bluuebunny/crossref_metadata_2025 huggingface dataset:
Frailty as a Risk Factor for Depression after COVID-19 Hospital Admission
Authors: Soler-Moratalla Isabel María , Salmerón Sergio , Lozoya-Moreno Silvia , Hermosilla-Pasamar Ana María , Henández-Martínez Antonio , Solís-García del Pozo Julián , Escribano-Talaya Margarita , Font-Payeras Maria Antonia , García-Alcaraz Francisco
Published: July 2024

Background: This work aims to establish the relationship between depression and epidemiological or imaging variables, frailty, and cognitive status in patients who suffered hospital admission for COVID-19. Methods: A longitudinal observational study investigated 72 patients admitted for COVID-19 to a hospital in Spain. Patients were evaluated at discharge and six months later. Clinical, analytical, and imaging variables were collected. A neurocognitive, nutritional, and frailty (FRAIL scale) assessment of the included patients was carried out. The risk of depression was considered for a result above 5 points on the PHQ-9 scale. Results: The variables that were significantly related to the risk of depression 6 months after admission for COVID-19 were frailty (p = 0.006 for pre-frail and p = 0.001 for frail), small-vessel vascular disease in imaging tests (p = 0.033), vitamin D level (p = 0.006), and taking antidepressants (p = 0.011). Factors that were negatively associated with the presence of depression 6 months after discharge were a higher score on the CAMCOG cognitive scale (p = 0.041) and older age (p = 0.006). Conclusions: Frailty worsened the score on the PHQ-9 depression scale in patients who required hospital admission for SARS-CoV-2 infection. It is important to implement prevention measures both for frailty and depression in these patients.
Simulation and Analysis of Bidirectional Reflection Factors of Southern Evergreen Fruit Trees Based on 3D Radiative Transfer Model
Authors: Hong Chaofan , Li Dan , Han Liusheng , Du Xiong , Chen Shuisen , Qi Jianbo , Wang Chongyang , Zhou Xia , Qin Boxiong , Jiang Hao , Jia Kai , Su Zuanxian
Published: July 2024

The canopy of perennial evergreen fruit trees in southern China has a unique Bidirectional Reflectance Factor (BRF) due to its complex multi-branch structure and density changes. This study aimed to address the lack of clarity regarding the changes in BRF of evergreen fruit trees in southern China. Litchi, a typical fruit tree in this region, was chosen as the subject for establishing a three-dimensional (3D) real structure model. The canopy BRF of litchi was simulated under different leaf components, illumination geometry, observed geometry, and leaf area index (LAI) using a 3D radiation transfer model. The corresponding changes in characteristics were subsequently analyzed. The findings indicate that the chlorophyll content and equivalent water thickness of leaves exert significant influences on canopy BRF, whereas the protein content exhibit relatively weak effects. Variation in illumination and observation geometry results in the displacement of hotspots, with the solar zenith angle and view zenith angle exerting significant influence on the BRF. As the LAI of the litchi orchard increases, the distribution of hotspots becomes more concentrated, and the differences in angle information are relatively smaller when observed from multiple angles. With the increase in LAI in litchi orchards, the BRF on the principal plane would be saturated, but observation at hotspots could alleviate this phenomenon. The above analysis provides a reference for quantitative inversion of vegetation parameters using remote sensing monitoring information of typical perennial evergreen fruit trees.
Transcriptomic Analyses Reveal the Mechanism by Which Different Light Qualities and Light Duration Induce Anthocyanin Biosynthesis in ‘Kyoho’ Grapes
Authors: Sun Wu , Yan Yingying , Muhammad Zafarullah , Zhang Guoqiang
Published: July 2024

