bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of New Defensin Antimicrobial Peptides and Their Expression in Bed Bugs in Response to Bacterial Ingestion and Injection
Authors: Meraj Sanam , Dhari Arshvir Singh , Mohr Emerson , Lowenberger Carl , Gries Gerhard
Published: September 2022

Common bed bugs, Cimex lectularius, can carry, but do not transmit, pathogens to the vertebrate hosts on which they feed. Some components of the innate immune system of bed bugs, such as antimicrobial peptides (AMPs), eliminate the pathogens. Here, we determined the molecular characteristics, structural properties, and phylogenetic relatedness of two new defensins (CL-defensin1 (XP_024085718.1), CL-defensin2 (XP_014240919.1)), and two new defensin isoforms (CL-defensin3a (XP_014240918.1), CL-defensin3b (XP_024083729.1)). The complete amino acid sequences of CL-defensin1, CL-defensin2, CL-defensin3a, and CL-defensin3b are strongly conserved, with only minor differences in their signal and pro-peptide regions. We used a combination of comparative transcriptomics and real-time quantitative PCR to evaluate the expression of these defensins in the midguts and the rest of the body of insects that had been injected with bacteria or had ingested blood containing the Gram-positive (Gr+) bacterium Bacillus subtilis and the Gram-negative (Gr–) bacterium Escherichia coli. We demonstrate, for the first time, sex-specific and immunization mode-specific upregulation of bed bug defensins in response to injection or ingestion of Gr+ or Gr– bacteria. Understanding the components, such as these defensins, of the bed bugs’ innate immune systems in response to pathogens may help unravel why bed bugs do not transmit pathogens to vertebrates.
Association of Common Variants in OLA1 Gene with Preclinical Atherosclerosis
Authors: Lin Ting-Fong , Chou Chao-Liang , Hsieh Chu-Jui , Wu Yih-Jer , Chen Yi-Cheng , Wu Tzu-Wei , Lu Shu-Xin , Juang Yue-Li , Wang Li-Yu
Published: September 2022

Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case–control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima–media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3′-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.
Nitric Oxide Acts as an Inhibitor of Postharvest Senescence in Horticultural Products
Authors: Zhu Yongchao , Du Mei , Jiang Xianping , Huang Miao , Zhao Jin
Published: September 2022

Horticultural products display fast senescence after harvest at ambient temperatures, resulting in decreased quality and shorter shelf life. As a gaseous signal molecule, nitric oxide (NO) has an important physiological effect on plants. Specifically, in the area of NO and its regulation of postharvest senescence, tremendous progress has been made. This review summarizes NO synthesis; the effect of NO in alleviating postharvest senescence; the mechanism of NO-alleviated senescence; and its interactions with other signaling molecules, such as ethylene (ETH), abscisic acid (ABA), melatonin (MT), hydrogen sulfide (H2S), hydrogen gas (H2), hydrogen peroxide (H2O2), and calcium ions (Ca2+). The aim of this review is to provide theoretical references for the application of NO in postharvest senescence in horticultural products.
Role of m6A RNA Methylation in Thyroid Cancer Cell Lines
Authors: Allegri Lorenzo , Baldan Federica , Molteni Elisabetta , Mio Catia , Damante Giuseppe
Published: September 2022

N6-methyladenosine (m6A) is the most abundant internal modification of RNA in eukaryotic cells, and, in recent years, it has gained increasing attention. A good amount of data support the involvement of m6A modification in tumorigenesis, tumor progression, and metastatic dissemination. However, the role of this RNA modification in thyroid cancer still remains poorly investigated. In this study, m6A-related RNA methylation profiles are compared between a normal thyroid cell line and different thyroid cancer cell lines. With this approach, it was possible to identify the different patterns of m6A modification in different thyroid cancer models. Furthermore, by silencing METTL3, which is the main player in the RNA methylation machinery, it was possible to evaluate the impact of m6A modification on gene expression in an anaplastic thyroid cancer model. This experimental approach allowed us to identify DDI2 as a gene specifically controlled by the m6A modification in anaplastic thyroid cancer cell lines. Altogether, these data are a proof of concept that RNA methylation widely occurs in thyroid cancer cell models and open a way forward in the search for new molecular patterns for diagnostic discrimination between benign and malignant lesions.
Axenic Culture of Caenorhabditis elegans Alters Lysosomal/Proteasomal Balance and Increases Neuropeptide Expression
Authors: Cai Huaihan , Wu Ping , Vandemeulebroucke Lieselot , Dhondt Ineke , Rasulova Madina , Vierstraete Andy , Braeckman Bart P.
Published: September 2022

