bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 and the Vasculature: Current Aspects and Long-Term Consequences
Authors: Martínez-Salazar Berenice , Holwerda Melle , Stüdle Chiara , Piragyte Indre , Mercader Nadia , Engelhardt Britta , Rieben Robert , Döring Yvonne
Published: February 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first identified in December 2019 as a novel respiratory pathogen and is the causative agent of Corona Virus disease 2019 (COVID-19). Early on during this pandemic, it became apparent that SARS-CoV-2 was not only restricted to infecting the respiratory tract, but the virus was also found in other tissues, including the vasculature. Individuals with underlying pre-existing co-morbidities like diabetes and hypertension have been more prone to develop severe illness and fatal outcomes during COVID-19. In addition, critical clinical observations made in COVID-19 patients include hypercoagulation, cardiomyopathy, heart arrythmia, and endothelial dysfunction, which are indicative for an involvement of the vasculature in COVID-19 pathology. Hence, this review summarizes the impact of SARS-CoV-2 infection on the vasculature and details how the virus promotes (chronic) vascular inflammation. We provide a general overview of SARS-CoV-2, its entry determinant Angiotensin-Converting Enzyme II (ACE2) and the detection of the SARS-CoV-2 in extrapulmonary tissue. Further, we describe the relation between COVID-19 and cardiovascular diseases (CVD) and their impact on the heart and vasculature. Clinical findings on endothelial changes during COVID-19 are reviewed in detail and recent evidence from in vitro studies on the susceptibility of endothelial cells to SARS-CoV-2 infection is discussed. We conclude with current notions on the contribution of cardiovascular events to long term consequences of COVID-19, also known as “Long-COVID-syndrome”. Altogether, our review provides a detailed overview of the current perspectives of COVID-19 and its influence on the vasculature.
Proteolysis-Targeting Chimera (PROTAC): Is the Technology Looking at the Treatment of Brain Tumors?
Authors: Lospinoso Severini Ludovica , Bufalieri Francesca , Infante Paola , Di Marcotullio Lucia
Published: February 2022

Post-translational modifications, such as ubiquitylation, need to be tightly controlled to guarantee the accurate localization and activity of proteins. Ubiquitylation is a dynamic process primarily responsible for proteasome-mediated degradation of substrate proteins and crucial for both normal homeostasis and disease. Alterations in ubiquitylation lead to the upregulation of oncoproteins and/or downregulation of tumor suppressors, thus concurring in tumorigenesis. PROteolysis-TArgeting Chimera (PROTAC) is an innovative strategy that takes advantage by the cell’s own Ubiquitin-Proteasome System (UPS). Each PROTAC molecule is composed by a ligand that recruits the target protein of interest (POI), a ligand specific for an E3 ubiquitin ligase enzyme, and a linker that connects these units. Upon binding to the POI, the PROTAC recruits the E3 inducing ubiquitylation-dependent proteasome degradation of the POI. To date, PROTAC technology has entered in clinical trials for several human cancers. Here, we will discuss the advantages and limitations of PROTACs development and safety considerations for their clinical application. Furthermore, we will review the potential of PROTAC strategy as therapeutic option in brain tumor, focusing on glioblastoma.
Recent Advances in Electron Microscopy of Carbohydrate Nanoparticles
Authors: Ogawa Yu , Putaux Jean-Luc
Published: February 2022

Carbohydrate nanoparticles, both naturally derived and synthetic ones, have attracted scientific and industrial attention as high-performance renewable building blocks of functional materials. Electron microscopy (EM) has played a central role in investigations of their morphology and molecular structure, although the intrinsic radiation sensitivity of carbohydrate crystals has often hindered the in-depth characterization with EM techniques. This contribution reviews the recent advances in the electron microscopy of the carbohydrate nanoparticles. In particular, we highlight the recent efforts made to understand the three-dimensional shape and structural heterogeneity of nanoparticles using low-dose electron tomography and electron diffraction techniques coupled with cryogenic transmission electron microscopy.
Characterization of Differentially Abundant Proteins Among Leishmania (Viannia) braziliensis Strains Isolated From Atypical or Typical Lesions
Authors: Esteves Bárbara B. , Melo-Braga Marcella N. , Gorshkov Vladimir , Verano-Braga Thiago , Larsen Martin R. , Gontijo Célia M. F. , Quaresma Patricia F. , Andrade Helida M.
Published: February 2022

Leishmania (Viannia) braziliensis is the main etiological agent of cutaneous and mucocutaneous leishmaniasis in Latin America. Non-ulcerated atypical tegumentary leishmaniasis cases caused by L. braziliensis have been reported in several regions of the American continent, including the Xacriabá indigenous reserve in São João das Missões/Minas Gerais, Brazil. Parasites isolated from these atypical clinical lesions are resistant to antimony-based therapeutics. In the present study, proteins displaying differential abundance in two strains of L. braziliensis isolated from patients with atypical lesions compared with four strains isolated from patients with typical lesions were identified using a quantitative proteomics approach based on tandem mass tag labeling (TMT) and mass spectrometry. A total of 532 (P<0.05) differentially abundant proteins were identified (298 upregulated and 234 downregulated) in strains from atypical lesions compared to strains from typical lesions. Prominent positively regulated proteins in atypical strains included those that may confer greater survival inside macrophages, proteins related to antimony resistance, and proteins associated with higher peroxidase activity. Additionally, we identified proteins showing potential as new drug and vaccine targets. Our findings contribute to the characterization of these intriguing L. braziliensis strains and provide a novel perspective on Atypical Cutaneous Leishmaniasis (ACL) cases that have been associated with therapeutic failures.
Guidelines to Facilitate Human-Wildlife Interactions in Conservation Translocations
Authors: Consorte-McCrea Adriana , Kolipaka Shekhar , Owens Jacob R. , Ruiz-Miranda Carlos R. , Waters Siân
Published: February 2022

