bluuebunny/crossref_metadata_2025 huggingface dataset:
The Greater Impact of Paternal, Compared to Maternal, Hereditary Background on Depressive-Like Behavior in Wistar Kyoto Rats with Different Amino Acid Metabolism in the Pup Brain
Authors: Ihara Tsubasa , Hamada Mizuki , Furuse Mitsuhiro
Published: February 2023

In the pathogenesis of depression, heredity is believed to be a major factor. However, the mechanism by which heredity contributes to the onset of depression is not fully understood. Wistar Kyoto (WKY) rats have been used as an animal model for depression because of their increased depression-like behavior compared to Wistar (WIS) rats. In the present study, pups crossbred from WKY × WIS rats were used to evaluate locomotor activity in an open field test (OFT) and depression-like behavior in a forced swimming test (FST), with a focus on amino acid metabolism. Pups in the WKY♂ × WKY♀ group showed lower locomotor activity in the OFT and higher depression-like behavior in the FST than those in the WIS♂ × WIS♀ group. In addition, multiple regression analysis showed that the paternal strain had a greater effect than the maternal strain on locomotor activity and depression-like behavior in OFT and FST, respectively. Several amino acids in the brainstem, hippocampus, and striatum were significantly decreased through the influence of the WKY paternal strain, but not the WKY maternal strain. Based on these data from comparing WKY and WIS rats, we hypothesize that the hereditary effects of the WKY paternal strain on behavioral tests are partially caused by dysregulation of the amino acid metabolism in the brain.
Characterization of Oil Body and Starch Granule Dynamics in Developing Seeds of Brassica napus
Authors: Chen Kang , Yin Yongtai , Ding Yiran , Chao Hongbo , Li Maoteng
Published: February 2023

Brassica napus is the most important oilseed crop in the world, and the lipid was stored in the oil body (OB) in the form of triacylglycerol. At present, most of studies on the relationship between oil body morphology and seed oil content in B. napus was focused on mature seeds. In the present study, the OBs in different developing seeds of B. napus with relatively high oil content (HOC) of about 50% and low oil content (LOC) of about 39% were analyzed. It was revealed that the size of OBs was first increased and then decreased in both materials. And in late seed developmental stages, the average OB size of rapeseed with HOC was higher than that of LOC, while it was reversed in the early seed developmental stages. No significant difference was observed on starch granule (SG) size in HOC and LOC rapeseed. Further results indicated that the expression of genes that involved in malonyl-CoA metabolism, fatty acid carbon chain extension, lipid metabolism, and starch synthesis in the rapeseed with HOC was higher than that of rapeseed with LOC. These results give some new insight for understanding the dynamics of OBs and SGs in embryos of B. napus.
GPR41 Regulates the Proliferation of BRECs via the PIK3-AKT-mTOR Pathway
Authors: Meng Zitong , Tan Dejin , Cheng Zhiqiang , Jiang Maocheng , Zhan Kang
Published: February 2023

Short-chain fatty acids (SCFAs) play a pivotal role in regulating the proliferation and development of bovine rumen epithelial cells (BRECs). G protein-coupled receptor 41 (GPR41) is involved in the signal transduction in BRECs as a receptor for SCFAs. Nevertheless, the impact of GPR41 on the proliferation of BRECs has not been reported. The results of this research showed that the knockdown of GPR41 (GRP41KD) decreased BRECs proliferation compared with the wild-type BRECs (WT) (p < 0.001). The RNA sequencing (RNA-seq) analysis showed that the gene expression profiles differed between WT and GPR41KD BRECs, with the major differential genes enriched in phosphatidylinositol 3-kinase (PIK3) signaling, cell cycle, and amino acid transport pathways (p < 0.05). The transcriptome data were further validated by Western blot and qRT-PCR. It was evident that the GPR41KD BRECs downregulated the level of the PIK3-Protein kinase B (AKT)-mammalian target of the rapamycin (mTOR) signaling pathway core genes, such as PIK3, AKT, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) and mTOR contrasted with the WT cells (p < 0.01). Furthermore, the GPR41KD BRECs downregulated the level of Cyclin D2 p < 0.001) and Cyclin E2 (p < 0.05) compared with the WT cells. Therefore, it was proposed that GPR41 may affect the proliferation of BRECs by mediating the PIK3-AKT-mTOR signaling pathway.
A Dual-Modality Imaging Method Based on Polarimetry and Second Harmonic Generation for Characterization and Evaluation of Skin Tissue Structures
Authors: Deng Liangyu , Fan Zhipeng , Chen Binguo , Zhai Haoyu , He Honghui , He Chao , Sun Yanan , Wang Yi , Ma Hui
Published: February 2023