The light plays a key role in regulating anthocyanin biosynthesis in plants. However, the molecular basis of anthocyanin synthesis in grape skins irradiated at night with supplemental white light (W), red light (R), blue light (B), and blue light for 3 h, 6 h, 9 h, and 12 h (B3, B6, B9, and B12) is not known. In the present study, the total anthocyanin content in grape skins was significant under different light (DL) and blue-light time (DT) treatments, and the best result was obtained with B9. Analysis of RNA-seq data determined that the key genes in the anthocyanin synthesis pathway, PAL, CHS, DFR, GT, CFIP, VIT_14s0068g00920, VIT_06s0009g02860, and VIT_06s0004g08150, were significantly up-regulated under night-time supplemental light treatments, which led to the significant expression of the phenylpropanoid biosynthesis, phenylalanine metabolism, flavonoid biosynthesis, flavone and flavonol biosynthesis, and the anthocyanin biosynthesis pathway, which were significantly expressed, promoting the accumulation of anthocyanin. The B caused significant expression of PAL (VIT_08s0040g01710), CFIP (VIT_13s0067g03820, VIT_13s0067g02870) and DFR (VIT_18s0001g12800), which may be one of the reasons for the better effect of B compared to W anthocyanin enrichment in grape skins. The DT treatment resulted in significant expression of GT (VIT_11s0052g01600), Peroxidase, VIT_09s0018g01190, and VIT_11s0037g00570. In addition, many TFs such as bHLH, MYB, ERF, WRKY, C2H2, MYB-related, and NAC were found to be involved in the synthesis of anthocyanins under light regulation. These results provide new insights into plants’ nocturnal supplemental-light regulation of anthocyanin accumulation.
Chemical Profiles and Antimicrobial Properties of Essential Oils from Orange, Pummelo, and Tangelo Cultivated in Greece
Authors: Anastasopoulou Eleni , Graikou Konstantia , Ziogas Vasileios , Ganos Christos , Calapai Fabrizio , Chinou Ioanna
Published: July 2024

In the framework of our studies on Citrus cultivars in Greece, the chemical composition of the essential oils (EOs) from the peels and leaves of orange, pummelo, and tangelo (mandarin × grapefruit hybrid) cultivated in Greece have been studied. All EOs have been analyzed through GC-MS, and a total of 47 and 87 metabolites were identified in the peels and leaves, respectively. These metabolites are classified into the chemical groups of terpenes, alcohols, aldehydes, esters, ketones, and organic acids. Limonene was the most abundant compound in the peel EOs. Moreover, bioactive polymethoxyflavones (PMFs) were isolated and structurally determined from the peels of orange and tangelo, highlighting them as a good potential source of natural PMFs. All EOs were evaluated for their antimicrobial activity against nine human pathogenic microorganisms (six bacteria and three fungi), showing an interesting profile. The EOs from the peels of all Citrus species exhibited a stronger antimicrobial activity compared to those from the leaves. The susceptibility of the assayed Gram-positive bacteria was observed to be greater than that of Gram-negative bacteria, while the fungi were also relatively less resistant than bacteria. The rootstock choice did not influence the EO profile of the fruit peel but exerted an influence on the chemical profile of the leaves.
The Knowledge Acquired by Parents in Pregnancy Monitoring Consultations
Authors: Cerdeira Raquel , Zangão Otília
Published: July 2024

(1) Pregnancy surveillance nursing consultations in the pandemic context have undergone some changes, namely the restriction of accompanying persons. In this sense, assessing the knowledge acquired by parents in pregnancy surveillance is of great importance. Since there are no studies on the subject in the period before the pandemic, we will only assess the knowledge acquired by parents in pregnancy monitoring. (2) For this reason, the aim of our study is to evaluate the knowledge acquired by parents in pregnancy surveillance. (3) This study is descriptive, cross-sectional and quantitative in nature, with a sample of 196 couples. A questionnaire was administered about the knowledge acquired by parents in pregnancy surveillance nursing consultations. (4) Pregnant mothers and their partners reported having some knowledge. The classification was assessed using a questionnaire with quantifiable response options from 1 to 5 points. Items with a score of 1 indicate a low level of knowledge and 5 indicates a higher level of knowledge. (5) We can verify that the level of knowledge acquired by the pregnant mother during the pregnancy surveillance nursing consultation is higher than the level of knowledge acquired by the father during the same consultation. Most parents consider it important to receive information through the pregnancy surveillance nursing consultations carried out by Maternal and Obstetric Health Nurse Specialists (midwives).
Health, Performance Ratings and Approachability of 50–60-Year-Old Sedentary Adults (ActIv-Study): Key Insights for Health Economy and Exercise Promotion
Authors: Leyk Dieter , Hartmann Nadine , Vits Emanuel , Rüther Thomas , Klatt Stefanie , Lämmel Ralf , Löllgen Herbert
Published: July 2024