Species reintroductions and translocations are widely used management interventions to restore locally extinct or augment severely depleted species. In such projects, the human dimension issues that influence the success of these conservation interventions are encountered at five different stages of the project life cycle: (1) planning, (2) initiation, (3) implementation, (4) ending stage, and (5) post-exit. Overlooking or failing to consider the human dimension in any of these phases could jeopardise the conservation translocation project's success. When the human dimensions are included there is greater possibility of community involvement, peers' acceptance and support from various interest groups and avoidance of conflict situations. The Human-Wildlife Interactions Working Group (HWIWG) was formed in 2018 by members of the IUCN Conservation Translocation Specialist Group (CTSG). HWIWG has facilitated online discussions and workshops with practitioners, researchers and academics from across the globe, on a range of aspects of human-wildlife interactions in conservation translocations, as well as leading discussion sessions during international research conferences. These events have provided a rich source of material from which to draw a series of recommendations. In this paper we discuss findings from the HWIWG that illustrate how, in each of the five stages of the project life cycle, human-dimensions influenced conservation translocation projects. Our aim is to provide useful and multidimensional insights for those working in species' reintroductions and translocations.
Outcomes of Hospitalized Patients With COVID-19 With Acute Kidney Injury and Acute Cardiac Injury
Authors: Lu Justin Y. , Buczek Alexandra , Fleysher Roman , Hoogenboom Wouter S. , Hou Wei , Rodriguez Carlos J. , Fisher Molly C. , Duong Tim Q.
Published: February 2022

Purpose

This study investigated the incidence, disease course, risk factors, and mortality in COVID-19 patients who developed both acute kidney injury (AKI) and acute cardiac injury (ACI), and compared to those with AKI only, ACI only, and no injury (NI).

Methods

This retrospective study consisted of hospitalized COVID-19 patients at Montefiore Health System in Bronx, New York between March 11, 2020 and January 29, 2021. Demographics, comorbidities, vitals, and laboratory tests were collected during hospitalization. Predictive models were used to predict AKI, ACI, and AKI-ACI onset. Longitudinal laboratory tests were analyzed with time-lock to discharge alive or death.

Results

Of the 5,896 hospitalized COVID-19 patients, 44, 19, 9, and 28% had NI, AKI, ACI, and AKI-ACI, respectively. Most ACI presented very early (within a day or two) during hospitalization in contrast to AKI (p < 0.05). Patients with combined AKI-ACI were significantly older, more often men and had more comorbidities, and higher levels of cardiac, kidney, liver, inflammatory, and immunological markers compared to those of the AKI, ACI, and NI groups. The adjusted hospital-mortality odds ratios were 17.1 [95% CI = 13.6–21.7, p < 0.001], 7.2 [95% CI = 5.4–9.6, p < 0.001], and 4.7 [95% CI = 3.7–6.1, p < 0.001] for AKI-ACI, ACI, and AKI, respectively, relative to NI. A predictive model of AKI-ACI onset using top predictors yielded 97% accuracy. Longitudinal laboratory data predicted mortality of AKI-ACI patients up to 5 days prior to outcome, with an area-under-the-curve, ranging from 0.68 to 0.89.

Conclusions

COVID-19 patients with AKI-ACI had markedly worse outcomes compared to those only AKI, ACI and NI. Common laboratory variables accurately predicted AKI-ACI. The ability to identify patients at risk for AKI-ACI could lead to earlier intervention and improvement in clinical outcomes.
Imaging Modalities for Intracranial Aneurysm: More Than Meets the Eye
Authors: Maupu Clémence , Lebas Héloïse , Boulaftali Yacine
Published: February 2022

Intracranial aneurysms (IA) are often asymptomatic and have a prevalence of 3 to 5% in the adult population. The risk of IA rupture is low, however when it occurs half of the patients dies from subarachnoid hemorrhage (SAH). To avoid this fatal evolution, the main treatment is an invasive surgical procedure, which is considered to be at high risk of rupture. This risk score of IA rupture is evaluated mainly according to its size and location. Therefore, angiography and anatomic imaging of the intracranial aneurysm are crucial for its diagnosis. Moreover, it has become obvious in recent years that several other factors are implied in this complication, such as the blood flow complexity or inflammation. These recent findings lead to the development of new IA imaging tools such as vessel wall imaging, 4D-MRI, or molecular MRI to visualize inflammation at the site of IA in human and animal models. In this review, we will summarize IA imaging techniques used for the patients and those currently in development.
Geomechanical Modeling and Inversion Analysis of the in-situ Stress Field in Deep Marine Shale Formations: A Case Study of the Longmaxi Formation, Dingshan Area, China
Authors: Liu Qinjie , Fu Qiang , Yang Ke , Wei Quanchao , Liu Huihu , Wu Haibo
Published: February 2022