Axenically cultured C. elegans show many characteristic traits of worms subjected to dietary restriction, such as slowed development, reduced fertility, and increased stress resistance. Hence, the term axenic dietary restriction (ADR) is often applied. ADR dramatically extends the worm lifespan compared to other DR regimens such as bacterial dilution. However, the underlying molecular mechanisms still remain unclear. The primary goal of this study is to comprehensively investigate transcriptional alterations that occur when worms are subjected to ADR and to estimate the molecular and physiological changes that may underlie ADR-induced longevity. One of the most enriched clusters of up-regulated genes under ADR conditions is linked to lysosomal activity, while proteasomal genes are significantly down-regulated. The up-regulation of genes specifically involved in amino acid metabolism is likely a response to the high peptide levels found in axenic culture medium. Genes related to the integrity and function of muscles and the extracellular matrix are also up-regulated. Consistent down-regulation of genes involved in DNA replication and repair may reflect the reduced fertility phenotype of ADR worms. Neuropeptide genes are found to be largely up-regulated, suggesting a possible involvement of neuroendocrinal signaling in ADR-induced longevity. In conclusion, axenically cultured worms seem to rely on increased amino acid catabolism, relocate protein breakdown from the cytosol to the lysosomes, and do not invest in DNA maintenance but rather retain muscle integrity and the extracellular matrix. All these changes may be coordinated by peptidergic signaling.
Nanomaterials: A Review about Halloysite Nanotubes, Properties, and Application in the Biological Field
Authors: Biddeci Giuseppa , Spinelli Gaetano , Colomba Paolo , Di Blasi Francesco
Published: September 2022

The use of synthetic materials and the attention towards environmental hazards and toxicity impose the development of green composites with natural origins. Clay is one of the candidates for this approach. Halloysite is a natural clay mineral, a member of the Kaolin group, with characteristic tubular morphology, usually named halloysite nanotubes (HNTs). The different surface chemistry of halloysite allows the selective modification of both the external surface and the inner lumen by supramolecular or covalent interactions. An interesting aspect of HNTs is related to the possibility of introducing different species that can be released more slowly compared to the pristine compound. Due to their unique hollow morphology and large cavity, HNTs can be employed as an optimal natural nanocarrier. This review discusses the structure, properties, and application of HNTs in the biological field, highlighting their high biocompatibility, and analyse the opportunity to use new HNT hybrids as drug carriers and delivery systems.
Nitrate–Nitrite–Nitric Oxide Pathway: A Mechanism of Hypoxia and Anoxia Tolerance in Plants
Authors: Timilsina Arbindra , Dong Wenxu , Hasanuzzaman Mirza , Liu Binbin , Hu Chunsheng
Published: September 2022

Oxygen (O2) is the most crucial substrate for numerous biochemical processes in plants. Its deprivation is a critical factor that affects plant growth and may lead to death if it lasts for a long time. However, various biotic and abiotic factors cause O2 deprivation, leading to hypoxia and anoxia in plant tissues. To survive under hypoxia and/or anoxia, plants deploy various mechanisms such as fermentation paths, reactive oxygen species (ROS), reactive nitrogen species (RNS), antioxidant enzymes, aerenchyma, and adventitious root formation, while nitrate (NO3−), nitrite (NO2−), and nitric oxide (NO) have shown numerous beneficial roles through modulating these mechanisms. Therefore, in this review, we highlight the role of reductive pathways of NO formation which lessen the deleterious effects of oxidative damages and increase the adaptation capacity of plants during hypoxia and anoxia. Meanwhile, the overproduction of NO through reductive pathways during hypoxia and anoxia leads to cellular dysfunction and cell death. Thus, its scavenging or inhibition is equally important for plant survival. As plants are also reported to produce a potent greenhouse gas nitrous oxide (N2O) when supplied with NO3− and NO2−, resembling bacterial denitrification, its role during hypoxia and anoxia tolerance is discussed here. We point out that NO reduction to N2O along with the phytoglobin-NO cycle could be the most important NO-scavenging mechanism that would reduce nitro-oxidative stress, thus enhancing plants’ survival during O2-limited conditions. Hence, understanding the molecular mechanisms involved in reducing NO toxicity would not only provide insight into its role in plant physiology, but also address the uncertainties seen in the global N2O budget.
Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?
Authors: Sala-Jarque Julia , Zimkowska Karolina , Ávila Jesús , Ferrer Isidro , del Río José Antonio
Published: September 2022

Tauopathies are a group of neurodegenerative diseases characterized by the hyperphosphorylation and deposition of tau proteins in the brain. In Alzheimer’s disease, and other related tauopathies, the pattern of tau deposition follows a stereotypical progression between anatomically connected brain regions. Increasing evidence suggests that tau behaves in a “prion-like” manner, and that seeding and spreading of pathological tau drive progressive neurodegeneration. Although several advances have been made in recent years, the exact cellular and molecular mechanisms involved remain largely unknown. Since there are no effective therapies for any tauopathy, there is a growing need for reliable experimental models that would provide us with better knowledge and understanding of their etiology and identify novel molecular targets. In this review, we will summarize the development of cellular models for modeling tau pathology. We will discuss their different applications and contributions to our current understanding of the “prion-like” nature of pathological tau.
High Immobilization Efficiency of Basic Protein within Heparin-Immobilized Calcium Phosphate Nanoparticles
Authors: Nakamura Maki , Bunryo Wakako , Narazaki Aiko , Oyane Ayako
Published: September 2022

