bluuebunny/crossref_metadata_2025 huggingface dataset:
The Andronowski Skeletal Collection for Histological Research: A Modern Anatomical Contribution
Authors: Andronowski Janna M. , Taylor Joshua T.
Published: February 2022

The Andronowski Skeletal Collection for Histological Research (ASCHR) comprises the fastest-growing documented modern human skeletal collection in the world developed specifically for histological and imaging research. Initiated in 2017 by Dr. Janna M. Andronowski, the ASCHR provides a resource for the study of skeletal microarchitectural variability with advancing age and between the sexes. The primary objective is to use this unique skeletal archive for histological and imaging research, with the goal of furthering knowledge of human bone biology. Bone procurement has focused on two sites commonly used in histological age-at-death estimation in anthropology: the mid-shaft sixth rib and femoral mid-shaft. The ASCHR consists of over 1200 bone samples from 621 individuals and thousands of imaging files, with age-at-death ranging from 15–105 years. Additional information collected about ASCHR donors includes occupational history; alcohol, tobacco, and drug use history; a health questionnaire; and cause and manner of death. The ASCHR offers a novel opportunity to devise regression formulae for histological age-at-death estimation and answer questions concerning age-related microarchitectural changes and biomechanical processes. It further serves as a skeletal reference database for researchers from various disciplines, including medicine, anthropology, and the biological sciences. Here, we describe the background of the collection, ethical considerations, bone procurement processes, demographic composition, and existing imaging and histological data available to researchers. Our primary aims are to (1) introduce the scientific community to ASCHR, (2) present descriptive and demographic information regarding the collection, and (3) encourage collaboration among national and international researchers interested in human skeletal biology.
Exome Evaluation of Autism-Associated Genes in Amazon American Populations
Authors: da Costa Giovana E. , Fernandes Giordane L. , Rodrigues Juliana C. G. , da V. B. Leal Diana F. , Pastana Lucas F. , Pereira Esdras E. B. , Assumpção Paulo P. , Burbano Rommel M. R. , dos Santos Sidney E. B. , Guerreiro João F. , Fernandes Marianne R. , dos Santos Ney P. C.
Published: February 2022

Autism spectrum disorder is a neurodevelopmental disorder, affecting one in 160 children worldwide. The causes of autism are still poorly understood, but research shows the relevance of genetic factors in its pathophysiology, including the CHD8, SCN2A, FOXP1 and SYNGAP1 genes. Information about the genetic influence on various diseases, including autism, in the Amerindian population from Amazon, is still scarce. We investigated 35 variants of the CHD8, SCN2A, FOXP1, and SYNGAP1 gene in Amazonian Amerindians in comparison with publicly available population frequencies from the 1000 Genomes Project database. Our study identified 16 variants in the Amerindian population of the Amazon with frequencies significantly different from the other populations. Among them, the SCN2A (rs17183814, rs75109281, and rs150453735), FOXP1 (rs56850311 and rs939845), and SYNGAP1 (rs9394145 and rs115441992) variants presented higher frequency than all other populations analyzed. In addition, nine variants were found with lower frequency among the Amerindians: CHD8 (rs35057134 and rs10467770), SCN2A (rs3769951, rs2304014, rs1838846, and rs7593568), FOXP1 (rs112773801 and rs56850311), and SYNGAP1 (rs453590). These data show the unique genetic profile of the indigenous population of the Brazilian Amazon. Knowledge of these variants can help to understand the pathophysiology and diagnosis of autism among Amerindians, Brazilians, and in admixed populations that have contributions from this ethnic group.
An Identification and Characterization of the Axolotl (Ambystoma mexicanum, Amex) Telomerase Reverse Transcriptase (Amex TERT)
Authors: Springhetti Sina , Bucan Vesna , Liebsch Christina , Lazaridis Andrea , Vogt Peter Maria , Strauß Sarah
Published: February 2022

The Mexican axolotl is one of the few vertebrates that is able to replace its lost body parts during lifespan. Due to its remarkable regenerative abilities, the axolotl emerged as a model organism especially for limb regeneration. Telomeres and the telomerase enzyme are crucial for regeneration and protection against aging processes and degenerating diseases. Despite its relevance for regeneration, the axolotl telomerase and telomere length have not yet been investigated. Therefore, in the present paper, we reveal the sequence of the axolotl telomerase reverse transcriptase gene (Tert) and protein (TERT). Multiple sequence alignment (MSA) showed the known conserved RT- and TERT-specific motifs and residues found in other TERTs. In addition, we establish methods to determine the Tert expression (RT-PCR) and telomerase activity (Q-TRAP) of adult axolotl and blastema tissues. We found that both differentiated forelimb tissue and regenerating blastema tissue express Tert and show telomerase activity. Furthermore, blastema tissue appears to exhibit a higher Tert expression and telomerase activity. The presence of active telomerase in adult somatic cells is a decisive difference to somatic cells of non-regenerating vertebrates, such as humans. These findings indicate that telomere biology may play a key role in the regenerative abilities of cells.
Was the Last Bacterial Common Ancestor a Monoderm after All?
Authors: Léonard Raphaël R. , Sauvage Eric , Lupo Valérian , Perrin Amandine , Sirjacobs Damien , Charlier Paulette , Kerff Frédéric , Baurain Denis
Published: February 2022