Based on the comprehensive analysis of wellbore characteristics in a deep shale gas field, the in-situ stress state of the shale reservoir was assessed in this study for the Longmaxi formation in the Dingshan area, Southwestern China. The data obtained from hydraulic fracturing, drilling-induced fractures, and in-situ core testing were used to determine the magnitude and direction of the maximum principal horizontal stress in five wells. Besides, hydraulic fracturing and cross-multipole array acoustic logging (XMAC) were employed to determine the vertical variation of the in-situ stress. Based on the logging interpretation and mechanical test results, the spatial distribution of rock mechanical parameters in the Dingshan area was assessed by the amplitude variation versus offset (AVO) seismic inversion. A 3D heterogeneous mechanical inversion model was realized via the ANSYS and CATIA3D finite element software packages, providing the area in-situ stress field simulation. The depth, fault strike, and position change effects on the main stress, horizontal stress difference, and horizontal stress difference coefficient were numerically simulated. The results show that the maximum principal stress azimuth was mainly concentrated in the NE20°-NE80° sector. Moreover, the development zone of natural fractures was related to the area with the highest principal stress differences. The maximum principal stress variation in the study area was mainly in the compressive range from −135 to −45 MPa, gradually increasing from east to west and south to north. The stress type mainly depended on the depth, fault strike, and rock mechanical parameters, while the stress difference and stress difference coefficient near the fault structure were relatively small. This study’s findings are considered instrumental in improving the borehole stability, determining the casing setting point, and optimizing the well location in deep shale reservoirs with similar geological conditions.
A Deep Active Learning Approach to the Automatic Classification of Volcano-Seismic Events
Authors: Manley Grace F. , Mather Tamsin A. , Pyle David M. , Clifton David A. , Rodgers Mel , Thompson Glenn , Londoño John Makario
Published: February 2022

Volcano-seismic event classification represents a fundamental component of volcanic monitoring. Recent advances in techniques for the automatic classification of volcano-seismic events using supervised deep learning models achieve high accuracy. However, these deep learning models require a large, labelled training dataset to successfully train a generalisable model. We develop an approach to volcano-seismic event classification making use of active learning, where a machine learning model actively selects the training data which it learns from. We apply a diversity-based active learning approach, which works by selecting new training points which are most dissimilar from points already in the model according to a distance-based calculation applied to the model features. We combine the active learning with an existing volcano-seismic event classifier and apply the model to data from two volcanoes: Nevado del Ruiz, Colombia and Llaima, Chile. We find that models with data selected using an active learning approach achieve better testing accuracy and AUC (Area Under the Receiver Operating Characteristic Curve) than models with data selected using random sampling. Additionally, active learning decreases the labelling burden for the Nevado del Ruiz dataset but offers no increase in performance for the Llaima dataset. To explain these results, we visualise the features from the two datasets and suggest that active learning can reduce the quantity of labelled data required for less separable data, such as the Nevado del Ruiz dataset. This study represents the first evaluation of an active learning approach in volcano-seismology.
Key Processes on Triggering the Moderate 2020/21 La Niña Event as Depicted by the Clustering Approach
Authors: Cao Ting‐Wei , Zheng Fei , Fang Xiang‐Hui
Published: February 2022

The 2020/21 La Niña was not well predicted by most climate models when it started in early-mid 2020. This paper adopted an El Niño-Southern Oscillation (ENSO) ensemble prediction system to evaluate the key physical processes in the development of this cold event by performing a clustering analysis of 100 ensemble member predictions 1 year in advance. The abilities of two clustering approaches were first examined in regard to capturing the development of the 2020/21 La Niña event. One approach was index clustering, which adopted only the 12-month Niño3.4 indices in 2020 as an indicator, and the other was pattern clustering through contrasting the evolution of sea surface temperature (SST) anomalies over the tropical Pacific in 2020 for clustering. Pattern clustering surpasses index clustering in better describing the evolution over the off-equatorial and equatorial regions during the 2020/21 La Niña. Consequently, based on the pattern clustering approach, a comparison of the selected most (five best) and least (five worst) representative ensemble members illustrated that the predominance of anomalous southeasterly winds over the central equatorial Pacific in spring 2020 played a crucial role in initiating the moderate La Niña event in 2020/21, by preventing the development of westerly winds over the warm pool. Moreover, the inherent spring predictability barrier (SPB) was still a major challenge for improving the prediction skill of the 2020/21 La Niña event when the prediction occurred across the spring season.
Association Between Weight Gain From Young to Middle Adulthood and Metabolic Syndrome Across Different BMI Categories at Young Adulthood
Authors: Wang Xiuling , Song Jiali , Gao Yan , Wu Chaoqun , Zhang Xingyi , Li Teng , Cui Jianlan , Song Lijuan , Xu Wei , Yang Yang , Zhang Haibo , Lu Jiapeng , Li Xi , Liu Jiamin , Zheng Xin
Published: February 2022

Objectives

We aimed to assess the dose–response association between weight gain from young to middle adulthood and odds of metabolic syndrome, across body mass index (BMI) categories at young adulthood.

Methods

Based on a national population-based screening project, middle-aged (35–64 years) participants who recalled weight at age 25 years and received standardized measurements were included. Multivariable adjusted restricted cubic splines and logistic regression models were applied.

Results

In total, 437,849 participants were included (62.1% women, 52.0 ± 7.6 years). Larger weight gains from young to middle adulthood were associated with higher odds of metabolic syndrome at middle adulthood, with odds of 2.01 (1.98–2.05), 1.93 (1.92–1.94), and 1.67 (1.64–1.7) per 5-kg weight gain across participants who were underweight, normal-weight, and overweight/obese at young adulthood, respectively. After further adjusting for current BMI, larger weight gains still correlated with higher odds of metabolic syndrome among underweight and normal-weight participants, while an inverted U-shaped association was observed in overweight/obese participants.