The characterization and evaluation of skin tissue structures are crucial for dermatological applications. Recently, Mueller matrix polarimetry and second harmonic generation microscopy have been widely used in skin tissue imaging due to their unique advantages. However, the features of layered skin tissue structures are too complicated to use a single imaging modality for achieving a comprehensive evaluation. In this study, we propose a dual-modality imaging method combining Mueller matrix polarimetry and second harmonic generation microscopy for quantitative characterization of skin tissue structures. It is demonstrated that the dual-modality method can well divide the mouse tail skin tissue specimens’ images into three layers of stratum corneum, epidermis, and dermis. Then, to quantitatively analyze the structural features of different skin layers, the gray level co-occurrence matrix is adopted to provide various evaluating parameters after the image segmentations. Finally, to quantitatively measure the structural differences between damaged and normal skin areas, an index named Q-Health is defined based on cosine similarity and the gray-level co-occurrence matrix parameters of imaging results. The experiments confirm the effectiveness of the dual-modality imaging parameters for skin tissue structure discrimination and assessment. It shows the potential of the proposed method for dermatological practices and lays the foundation for further, in-depth evaluation of the health status of human skin.
Inhibition of Melanogenesis by Essential Oils from the Citrus Cultivars Peels
Authors: Yang Jiyoon , Lee Su-Yeon , Jang Soo-Kyeong , Kim Ki-Joong , Park Mi-Jin
Published: February 2023

Citrus is one of the most popular and widely grown fruit crops in the world. However, the bioactivity of only certain species of citrus cultivars is studied. In this study, the effects of essential oils from 21 citrus cultivars on melanogenesis were investigated in an effort to identify active anti-melanogenesis constituents. The essential oils from the peels of 21 citrus cultivars obtained by hydro-distillation were analyzed using gas chromatography–mass spectrometry. Mouse melanoma B16BL6 cells were used in all assays conducted in this study. The tyrosinase activity and melanin content were determined using the lysate of α-Melanocyte-stimulated B16BL6 cells. In addition, the melanogenic gene expression was determined by quantitative reverse transcription-polymerase chain reaction. Overall, the essential oils of (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulata provided the best bioactivity and comprised five distinct constituents compared to other essential oils such as limonene, farnesene, β-elemene, terpinen-4-ol, and sabinene. The anti-melanogenesis activities of the five individual compounds were evaluated. Among the five essential oils, β-elemene, farnesene, and limonene showed dominating properties. The experimental results indicated that (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulara are potential candidates with anti-melanogenesis activity for use as cosmetics and pharmaceutical agents against skin hyperpigmentation.
Critical Role of the Transcription Factor AKNA in T-Cell Activation: An Integrative Bioinformatics Approach
Authors: Ramírez-González Abrahan , Ávila-López Pedro , Bahena-Román Margarita , Contreras-Ochoa Carla O. , Lagunas-Martínez Alfredo , Langley Elizabeth , Manzo-Merino Joaquín , Madrid-Marina Vicente , Torres-Poveda Kirvis
Published: February 2023

The human akna gene encodes an AT-hook transcription factor, the expression of which is involved in various cellular processes. The goal of this study was to identify potential AKNA binding sites in genes that participate in T-cell activation and validate selected genes. Here we analyzed ChIP-seq and microarray assays to determine AKNA-binding motifs and the cellular process altered by AKNA in T-cell lymphocytes. In addition, we performed a validation analysis by RT-qPCR to assess AKNA’s role in promoting IL-2 and CD80 expression. We found five AT-rich motifs that are potential candidates as AKNA response elements. We identified these AT-rich motifs in promoter regions of more than a thousand genes in activated T-cells, and demonstrated that AKNA induces the expression of genes involved in helper T-cell activation, such as IL-2. The genomic enrichment and prediction of AT-rich motif analyses demonstrated that AKNA is a transcription factor that can potentially modulate gene expression by recognizing AT-rich motifs in a plethora of genes that are involved in different molecular pathways and processes. Among the cellular processes activated by AT-rich genes, we found inflammatory pathways potentially regulated by AKNA, suggesting AKNA is acting as a master regulator during T-cell activation.
E. coli Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism
Authors: AlMalki Reem , Sebaa Rajaa , Al-Ansari Mysoon , Al-Alwan Monther , Alwehaibi Moudi , Rahman Anas
Published: February 2023

Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that E. coli, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the E. coli secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the E. coli secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the E. coli secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from E. coli in the culture media of MDA-MB-231 cells. The cells treated with the E. coli secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the E. coli secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells.
In Silico Analysis of Ferroptosis-Related Genes and Its Implication in Drug Prediction against Fluorosis
Authors: Liu Bin , Fu Xiaoli , Du Yuhui , Feng Zichen , Liu Xiaoxue , Li Zhiyuan , Yu Fangfang , Zhou Guoyu , Ba Yue
Published: February 2023