The very nature of the last bacterial common ancestor (LBCA), in particular the characteristics of its cell wall, is a critical issue to understand the evolution of life on earth. Although knowledge of the relationships between bacterial phyla has made progress with the advent of phylogenomics, many questions remain, including on the appearance or disappearance of the outer membrane of diderm bacteria (also called Gram-negative bacteria). The phylogenetic transition between monoderm (Gram-positive bacteria) and diderm bacteria, and the associated peptidoglycan expansion or reduction, requires clarification. Herein, using a phylogenomic tree of cultivated and characterized bacteria as an evolutionary framework and a literature review of their cell-wall characteristics, we used Bayesian ancestral state reconstruction to infer the cell-wall architecture of the LBCA. With the same phylogenomic tree, we further revisited the evolution of the division and cell-wall synthesis (dcw) gene cluster using homology- and model-based methods. Finally, extensive similarity searches were carried out to determine the phylogenetic distribution of the genes involved with the biosynthesis of the outer membrane in diderm bacteria. Quite unexpectedly, our analyses suggest that all cultivated and characterized bacteria might have evolved from a common ancestor with a monoderm cell-wall architecture. If true, this would indicate that the appearance of the outer membrane was not a unique event and that selective forces have led to the repeated adoption of such an architecture. Due to the lack of phenotypic information, our methodology cannot be applied to all extant bacteria. Consequently, our conclusion might change once enough information is made available to allow the use of an even more diverse organism selection.
A Primer for Single-Cell Sequencing in Non-Model Organisms
Authors: Alfieri James M. , Wang Guosong , Jonika Michelle M. , Gill Clare A. , Blackmon Heath , Athrey Giridhar N.
Published: February 2022

Single-cell sequencing technologies have led to a revolution in our knowledge of the diversity of cell types, connections between biological levels of organization, and relationships between genotype and phenotype. These advances have mainly come from using model organisms; however, using single-cell sequencing in non-model organisms could enable investigations of questions inaccessible with typical model organisms. This primer describes a general workflow for single-cell sequencing studies and considerations for using non-model organisms (limited to multicellular animals). Importantly, single-cell sequencing, when further applied in non-model organisms, will allow for a deeper understanding of the mechanisms between genotype and phenotype and the basis for biological variation.
Biostratigraphy and Paleoenvironmental Reconstruction at the Gebel Nezzazat (Central Sinai, Egypt): A Paleocene Record for the Southern Tethys
Authors: Kasem Atef M. , Faris Mahmoud , Jovane Luigi , Ads Taysir Abdelhamid , Frontalini Fabrizio , Zaky Amr S.
Published: February 2022

The variations in assemblages of calcareous nannofossils are tracked in the Dakhla and Tarawan Formations exposed at Gebel Nezzazat (central Sinai, Egypt). Five calcareous nannofossil biozones, namely NP2/3, NP4, NP5, NP6, and NP7/8 are identified. A distinct marker bed related to the Latest Danian Event (LDE) occurs within the Dakhla Fm. The earliest representative of fasciculiths, Lithoptychius schmitzii, first occurs just below the LDE distinct bed and is followed by the Los of Diantholitha alata, D. mariposa, L. varolii, L. felis, and L. collaris. The abundance of calcareous nannofossils drops within the LDE distinctive bed. The base of Selandian Stage is here approximated at the base of Zone NP5 in concurrence with a sudden drop in the abundance of calcareous nannofossils. No considerable lithological changes are noted across this transition. The absence of subsequent occurrences of L. ulii, L. janii, L. billii, and L. stegostus suggest inconsistent lowest occurrences (Los) of these taxa, insufficient sampling resolution, and/or a hiatus. The base of Thanetian is approximated with the base of Zone NP7/8 in the topmost of Dakhla Fm. No considerable changes in calcareous nannofossil assemblages are associated in correspondence to this transition except the LO of D. mohleri, lowest continuous occurrence (LctO) of Bomolithus megastypus, and the increase in abundance of Heliolithus kleinpellii as well as a sudden drop in abundance within Zone NP7/8. The variations in calcareous nannofossil assemblages at Gebel Nezzazat suggest prevailing warm-water and oligotrophic conditions during the Paleocene and particularly along the Danian Stage that are interrupted by minor fluctuations in paleoclimatic conditions. In particular, the Danian–Selandian transition marks a decrease in warm and oligotrophic conditions that persisted along the Selandian Stage. The Selandian–Thanetian transition shows an increase of warm and oligotrophic conditions prevailed in the Thanetian record. The sudden decrease in abundance of calcareous nannofossils in both the Selandian and Thanetian is likely resulted from an increase in dissolution of carbonates rather than variations in the paleotemperature and/or paleofertility.
Volunteered Geographical Information and Recreational Uses within Metropolitan and Rural Contexts
Authors: Santos Teresa , Nogueira Mendes Ricardo , Farías-Torbidoni Estela I. , Julião Rui Pedro , Pereira da Silva Carlos
Published: February 2022