Conclusions

Weight maintenance from young to middle adulthood could be effective to mitigate metabolic syndrome burden, especially among underweight and normal-weight people. Historical weight gain confers varied information about metabolic syndrome risk independent of attained BMI across BMI categories at young adulthood.
Oxytocin in Women’s Health and Disease
Authors: Liu Ning , Yang Haipeng , Han Liqun , Ma Mingxing
Published: February 2022

Oxytocin (OT) is a nonapeptide mainly produced in the supraoptic and paraventricular nuclei. OT in the brain and blood has extensive functions in both mental and physical activities. These functions are mediated by OT receptors (OTRs) that are distributed in a broad spectrum of tissues with dramatic sexual dimorphism. In both sexes, OT generally facilitates social cognition and behaviors, facilitates parental behavior and sexual activity and inhibits feeding and pain perception. However, there are significant differences in OT levels and distribution of OTRs in men from women. Thus, many OT functions in men are different from women, particularly in the reproduction. In men, the reproductive functions are relatively simple. In women, the reproductive functions involve menstrual cycle, pregnancy, parturition, lactation, and menopause. These functions make OT regulation of women’s health and disease a unique topic of physiological and pathological studies. In menstruation, pre-ovulatory increase in OT secretion in the hypothalamus and the ovary can promote the secretion of gonadotropin-releasing hormone and facilitate ovulation. During pregnancy, increased OT synthesis and preterm release endow OT system the ability to promote maternal behavior and lactation. In parturition, cervix expansion-elicited pulse OT secretion and uterine OT release accelerate the expelling of fetus and reduce postpartum hemorrhage. During lactation, intermittent pulsatile OT secretion is necessary for the milk-ejection reflex and maternal behavior. Disorders in OT secretion can account for maternal depression and hypogalactia. In menopause, the reduction of OT secretion accounts for many menopausal symptoms and diseases. These issues are reviewed in this work.
Gender Differences in Body Composition in Pre-Frail Older Adults With Diabetes Mellitus
Authors: Merchant Reshma Aziz , Soong John Tshon Yit , Morley John E.
Published: February 2022

Background & Aims

Ageing is a risk factor for diabetes mellitus (DM) and frailty. It is associated with body composition changes including increase in fat mass (FM), central fat distribution, decrease in fat free mass (FFM) and skeletal muscle which are risk factors for DM. This study aims to evaluate gender differences in body composition in pre-frail diabetics and association with physical performance, cognitive function and perceived health. In addition, we aim to explore the association of obesity, sarcopenia, sarcopenic obesity, and body composition in pre-frail older adults to DM status.

Methods

Cross-sectional study of 192 pre-frail community dwelling older adults (≥ 65 years). Data was collected on demographics, physical function, cognition, frailty, sarcopenia, perceived health and body composition using the InBody S10. Univariate and multivariate logistic regression were undertaken to explore the association of sarcopenic obesity, obesity, sarcopenia and body composition measures to DM status.

Results

There were insignificant within-gender differences for physical function, cognition and body composition, except for a higher prevalence of obesity defined by body mass index (BMI) and body fat percentage (BF%), increased fat mass index(FMI) and fat free mass index(FFMI) in females with DM. There were significant between-gender differences for those with DM where females overall had lower education levels, lower perceived health, higher prevalence of depression and low mental vitality, lower overall physical function (low short physical performance battery scores, low gait speed and hand grip strength), lower cognitive scores, lower muscle mass and muscle quality with higher FMI, FM/FFM and visceral fat area(VFA). BMI, VFA>100 cm2, FMI and FFMI were found to be independently associated with DM status after multivariable adjustment.

Conclusion

Within pre-frail DM vs non-DM, there were insignificant differences in body composition, physical function, cognition and perceived health within gender except for FMI, BF% and FFMI in females. There were significant differences between gender in pre-frail DM in muscle mass, quality, functional, cognitive and mental status. Further longitudinal studies are required to understand the pathogenesis, trajectory of DM and protective role of oral hypoglycemics in pre-frail older adults.
Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis
Authors: Huang Xin , Zhang Kai-jie , Jiang Jun-jie , Jiang Shou-yin , Lin Jia-bin , Lou Yi-jia
Published: February 2022