Fluorosis is a serious global public health problem. Interestingly, so far, there is no specific drug treatment for the treatment of fluorosis. In this paper, the potential mechanisms of 35 ferroptosis-related genes in U87 glial cells exposed to fluoride were explored by bioinformatics methods. Significantly, these genes are involved in oxidative stress, ferroptosis, and decanoate CoA ligase activity. Ten pivotal genes were found by the Maximal Clique Centrality (MCC) algorithm. Furthermore, according to the Connectivity Map (CMap) and the Comparative Toxicogenomics Database (CTD), 10 possible drugs for fluorosis were predicted and screened, and a drug target ferroptosis-related gene network was constructed. Molecular docking was used to study the interaction between small molecule compounds and target proteins. Molecular dynamics (MD) simulation results show that the structure of the Celestrol–HMOX1 composite is stable and the docking effect is the best. In general, Celastrol and LDN-193189 may target ferroptosis-related genes to alleviate the symptoms of fluorosis, which may be effective candidate drugs for the treatment of fluorosis.
Polydopamine Incorporation Enhances Cell Differentiation and Antibacterial Properties of 3D-Printed Guanosine-Borate Hydrogels for Functional Tissue Regeneration
Authors: Merino-Gómez Maria , Gil Javier , Perez Roman A. , Godoy-Gallardo Maria
Published: February 2023

Tissue engineering focuses on the development of materials as biosubstitutes that can be used to regenerate, repair, or replace damaged tissues. Alongside this, 3D printing has emerged as a promising technique for producing implants tailored to specific defects, which in turn increased the demand for new inks and bioinks. Especially supramolecular hydrogels based on nucleosides such as guanosine have gained increasing attention due to their biocompatibility, good mechanical characteristics, tunable and reversible properties, and intrinsic self-healing capabilities. However, most existing formulations exhibit insufficient stability, biological activity, or printability. To address these limitations, we incorporated polydopamine (PDA) into guanosine-borate (GB) hydrogels and developed a PGB hydrogel with maximal PDA incorporation and good thixotropic and printability qualities. The resulting PGB hydrogels exhibited a well-defined nanofibrillar network, and we found that PDA incorporation increased the hydrogel’s osteogenic activity while having no negative effect on mammalian cell survival or migration. In contrast, antimicrobial activity was observed against the Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis. Thus, our findings suggest that our PGB hydrogel represents a significantly improved candidate as a 3D-printed scaffold capable of sustaining living cells, which may be further functionalized by incorporating other bioactive molecules for enhanced tissue integration.
Roles of RNA Methylations in Cancer Progression, Autophagy, and Anticancer Drug Resistance
Authors: Jo Hyein , Shim Kyeonghee , Jeoung Dooil
Published: February 2023

RNA methylations play critical roles in RNA processes, including RNA splicing, nuclear export, nonsense-mediated RNA decay, and translation. Regulators of RNA methylations have been shown to be differentially expressed between tumor tissues/cancer cells and adjacent tissues/normal cells. N6-methyladenosine (m6A) is the most prevalent internal modification of RNAs in eukaryotes. m6A regulators include m6A writers, m6A demethylases, and m6A binding proteins. Since m6A regulators play important roles in regulating the expression of oncogenes and tumor suppressor genes, targeting m6A regulators can be a strategy for developing anticancer drugs. Anticancer drugs targeting m6A regulators are in clinical trials. m6A regulator-targeting drugs could enhance the anticancer effects of current chemotherapy drugs. This review summarizes the roles of m6A regulators in cancer initiation and progression, autophagy, and anticancer drug resistance. The review also discusses the relationship between autophagy and anticancer drug resistance, the effect of high levels of m6A on autophagy and the potential values of m6A regulators as diagnostic markers and anticancer therapeutic targets.
The RadScopal Technique as an Immune Adjuvant to Treat Cancer
Authors: Barsoumian Hampartsoum B. , Hsu Jerry , Nanez Selene , Hu Yun , Hsu Ethan Y. , Riad Thomas S. , Puebla-Osorio Nahum , Angelica Cortez Maria , Welsh James W.
Published: February 2023

Since the momentous discovery of X-rays, high-dose radiotherapy (H-XRT) has been a cornerstone for combating cancer. The high-energy electromagnetic waves induce direct damage to tumor-cells’ DNA, thereby halting cell growth and proliferation, and eventually leading to tumor eradication. Furthermore, recent evidence suggests that H-XRT may have immunomodulatory properties which arise from its ability to induce the release of neoantigens, which in turn prime T-cells and contribute to T-cell repertoire diversity. Throughout the years, there have been different treatment modalities introduced as complements to H-XRT that have yielded greater results than monotherapy alone. In this review, we will discuss preclinical and clinical data related to the recently introduced low-dose radiotherapy (L-XRT) modality. We will also explore the justification for combining L-XRT and H-XRT, which became known as the “RadScopal Technique”, as a novel immune adjuvant to treat cancer. In this analysis, we detail and dissect the physiological mechanisms of action of each modality and describe the synergistic amalgamation effect observed on primary and metastatic tumors. Finally, we will explore the impetus for further studies to investigate combinations of the “RadScopal Technique” with various immune-oncology drug candidates.
GATUGU: Six Perspectives of Evaluation of Gamified Systems
Authors: Swacha Jakub , Queirós Ricardo , Paiva José Carlos
Published: February 2023