Data obtained through Volunteered Geographical Information (VGI) have gradually been used to monitor and support planning mainly in urban contexts. Regarding recreational activities in peri-urban green and natural areas, VGI has been used to map, measure use intensity, profile users, and evaluate their preferences and motivations. Given their extensive use, it is now worthwhile to assess the value of VGI data to (1) compare recreational uses, profile users and map recreational activities in different contexts (metropolitan vs. rural areas), and (2) evaluate outdoor and adventure tourist products such as Grand Routes (GR). Data from former GPSies (AllTrails nowadays), one of the most popular web-share services, were used to assess recreational uses in Lisbon Metropolitan Area (LMA) and southwest Portugal (SWPT). A set of 22,031 tracks of “on foot” and “on wheels” activities, submitted by 3297 national and foreign users, covering 12 years, was analysed within a GIS modelling environment. Results indicate that, although there are many more submissions in the LMA, the influence of foreigners in the SWPT is higher (11% vs. 19%). The existing GR in SWPT concentrates the foreign use for hiking (71% of foreign vs. 28% of national users), demonstrating its attractiveness. For the favourite activity in both areas—Mountain biking—results show a higher spatial dispersion, yet part of the activity in SWPT still conforms to the GR (16% of foreign and 20% of national use). This study proves other applications for VGI, showing its usefulness for assessing recreational uses in both metropolitan and rural areas. Spatial knowledge about recreational uses is a valuable tool to evaluate and monitor such activities, and to know what users like to do, and where, and is also useful information when designing recreational products considering their tourist potential, thus adding value to these offers.
Assignment of a Synthetic Population for Activity-Based Modeling Employing Publicly Available Data
Authors: Agriesti Serio , Roncoli Claudio , Nahmias-Biran Bat-hen
Published: February 2022

Agent-based modeling has the potential to deal with the ever-growing complexity of transport systems, including future disrupting mobility technologies and services, such as automated driving, Mobility as a Service, and micromobility. Although different software dedicated to the simulation of disaggregate travel demand have emerged, the amount of needed input data, in particular the characteristics of a synthetic population, is large and not commonly available, due to legit privacy concerns. In this paper, a methodology to spatially assign a synthetic population by exploiting only publicly available aggregate data is proposed, providing a systematic approach for an efficient treatment of the data needed for activity-based demand generation. The assignment of workplaces exploits aggregate statistics for economic activities and land use classifications to properly frame origins and destination dynamics. The methodology is validated in a case study for the city of Tallinn, Estonia, and the results show that, even with very limited data, the assignment produces reliable results up to a 500 × 500 m resolution, with an error at district level generally around 5%. Both the tools needed for spatial assignment and the resulting dataset are available as open source, so that they may be exploited by fellow researchers.
Lignin Synthesis, Affected by Sucrose in Lotus (Nelumbo nucifera) Seedlings, Was Involved in Regulation of Root Formation in the Arabidopsis thanliana
Authors: Cheng Libao , Zhao Chen , Zhao Minrong , Han Yuyan , Li Shuyan
Published: February 2022

Adventitious roots (ARs) have an unmatched status in plant growth and metabolism due to the degeneration of primary roots in lotuses. In the present study, we sought to assess the effect of sucrose on ARs formation and observed that lignin synthesis was involved in ARs development. We found that the lignification degree of the ARs primordium was weaker in plants treated with 20 g/L sucrose than in 50 g/L sucrose treatment and control plants. The contents of lignin were lower in plants treated with 20 g/L sucrose and higher in plants treated with 50 g/L sucrose. The precursors of monomer lignin, including p-coumaric acid, caffeate, sinapinal aldehyde, and ferulic acid, were lower in the GL50 library than in the GL20 library. Further analysis revealed that the gene expression of these four metabolites had no novel difference in the GL50/GL20 libraries. However, a laccase17 gene (NnLAC17), involved in polymer lignin synthesis, had a higher expression in the GL50 library than in the GL20 library. Therefore, NnLAC17 was cloned and the overexpression of NnLAC17 was found to directly result in a decrease in the root number in transgenic Arabidopsis plants. These findings suggest that lignin synthesis is probably involved in ARs formation in lotus seedlings.
Linking Multi-Omics to Wheat Resistance Types to Fusarium Head Blight to Reveal the Underlying Mechanisms
Authors: Wu Fan , Zhou Yao , Shen Yingying , Sun Zhengxi , Li Lei , Li Tao
Published: February 2022

Fusarium head blight (FHB) caused by Fusarium graminearum is a worldwide disease which has destructive effects on wheat production, resulting in severe yield reduction and quality deterioration, while FHB-infected wheat grains are toxic to people and animals due to accumulation of fungal toxins. Although impressive progress towards understanding host resistance has been achieved, our knowledge of the mechanism underlying host resistance is still quite limited due to the complexity of wheat–pathogen interactions. In recent years, disease epidemics, the resistance germplasms and components, the genetic mechanism of FHB, and disease management and control, etc., have been well reviewed. However, the resistance mechanism of FHB is quite complex with Type I, II to V resistances. In this review, we focus on the potential resistance mechanisms by linking different resistance types to multi-omics and emphasize the pathways or genes that may play significant roles in the different types of resistance. Deciphering the complicated mechanism of FHB resistance types in wheat at the integral levels based on multi-omics may help discover the genes or pathways that are critical for different FHB resistance, which could then be utilized and manipulated to improve FHB resistance in wheat breeding programs by using transgenic approaches, gene editing, or marker assisted selection strategies.
Modification of TiAlV Alloys with Hybrid Layers Containing Metallic Nanoparticles Obtained by the Sol–Gel Method: Surface and Structural Properties
Authors: Ziąbka Magdalena , Matysiak Katarzyna , Walczak Katarzyna , Gajek Marcin , Cholewa-Kowalska Katarzyna
Published: February 2022