Type 2 diabetes (T2D) patients with SARS-CoV-2 infection hospitalized develop an acute cardiovascular syndrome. It is urgent to elucidate underlying mechanisms associated with the acute cardiac injury in T2D hearts. We performed bioinformatic analysis on the expression profiles of public datasets to identify the pathogenic and prognostic genes in T2D hearts. Cardiac RNA-sequencing datasets from db/db or BKS mice (GSE161931) were updated to NCBI-Gene Expression Omnibus (NCBI-GEO), and used for the transcriptomics analyses with public datasets from NCBI-GEO of autopsy heart specimens with COVID-19 (5/6 with T2D, GSE150316), or dead healthy persons (GSE133054). Differentially expressed genes (DEGs) and overlapping homologous DEGs among the three datasets were identified using DESeq2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were conducted for event enrichment through clusterProfile. The protein-protein interaction (PPI) network of DEGs was established and visualized by Cytoscape. The transcriptions and functions of crucial genes were further validated in db/db hearts. In total, 542 up-regulated and 485 down-regulated DEGs in mice, and 811 up-regulated and 1399 down-regulated DEGs in human were identified, respectively. There were 74 overlapping homologous DEGs among all datasets. Mitochondria inner membrane and serine-type endopeptidase activity were further identified as the top-10 GO events for overlapping DEGs. Cardiac CAPNS1 (calpain small subunit 1) was the unique crucial gene shared by both enriched events. Its transcriptional level significantly increased in T2D mice, but surprisingly decreased in T2D patients with SARS-CoV-2 infection. PPI network was constructed with 30 interactions in overlapping DEGs, including CAPNS1. The substrates Junctophilin2 (Jp2), Tnni3, and Mybpc3 in cardiac calpain/CAPNS1 pathway showed less transcriptional change, although Capns1 increased in transcription in db/db mice. Instead, cytoplasmic JP2 significantly reduced and its hydrolyzed product JP2NT exhibited nuclear translocation in myocardium. This study suggests CAPNS1 is a crucial gene in T2D hearts. Its transcriptional upregulation leads to calpain/CAPNS1-associated JP2 hydrolysis and JP2NT nuclear translocation. Therefore, attenuated cardiac CAPNS1 transcription in T2D patients with SARS-CoV-2 infection highlights a novel target in adverse prognostics and comprehensive therapy. CAPNS1 can also be explored for the molecular signaling involving the onset, progression and prognostic in T2D patients with SARS-CoV-2 infection.
The Chironomid Microbiome Plays a Role in Protecting Its Host From Toxicants
Authors: Sela Rotem , Halpern Malka
Published: February 2022

Organisms are assemblages of the host and their endogenous bacteria, which are defined as microbiomes. The host and its microbiome undergo a mutual evolutionary process to adapt to changes in the environment. Chironomids (Diptera; Chironomidae), are aquatic insects that grow and survive in polluted environments; however, the mechanisms that protect them under these conditions are not fully understood. Here we present evidence that the chironomids’ microbiome enables them to survival in polluted environments. It has been demonstrated that about 40% of the microbiota that inhabit Chironomus transvaalensis egg masses and larvae has the potential to detoxify different toxicants. Metagenomic analysis of Chironomus ramosus larvae demonstrated the presence of genes in the insects’ microbiome that can help the insects to survive in hostile environments. A set of experiments demonstrated that short exposure of C. transvaalensis larvae to metals significantly changed their microbiota composition in comparison to unexposed larvae. Another experiment, that followed Koch’s postulates, demonstrated that disinfected C. transvaalensis larvae can survive toxic lead and chromium exposure when they are recolonized with bacteria that can detoxify these toxic metals. This accumulating research, points to the conclusion that the chironomid microbiome plays a role in protecting its host from toxicants.
Sex Pheromone Receptors of Lepidopteran Insects
Authors: Yang Chan , Cheng Jie , Lin Jingyu , Zheng Yuan , Yu Xiao , Sun Jinpeng
Published: February 2022

The sex pheromone receptors (SPRs) of Lepidopteran insects play important roles in chemical communication. In the sex pheromone detection processes, sex pheromone molecule (SPM), SPR, co-receptor (Orco), pheromone binding protein (PBP), sensory neuron membrane protein (SNMP), and pheromone degradation enzyme (PDE) play individual and cooperative roles. Commonly known as butterfly and moth, the Lepidopteran insects are widely distributed throughout the world, most of which are pests. Comprehensive knowledge of the SPRs of Lepidopteran insects would help the development of sex lure technology and the sex communication pathway research. In this review, we summarized SPR/Orco information from 10 families of Lepidopteran insects from corresponding studies. According to the research progress in the literature, we speculated the evolution of SPRs/Orcos and phylogenetically analyzed the Lepidopteran SPRs and Orcos with the neighbor-joining tree and further concluded the relationship between the cluster of SPRs and their ligands; we analyzed the predicted structural features of SPRs and gave our prediction results of SPRs and Orcos with Consensus Constrained TOPology Prediction (CCTOP) and SwissModel; we summarized the functional characterization of Lepidopteran SPRs and SPR-ligand interaction and then described the progress in the sex pheromone signaling pathways and metabotropic ion channel. Further studies are needed to work out the cryo-electron microscopy (EM) structure of SPR and the SPR-ligand docking pattern in a biophysical perspective, which will directly facilitate the understanding of sex pheromone signal transduction pathways and provide guidance in the sex lure technology in field pest control.
The Curious Case of Multicellularity in the Volvocine Algae
Authors: Jiménez-Marín Berenice , Olson Bradley J. S. C.
Published: February 2022

The evolution of multicellularity is a major evolutionary transition that underlies the radiation of many species in all domains of life, especially in eukaryotes. The volvocine green algae are an unconventional model system that holds great promise in the field given its genetic tractability, late transition to multicellularity, and phenotypic diversity. Multiple efforts at linking multicellularity-related developmental landmarks to key molecular changes, especially at the genome level, have provided key insights into the molecular innovations or lack thereof that underlie multicellularity. Twelve developmental changes have been proposed to explain the evolution of complex differentiated multicellularity in the volvocine algae. Co-option of key genes, such as cell cycle and developmental regulators has been observed, but with few exceptions, known co-option events do not seem to coincide with most developmental features observed in multicellular volvocines. The apparent lack of “master multicellularity genes” combined with no apparent correlation between gene gains for developmental processes suggest the possibility that many multicellular traits might be the product gene-regulatory and functional innovations; in other words, multicellularity can arise from shared genomic repertoires that undergo regulatory and functional overhauls.
OIP5 Is a Novel Prognostic Biomarker in Clear Cell Renal Cell Cancer Correlating With Immune Infiltrates
Authors: Gong Mancheng , Li Yongxiang , Song Erlin , Li Miaoyuan , Qiu Shaopeng , Dong Wenjing , Yuan Runqiang
Published: February 2022