Despite significant prevention efforts, the numbers of physically inactive individuals, chronic illnesses, exhaustion syndromes and sick leaves are increasing. A still unresolved problem with exercise promotion is the low participation of sedentary persons. This collective term covers heterogeneous subgroups. Their engagement with movement campaigns and resistance to change are influenced by numerous factors. Our aim was to analyse survey data on health, performance, lifestyle habits and the approachability to physical activity campaigns obtained from the Germany-wide ActIv survey. From 2888 study participants aged 50–60 years, 668 persons were categorised into the subgroups “never-athletes”, “sports-dropouts”, “always-athletes” and “sports-beginners”. Large and significant group differences were found for BMI, assessment of quality of life, health and fitness, risk factors and health problems. In total, 42.5% of “never-athletes” and 32.5% of “sports-dropouts” did not state any barriers to sport. There are substantial disparities between the non-athlete groups in terms of their motivation to exercise. In contrast, there are comparatively minor differences in motivation between “sports-dropouts” and “sports-beginners”, whose health and fitness are the primary motivators for sport. Our analyses suggest that (i) negative health and performance trends cannot be compensated for by appeals for voluntary participation in exercise programmes and (ii) powerful incentive systems are required.
Parenting Stress Following a Neonatal Intensive Care Unit Hospitalization: A Longitudinal Study of Mothers and Fathers
Authors: Klein Corinna C. , McDonald Nicole M.
Published: July 2024

A neonatal intensive care unit (NICU) hospitalization can add significant stress to the postpartum period. Parents experience isolation and uncertainty, which can affect their capacity to bond with their new baby. Understanding how stress is shaped by and changes following a NICU experience will help in developing supports for these families. We examined patterns of parenting stress over the first year of life following a NICU stay to better understand changes in stress, differences in maternal and paternal stress, and how medical and developmental variables impact parent stress. Parents of infants (n = 51) who had experienced a NICU hospitalization and met criteria for California’s High-Risk Infant Follow-Up program completed assessments at 6, 9, and 12 months. A comparison group (n = 38) from a historic dataset included parents of infants born full term without medical complications. NICU parents reported higher levels of parenting stress at 6 months, but not 12 months, with mothers and fathers reporting similar stress levels. Parenting-related stress was found to be relatively stable and consistent over this period. Among NICU parents, lower developmental level at 12 months was associated with more distress in interacting with their child. These findings highlight the importance of monitoring parenting stress following discharge from the NICU and developing interventions for supporting parents of NICU graduates showing developmental delays.
Overexpression of miR-199b-5p in Colony Forming Unit-Hill’s Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression
Authors: Bakhashab Sherin , Barber Rosie , O’Neill Josie , Arden Catherine , Weaver Jolanta U.
Published: July 2024

Well-controlled type 1 diabetes (T1DM) is characterized by inflammation and endothelial dysfunction, thus constituting a suitable model of subclinical cardiovascular disease (CVD). miR-199b-5p overexpression in murine CVD has shown proatherosclerotic effects. We hypothesized that miR-199b-5p would be overexpressed in subclinical CVD yet downregulated following metformin therapy. Inflammatory and vascular markers were measured in 29 individuals with T1DM and 20 matched healthy controls (HCs). miR-199b-5p expression in CFU-Hill’s colonies was analyzed from each study group, and correlations with inflammatory/vascular health indices were evaluated. Significant upregulation of miR-199b-5p was observed in T1DM, which was significantly downregulated by metformin. miR-199b-5p correlated positively with vascular endothelial growth factor-D and c-reactive protein (CRP: nonsignificant). ROC analysis determined miR-199b-5p to define subclinical CVD by discriminating between HCs and T1DM individuals. ROC analyses of HbA1c and CRP showed that the upregulation of miR-199b-5p in T1DM individuals defined subclinical CVD at HbA1c > 44.25 mmol and CRP > 4.35 × 106 pg/mL. Ingenuity pathway analysis predicted miR-199b-5p to inhibit the target genes SIRT1, ETS1, and JAG1. Metformin was predicted to downregulate miR-199b-5p via NFATC2 and STAT3 and reverse its downstream effects. This study validated the antiangiogenic properties of miR-199b-5p and substantiated miR-199b-5p overexpression as a biomarker of subclinical CVD. The downregulation of miR-199b-5p by metformin confirmed its cardio-protective effect.
Functional Validation of Endogenous Redox Partner Cytochrome P450 Reductase Reveals the Key P450s CYP6P9a/-b as Broad Substrate Metabolizers Conferring Cross-Resistance to Different Insecticide Classes in Anopheles funestus
Authors: Ibrahim Sulaiman S. , Kouamo Mersimine F. M. , Muhammad Abdullahi , Irving Helen , Riveron Jacob M. , Tchouakui Magellan , Wondji Charles S.
Published: July 2024