The aim of the work was to obtain hybrid coatings containing silver, copper, and zinc nanoparticles on the TiAlV medical alloy via a sol–gel process. The developed layers were designed to bring about a bactericidal and fungicidal effect, as well as for protection against surgical scratches during the implantation of implants used in veterinary medicine. In this work, the authors focused on evaluating the microstructure (SEM + EDS); the structure (XRD, FTIR); and the surface properties, such as wettability, free surface energy, and roughness of layers with various concentrations of metallic nanoparticles (2 and 5 mol %). Our results confirmed that the sol–gel method enables the easy manufacturing of hybrid layers endowed with different porosity values as well as various shapes and sizes of metallic nanoparticles. A higher concentration of nanoparticles was observed on the surface containing 5 mol % of metallic salts. The highest degree of homogeneity was obtained for the layers containing silver nanoparticles. In addition, the silver nanoparticles were round and had the smallest dimensions, even below 20 nm. The FTIR and XRD structural studies confirmed the presence of an organosilicon matrix containing all three types of the metallic particles. We conclude that the higher concentration of nanoparticles influenced the alloy surface parameters.
Knockout of the P2Y6 Receptor Prevents Peri-Infarct Neuronal Loss after Transient, Focal Ischemia in Mouse Brain
Authors: Milde Stefan , Brown Guy C.
Published: February 2022

After stroke, there is a delayed neuronal loss in brain areas surrounding the infarct, which may in part be mediated by microglial phagocytosis of stressed neurons. Microglial phagocytosis of stressed or damaged neurons can be mediated by UDP released from stressed neurons activating the P2Y6 receptor on microglia, inducing microglial phagocytosis of such neurons. We show evidence here from a small trial that the knockout of the P2Y6 receptor, required for microglial phagocytosis of neurons, prevents the delayed neuronal loss after transient, focal brain ischemia induced by endothelin-1 injection in mice. Wild-type mice had neuronal loss and neuronal nuclear material within microglia in peri-infarct areas. P2Y6 receptor knockout mice had no significant neuronal loss in peri-infarct brain areas seven days after brain ischemia. Thus, delayed neuronal loss after stroke may in part be mediated by microglial phagocytosis of stressed neurons, and the P2Y6 receptor is a potential treatment target to prevent peri-infarct neuronal loss.
Embedded Human Periodontal Ligament Stem Cells Spheroids Enhance Cementogenic Differentiation via Plasminogen Activator Inhibitor 1
Authors: Yasunaga Madoka , Ishikawa Hiroyuki , Tamaoki Sachio , Maeda Hidefumi , Ohno Jun
Published: February 2022

Spheroids reproduce the tissue structure that is found in vivo more accurately than classic two-dimensional (2D) monolayer cultures. We cultured human periodontal ligament stem cells (HPLSCs) as spheroids that were embedded in collagen gel to examine whether their cementogenic differentiation could be enhanced by treatment with recombinant human plasminogen activator inhibitor-1 (rhPAI-1). The upregulated expression of cementum protein 1 (CEMP1) and cementum attachment protein (CAP), established cementoblast markers, was observed in the 2D monolayer HPLSCs that were treated with rhPAI-1 for 3 weeks compared with that in the control and osteogenic-induction medium groups. In the embedded HPLSC spheroids, rhPAI-1 treatment induced interplay between the spheroids and collagenous extracellular matrix (ECM), indicating that disaggregated HPLSCs migrated and spread into the surrounding ECM 72 h after three-dimensional (3D) culture. Western blot and immunocytochemistry analyses showed that the CEMP1 expression levels were significantly upregulated in the rhPAI-1-treated embedded HPLSC spheroids compared with all the 2D monolayer HPLSCs groups and the 3D spheroid groups. Therefore, 3D collagen-embedded spheroid culture in combination with rhPAI-1 treatment may be useful for facilitating cementogenic differentiation of HPLSCs.
Data Quality Barriers for Transparency in Public Procurement
Authors: Soylu Ahmet , Corcho Óscar , Elvesæter Brian , Badenes-Olmedo Carlos , Yedro-Martínez Francisco , Kovacic Matej , Posinkovic Matej , Medvešček Mitja , Makgill Ian , Taggart Chris , Simperl Elena , Lech Till C. , Roman Dumitru
Published: February 2022

Governments need to be accountable and transparent for their public spending decisions in order to prevent losses through fraud and corruption as well as to build healthy and sustainable economies. Open data act as a major instrument in this respect by enabling public administrations, service providers, data journalists, transparency activists, and regular citizens to identify fraud or uncompetitive markets through connecting related, heterogeneous, and originally unconnected data sources. To this end, in this article, we present our experience in the case of Slovenia, where we successfully applied a number of anomaly detection techniques over a set of open disparate data sets integrated into a Knowledge Graph, including procurement, company, and spending data, through a linked data-based platform called TheyBuyForYou. We then report a set of guidelines for publishing high quality procurement data for better procurement analytics, since our experience has shown us that there are significant shortcomings in the quality of data being published. This article contributes to enhanced policy making by guiding public administrations at local, regional, and national levels on how to improve the way they publish and use procurement-related data; developing technologies and solutions that buyers in the public and private sectors can use and adapt to become more transparent, make markets more competitive, and reduce waste and fraud; and providing a Knowledge Graph, which is a data resource that is designed to facilitate integration across multiple data silos by showing how it adds context and domain knowledge to machine-learning-based procurement analytics.
Studies on the Volatiles Composition of Stored Sheep Wool, and Attractancy toward Aedes aegypti Mosquitoes
Authors: Tsikolia Maia , Tabanca Nurhayat , Kline Daniel L. , Demirci Betul , Yang Liu , Linthicum Kenneth J. , Bloomquist Jeffrey R. , Bernier Ulrich R.
Published: February 2022