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, its contribution to cancer immunity remains unknown. Furthermore, the relationship between OIP5 and cancer immunity remains uncertain. In our research, we explored the different expression of OIP5 between 539 ccRCC and 72 normal renal tissues base on TCGA data set. We analyzed the associations between OIP5 expression with ccRCC progression and survival. Next, we compared immune cell profiles in cancer tissues and normal tissues in the Cancer Genome Atlas (TCGA) ccRCC cohort. We found that the level of immune cell infiltration was correlated with the copy number of OIP5 gene in ccRCC. The effect of OIP5 on immune activity was verified by Gene Set Enrichment Analysis of RNA-seq data from 32 ccRCC cell lines in the public database. Moreover, a pathway enrichment analysis of 49 OIP5-associated immunomodulators demonstrated the involvement of the T cell receptor signaling pathway, the JAK-STAT signaling pathway, the NF-kappa B signaling pathway and the primary immunodeficiency pathway. In addition, using OIP5-associated immunomodulators, we constructed multiple-gene risk prediction signatures using the Cox regression model. Our results provided insights into the role of OIP5 in tumor immunity and revealed that OIP5 may be a potential immunotherapeutic target for ccRCC. Designated immune signature is a promising prognostic biomarker in ccRCC.
Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency
Authors: Chan Samantha , Godsell Jack , Horton Miles , Farchione Anthony , Howson Lauren J. , Margetts Mai , Jin Celina , Chatelier Josh , Yong Michelle , Sasadeusz Joseph , Douglass Jo A. , Slade Charlotte A. , Bryant Vanessa L.
Published: February 2022

Background

Common Variable Immunodeficiency (CVID) is classified as a ‘Predominantly Antibody Deficiency’ (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with cytomegalovirus (CMV) infection, a hallmark of ‘combined immunodeficiency’. CMV infection also has the potential to drive immune dysregulation contributing to significant morbidity and mortality in CVID. We aim to determine the extent of cellular immune dysfunction in CVID patients, and whether this correlates with CMV infection status.

Methods

We conducted a single-center retrospective cohort study of individuals with CVID at the Royal Melbourne Hospital, and identified patients with and without CMV disease or viraemia. We then isolated T-cells from patient and healthy donor blood samples and examined T-cell proliferation and function.

Results

Six patients (7.6%, 6/79) had either CMV disease (pneumonitis or gastrointestinal disease), or symptomatic CMV viraemia. A high mortality rate in the cohort of patients with CVID and CMV disease was observed, with 4 deaths in the period of analysis (66.6%, 4/6). Individuals with CMV infection showed reduced T-cell division in response to T-cell receptor (TCR) stimulation when compared with CMV-negative patients.

Discussion

This study demonstrates the morbidity and mortality associated with CMV in CVID, and highlights the need for focused interventions for patients with CVID at risk of CMV disease.
Proteus mirabilis Vesicles Induce Mitochondrial Apoptosis by Regulating miR96-5p/Abca1 to Inhibit Osteoclastogenesis and Bone Loss
Authors: Wang Tingting , Mo Lixia , Ou Jiaxin , Fang Qinghua , Wu Huimei , Wu Yuzhe , Nandakumar Kutty Selva
Published: February 2022

Bone loss due to an increased osteoclast activity is common in osteoporosis and rheumatoid arthritis. For the first time, we observed an inhibition of osteoclast formation and bone resorption by outer-membrane vesicles (OMVs) from a Gram-negative, pathogenic bacterium, Proteus mirabilis (P.M). Gene ontogeny and KEGG enrichment analyses of miRNA and mRNA sequencing data demonstrated a significant effect of P.M OMVs on mitochondrial functions and apoptotic pathways. OMVs induced mitochondrial dysfunction through an increased level of intracellular ROS, collapse of mitochondrial membrane potential (ΔΨm), and modulation of Bax, Bcl-2, caspase-3, and cytochrome c expression. In addition, P.M OMVs strongly inhibited miR-96-5p expression, which caused an upregulation of ATP binding cassette subfamily A member 1 (Abca1) in osteoclasts leading to an increased level of mitochondria-dependent apoptosis. Moreover, treatment with P.M but not Escherichia coli OMVs attenuated bone loss in experimental osteoporosis and collagen-induced arthritis. Collectively, we demonstrated osteoprotective functions of OMVs from Proteus mirabilis, which downregulated miR-96-5p causing an increased Abca1 expression and mitochondria-dependent apoptosis.
A First for Human Vaccinology: GMP Compliant Radiation Attenuation of Plasmodium falciparum Sporozoites for Production of a Vaccine Against Malaria
Authors: James Eric R. , Matheny Steve , Overby James , Sim B. Kim Lee , Eappen Abraham G. , Li Tao , Li Ming Lin , Richie Thomas L. , Chakravarty Sumana , Gunasekera Anusha , Murshedkar Tooba , Billingsley Peter F. , Hoffman Stephen L.
Published: February 2022