As gamification spreads to new areas, new applications are being developed and the interest in evaluating gamified systems continues to grow. To date, however, no one has comprehensively approached this topic: multiple evaluation dimensions and measures have been proposed and applied without any effort to organize them into a full gamut of tools for the multi-dimensional evaluation of gamified systems. This paper addresses this gap by proposing GATUGU, a set of six perspectives of evaluation of gamified systems: General effects of gamification, Area-specific effects of gamification, Technical quality of gamified systems, Use of gamified systems, Gamefulness of gamified systems, and User experience of gamified systems. For each perspective, GATUGU indicates the relevant dimensions of evaluation, and, for each dimension, one measure is suggested. GATUGU does not introduce any new measurement tools but merely recommends one of the available tools for each dimension, considering their popularity and ease of use. GATUGU can guide researchers in selecting gamification system evaluation perspectives and dimensions and in finding adequate measurement tools. Thanks to conforming to GATUGU, the published gamification system evaluation results will become easier to compare and to perform various kinds of meta-analyses on them.
Higher Essential Amino Acid and Crude Protein Contents in Pollen Accelerate the Oviposition and Colony Foundation of Bombus breviceps (Hymenoptera: Apidae)
Authors: Ren Chang-Shi , Chang Zhi-Min , Han Lei , Chen Xiang-Sheng , Long Jian-Kun
Published: February 2023

Pollen is an important source of nutrition for bumblebees to survive, reproduce, and raise their offspring. To explore the nutritional requirements for the egg laying and hatching of queenright Bombus breviceps colonies, camellia pollen, oilseed rape pollen, apricot pollen, and mixtures of two or three types of pollen in equal proportions were used to feed the queens in this study. The results showed that the camellia pollen with a higher essential amino acid content was superior to the pollen with a lower essential amino acid content in the initial egg-laying time (p < 0.05), egg number (p < 0.05), larval ejection (p < 0.01), time of first worker emergence (p < 0.05), and the average weight of workers in the first batch (p < 0.01). It took less time for colonies under the camellia pollen and camellia–oilseed rape–apricot pollen mix treatments, both with a higher crude protein content, to reach ten workers in the colony (p < 0.01). On the contrary, the queens fed apricot pollen never laid an egg, and larvae fed oilseed rape pollen were all ejected—both pollens with a lower essential amino acid content. The results emphasize that the diet should be rationally allocated to meet the nutritional needs of local bumblebees at various stages when guiding them to lay eggs, hatch, and develop a colony.
Behavioural and Electrophysiological Response of Anastrepha fraterculus (Diptera: Tephritidae) to a γ-Lactone Synthetic Semiochemical
Authors: Goane Lucía , Carrizo Beatriz N. , Ruiz María Josefina , Bachmann Guillermo E. , Milla Fabian H. , Segura Diego F. , Kuzmich Dan , Walse Spencer , Vera María Teresa
Published: February 2023

Attractants are a powerful tool for pest management. The lack of specific attractants for the South American fruit fly, Anastrepha fraterculus, a complex of cryptic species of great economic importance in South America, makes it difficult to monitor the pest in the field. The γ-lactone male sex and aggregation pheromones of several Anastrepha species, naturally released in a 7:3 epianastrephin to anastrephin ratio, and a structurally related naturally occurring γ-lactone ((±)-trans-tetrahydroactinidiolide) with gem-dimethyl groups (dimethyl) at C(4), were evaluated as potential attractants of this species. Different age and mating conditions of A. fraterculus males and females were evaluated during electroantennography (EAG) and field cage experiments in which polymeric lures were deployed to contain 100 mg of attractant. Epianastrephin and dimethyl were EAG+ for all fly conditions, with epianastrephin eliciting the highest response for both sexes and immature flies showing greater responsiveness than mature flies. In the field cage experiments, immature flies were only attracted to leks; virgin females were attracted to leks, dimethyl, and both epianastrephin-anastrephin formulations (95 and 70 wt.% epianastrephin); mature-mated males were attracted to leks, dimethyl and 70 wt.% epianastrephin; and mature-mated females were only attracted to leks. Our bioassays showed a promising performance of the analog dimethyl since it elicited the same response as epianastrephin, requires fewer steps to synthesize, and contains one less chiral center than the natural pheromones. The attraction to leks was recorded for all mating conditions and ages of flies and suggests that air-borne volatiles of calling males contain cues that could act as sensory traps. The addition of any of these compounds in the synthetic attractants may result in a greater attraction and thus deserves further evaluation. Dose-response experiments will provide additional information to move a step forward and validate the results obtained in open-field conditions.
Effects of Species Invasion and Inundation on the Collembola Community in Coastal Mudflat Wetland from the Perspective of Functional Traits
Authors: Li Jing-Yang , Gao Yun-Xia , Li Chun-Yang , Jin Ya-Li , Yang Si-Qi , Xia Jian-Hong , Zhang Yun-Fei , Bu Yun , Li Kai
Published: February 2023