To discover new natural materials for insect management, commercially available stored sheep wool was investigated for attractancy to female adult Aedes aegypti mosquitoes. The volatiles from sheep wool were collected by various techniques of headspace (HS) extractions and hydrodistillation. These extracts were analyzed using gas chromatography–mass spectrometry (GC-MS) and gas chromatography–flame ionization detector (GC-FID) coupled with GC-MS. Fifty-two volatile compounds were detected, many of them known for their mosquito attractant activity. Seven compounds were not previously reported in sheep products. The volatile composition of the extracts varied significantly across collections, depending on the extraction techniques or types of fibers applied. Two types of bioassay were conducted to study attractancy of the sheep wool volatiles to mosquitoes: laboratory bioassays using glass tubes, and semi-field bioassays using large, screened outdoor cages. In bioassays with glass tubes, the sheep wool hydrodistillate and its main component, thialdine, did not show any significant attractant activity against female adult Ae. aegypti mosquitoes. Semi-field bioassays in two large screened outdoor cages, each equipped with a U.S. Centers for Disease Control (CDC) trap and the various bait setups with Vortex apparatus, revealed that vibrating wool improved mosquito catches compared to the setups without wool or with wool but not vibrating. Sheep wool, when vibrated, may release intensively volatile compounds, which could serve as olfactory cues, and play significant role in making the bait attractive to mosquitoes. Sheep wool is a readily available, affordable, and environment-friendly material. It should have the potential to be used as a mosquito management and surveillance component in dynamic bait setups.
Association between Right Ventricular Function and Exercise Capacity in Patients with Chronic Heart Failure
Authors: Ohara Kazumasa , Imamura Teruhiko , Ihori Hiroyuki , Chatani Kenichi , Nonomura Makoto , Kameyama Tomoki , Inoue Hiroshi
Published: February 2022

Background: The association between right ventricular function and exercise capacity in patients with chronic heart failure remains uncertain. Several studies very recently mentioned the association between right ventricular reserve and exercise capacity, whereas the implication of tricuspid annular plane systolic excursion (TAPSE) remains uninvestigated. We aimed to assess the impact of TAPSE on exercise capacity in cardiac rehabilitation candidates. Methods: Data from patients with chronic heart failure who received cardiopulmonary exercise tests and transthoracic echocardiography prior to cardiac rehabilitation were retrospectively collected, and their association was investigated. Results: A total of 169 patients with chronic heart failure (70.3 ± 11.7 years old, 74.6% men) were included. Tertiled tricuspid annular plane systolic excursion significantly stratified anaerobic threshold (10.2 ± 2.2, 11.4 ± 2.2, and 12.2 ± 2.8 mm; p < 0.01) and peak oxygen consumption (15.9 ± 4.5, 18.3 ± 5.3, and 19.8 ± 5.6 mm; p < 0.01). In the multivariate logistic regression analyses, TAPSE was an independent factor associated with anaerobic threshold and peak oxygen consumption (p < 0.05 for both). Conclusions: Right ventricular impairment was associated with reduced exercise capacity in patients with chronic heart failure. Such knowledge would be useful to estimate patients’ exercise capacity and prescribe cardiac rehabilitation. Its longitudinal association and clinical implication need further studies.
Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma
Authors: Exley Mark A. , Garcia Samantha , Zellander Amelia , Zilberberg Jenny , Andrews David W.
Published: February 2022

Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and in combination with potentially synergistic immunotherapeutic and other strategies. Here, we review the current understanding of myeloid cell immunosuppression of anti-tumor responses as well as potential targets, challenges, and developing means to reverse immunosuppression with various therapeutics and their status. Targets include myeloid cell colony stimulating factors (CSFs), insulin-like growth factor 1 (IGF1), several cytokines and chemokines, as well as CD40 activation and COX2 inhibition. Approaches in clinical development include antibodies, antisense RNA-based drugs, cell-based combinations, polarizing cytokines, and utilizing Macs as a platform for Chimeric Antigen Receptors (CAR)-based tumor targeting, like with CAR-T cells. To date, promising clinical results have been reported with several of these approaches.
The Treatment of Aortic Valve Stenosis in Intermediate and Low-Risk Patients—When, How and Where
Authors: Ribichini Flavio L. , Ferrero Valeria
Published: February 2022

Until now, treatment of severe aortic stenosis (AS) is recommended after the disease becomes symptomatic or causes “silent” damages such as myocardial dysfunction [...]
Impaired Lung Function and Lung Cancer Incidence: A Nationwide Population-Based Cohort Study
Authors: Kang Hye Seon , Park Yong-Moon , Ko Seung-Hyun , Kim Seung Hoon , Kim Shin Young , Kim Chi Hong , Han Kyungdo , Kim Sung Kyoung
Published: February 2022