The versatility of cytochrome P450 reductase (CPR) in transferring electrons to P450s from other closely related species has been extensively exploited, e.g., by using An. gambiae CPR (AgCPR), as a homologous surrogate, to validate the role of An. funestus P450s in insecticide resistance. However, genomic variation between the AgCPR and An. funestus CPR (AfCPR) suggests that the full metabolism spectrum of An. funestus P450s might be missed when using AgCPR. To test this hypothesis, we expressed AgCPR and AfCPR side-by-side with CYP6P9a and CYP6P9b and functionally validated their role in the detoxification of insecticides from five different classes. Major variations were observed within the FAD- and NADP-binding domains of AgCPR and AfCPR, e.g., the coordinates of the second FAD stacking residue AfCPR-Y456 differ from that of AgCPR-His456. While no significant differences were observed in the cytochrome c reductase activities, when co-expressed with their endogenous AfCPR, the P450s significantly metabolized higher amounts of permethrin and deltamethrin, with CYP6P9b-AfCPR membrane metabolizing α-cypermethrin as well. Only the CYP6P9a-AfCPR membrane significantly metabolized DDT (producing dicofol), bendiocarb, clothianidin, and chlorfenapyr (bioactivation into tralopyril). This demonstrates the broad substrate specificity of An. funestus CYP6P9a/-b, capturing their role in conferring cross-resistance towards unrelated insecticide classes, which can complicate resistance management.
An In Vivo Model of Propionic Acid-Rich Diet-Induced Gliosis and Neuro-Inflammation in Mice (FVB/N-Tg(GFAPGFP)14Mes/J): A Potential Link to Autism Spectrum Disorder
Authors: Lagod Piotr P. , Abdelli Latifa S. , Naser Saleh A.
Published: July 2024

Evidence shows that Autism Spectrum Disorder (ASD) stems from an interplay of genetic and environmental factors, which may include propionic acid (PPA), a microbial byproduct and food preservative. We previously reported that in vitro treatment of neural stem cells with PPA leads to gliosis and neuroinflammation. In this study, mice were exposed ad libitum to a PPA-rich diet for four weeks before mating. The same diet was maintained through pregnancy and administered to the offspring after weaning. The brains of the offspring were studied at 1 and 5 months postpartum. Glial fibrillary acidic protein (astrocytic marker) was significantly increased (1.53 ± 0.56-fold at 1 M and 1.63 ± 0.49-fold at 5 M) in the PPA group brains. Tubulin IIIβ (neuronal marker) was significantly decreased in the 5 M group. IL-6 and TNF-α expression were increased in the brain of the PPA group (IL-6: 2.48 ± 1.25-fold at 5 M; TNF-α: 2.84 ± 1.16-fold at 1 M and 2.64 ± 1.42-fold, at 5 M), while IL-10 was decreased. GPR41 and p-Akt were increased, while PTEN (p-Akt inhibitor) was decreased in the PPA group. The data support the role of a PPA-rich diet in glia over-proliferation and neuro-inflammation mediated by the GPR41 receptor and PTEN/Akt pathway. These findings strongly support our earlier study on the role of PPA in ASD.
Deciphering the Effects of the PYCR Family on Cell Function, Prognostic Value, Immune Infiltration in ccRCC and Pan-Cancer
Authors: Chen Hongquan , Chen Qing , Chen Jinyang , Mao Yazhen , Duan Lidi , Ye Dongjie , Cheng Wenxiu , Chen Jiaxi , Gao Xinrong , Lin Renxi , Lin Weibin , Zhang Mingfang , Qi Yuanlin
Published: July 2024

Pyrroline-5-carboxylate reductase (PYCR) is pivotal in converting pyrroline-5-carboxylate (P5C) to proline, the final step in proline synthesis. Three isoforms, PYCR1, PYCR2, and PYCR3, existed and played significant regulatory roles in tumor initiation and progression. In this study, we first assessed the molecular and immune characteristics of PYCRs by a pan-cancer analysis, especially focusing on their prognostic relevance. Then, a kidney renal clear cell carcinoma (KIRC)-specific prognostic model was established, incorporating pathomics features to enhance predictive capabilities. The biological functions and regulatory mechanisms of PYCR1 and PYCR2 were investigated by in vitro experiments in renal cancer cells. The PYCRs’ expressions were elevated in diverse tumors, correlating with unfavorable clinical outcomes. PYCRs were enriched in cancer signaling pathways, significantly correlating with immune cell infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI). In KIRC, a prognostic model based on PYCR1 and PYCR2 was independently validated statistically. Leveraging features from H&E-stained images, a pathomics feature model reliably predicted patient prognosis. In vitro experiments demonstrated that PYCR1 and PYCR2 enhanced the proliferation and migration of renal carcinoma cells by activating the mTOR pathway, at least in part. This study underscores PYCRs’ pivotal role in various tumors, positioning them as potential prognostic biomarkers and therapeutic targets, particularly in malignancies like KIRC. The findings emphasize the need for a broader exploration of PYCRs’ implications in pan-cancer contexts.
Effect of Torilis japonica Fruit Extract for Endothelium-Independent Vasorelaxation and Blood Pressure Lowering in Rats
Authors: Park Junkyu , Shin Sujin , Kim Youngmin , Bu Youngmin , Choi Ho-Young , Lee Kyungjin
Published: July 2024