The group of soil arthropods known as Collembola is characterized by its abundance and sensitivity to environmental changes. They are ideal an species for soil indicators. In order to clarify the effects of species invasion and inundation on the Collembola community in coastal mudflat wetlands, the correlation between the collembolan functional traits and environmental factors was studied in Shanghai Jiuduansha Wetland National Nature Reserve for the first time. Five sample plots, including three vegetations—Spartina alterniflora (an invasive species), Phragmites australis, and Zizania latifolia—were set up following the differences in vegetation types and between high and low tidal flats. Data on the diversity of the Collembolan species and their functional traits were collected and combined with the soil physicochemical properties and vegetation environment factors in different tidal flats. The key findings and conclusions of the study are as follows: a total of 18 species, four families, and three orders make up the obtained Collembola, two species of Proisotoma are dominant species that account for 49.59% and 24.91% of the total, respectively. The maintenance of the species diversity of Collembola is disturbed by the higher conversion efficiency of Spartina alterniflora rather than Phragmites australis with lower organic carbon (C) content and higher total nitrogen (N) content. The primary environmental variables influencing species distribution were the C/N ratio, total N, and bulk soil density. The bulk density of the soil impacts the movement and dispersal of the functional traits. The depth of the soil layer is related to the functional traits of the sensory ability. The analysis of the functional traits and environment is fairly helpful in exploring how species respond to their environment and offers a better explanation for the habitat selection of Collembola.
The Effect of Metabolic Syndrome and Its Individual Components on Renal Function: A Meta-Analysis
Authors: Li Xu , Liang Qichen , Zhong Junfeng , Gan Liangying , Zuo Li
Published: February 2023

Background: Observational studies have reported inconsistent findings in the relationship between metabolic syndrome (MetS), its components, and loss of renal function, mainly including eGFR decline, new-onset CKD, and ESRD. This meta-analysis was performed to investigate their potential associations. Methods: PubMed and EMBASE were systematically searched from their inception to 21 July 2022. Observational cohort studies in English assessing the risk of renal dysfunction in individuals with MetS were identified. Risk estimates and their 95% confidence intervals (CIs) were extracted and pooled using the random-effects approach. Results: A total of 32 studies with 413,621 participants were included in the meta-analysis. MetS contributed to higher risks of renal dysfunction (RR = 1.50, 95% CI = 1.39–1.61) and, specifically, rapid decline in eGFR (RR 1.31, 95% CI 1.13–1.51), new-onset CKD (RR 1.47, 95% CI 1.37–1.58), as well as ESRD (RR 1.55, 95% CI 1.08–2.22). Moreover, all individual components of MetS were significantly associated with renal dysfunction, while elevated BP conveyed the highest risk (RR = 1.37, 95% CI = 1.29–1.46), impaired fasting glucose with the lowest and diabetic-dependent risk (RR = 1.20, 95% CI = 1.09–1.33). Conclusions: Individuals with MetS and its components are at higher risk of renal dysfunction.
The Landscape of Cytogenetic Aberrations in Light-Chain Amyloidosis with or without Coexistent Multiple Myeloma
Authors: He Haiyan , Lu Jing , Qiang Wanting , Liu Jin , Liang Aibin , Du Juan
Published: February 2023

Interphase fluorescence in situ hybridization (iFISH) has been well established in the preliminary prognostic evaluation of multiple myeloma (MM). However, the chromosomal aberrations in patients with systemic light-chain amyloidosis, notably in patients with coexistent MM, have been rarely investigated. This study aimed to evaluate the effect of iFISH aberrations on the prognosis of systemic light-chain amyloidosis (AL) with and without concurrent MM. The iFISH results and clinical characteristics of 142 patients with systemic light-chain amyloidosis were analyzed, and survival analysis was conducted. Among the 142 patients, 80 patients had AL amyloidosis alone, and the other 62 patients had concurrent MM. The incidence rate of 13q deletion, t(4;14), was higher in AL amyloidosis patients with concurrent MM than that of primary AL amyloidosis patients (27.4% vs. 12.5%, and 12.9% vs. 5.0%, respectively), and the incidence rate of t(11;14) in primary AL amyloidosis patients was higher than that in AL amyloidosis patients with concurrent MM (15.0% vs. 9.7%). Moreover, the two groups had the similar incidence rates of 1q21 gain (53.8% and 56.5%, respectively). The result of the survival analysis suggested that patients with t(11;14) and 1q21 gain had a shorter median overall survival (OS) and progression-free survival (PFS), irrespective of the presence or absence of MM, and patients with AL amyloidosis and concurrent MM carrying t(11;14) had the poorest prognosis, with a median OS time of 8.1 months.
Fetal Growth Restriction and Long-Term Cardiovascular Morbidity of Offspring in Dichorionic–Diamniotic Twin Pregnancies
Authors: Tzafrir Tuval , Wainstock Tamar , Sheiner Eyal , Miodownik Shayna , Pariente Gali
Published: February 2023