Background: It is unclear whether the presence of minimal lung function impairment is an independent risk factor for the development of lung cancer in general populations. Methods: We conducted a population-based cohort study using nationally representative data from the Korean National Health and Nutrition Examination Survey and the Korean National Health Insurance Service. Results: Of 20,553 participants, 169 were diagnosed with lung cancer during follow-up (median, 6.5 years). Participants with obstructive lung function impairment had increased risk of lung cancer (aHR: 2.51; 95% CI: 1.729–3.629) compared with those with normal lung function. The lower was the quartile or decile of forced expiratory volume in one second (FEV1) or the FEV1/forced vital capacity (FVC) ratio, the significantly higher was the incidence rate of lung cancer (p for trend < 0.0001). With FEV1 values in the lowest quartile (Q4), the incidence of lung cancer was significantly increased regardless of FVC (FEV1 Q4 and FVC values in the higher three quartiles Q1–3: aHR 1.754; 95% CI 1.084–2.847, FEV1 Q4 and FVC Q4: aHR 1.889; 95% CI 1.331–2.681). Conclusion: Our findings suggest that minimal lung function impairment, as expressed by lower FEV1 or FEV1/FVC value, may be associated with increased risk of lung cancer
Update on Suture Techniques in Corneal Transplantation: A Systematic Review
Authors: Pagano Luca , Shah Haider , Al Ibrahim Omar , Gadhvi Kunal A. , Coco Giulia , Lee Jason W. , Kaye Stephen B. , Levis Hannah J. , Hamill Kevin J. , Semeraro Francesco , Romano Vito
Published: February 2022

Effective suturing remains key to achieving successful outcomes in corneal surgery, especially anterior lamellar keratoplasty and full thickness transplantation. Limitations in the technique may result in complications such as wound leak, infection, or high astigmatism post corneal graft. By using a systematic approach, this study reviews articles and conducts content analysis based on update 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria). The aim of this paper is to summarize the state of the art of corneal suturing techniques for every type of corneal transplant and patient age and also their outcomes regarding astigmatism and complications. Future developments for corneal transplantation will be also discussed. This is important because especially the young surgeon must have knowledge of the implications of every suture performed in order to achieve consistent and predictable post-operative outcomes and also be aware of all the possible complications.
Celiac Disease in Juvenile Idiopathic Arthritis and Other Pediatric Rheumatic Disorders
Authors: Poddighe Dimitri , Romano Micol , Dossybayeva Kuanysh , Abdukhakimova Diyora , Galiyeva Dinara , Demirkaya Erkan
Published: February 2022

Celiac Disease (CD) is an immune-mediated and gluten-related disorder whose prevalence is higher in children affected with other autoimmune disorders, including diabetes mellitus type 1, autoimmune thyroiditis, and others. As regards Juvenile Idiopathic Arthritis (JIA) and other pediatric rheumatic disorders, there is no clear recommendation for CD serological screening. In this review, we analyze all the available clinical studies investigating CD among children with JIA (and other rheumatic diseases), in order to provide objective data to better understand the necessity of CD serological screening during the follow-up. Based on the present literature review and analysis, >2.5% patients with JIA were diagnosed with CD; however, the CD prevalence in JIA patients may be even higher (>3–3.5%) due to several study limitations that could have underestimated CD diagnosis to a variable extent. Therefore, serological screening for CD in children affected with JIA could be recommended due to the increased CD prevalence in these patients (compared to the general pediatric population), and because these JIA patients diagnosed with CD were mostly asymptomatic. However, further research is needed to establish a cost-effective approach in terms of CD screening frequency and modalities during the follow-up for JIA patients. Conversely, at the moment, there is no evidence supporting a periodical CD screening in children affected with other rheumatic diseases (including pediatric systemic lupus erythematosus, juvenile dermatomyositis, and systemic sclerosis).
Factors Affecting Long-Term Compliance with Rigid Gas-Permeable Contact Lens Wear in Patients with Keratoconus
Authors: Xue Yu , Zhou Jiaqi , Chen Zhi , Xue Feng , Zeng Li , Qu Xiaomei , Zhou Xingtao
Published: February 2022

The purpose of the study was to investigate the factors affecting long-term compliance with rigid gas-permeable contact lens (RGPCL) wear in patients with keratoconus (KC). A total of 189 patients with KC (374 eyes) were included in the study, and were divided into two groups: the compliant group and the non-compliant group. Corneal topographic measurements, refractive results, and RGPCL parameters were compared between the two groups. A vision-related quality of life questionnaire was completed by all of the patients. The results demonstrated that patients diagnosed with bilateral KC were more compliant with RGPCL wear than patients diagnosed with unilateral KC (p = 0.0167). There were no significant differences between the compliant and non-compliant groups in terms of their corneal topographic measurements, refractive results, RGPCL parameters, or corneal cross-linking surgery history (all p > 0.05). In contrast, KC patients’ subjective experience with RGPCL wear—including visual acuity (p = 0.006), overall satisfaction (p < 0.001), quality of life (p < 0.001), and good adaptation during the short-term (p < 0.001)—had a significant effect on the long-term compliance with RGPCL wear. In conclusion, patients’ subjective experiences, rather than their ocular biometrics, significantly influence their long-term compliance with RGPCL wear.
Efficacy of Intraoperative Vein Graft Storage Solutions in Preserving Endothelial Cell Integrity during Coronary Artery Bypass Surgery
Authors: Toto Francesca , Torre Tiziano , Turchetto Lucia , Lo Cicero Viviana , Soncin Sabrina , Klersy Catherine , Demertzis Stefanos , Ferrari Enrico
Published: February 2022