Previously, we achieved one-pot fabrication of heparin-immobilized calcium phosphate (CaP) nanoparticles with high dispersibility by a precipitation process in a highly supersaturated reaction solution. In this study, we revealed that the heparin-immobilized CaP nanoparticles have a greater co-immobilizing capacity for basic proteins than for acidic proteins. In this process, heparin acted as not only a particle-dispersing agent but also as an immobilizing agent for basic proteins; it remarkably (approximately three-fold) improved the immobilization efficiency of cytochrome C (a model basic protein) within the CaP nanoparticles. The content of cytochrome C immobilized within the nanoparticles was increased with an increase in cytochrome C concentration in the reaction solution and by aging the nanoparticles. The obtained nanoparticles were dispersed well in water owing to their large negative zeta potentials derived from heparin, irrespective of the content of cytochrome C. Similar results were obtained also for another basic protein, lysozyme, but not for an acidic protein, albumin; the immobilization efficiency of albumin within the nanoparticles was decreased by heparin. These findings provide new insights into the co-immobilization strategy of proteins within heparin-immobilized CaP nanoparticles and will be useful in the design and fabrication of nanocarriers for protein delivery applications.
AtGSTU19 and AtGSTU24 as Moderators of the Response of Arabidopsis thaliana to Turnip mosaic virus
Authors: Otulak-Kozieł Katarzyna , Kozieł Edmund , Horváth Edit , Csiszár Jolán
Published: September 2022

Plants produce glutathione as a response to the intercellular redox state. Glutathione actively participates in the reactive oxygen species (ROS)-dependent signaling pathway, especially under biotic stress conditions. Most of the glutathione S-transferases (GSTs) are induced in cells during the defense response of plants not only through highly specific glutathione-binding abilities but also by participating in the signaling function. The tau class of GSTs has been reported to be induced as a response under stress conditions. Although several studies have focused on the role of the tau class of GSTs in plant–pathogen interactions, knowledge about their contribution to the response to virus inoculation is still inadequate. Therefore, in this study, the response of Atgstu19 and Atgstu24 knockout mutants to mechanical inoculation of Turnip mosaic virus (TuMV) was examined. The systemic infection of TuMV was more dynamically promoted in Atgstu19 mutants than in wild-type (Col-0) plants, suggesting the role of GSTU19 in TuMV resistance. However, Atgstu24 mutants displayed virus limitation and downregulation of the relative expression of TuMV capsid protein, accompanied rarely by TuMV particles only in vacuoles, and ultrastructural analyses of inoculated leaves revealed the lack of virus cytoplasmic inclusions. These findings indicated that Atgstu24 mutants displayed a resistance-like reaction to TuMV, suggesting that GSTU24 may suppress the plant resistance. In addition, these findings confirmed that GSTU1 and GSTU24 are induced and contribute to the susceptible reaction to TuMV in the Atgstu19–TuMV interaction. However, the upregulation of GSTU19 and GSTU13 highly correlated with virus limitation in the resistance-like reaction in the Atgstu24–TuMV interaction. Furthermore, the highly dynamic upregulation of GST and glutathione reductase (GR) activities resulted in significant induction (between 1 and 14 days post inoculation [dpi]) of the total glutathione pool (GSH + GSSG) in response to TuMV, which was accompanied by the distribution of active glutathione in plant cells. On the contrary, in Atgstu19, which is susceptible to TuMV interaction, upregulation of GST and GR activity only up to 7 dpi symptom development was reported, which resulted in the induction of the total glutathione pool between 1 and 3 dpi. These observations indicated that GSTU19 and GSTU24 are important factors in modulating the response to TuMV in Arabidopsis thaliana. Moreover, it was clear that glutathione is an important component of the regulatory network in resistance and susceptible response of A. thaliana to TuMV. These results help achieve a better understanding of the mechanisms regulating the Arabidopsis–TuMV pathosystem.
Growth Hormone (GH) Crosses the Blood–Brain Barrier (BBB) and Induces Neuroprotective Effects in the Embryonic Chicken Cerebellum after a Hypoxic Injury
Authors: Baltazar-Lara Rosario , Zenil Janeth Mora , Carranza Martha , Ávila-Mendoza José , Martínez-Moreno Carlos G. , Arámburo Carlos , Luna Maricela
Published: September 2022

Several motor, sensory, cognitive, and behavioral dysfunctions are associated with neural lesions occurring after a hypoxic injury (HI) in preterm infants. Growth hormone (GH) expression is upregulated in several brain areas when exposed to HI conditions, suggesting actions as a local neurotrophic factor. It is known that GH, either exogenous and/or locally expressed, exerts neuroprotective and regenerative actions in cerebellar neurons in response to HI. However, it is still controversial whether GH can cross the blood–brain barrier (BBB), and if its effects are exerted directly or if they are mediated by other neurotrophic factors. Here, we found that in ovo microinjection of Cy3-labeled chicken GH resulted in a wide distribution of fluorescence within several brain areas in the chicken embryo (choroid plexus, cortex, hypothalamus, periventricular areas, hippocampus, and cerebellum) in both normoxic and hypoxic conditions. In the cerebellum, Cy3-GH and GH receptor (GHR) co-localized in the granular and Purkinje layers and in deep cerebellar nuclei under hypoxic conditions, suggesting direct actions. Histological analysis showed that hypoxia provoked a significant modification in the size and organization of cerebellar layers; however, GH administration restored the width of external granular layer (EGL) and molecular layer (ML) and improved the Purkinje and granular neurons survival. Additionally, GH treatment provoked a significant reduction in apoptosis and lipoperoxidation; decreased the mRNA expression of the inflammatory mediators (TNFα, IL-6, IL-1β, and iNOS); and upregulated the expression of several neurotrophic factors (IGF-1, VEGF, and BDNF). Interestingly, we also found an upregulation of cerebellar GH and GHR mRNA expression, which suggests the existence of an endogenous protective mechanism in response to hypoxia. Overall, the results demonstrate that, in the chicken embryo exposed to hypoxia, GH crosses the BBB and reaches the cerebellum, where it exerts antiapoptotic, antioxidative, anti-inflammatory, neuroprotective, and neuroregenerative actions.
A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population
Authors: Padua-Bracho Alejandra , Velázquez-Aragón José A. , Fragoso-Ontiveros Verónica , Nuñez-Martínez Paulina María , Mejía Aguayo María de la Luz , Sánchez-Contreras Yuliana , Ramirez-Otero Miguel Angel , De la Fuente-Hernández Marcela Angélica , Vidal-Millán Silvia , Wegman-Ostrosky Talia , Pedroza-Torres Abraham , Arriaga-Canon Cristian , Herrera-Montalvo Luis A. , Alvarez-Gómez Rosa Maria
Published: September 2022