Objective: We opted to investigate whether fetal growth restriction (FGR) in dichorionic–diamniotic twins is a risk factor for long-term cardiovascular morbidity in offspring. Study design: A population-based retrospective cohort study, comparing long-term cardiovascular morbidity among FGR and non-FGR twins, born between the years 1991 and 2021 in a tertiary medical center. Study groups were followed until 18 years of age (6570 days) for cardiovascular-related morbidity. A Kaplan–Meier survival curve compared the cumulative cardiovascular morbidity. A Cox proportional hazard model assisted with adjusting for confounders. Results: In this study, 4222 dichorionic–diamniotic twins were included; 116 were complicated with FGR and demonstrated a significantly higher rate of long-term cardiovascular morbidity (4.4% vs. 1.3%, OR = 3.4, 95% CI 1.35–8.78, p = 0.006). The cumulative incidence of long-term cardiovascular morbidity was significantly higher among FGR twins (Kaplan–Meier Log rank test p = 0.007). A Cox proportional-hazard model found an independent association between FGR and long-term cardiovascular morbidity, when adjusted for both birth order and gender (adjusted HR 3.3, 95% CI 1.31–8.19, p = 0.011). Conclusions: FGR in dichorionic–diamniotic twins is independently associated with an increased risk for long-term cardiovascular morbidity in offspring. Therefore, increased surveillance may be beneficial.
Long-Term Use of Insomnia Medications: An Appraisal of the Current Clinical and Scientific Evidence
Authors: Zee Phyllis C. , Bertisch Suzanne M. , Morin Charles M. , Pelayo Rafael , Watson Nathaniel F. , Winkelman John W. , Krystal Andrew D.
Published: February 2023

While evidence supports the benefits of medications for the treatment of chronic insomnia, there is ongoing debate regarding their appropriate duration of use. A panel of sleep experts conducted a clinical appraisal regarding the use of insomnia medications, as it relates to the evidence supporting the focus statement, “No insomnia medication should be used on a daily basis for durations longer than 3 weeks at a time”. The panelists’ assessment was also compared to findings from a national survey of practicing physicians, psychiatrists, and sleep specialists. Survey respondents revealed a wide range of opinions regarding the appropriateness of using the US Food and Drug Administration (FDA)-approved medications for the treatment of insomnia lasting more than 3 weeks. After discussion of the literature, the panel unanimously agreed that some classes of insomnia medications, such as non-benzodiazepines hypnotics, have been shown to be effective and safe for long-term use in the appropriate clinical setting. For eszopiclone, doxepin, ramelteon and the newer class of dual orexin receptor antagonists, the FDA label does not specify that their use should be of a limited duration. Thus, an evaluation of evidence supporting the long-term safety and efficacy of newer non-benzodiazepine hypnotics is timely and should be considered in practice recommendations for the duration of pharmacologic treatment of chronic insomnia.
Differentiation of Adipose-Derived Stem Cells into Smooth Muscle Cells in an Internal Anal Sphincter-Targeting Anal Incontinence Rat Model
Authors: Kim Minsung , Oh Bo-Young , Lee Ji-Seon , Yoon Dogeon , Kim You-Rin , Chun Wook , Kim Jong Wan , Son Il Tae
Published: February 2023

Objective: Studies on development of an anal incontinence (AI) model targeting smooth muscle cells (SMCs) of the internal anal sphincter (IAS) have not been reported. The differentiation of implanted human adipose-derived stem cells (hADScs) into SMCs in an IAS-targeting AI model has also not been demonstrated. We aimed to develop an IAS-targeting AI animal model and to determine the differentiation of hADScs into SMCs in an established model. Materials and Methods: The IAS-targeting AI model was developed by inducing cryoinjury at the inner side of the muscular layer via posterior intersphincteric dissection in Sprague–Dawley rats. Dil-stained hADScs were implanted at the IAS injury site. Multiple markers for SMCs were used to confirm molecular changes before and after cell implantation. Analyses were performed using H&E, immunofluorescence, Masson’s trichrome staining, and quantitative RT–PCR. Results: Impaired smooth muscle layers accompanying other intact layers were identified in the cryoinjury group. Specific SMC markers, including SM22α, calponin, caldesmon, SMMHC, smoothelin, and SDF-1 were significantly decreased in the cryoinjured group compared with levels in the control group. However, CoL1A1 was increased significantly in the cryoinjured group. In the hADSc-treated group, higher levels of SMMHC, smoothelin, SM22α, and α-SMA were observed at two weeks after implantation than at one week after implantation. Cell tracking revealed that Dil-stained cells were located at the site of augmented SMCs. Conclusions: This study first demonstrated that implanted hADSc restored impaired SMCs at the injury site, showing stem cell fate corresponding to the established IAS-specific AI model.
Simpson’s Paradox in Clinical Research: A Cautionary Tale
Authors: Bonovas Stefanos , Piovani Daniele
Published: February 2023