(1) Introduction: Intraoperative preservation solutions for saphenous vein grafts may influence the endothelial structure and increase the risk of graft failure after coronary surgery. The aim of the study was to compare the efficacy of three solutions in maintaining the endothelial cell integrity of venous segments. (2) Methods: We tested the efficacy of physiological saline solution (PSS), heparinized autologous blood (HAB) and DuraGraft® in preserving the endothelium of vein segments by evaluating the degree of endothelial cell apoptosis. Two incubation times (2 and 4 h from harvesting) were used for each solution. The quantification of apoptotic cells was computed as the intensity nuclei/intensity area ratio. (3) Results: After 2 h of ischemia, the degree of apoptosis decreased progressively across the use of DuraGraft, HAB and PSS (p = 0.004), although only the difference between DuraGraft and PSS yielded a statistical significance (p = 0.002). After 4 h, a similar decrease in apoptosis was shown across the three media; however, statistical significance was not reached. The analysis of the elapsed time (2 or 4 h of incubation) showed that this was a relevant factor in maintaining the endothelial structural integrity independently from the storage solution (test for interaction of media and time p = 0.010). (4) Conclusion: Within 2 h of incubation, endothelial structural integrity depended on the incubating medium. DuraGraft better protected the SVG against ischemic-induced apoptosis when compared to saline solution. Prolonged ischemia was associated with extended endothelium damage and none of the studied solutions protected the vein graft.
Performance of Coronary Angiography in the Detection of Coronary Artery Disease in Patients with Systolic Left Ventricular Dysfunction and No Prior Ischemic Heart Disease
Authors: Peiró Óscar M. , Ferrero Maria , Romeu Alba , Carrasquer Anna , Bonet Gil , Mohandes Mohsen , Pernigotti Alberto , Bardají Alfredo
Published: February 2022

The diagnosis of ischemic cardiomyopathy is not well established. Our objective is to determine predictive variables of coronary disease in unselected patients with ventricular dysfunction. This study is a retrospective cohort study of consecutive patients with left ventricular dysfunction and no known history of ischemic heart disease. We analyse the demographic variables, clinical data, electrocardiogram, and echocardiogram that are associated with the presence of coronary stenosis on coronary angiography. A total of 536 patients with left ventricular dysfunction were studied, with 135 (25.2%) of them having significant coronary lesions. In the multivariate logistic regression analysis, age ≤ 50 years, female gender, and the presence of atrial fibrillation on the electrocardiogram (ECG) were predictors of the absence of coronary lesions. Diabetes, hypercholesterolemia, the existence of Q waves in the ECG, and segmental alterations in contractility in the echocardiogram were predictors of coronary heart disease (C-Statistics 0.771, 95% CI 0.727 to 0.814). The information obtained from the clinical history, the ECG, and the echocardiogram of patients with ventricular dysfunction allows us to select subjects in whom coronary angiography has shown poor performance in diagnosing coronary disease.
Rapid Genetic Diagnosis for Okinawan Patients with Enlarged Vestibular Aqueduct Using Single-Stranded Tag Hybridization Chromatographic Printed-Array Strip
Authors: Ganaha Akira , Hishinuma Eiji , Kaname Tadashi , Hiratsuka Masahiro , Kondo Shunsuke , Tono Tetsuya
Published: February 2022

Both Pendred syndrome (PS) and nonsyndromic hearing loss with an enlarged vestibular aqueduct (EVA) are autosomal recessive disorders caused by SLC26A4 pathogenic variants. The spectrum of SLC26A4 pathogenic variants varies with the ethnic background. Among the patients with EVA in Okinawa, 94% had some combination of NM_000441.2(SLC26A4):c.1707+5G>A and NM_000441.2(SLC26A4):c.2168A>G(p.His723Arg), the two SLC26A4 pathogenic variants that are the most common in this population. We identified these two pathogenic variants using a novel genotyping method that employed an allele-specific polymerase chain reaction (PCR) from a gDNA and single-stranded tag hybridization chromatographic printed-array strip (STH-PAS) in DNA samples obtained from 48 samples in Okinawa, including 34 patients with EVA and 14 carriers of c.1707+5G>A or c.2168A>G. In addition, whole blood and saliva samples were used for analysis in this genotyping method with direct PCR. The results of STH-PAS genotyping were consistent with those obtained using standard Sanger sequencing for all samples. The accuracy of the STH-PAS method is 100% under the optimized conditions. STH-PAS genotyping provided a diagnosis in 30 out of 34 patients (88%) in Okinawan patients with EVA in under 3 h. The turn-around time for STH-PAS genotyping used with direct PCR was 2 h as a result of the omission of the DNA extraction and purification steps. Using information about the ethnic distribution of pathogenic variants in the SLC26A4 gene, STH-PAS genotyping performs a rapid genetic diagnosis that is simple and has a considerably improved efficiency.
Major Pulmonary Resection for Non-Small Cell Lung Carcinoma during the COVID-19 Pandemic—Single Israeli Center Cross-Sectional Study
Authors: Peer Michael , Azzam Sharbel , Kolodii Marina , Abramov Yaacov , Shaylor Ruth , Verenkin Vladimir , Nesher Nachum , Matot Idit
Published: February 2022