Lynch syndrome (LS) is the main hereditary colorectal cancer syndrome. There have been few reports regarding the clinical and molecular characteristics of LS patients in Latin America; this is particularly true in the Mexican population, where no information is available. The present study aims to describe the clinical and molecular spectrum of variants in a cohort of patients diagnosed with LS in Mexico. We present a retrospective analysis of 412 patients with suspected LS, whose main site of cancer diagnosis was the colon (58.25%), followed by the endometrium (18.93%). Next-generation sequencing analysis, with an extensive multigene panel, showed that 27.1% (112/414) had a variant in one of the genes of the mismatch repair pathway (MMR); 30.4% (126/414) had a variant in non-MMR genes such as CHEK2, APC, MUTYH, BRCA1, and BRCA2; and 42.5% (176/414) had no genetic variants. Most of the variants were found in MLH1. Pathogenic variants (PVs) in MMR genes were identified in 65.7% (96/146) of the total PVs, and 34.24% (45/146) were in non-MMR genes. Molecular and clinical characterization of patients with LS in specific populations allowed personalized follow-up, with the option for targeted treatment with immune checkpoint inhibitors and the development of public health policies. Moreover, such characterization allows for family cascade testing and consequent prevention strategies.
Neutron-Enhanced Information on the Laboratory Characterization of Ancient Egyptian Leathers: Hydration and Preservation Status
Authors: Romanelli Giovanni , Andreani Carla , Ferraris Enrico , Greco Christian , Ikram Salima , Licoccia Silvia , Paladini Giuseppe , Parker Stewart F. , Preziosi Enrico , Senesi Roberto , Skinner Lucy , Veldmeijer André J. , Venuti Valentina , Turina Valentina
Published: September 2022

The Museo Egizio’s collection contains 200 precious and unique leather artifacts belonging to different historical periods. The materials used during the tanning and curing procedures affect the chemical and elemental composition of the surface of the samples as well as their preservation status, specifically through the hydration level within the bulk. Here we provide an experimental characterization of a series of samples from Museo Egizio that document an extensive denaturation phenomenon (gelatinization), by combining non-destructive techniques including surface probes (X-ray fluorescence, Raman scattering, and scanning electron microscopy enhanced by X-ray energy spectroscopy) and neutron-based bulk techniques (inelastic and deep-inelastic neutron scattering). Results show partial dehydration of the samples in the bulk, affecting the morphology of their surface, the presence of potassium alum, and iron oxides, as well as phosphates and hydroxides related to the tanning and curing procedures. Finally, we briefly discuss the need for a versatile and adaptable software package that is capable of combining quantitative analyses with complementary techniques including morphological, elemental, and chemical composition.
Characterization of the Complete Mitochondrial Genome of Eight Diurnal Hawkmoths (Lepidoptera: Sphingidae): New Insights into the Origin and Evolution of Diurnalism in Sphingids
Authors: Huang Yi-Xin , Xing Zhi-Ping , Zhang Hao , Xu Zhen-Bang , Tao Li-Long , Hu Hao-Yuan , Kitching Ian J. , Wang Xu
Published: September 2022

In this study, the mitochondrial genomes of 22 species from three subfamilies in the Sphingidae were sequenced, assembled, and annotated. Eight diurnal hawkmoths were included, of which six were newly sequenced (Hemaris radians, Macroglossum bombylans, M. fritzei, M. pyrrhosticta, Neogurelca himachala, and Sataspes xylocoparis) and two were previously published (Cephonodes hylas and Macroglossum stellatarum). The mitochondrial genomes of these eight diurnal hawkmoths were comparatively analyzed in terms of sequence length, nucleotide composition, relative synonymous codon usage, non-synonymous/synonymous substitution ratio, gene spacing, and repeat sequences. The mitogenomes of the eight species, ranging in length from 15,201 to 15,461 bp, encode the complete set of 37 genes usually found in animal mitogenomes. The base composition of the mitochondrial genomes showed A+T bias. The most commonly used codons were UUA (Leu), AUU (Ile), UUU (Phe), AUA (Met), and AAU (Asn), whereas GCG (Ala) and CCG (Pro) were rarely used. A phylogenetic tree of Sphingidae was constructed based on both maximum likelihood and Bayesian methods. We verified the monophyly of the four current subfamilies of Sphingidae, all of which had high support. In addition, we performed divergence time estimation and ancestral character reconstruction analyses. Diurnal behavior in hawkmoths originated 29.19 million years ago (Mya). It may have been influenced by the combination of herbaceous flourishing, which occurred 26–28 Mya, the uplift of the Tibetan Plateau, and the large-scale evolution of bats in the Oligocene to Pre-Miocene. Moreover, diurnalism in hawkmoths had multiple independent origins in Sphingidae.
Feeding Preferences and Responses of Monochamus saltuarius to Volatile Components of Host Pine Trees
Authors: Wang Jue , Zhang Sufang , Zheng Yanan
Published: September 2022