The word paradox comes from the Greek paradoxon, meaning something that was contrary to, or contradicted, common sense [...]
Auditory Domain Sensitivity and Neuroplasticity-Based Targeted Cognitive Training in Autism Spectrum Disorder
Authors: Tseng Angela , DuBois Megan , Biagianti Bruno , Brumley Caroline , Jacob Suma
Published: February 2023

Sensory processing, along with the integration of external inputs into stable representations of the environment, is integral to social cognitive functioning; challenges in these processes have been reported in Autism Spectrum Disorder (ASD) since the earliest descriptions of autism. Recently, neuroplasticity-based targeted cognitive training (TCT) has shown promise as an approach to improve functional impairments in clinical patients. However, few computerized and adaptive brain-based programs have been trialed in ASD. For individuals with sensory processing sensitivities (SPS), the inclusion of some auditory components in TCT protocols may be aversive. Thus, with the goal of developing a web-based, remotely accessible intervention that incorporates SPS concerns in the auditory domain, we assessed auditory SPS in autistic adolescents and young adults (N = 25) who started a novel, computerized auditory-based TCT program designed to improve working memory and information processing speed and accuracy. We found within-subject gains across the training program and between pre/post-intervention assessments. We also identified auditory, clinical, and cognitive characteristics that are associated with TCT outcomes and program engagement. These initial findings may be used to inform therapeutic decisions about which individuals would more likely engage in and benefit from an auditory-based, computerized TCT program.
Clinical Significance and Outcome in Patients with Asymptomatic Versus Symptomatic Subsegmental Pulmonary Embolism
Authors: Rodríguez-Cobo Ana , Fernández-Capitán Carmen , Tung-Chen Yale , Salgueiro-Origlia Giorgina , Ballaz Aitor , Bortoluzzi Cristiano , Sarlon-Bartoli Gabrielle , Pesce Maria Lourdes , Najib Dally , Monreal Manuel ,   The RIETE Investigators
Published: February 2023

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37–9.74), DVT (HR: 0.53; 95% CI: 0.03–2.80), or major bleeding (HR: 0.85; 95% CI: 0.21–2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25–2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20–4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92–4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.
Demodicosis in Different Age Groups and Alternative Treatment Options—A Review
Authors: Chudzicka-Strugała Izabela , Gołębiewska Iwona , Brudecki Grzegorz , Elamin Wael , Zwoździak Barbara
Published: February 2023

Infestation with Demodex mites is a common occurrence, especially in adults and the elderly. More recent attention has been paid to the presence of Demodex spp. mites in children, even ones without comorbidities. It causes both dermatological and ophthalmological problems. The presence of Demodex spp. is often asymptomatic, thus it is suggested to include parasitological investigation tests in dermatological diagnostics, in addition to bacteriological analysis. Literature reports show that Demodex spp. are related to the pathogenesis of numerous dermatoses, including rosacea or demodicosis gravis, and common eye pathologies reported by patients such as dry eye syndrome or ocular surface inflammatory conditions, such as blepharitis, chalazia, Meibomian gland dysfunction, and keratitis. Treatment of patients is a challenge and is usually prolonged, therefore it is important to carefully diagnose and properly select the therapy regimen for the treatment to be successful, and with minimal side effects, especially for young patients. Apart from the use of essential oils, research is ongoing for new alternative preparations active against Demodex sp. Our review was focused on the analysis of the current literature data on the available agents in the treatment of demodicosis in adults and children.
Utility of Doppler-Ultrasound and Liver Elastography in the Evaluation of Patients with Suspected Pregnancy-Related Liver Disease
Authors: Serra Carla , Dajti Elton , De Molo Chiara , Montaguti Elisa , Porro Alberto , Seidenari Anna , Angilletta Emiliana , Bernardi Vito , Salsi Ginevra , Bakken Sofia Maria , Montagnani Marco , Mazzella Giuseppe , Azzaroli Francesco
Published: February 2023

Grayscale abdomen ultrasound (US) is routinely performed in pregnant women with suspected pregnancy-related liver dysfunction, but its diagnostic yield is very low. We aimed to investigate the association between Doppler-US findings, liver stiffness measurement (LSM) and different causes of pregnancy-related liver dysfunction. This is a prospective cohort study of pregnant women referred to our tertiary center for any suspected gastrointestinal disease between 2017 and 2019 and undergoing Doppler-US and liver elastography. Patients with previous liver disease were excluded from the analysis. For group comparisons of categorical and continuous variables, the chi-square test or Mann–Whitney test, and the McNemar test were used, as appropriate. A total of 112 patients were included in the final analysis, of whom 41 (36.6%) presented with suspected liver disease: 23 intrahepatic cholestasis of pregnancy (ICP), six with gestational hypertensive disorders and 12 cases with undetermined causes of elevated liver enzymes. Values of LSM were higher and significantly associated with a diagnosis of gestational hypertensive disorder (AUROC = 0.815). No significant differences at Doppler-US or LSM were found between ICP patients and controls. Patients with undetermined causes of hypertransaminasemia showed higher hepatic and splenic resistive indexes than controls, suggesting splanchnic congestion. The evaluation of Doppler-US and liver elastography is clinically useful in patients with suspected liver dysfunction during pregnancy. Liver stiffness represents a promising non-invasive tool for the assessment of patients with gestational hypertensive disorders.
Delving into Acromegaly
Authors: Störmann Sylvère , Schilbach Katharina
Published: February 2023