Background: The highly contagious COVID-19 has created unprecedented challenges in providing care to patients with resectable non-small cell lung carcinoma (NSCLC). Surgical management now needs to consider the risks of malignant disease progression by delaying surgery, and those of COVID-19 transmission to patients and operating room staff. The goal of our study was to describe our experience in providing both emergent and elective surgical procedures for patients with NSCLC during the COVID-19 pandemic in Israel, and to present our point of view regarding the safety of performing lung cancer surgery. Methods: This observational cross-sectional study included all consecutive patients with NSCLC who operated at Tel Aviv Medical Center, a large university-affiliated hospital, from February 2020 through December 2020, during the COVID-19 pandemic in Israel. The patients’ demographics, COVID-19 preoperative screening results, type and side of surgery, pathology results, morbidity and mortality rates, postoperative complications, including pulmonary complications management, and hospital stay were evaluated. Results: Included in the study were 113 patients, 68 males (60.2%) and 45 females (39.8%), with a median age of 68.2 years (range, 41–89). Of these 113 patients, 83 (73.5%) underwent video-assisted thoracic surgeries (VATS), and 30 (26.5%) underwent thoracotomies. Fifty-five patients (48.7%) were preoperatively screened for COVID-19 and received negative results. Fifty-six postoperative complications were reported in 35 patients (30.9%). A prolonged air leak was detected in 11 patients (9.7%), atrial fibrillation in 11 patients (9.7%), empyema in 5 patients (4.4%), pneumonia in 9 patients (7.9%) and lobar atelectasis in 7 patients (6.2%). Three patients (2.7%) with postoperative pulmonary complications required mechanical ventilation, and two of them (1.6%) underwent tracheostomy. Two patients (1.6%) were postoperatively diagnosed as positive for COVID-19. Conclusions: Our data demonstrate the feasibility and efficacy of implementing precautionary strategies to ensure the safety of lung cancer patients undergoing pulmonary resection during the COVID-19 pandemic. The strategy was equally effective in protecting the surgical staff and healthcare providers, and we recommend performing lung cancer surgery during the pandemic era.
Cryopreservation in a Standard Freezer: −28 °C as Alternative Storage Temperature for Amniotic Membrane Transplantation
Authors: Witt Joana , Grumm Luis , Salla Sabine , Geerling Gerd , Menzel-Severing Johannes
Published: February 2022

Human amniotic membrane (hAM) is usually stored at −80 °C. However, in many regions, cryopreservation at −80 °C is not feasible, making hAM unavailable. Therefore, the possibility of cryopreservation at −28 °C (household freezer) was investigated. hAMs (n = 8) were stored at −80 °C or −28 °C for a mean time of 8.2 months. hAM thickness, epithelial integrity and basement membrane were assessed histologically. The collagen content, concentration of hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF) were determined. Elastic modulus and tensile strength were measured. The mean thickness of hAM stored at −28 °C was 33.1 ± 21.6 µm (range 9.7–74.9); thickness at −80 °C was 30.8 ± 14.7 µm (range 13.1–50.7; p = 0.72). Mean collagen content, epithelial cell number and integrity score showed no significant difference between samples stored at −28 °C or −80 °C. Basement membrane proteins were well preserved in both groups. Mean tensile strength and elastic modulus were not significantly different. Concentration of bFGF at −28 °C was 1063.2 ± 680.3 pg/g (range 369.2–2534.2), and 1312.1 ± 778.2 pg/g (range 496.2–2442.7) at −80 °C (p = 0.11). HGF was 5322.0 ± 2729.3 pg/g (range 603.3–9149.8) at −28 °C, and 11338.5 ± 6121.8 pg/g (range 4143.5 to 19806.7) at −80 °C (p = 0.02). No microbiological contamination was detected in any sample. The cryopreservation of hAM at −28 °C has no overt disadvantages compared to −80 °C; the essential characteristics of hAM are preserved. This temperature could be used in an alternative storage method whenever storage at −80 °C is unavailable.
High Levels of Sedentary Time in Patients with COVID-19 after Hospitalisation
Authors: van Bakel Bram M. A. , van den Heuvel Frederik M. A. , Vos Jacqueline L. , Rotbi Hajar , Bakker Esmée A. , Nijveldt Robin , Thijssen Dick H. J. , Eijsvogels Thijs M. H.
Published: February 2022

Many patients with COVID-19 experience severe and even fatal disease. Survivors may have long-term health consequences, but data on physical activity and sedentary behaviour are scarce. Therefore, we objectively assessed physical activity (PA) patterns among post-hospitalised patients with COVID-19 and explored associations with patient characteristics, disease severity and cardiac dysfunction. We objectively assessed PA, sedentary behaviour and sleep duration for 24 h/day during 8 days at 3-6 months after COVID-19 hospitalisation. PA and sedentary time were compared across pre-defined subgroups based on patient and disease characteristics, cardiac biomarker release during hospitalisation, abnormal transthoracic echocardiogram at 3-6 months post-hospitalisation and persistence of symptoms post-discharge. PA and sedentary behaviour were assessed in 37 patients (60 ± 10 years old; 78% male). Patients spent 4.2 [3.2; 5.3] h/day light-intensity PA and 1.0 [0.8; 1.4] h/day moderate-to-vigorous intensity PA. Time spent sitting was 9.8 [8.7; 11.2] h/day, which was accumulated in 6 [5; 7] prolonged sitting bouts (≥30 min) and 41 [32; 48] short sitting bouts (<30 min). No differences in PA and sedentary behaviour were found across subgroups, but sleep duration was higher in patients with versus without persistent symptoms (9.1 vs. 8.3 h/day, p = 0.02). Taken together, high levels of sedentary time are common at 3–6 months after COVID-19 hospitalisation, whilst PA and sedentary behaviour are not impacted by patient or disease characteristics.