Ionizing radiation (UV, X-ray and ɣ) administered at an appropriate dose to pathogenic organisms can prevent replication while preserving metabolic activity. We have established the GMP process for attenuation by ionizing radiation of the Plasmodium falciparum (Pf) sporozoites (SPZ) in Sanaria® PfSPZ Vaccine, a protective vaccine against malaria. Mosquitoes raised and infected aseptically with Pf were transferred into infected mosquito transport containers (IMTC) and ɣ-irradiated using a 60Co source. PfSPZ were then extracted, purified, vialed, and cryopreserved. To establish the appropriate radiation conditions, the irradiation field inside the IMTCs was mapped using radiochromic film and alanine transfer dosimeters. Dosimeters were irradiated for times calculated to provide 120-170 Gy at the minimum dose location inside the IMTC and regression analysis was used to determine the time required to achieve a lower 95% confidence interval for 150 Gy. A formula incorporating the half-life of 60Co was then used to construct tables of irradiation times for each calendar day. From the mapping studies, formulae were derived to estimate the minimum and maximum doses of irradiation received inside the IMTC from a reference dosimeter mounted on the outside wall. For PfSPZ Vaccine manufacture a dose of 150 Gy was targeted for each irradiation event, a dose known to completely attenuate PfSPZ. The reference dosimeters were processed by the National Institute of Standards and Technology. There have been 587 irradiation events to produce PfSPZ Vaccine during 13 years which generated multiple lots released for pre-clinical studies and clinical trials. The estimated doses at the minimum dose location (mean 154.3 ± 1.77 Gy; range 150.0-159.3 Gy), and maximum dose location (mean 166.3 ± 3.65 Gy, range 155.7 to 175.3 Gy), in IMTCs were normally distributed. Overall dose uniformity was 1.078 ± 0.012. There was no siginifcant change in measured dose over 13 years. As of January 2022, 21 clinical trials of PfSPZ Vaccine have been conducted, with 1,740 volunteers aged 5 months to 61 years receiving 5,648 doses of PfSPZ Vaccine totalling >5.3 billion PfSPZ administered. There have been no breakthrough infections, confirming the consistency and robustness of the radiation attenuation process.
Case Series: Pediatric Human T-Lymphotropic Virus Type 1 and Its Clinical Expression
Authors: James Ingara Cristina , Mejía-Mertel Juliana , Gil Artunduaga Monica Alexandra , Rojas-Hernández Juan Pablo
Published: February 2022

Purpose

Human T-lymphotropic Virus type 1 (HTLV-1) was the first retrovirus to be identified and associated with oncogenic activity. It is estimated that approximately 10–20 million people in the world are infected with it. The clinical manifestations most commonly associated with HTLV-1 infection include T-cell leukemia/lymphoma and myelopathy associated to HTLV-1 infection. The purpose of this study is to describe clinical and demographic characteristics in pediatric patients with HTLV-1 infection.

Methodology and Patients

Ambispective case series analysis, with collection of medical records and subsequent description of demographic data (sex, origin, age) and clinical characteristics in 16 patients with HTLV-1 infection were collected. Twelve of these patients were part of an initially reported cohort and four were recruited later in the study. The patients were collected between January 2017 and July 2021 in a pediatric institution in Cali, in a reference hospital in the southwest region of Colombia.

Results

Thirteen of a total of sixteen patients came from the Colombian Pacific coast, where nine were with significant nutritional deficiencies. Seven showed dermatological compromise. Eight patients presented images compatible with inflammation and chronic lung injury, and six of the eight patients were with opportunistic infections. Coinfection with other microorganisms was also observed where one case presented with meningeal tuberculosis, another patient presented with simultaneous infections, namely, malaria, leptospirosis and toxoplasmosis, and a third patient presented intestinal parasitosis and soft tissue infection by Streptococcus pyogenes. Three patients had concomitant autoimmune diseases and a fourth patient was highly suspicious of having polymyositis.

Conclusions

The different clinical findings with simultaneous HTLV-1 infection broaden the panorama to suspect infection by this virus. More studies are required to achieve a direct association between structural lung disease, autoimmune diseases, immunodeficiency and HTLV-1 infection. This study aims to raise interest and awareness of an ancient but neglected disease.
Effect of Al3Zr Dispersoid on Microstructure and Mechanical Properties of Al-Cu-Li Alloy During Composite Spinning-Extrusion Forming
Authors: Zhang Jin , Zeng Huaqiang , Wang Cheng , Tang Zibo
Published: February 2022

The regulation of blank microstructure is the key to manufacturing high-quality ring cylinder by composite spinning - extrusion forming. In this paper, the precipitation morphologies of three Al3Zr dispersions were obtained by changing the heat treatment process, and their effects on the microstructure and mechanical properties of Al-Cu-Li alloy ring cylinder were investigated. The results show that the microstructure and mechanical properties of ring cylinder are affected by the different precipitation distribution of Al3Zr dispersoids in the blank. When the Al3Zr dispersoids precipitated and dispersed, the cracking of ring cylinder was eliminated, the thickness of coarse-grained layer decreases obviously, and the elongation is increased by 33.5%. In the T83 state, the average length of the T1 phase decreased from 100.3 to 77.5 nm, while the tensile strength and yield strength of ring cylinder increased by 16 and 20 MPa, respectively.
The Expansion of Myeloid-Derived Suppressor Cells Correlates With the Severity of Pneumonia in Kidney Transplant Patients
Authors: Peng Bo , Luo Yulin , Zhuang Quan , Li Junhui , Zhang Pengpeng , Yang Min , Zhang Yu , Kong Gangcheng , Cheng Ke , Ming Yingzi
Published: February 2022

Background

Pneumonia is one of the most frequent but serious infectious complications post kidney transplantation. Severe pneumonia induces sustained immunosuppression, but few parameters concerning immune status are used to assess the severity of pneumonia. Myeloid-derived suppressor cells (MDSCs) are induced under infection and have the strong immunosuppressive capacity, but the correlation between MDSCs and pneumonia in kidney transplant recipients (KTRs) is unknown.