Monochamus saltuarius is a vector of Bursaphelenchus xylophilus and has caused massive mortality in pine trees in Japan, South Korea, and the middle temperate zone of China. In this study, the feeding preferences of M. saltuarius to four common host pine species in the middle temperate zone of China were investigated in a laboratory. The volatiles of the four host pine species were sampled and analyzed by gas chromatography and mass spectrometry. The responses of M. saltuarius to host pine tree volatiles were measured using a four-arm olfactometer. The results showed that: (1) the preference of M. saltuarius for Pine tabulaeformis was significantly higher than the other ones. (2) The composition and content of the volatiles of the four tested host pine twigs were different, and the relative content of α-pinene was the highest. (3) M. saltuarius was highly sensitive to α-pinene, β-pinene, limonene, and 3-carene, and the attracting effect was enhanced by the mixture of volatile components. This study provides a reference for the development and application of attractants for M. saltuarius. Our results would be helpful in controlling M. saltuarius and pine wilt disease.
Insights into the Antennal Characteristics and Olfactory Strategy of the Endangered Rhino Stomach Bot Fly Gyrostigma rhinocerontis (Diptera: Oestridae)
Authors: Xu Wentian , Li Xinyu , Wang Qike , Zhang Chenglin , Yang Minghai , Zhou Tongshan , Li Kai , Zhang Dong
Published: September 2022

Gyrostigma rhinocerontis (Diptera: Oestridae) is a rare obligate intestinal parasite of both white and black rhinoceroses, which can induce severe myiasis, cause secondary infection, and lead to enormous economic and scientific loss. Antennae are the main sensory organs of G. rhinocerontis, which may have evolved a series of specialized adaptive structures to facilitate the exploitation of their hosts. Here, we thoroughly examine the antennae of G. rhinocerontis via light and scanning electron microscopy. Only microtrichia and chaetic sensilla were observed on the scape and pedicel, and the latter is enlarged, half-enveloping the postpedicel. Four types of sensilla (trichoid sensilla, basiconic sensilla, coeloconic sensilla, and clavate sensilla) and sensory pits are detected on the postpedicel. A set of coeloconic sensilla and a chaetic sensillum are located on the arista. Distribution, type, size, and ultrastructure of antennal sensilla are presented. The antennae of G. rhinocerontis are the largest among Oestridae species, with the most sensilla and the most sensory pits. These antennal characteristics could be correlated to their adaptation for more sensitive and accurate olfactory organs, used to locate their rare and endangered hosts. Accordingly, this morphological evidence supports that the host is an important driving factor in the diversity of antennal morphology in the bot flies.
APOL4, a Novel Immune-Related Prognostic Biomarker for Glioma
Authors: Zhu Hua , Hu Xinyao , Feng Shi , Li Yuntao , Zhang Yonggang , Qiu Sheng , Chen Ran , Ye Yingze , Gu Lijuan , Jian Zhihong , Xu Ximing , Xiong Xiaoxing
Published: September 2022

Glioma is the common, most aggressive and poorest prognostic tumor type in the brain. More and more biomarkers associated with glioma treatment, prognosis, and immunity are being discovered. Here, we aimed to explore the underlying biological functions and prognostic predictive value of Apolipoprotein L4 (APOL4) in glioma. We downloaded the expression data of APOL4 and clinical information from several databases and used R software for preprocessing. The clinical significance of APOL4 in a glioma outcome was explored by the Cox regression analysis and Kaplan–Meier survival analysis. In addition, immune infiltrates and microenvironmental indicators were assessed by CIBERSORT and TIMER. GO and KEGG analyses were used to analyze the potential functions of APOL4 in gliomas. APOL4 expression was increased in glioma specimens compared to normal tissues and correlated dramatically with the WHO grade. A survival analysis showed a shorter overall survival (OS) in glioma patients with APOL4 overexpression, and a Cox regression analysis showed that APOL4 was an independent prognostic factor for the OS of glioma patients. GSEA, GO, and KEGG enrichment analyses showed remarkable enrichment in immune-related pathways. APOL4 expression was positively correlated with immune infiltration (including DC cells, neutrophils, CD8+ T cells, B cells, macrophages, CD4+ T cells, etc.) and microenvironmental parameters (including immune, stromal, and ESTIMATE scores) in gliomas. Glioma patients with a higher expression of APOL4 may be more sensitive to immune checkpoint inhibitors (ICI). In conclusion, these findings suggest that APOL4 is associated with the tumor grade and immune infiltrates; APOL4 may be a new and potential biomarker for therapeutic and prognostic evaluations that may further suggest the therapeutic efficacy of immunotherapy.
The Relationship between Coping and Expressed Emotion in Substance Users
Authors: Wang Grace Y.
Published: September 2022

