affect the trigeminal nerve system. Debilitating pain, headache, and migraine are frequently experienced by FD patients with poor prognosis, while some individuals with similar bone lesions are asymptomatic. The clinical and biological factors that contribute to the etiopathogenesis of pain in craniofacial FD are largely unknown. We present two adult females with comparable craniofacial FD lesion size and location, as measured by 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT), yet their respective pain phenotypes differed significantly. Over 4 weeks, the average pain reported by Patient A was 0.4/0–10 scale. Patient B reported average pain of 7.8/0–10 scale distributed across the entire skull and left facial region. Patient B did not experience pain relief from analgesics or more aggressive treatments (denosumab). In both patients, evaluation of trigeminal nerve divisions (V1, V2, and V3) with CT and magnetic resonance imaging (MRI) revealed nerve compression and displacement with more involvement of the left trigeminal branches relative to the right. First-time employment of diffusion MRI and tractography suggested reduced apparent fiber density within the cisternal segment of the trigeminal nerve, particularly for Patient B and in the left hemisphere. These cases highlight heterogeneous clinical presentation and neurobiological properties in craniofacial FD and also, the disconnect between peripheral pathology and pain severity. We hypothesize that a detailed phenotypic characterization of patients that incorporates an advanced imaging approach probing the trigeminal system may provide enhanced insights into the variable experiences with pain in craniofacial FD.
Mothers’ Attachment Representations and Children’s Brain Structure
Authors: Fitter Megan H. , Stern Jessica A. , Straske Martha D. , Allard Tamara , Cassidy Jude , Riggins Tracy
Published: March 2022

Ample research demonstrates that parents’ experience-based mental representations of attachment—cognitive models of close relationships—relate to their children’s social-emotional development. However, no research to date has examined how parents’ attachment representations relate to another crucial domain of children’s development: brain development. The present study is the first to integrate the separate literatures on attachment and developmental social cognitive neuroscience to examine the link between mothers’ attachment representations and 3- to 8-year-old children’s brain structure. We hypothesized that mothers’ attachment representations would relate to individual differences in children’s brain structures involved in stress regulation—specifically, amygdala and hippocampal volumes—in part via mothers’ responses to children’s distress. We assessed 52 mothers’ attachment representations (secure base script knowledge on the Attachment Script Assessment and self-reported attachment avoidance and anxiety on the Experiences in Close Relationships scale) and children’s brain structure. Mothers’ secure base script knowledge was significantly related to children’s smaller left amygdala volume but was unrelated to hippocampal volume; we found no indirect links via maternal responses to children’s distress. Exploratory analyses showed associations between mothers’ attachment representations and white matter and thalamus volumes. Together, these preliminary results suggest that mothers’ attachment representations may be linked to the development of children’s neural circuitry related to stress regulation.
An in vivo Pig Model for Testing Novel Positron Emission Tomography Radioligands Targeting Cerebral Protein Aggregates
Authors: Raval Nakul Ravi , Nasser Arafat , Madsen Clara Aabye , Beschorner Natalie , Beaman Emily Eufaula , Juhl Morten , Lehel Szabolcs , Palner Mikael , Svarer Claus , Plavén-Sigray Pontus , Jørgensen Louise Møller , Knudsen Gitte Moos
Published: March 2022

Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-β or tau. Despite many attempts, it has not been possible to develop an appropriate radioligand for imaging aggregated α-synuclein in the brain for diagnosing, e.g., Parkinson’s Disease. Access to a large animal model with α-synuclein pathology would critically enable a more translationally appropriate evaluation of novel radioligands. We here establish a pig model with cerebral injections of α-synuclein preformed fibrils or brain homogenate from postmortem human brain tissue from individuals with Alzheimer’s disease (AD) or dementia with Lewy body (DLB) into the pig’s brain, using minimally invasive surgery and validated against saline injections. In the absence of a suitable α-synuclein radioligand, we validated the model with the unselective amyloid-β tracer [11C]PIB, which has a high affinity for β-sheet structures in aggregates. Gadolinium-enhanced MRI confirmed that the blood-brain barrier was intact. A few hours post-injection, pigs were PET scanned with [11C]PIB. Quantification was done with Logan invasive graphical analysis and simplified reference tissue model 2 using the occipital cortex as a reference region. After the scan, we retrieved the brains to confirm successful injection using autoradiography and immunohistochemistry. We found four times higher [11C]PIB uptake in AD-homogenate-injected regions and two times higher uptake in regions injected with α-synuclein-preformed-fibrils compared to saline. The [11C]PIB uptake was the same in non-injected (occipital cortex, cerebellum) and injected (DLB-homogenate, saline) regions. With its large brain and ability to undergo repeated PET scans as well as neurosurgical procedures, the pig provides a robust, cost-effective, and good translational model for assessment of novel radioligands including, but not limited to, proteinopathies.
A Model of Combined Exposure to Nicotine and Tetrahydrocannabinol via Electronic Cigarettes in Pregnant Rats
Authors: Breit Kristen R. , Rodriguez Cristina G. , Hussain Samirah , Thomas Karen J. , Zeigler Mikayla , Gerasimidis Ioanna , Thomas Jennifer D.
Published: March 2022

Nicotine and cannabis are two of the most commonly consumed licit and illicit drugs during pregnancy, often consumed together via e-cigarettes. Vaping is assumed to be a safer alternative than traditional routes of consumption, yet the potential consequences of prenatal e-cigarette exposure are largely unknown, particularly when these two drugs are co-consumed. In a novel co-exposure model, pregnant Sprague-Dawley rats received nicotine (36 mg/mL), tetrahydrocannabinol (THC) (100 mg/mL), the combination, or the vehicle via e-cigarettes daily from gestational days 5–20, mimicking the first and second human trimesters. Maternal blood samples were collected throughout pregnancy to measure drug and metabolite levels, and core body temperatures before and after exposure were also measured. Pregnant dams exposed to combined nicotine and THC had lower plasma nicotine and cotinine levels than those exposed to nicotine alone; similarly, the combined exposure group also had lower plasma THC and THC metabolite (THC-OH and THC-COOH) levels than those exposed to THC alone. Prenatal nicotine exposure gradually decreased initial core body temperatures each day, with chronic exposure, whereas exposure to THC decreased temperatures during the individual sessions. Despite these physiological effects, no changes were observed in food or water intake, weight gain, or basic litter outcomes. The use of this model can help elucidate the effects of co-exposure to THC and nicotine via e-cigarettes on both users and their offspring. Understanding the effects of co-use during pregnancy is critical for improving education for pregnant mothers about prenatal e-cigarette use and has important implications for public policy.
Pseudo-Temporal Analysis of Single-Cell RNA Sequencing Reveals Trans-Differentiation Potential of Greater Epithelial Ridge Cells Into Hair Cells During Postnatal Development of Cochlea in Rats
Authors: Chen Jianyong , Gao Dekun , Chen Junmin , Hou Shule , He Baihui , Li Yue , Li Shuna , Zhang Fan , Sun Xiayu , Jin Yulian , Sun Lianhua , Yang Jun
Published: March 2022

The hair cells of the cochlea play a decisive role in the process of hearing damage and recovery, yet knowledge of their regeneration process is still limited. Greater epithelial ridge (GER) cells, a type of cell present during cochlear development that has the characteristics of a precursor sensory cell, disappear at the time of maturation of hearing development. Its development and evolution remain mysterious for many years. Here, we performed single-cell RNA sequencing to profile the gene expression landscapes of rats’ cochlear basal membrane from P1, P7, and P14 and identified eight major subtypes of GER cells. Furthermore, single-cell trajectory analysis for GER cells and hair cells indicated that among the different subtypes of GER, four subtypes had transient cell proliferation after birth and could transdifferentiate into inner and outer hair cells, and two of them mainly transdifferentiated into inner hair cells. The other two subtypes eventually transdifferentiate into outer hair cells. Our study lays the groundwork for elucidating the mechanisms of the key regulatory genes and signaling pathways in the trans-differentiation of GER cell subtypes into hair cells and provides potential clues to understand hair cell regeneration.