Acromegaly is a rare and disabling disease with some distinct and striking clinical features that have fascinated (and frightened) laypeople and medical experts alike throughout history [...]
Comparative Study of Muscle Hardness during Water-Walking and Land-Walking Using Ultrasound Real-Time Tissue Elastography in Healthy Young People
Authors: Tanabe Naoya , Nishioka Yasuko , Imashiro Kyosuke , Hashimoto Hiromi , Kimura Hiroki , Taniguchi Yasuhiro , Nakai Koya , Umemoto Yasunori , Kouda Ken , Tajima Fumihiro , Mikami Yasuo
Published: February 2023

Compared with land-walking, water-walking is considered to be beneficial as a whole-body exercise because of the characteristics of water (buoyancy, viscosity, hydrostatic pressure, and water temperature). However, there are few reports on the effects of exercise in water on muscles, and there is no standard qualitative assessment method for muscle flexibility. Therefore, we used ultrasound real-time tissue elastography (RTE) to compare muscle hardness after water-walking and land-walking. Participants were 15 healthy young adult males (24.8 ± 2.3 years). The method consisted of land-walking and water-walking for 20 min on separate days. The strain ratio of the rectus femoris (RF) and medial head of gastrocnemius (MHGM) muscles were measured before and immediately after walking using RTE to evaluate muscle hardness. In water-walking, the strain ratio significantly decreased immediately after water-walking, with p < 0.01 for RF and p < 0.05 for MHGM, indicating a significant decrease in muscle hardness after water-walking. On the other hand, land-walking did not produce significant differences in RF and MHGM. Muscle hardness after aerobic exercise, as assessed by RTE, was not changed by land walking but was significantly decreased by water walking. The decrease in muscle hardness induced by water-walking was thought to be caused by the edema reduction effect produced by buoyancy and hydrostatic pressure.
An Improved Score for the Evaluation of Mucosal Healing in Inflammatory Bowel Disease—A Pilot Study
Authors: Neamți Lidia , Drugan Tudor , Drugan Cristina , Silaghi Ciprian , Ciobanu Lidia , Crăciun Alexandra
Published: February 2023

Inflammatory bowel diseases are chronic conditions characterized by periods of remission, alternating with episodes of exacerbation, in which the primary therapeutic target is mucosal healing. Although colonoscopy is currently considered the gold standard for assessing disease activity, it presents a significant number of disadvantages. Over time, various inflammatory biomarkers have been proposed to detect disease activation, but current biomarkers have many limitations. Our study aimed to analyze the most commonly used biomarkers for patient monitoring and follow-up both independently and taken together as a group, in order to propose an improved activity score that more accurately reflects the changes occurring at the intestinal level, in order to limit the number of colonoscopic interventions. By applying logistic regression as a method of statistical analysis to the retrospectively collected data, we obtained an easy-to-calculate improved score that quantifies the chance that a given patient may be in remission or in a period of endoscopic activity. To achieve a widely accessible score that is easily accessible in clinical practice, we have included only the most commonly used clinical and biological parameters.
Clinical Outcomes and Complication Rate after Single-Stage Hardware Removal and Total Hip Arthroplasty: A Matched-Pair Controlled Study
Authors: La Camera Francesco , de Matteo Vincenzo , Di Maio Marco , Verrazzo Raffaele , Grappiolo Guido , Loppini Mattia
Published: February 2023

Background: Single-stage hardware removal and total hip arthroplasty is a complex surgical procedure, comparable to revision surgery. The purpose of the current study is to evaluate single-stage hardware removal and THA outcomes, compare this technique with a matched control group that has undergone primary THA and assess the risk of periprosthetic joint infection with a 24-month minimum follow-up. Methods: This study included all those cases treated with THA and concomitant hardware removal from 2008 to 2018. The control group was selected on a 1:1 ratio among patients who underwent THA for primary OA. The Harris Hip (HHS) and University of California at Los Angeles Activity (UCLA) scores, infection rate and early and delayed surgical complications were recorded. Results: One hundred and twenty-three consecutive patients (127 hips) were included, and the same number of patients was assigned to the control group. The final functional scores were comparable between the two groups; a longer operative time and transfusion rate were recorded in the study group. Finally, an increased incidence of overall complications was reported (13.8% versus 2.4%), but no cases of early or delayed infection were found. Conclusions: Single-stage hardware removal and THA is a safe and effective but technically demanding technique, with a higher incidence of overall complications, making it more similar to revision THA than to primary THA.