The involvement of family is an integral part of the recovery process, and the use of adaptive coping strategies has an important implication for treatment outcomes. Little research to date has examined the relationship between coping and family dynamics in substance users, although this may help to unravel the mechanism underlining the increased risk of relapse for individuals from critical family environment. The aim of the present research was to assess the association between the level of expressed emotion (LEE) (i.e., criticism), coping style, and psychological distress (i.e., anxiety, depression) in people with substance use disorder (SUD). Compared to control subjects, persons with SUD reported less use of rational coping and detached coping, and perceived greater criticism and irritability from family. A higher degree of family criticism and lack of emotional support was associated with greater use of emotional and avoidance coping in persons with SUD, while psychological distress was more related to rational and detached coping. The present study reveals the unique connection between family relationships, coping and psychological distress, implicating the need to address the influence of family relationships and stress on persons’ coping in SUD treatment.
Laryngeal Cancer Surgery: History and Current Indications of Transoral Laser Microsurgery and Transoral Robotic Surgery
Authors: Hans Stéphane , Baudouin Robin , Circiu Marta P. , Couineau Florent , Lisan Quentin , Crevier-Buchman Lise , Lechien Jerome R.
Published: September 2022

The development of transoral laser microsurgery (TLM) was an important step in the history of conservative laryngeal surgery. TLM reported comparable oncological outcomes and better functional postoperative and rehabilitation outcomes than open partial laryngectomy. TLM is currently considered as the standard surgical approach for early-stage laryngeal carcinoma. However, TLM has many limitations, including the limited view of the surgical field through the laryngoscope, exposure difficulties for some tumor locations, and a long learning curve. The development of transoral robotic surgery (TORS) appears to be an important issue to overcome these limitations. The current robotic technologies used in surgery benefited from the research of the U.S. Military and National Aeronautics and Space Administration (NASA) in the 1970s and 1980s. The first application in humans started in the 2000s with the first robotic-assisted cholecystectomy in the US, performed by a surgeon located in France. The use of robots in otolaryngology occurred after the development of the Da Vinci system in digestive surgery, urology, and gynecology, and mainly concerns cT1-T2 and some selected cT3 oropharyngeal and supraglottic carcinomas. With the development of a new robotic system with smaller arms and instruments, TORS indications will probably evolve in the next few years, leading to better outcomes for laryngeal or hypopharyngeal carcinomas.
Perioperative Outcomes in Patients Who Received Spinal Chloroprocaine for Total Hip or Knee Arthroplasty—Consecutive Case Series Study
Authors: Alhefeiti Khaleifah , Patrascu Ana-Maria , Lustig Sebastien , Aubrun Frederic , Dziadzko Mikhail
Published: September 2022

Spinal anaesthesia is an established component of perioperative management for fast-track lower limbs arthroplasty. Short-acting local anaesthetics may present an interesting option for primary non-complicated knee (TKA) and hip (THA) arthroplasty. We describe the perioperative outcomes in patients operated under fixed 50 mg spinal chloroprocaine for total hip and knee replacement. In this retrospective case series study, 65 patients were analysed (median age 65 years, 55% females, benefit from THA (n = 31), TKA (n = 25), and unicompartmental knee arthroplasty (n = 9)). In all cases, anaesthesia duration (87 min) was sufficient for successful surgery (52 min). Up to 45% of patients (THA and less in TKA) developed postoperative pain in the post-anaesthesia care unit (PACU), requiring intravenous morphine titration (up to 7.5 mg). One patient developed severe breakthrough pain requiring advanced regional analgesia. The median PACU stay was up to 97 min (less in TKA), and the incidence of nausea and urinary retention was low. All patients were able to start physical therapy on the same day of surgery. These findings encourage the use of a short-acting agent for spinal anaesthesia in patients with primary non-complicated arthroplasty; however, the relay analgesia should be systematically implemented to avoid breakthrough pain in PACU.
Deep Learning and Machine Learning with Grid Search to Predict Later Occurrence of Breast Cancer Metastasis Using Clinical Data
Authors: Jiang Xia , Xu Chuhan
Published: September 2022