Methods

Peripheral blood MDSCs were longitudinally detected in 58 KTRs diagnosed with pneumonia using flow cytometry and in 29 stable KTRs as a control. The effectors of MDSCs were detected in the plasma. Spearman's rank correlation analysis was performed to determine the correlation between MDSCs and the severity of pneumonia as well as lymphopenia.

Results

The frequency of MDSCs and effectors, including arginase-1, S100A8/A9, and S100A12, were significantly increased in the pneumonia group compared with the stable group. CD11b+CD14+HLA-DRlow/−CD15− monocytic-MDSCs (M-MDSCs) were higher in the pneumonia group but showed no significant difference between the severe and non-severe pneumonia subgroups. CD11b+CD14−CD15+ low-density granulocytic-MDSCs (G-MDSCs) were specifically increased in the severe pneumonia subgroup and correlated with the severity of pneumonia as well as lymphopenia. During the study period of 2 weeks, the frequencies of MDSCs and G-MDSCs were persistently increased in the severe pneumonia subgroup.

Conclusions

MDSCs and G-MDSCs were persistently increased in KTRs with pneumonia. G-MDSCs were correlated with the severity of pneumonia and could thus be an indicator concerning immune status for assessing pneumonia severity.
Psychological Distress and Protective Behaviors During the COVID-19 Pandemic Among Different Populations: Hong Kong General Population, Taiwan Healthcare Workers, and Taiwan Outpatients
Authors: Chung Gary Ka-Ki , Strong Carol , Chan Yat-Hang , Chung Roger Yat-Nork , Chen Jung-Sheng , Lin Yi-Hsuan , Huang Ru-Yi , Lin Chung-Ying , Ko Nai-Ying
Published: February 2022

Purpose

The novel coronavirus disease 2019 (COVID-19) caused psychological distress and changed human living styles. However, rare studies have examined the psychological distress and protective behaviors across different populations. Therefore, the present study aimed to assess psychological distress, protective behaviors, and potential predictors of psychological distress and protective behaviors across the Hong Kong general population, Taiwan healthcare workers, and Taiwan outpatients.

Methods

A cross-sectional design was used to recruit participants from Hong Kong and Taiwan. Telephone interviews were carried out for Hong Kong participants (n = 1,067; 30.2% male participants); online surveys were used for Taiwan healthcare workers (n = 500; 8.0% male participants) and Taiwan outpatients (n = 192; 32.8% male participants). All the participants completed questions on psychological distress and protective behaviors. Multiple linear regressions and multivariable logistic regressions were employed to explore the potential predictors of psychological distress and protective behaviors, respectively.

Results

Hong Kong participants had significantly lower levels of psychological distress than Taiwan participants [mean (SD) = 0.16 (0.39) vs. 0.47 (0.59) in healthcare workers and 0.46 (0.65) in outpatients; p < 0.001]. Hong Kong participants (51.7%) and Taiwan outpatients had more people showing fear of COVID-19 (52.0%) than Taiwan healthcare providers (40.8%; p < 0.001). Moreover, Hong Kong participants engaged the most in protective behaviors, followed by Taiwan healthcare providers and Taiwan outpatients (p < 0.001). Moreover, being a female, fear of COVID-19 and worry about personal savings were associated with protective behaviors in general.

Conclusions

Despite the greater COVID-19 severity and fear of COVID-19 in Hong Kong, the general population in Hong Kong experienced less psychosocial distress with higher compliance to protective behaviors than the other groups in Taiwan.
Actinic Cheilitis — From Risk Factors to Therapy
Authors: Vasilovici Alina , Ungureanu Loredana , Grigore Lavinia , Cojocaru Elena , Şenilă Simona
Published: February 2022

Actinic cheilitis or solar cheilosis is considered a precursor of malignancy or even an in situ squamous cell carcinoma (SCC) of the lip, located most frequently on the lower lip. Actinic cheilitis (AC) has a higher likelihood of developing into invasive SCC of the lip, which is one of the deadliest non-melanoma skin cancers. Risk factors include chronic UV exposure, increasing age, male gender, fair phototypes, chronic scarring, immunosuppressive therapy, and tobacco use. From a clinical point of view, AC is characterized by dryness, scaling, atrophy, indistinct borders, and erosions. Ulceration and the appearance of a nodule often suggest the progression to invasive SCC. Dermoscopic examination reveals white structureless areas, scales, erosions, and white halos of the vermilion. Reflectance confocal microscopy shows disruption of the stratum corneum, parakeratosis, an atypical honeycomb pattern, solar elastosis, and dilated and tortuous blood vessels with increased blood flow. The rate of malignant transformation ranges from 10 to 30% and early diagnoses and treatment are essential in preventing the development of invasive SCC. Optimal treatment has not been established yet, but invasive and topical treatments can be tried. The present paper aims to review the existing data regarding epidemiology, risk factors, clinical picture, non-invasive imaging, diagnosis, and therapy in AC.