Background: It is important to be able to predict, for each individual patient, the likelihood of later metastatic occurrence, because the prediction can guide treatment plans tailored to a specific patient to prevent metastasis and to help avoid under-treatment or over-treatment. Deep neural network (DNN) learning, commonly referred to as deep learning, has become popular due to its success in image detection and prediction, but questions such as whether deep learning outperforms other machine learning methods when using non-image clinical data remain unanswered. Grid search has been introduced to deep learning hyperparameter tuning for the purpose of improving its prediction performance, but the effect of grid search on other machine learning methods are under-studied. In this research, we take the empirical approach to study the performance of deep learning and other machine learning methods when using non-image clinical data to predict the occurrence of breast cancer metastasis (BCM) 5, 10, or 15 years after the initial treatment. We developed prediction models using the deep feedforward neural network (DFNN) methods, as well as models using nine other machine learning methods, including naïve Bayes (NB), logistic regression (LR), support vector machine (SVM), LASSO, decision tree (DT), k-nearest neighbor (KNN), random forest (RF), AdaBoost (ADB), and XGBoost (XGB). We used grid search to tune hyperparameters for all methods. We then compared our feedforward deep learning models to the models trained using the nine other machine learning methods. Results: Based on the mean test AUC (Area under the ROC Curve) results, DFNN ranks 6th, 4th, and 3rd when predicting 5-year, 10-year, and 15-year BCM, respectively, out of 10 methods. The top performing methods in predicting 5-year BCM are XGB (1st), RF (2nd), and KNN (3rd). For predicting 10-year BCM, the top performers are XGB (1st), RF (2nd), and NB (3rd). Finally, for 15-year BCM, the top performers are SVM (1st), LR and LASSO (tied for 2nd), and DFNN (3rd). The ensemble methods RF and XGB outperform other methods when data are less balanced, while SVM, LR, LASSO, and DFNN outperform other methods when data are more balanced. Our statistical testing results show that at a significance level of 0.05, DFNN overall performs comparably to other machine learning methods when predicting 5-year, 10-year, and 15-year BCM. Conclusions: Our results show that deep learning with grid search overall performs at least as well as other machine learning methods when using non-image clinical data. It is interesting to note that some of the other machine learning methods, such as XGB, RF, and SVM, are very strong competitors of DFNN when incorporating grid search. It is also worth noting that the computation time required to do grid search with DFNN is much more than that required to do grid search with the other nine machine learning methods.
Association between Endometriosis, Irritable Bowel Syndrome and Eating Disorders: ENDONUT Pilot Study
Authors: Aupetit Alexandra , Grigioni Sébastien , Roman Horace , Coëffier Moïse , Bréant Amélie , Hennetier Clotilde , Achamrah Najate
Published: September 2022

Background and aim: Irritable bowel syndrome (IBS), eating disorders (ED) and endometriosis share common pathophysiological mechanisms, involving alterations of the gut–brain axis. The aim of the ENDONUT pilot study was to investigate an association between these three diseases by screening for IBS and ED in patients with endometriosis. Method: We included patients from the CIRENDO cohort (Inter-Regional North-West Cohort of women with ENDOmetriosis) with a recent documented diagnosis of endometriosis of less than 4 years, regardless of age, date of onset of symptoms, type of endometriosis (digestive or not), with or without endometriosis-related digestive surgery. Validated questionnaires were used to screen for IBS (Rome IV, Francis score), ED (SCOFF-F, EAT-26), and anxiety/depression (HAD). Anthropometric data and lifestyle habits were also collected. The primary composite endpoint was SCOFF-F and ROME-IV scores. Results: Among 100 patients meeting inclusion criteria, 54 patients completed all the questionnaires. Of these, 19 had a positive SCOFF-F score (35.2%), 26 had a positive ROME-IV score (48.1%), and 14 patients (25.9%) had both a positive SCOFF-F score and a positive ROME-IV score (p = 0.006). Patients with positive SCOFF-F and ROME-IV scores had significantly higher HAD-anxiety and depression scores (p < 0.05). Conclusion: These results suggest a significant association between IBS, ED and endometriosis. The prevalence of IBS and ED in our population is higher than in the general population. Larger studies are needed to confirm these results, to better understand this triad, and to improve the diagnostic and multidisciplinary therapeutic management of these patients.
Comparison of the Complications, Reoperations, and Clinical Outcomes between Open Reduction and Internal Fixation and Total Elbow Arthroplasty for Distal Humeral Fractures in the Elderly: A Systematic Review and Meta-Analysis
Authors: Seok Hyun-Gyu , Park Jeong-Jin , Park Sam-Guk
Published: September 2022

Distal humeral fractures are challenging injuries seen in the elderly. Open reduction and internal fixation (ORIF) are the gold standard treatments. Total elbow arthroplasty (TEA) is an alternative to ORIF. This study aimed to pool and analyze the outcomes and complications in elderly patients with distal humeral fractures treated with either ORIF or TEA by performing a meta-analysis. We searched the PubMed, Embase, Google Scholar, and Cochrane Library databases for studies that compared the clinical and functional outcomes of ORIF and TEA in patients aged 60 years or older. After screening and performing a quality assessment of the articles, we obtained one randomized control study and nine retrospective comparative studies. The odds ratio and standardized mean difference were used to analyze the differences in outcomes between the two surgical options. In terms of the flexion/extension arc, TEA produced significantly better outcomes than ORIF (p = 0.02). The rates of reoperation and elbow stiffness were significantly lower in the TEA group than in the ORIF group (p = 0.003 and p = 0.04, respectively). However, the functional scores and other ranges of motion (flexion, loss of extension, pronation, supination) after surgery were similar between the two groups. The outcomes from the present meta-analysis can provide guidance when selecting a surgical option for distal humeral fractures in the elderly.
Transcriptomic Analysis of Conserved Telomere Maintenance Component 1 (CTC1) and Its Association with Leukemia
Authors: Zia Saadiya , Khan Netasha , Tehreem Komal , Rehman Nazia , Sami Rokayya , Baty Roua S. , Tayeb Faris J. , Almashjary Majed N. , Alsubhi Nouf H. , Alrefaei Ghadeer I. , Shahid Ramla
Published: September 2022

Telomere length (TEL) regulation is important for genome stability and is governed by the coordinated role of shelterin proteins, telomerase (TERT), and CST (CTC1/OBFC1/TEN1) complex. Previous studies have shown the association of telomerase expression with the risk of acute lymphoblastic leukemia (ALL). However, no data are available for CST association with the ALL. The current pilot study was designed to evaluate the CST expression levels in ALL. In total, 350 subjects were recruited, including 250 ALL cases and 100 controls. The subjects were stratified by age and categorized into pediatrics (1–18 years) and adults (19–54 years). TEL and expression patterns of CTC1, OBFC1, and TERT genes were determined by qPCR. The univariable logistic regression analysis was performed to determine the association of gene expression with ALL, and the results were adjusted for age and sex in multivariable analyses. Pediatric and adult cases did not reflect any change in telomere lengths relative to controls. However, expression of CTC1, OBFC1, and TERT genes were induced among ALL cases. Multivariable logistic regression analyses showed association of CTC1 with ALL in pediatric [β estimate (standard error (SE)= −0.013 (0.007), p = 0.049, and adults [0.053 (0.023), p = 0.025]. The association of CTC1 remained significant when taken together with OBFC1 and TERT in a multivariable model. Furthermore, CTC1 showed significant association with B-cell ALL [−0.057(0.017), p = 0.002) and T-cell ALL [−0.050 (0.018), p = 0.008] in pediatric group while no such association was noted in adults. Together, our findings demonstrated that telomere modulating genes, particularly CTC1, are strongly associated with ALL. Therefore, CTC1 can potentially be used as a risk biomarker for the identification of ALL in both pediatrics and adults.
Using the Phecode System to Identify the Preoperative Clinical Phenotypes Associated with Surgical Site Infection in Patients Undergoing Primary Total Knee Arthroplasty: The Sex Differences
Authors: Hung Ting-Yu , Liu Kuan-Lin , Wen Shu-Hui
Published: September 2022

Sex-related differences among comorbid conditions associated with surgical site infection (SSI) after total knee arthroplasty (TKA) are unclear. This population-based cohort study used a novel approach with a Phecode system to evaluate preoperative clinical phenotypes (i.e., comorbid conditions) associated with SSI after TKA and delineate sex-related differences in phenotypes. Using the Taiwan National Health Insurance Research Database (2014–2018), 83,870 patients who underwent TKA were identified. Demographic and SSI data during the 90-day postoperative follow-up were obtained. Comorbidities identified by the International Classification of Diseases within 1 year before TKA were recorded and mapped into Phecodes representing phenotypes. The overall rate of 90-day SSI was 1.3%. In total, 1663 phenotypes were identified among 83,870 patients—1585 and 1458 phenotypes for female (n = 62,018) and male (n = 21,852) patients, respectively. According to multivariate logistic regression analysis, the SSI odds ratio significantly increased with the presence of each of the 16 phenotypes. Subgroup analysis revealed that the presence of 10 and 4 phenotypes significantly increased SSI risk in both sexes; only one phenotype was common to both sexes. Therefore, comorbid conditions and sex should be considered in preoperative SSI risk evaluation in patients undergoing primary TKA. These findings provide new perspectives on susceptibility, prevention, and treatment in these patients.
Clinical Criteria for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome: An Exploratory Analysis of Optimal Cut-Off Values for Biomarkers
Authors: Nakamura Kensuke , Ogura Kentaro , Ohbe Hiroyuki , Goto Tadahiro
Published: September 2022

Background: While clinical criteria have been proposed for persistent inflammation, immunosuppression, and catabolism syndrome (PICS) using C-reactive protein (CRP), albumin, and lymphocyte count, there is no substantial basis for their optimal cut-off values. We herein aimed to develop and externally validate clinical criteria for PICS by investigating the optimal cut-off values for these biomarkers using machine-learning approaches and confirmed it with external validation. Methods: To develop criteria, we included ICU patients treated at a tertiary care hospital in Japan between 2018 and 2021 (derivation cohort). We introduced CRP, albumin and lymphocyte counts at around day 14 into six machine-learning models to predict PICS, defined as the compound outcome of the Barthel index (BI) < 70 at hospital discharge and in-hospital death. We incorporated the results of these models to assess the optimal cut-off values for biomarkers. We then developed and externally validated criteria for PICS using a nationwide claims database in Japan (validation cohort). Results: In the derivation cohort, 291 out of 441 patients had BI < 70 or in-hospital death. Based on machine-learning models, the optimal cut-off values for biomarkers to predict them were a CRP of 2.0 mg/dL, albumin of 3.0 g/dL, and a lymphocyte count of 800/μL, with an AUROC of 0.67. In the external validation cohort, 4492 out of 15,302 patients had BI < 70 or in-hospital death. The AUROC of the criteria was 0.71, with sensitivity of 0.71 and specificity of 0.68 to predict PICS. Conclusions: We herein provide a fundamental basis for PICS clinical criteria with CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/μL on day 14. The criteria developed will identify patients with PICS whose long-term mortality and activity of daily living may be poor.