Torilis japonica (TJ) fruit, is a herb that is traditionally used for erectile dysfunction (ED). Given the shared mechanisms of ED and hypertension through vascular smooth muscle, we hypothesized that TJ would be effective in vasodilation and blood pressure reduction. This study confirmed the authenticity of TJ samples via DNA barcoding and quantified the main active compound, torilin, using HPLC. TJ was extracted with distilled water (TJW) and 50% ethanol (TJE), yielding torilin contents of 0.35 ± 0.01% and 2.84 ± 0.02%, respectively. Ex vivo tests on thoracic aortic rings from Sprague–Dawley rats showed that TJE (3–300 µg/mL) induced endothelium-independent, concentration-dependent vasodilation, unlike TJW. Torilin caused concentration-dependent relaxation with an EC50 of 210 ± 1.07 µM. TJE’s effects were blocked by a voltage-dependent K+ channel blocker and alleviated contractions induced by CaCl2 and angiotensin II. TJE inhibited vascular contraction induced by phenylephrine or KCl via extracellular CaCl2 and enhanced inhibition with nifedipine, indicating involvement of voltage-dependent and receptor-operated Ca2+ channels. Oral administration of TJE (1000 mg/kg) significantly reduced blood pressure in spontaneously hypertensive rats. These findings suggest TJ extract’s potential for hypertension treatment through vasorelaxant mechanisms, though further research is needed to confirm its efficacy and safety.
Harmonic Generation in Molecular Ag2S Plasma
Authors: Ganeev Rashid A.
Published: July 2024

The molecular laser-induced plasma (LIP) produced during the ablation of silver sulfide (Ag2S) was used as a medium for high-order harmonic generation in the extreme ultraviolet range. The role of LIP formation, the plasma components, and the geometry of plasma in the harmonic conversion efficiency was analyzed. We also analyzed the influence of the driving pulses (chirp, single-color pump, two-color pump, and delay between heating and converting pulses) on the harmonic yield in Ag2S LIP. The application of molecular plasma was compared with the application of atomic plasma, which comprised similar metallic elements (Ag) as well as other metal LIPs. The harmonics from the Ag2S LIP were 4 to 10 times stronger than those from the Ag LIP. The harmonics up to the 59th order were achieved under the optimal conditions for the molecular plasma.
MMP-14 Exhibits Greater Expression, Content and Activity Compared to MMP-15 in Human Renal Carcinoma
Authors: Młynarczyk Grzegorz , Tokarzewicz Anna , Gudowska-Sawczuk Monika , Mroczko Barbara , Novák Vojtěch , Novák Adam , Mitura Przemysław , Romanowicz Lech
Published: July 2024

Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity—both actual and specific—was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.
4-Phenylbutyric Acid Treatment Reduces Low-Molecular-Weight Proteinuria in a Clcn5 Knock-in Mouse Model for Dent Disease-1
Authors: Perdomo-Ramírez Ana , Ramos-Trujillo Elena , Machado Jose David , García-Nieto Victor , Mura-Escorche Glorián , Claverie-Martin Félix
Published: July 2024

Dent disease-1 (DD-1) is a rare X-linked tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, nephrolithiasis and nephrocalcinosis. This disease is caused by inactivating mutations in the CLCN5 gene which encodes the voltage-gated ClC-5 chloride/proton antiporter. Currently, the treatment of DD-1 is only supportive and focused on delaying the progression of the disease. Here, we generated and characterized a Clcn5 knock-in mouse model that carries a pathogenic CLCN5 variant, c. 1566_1568delTGT; p.Val523del, which has been previously detected in several DD-1 unrelated patients, and presents the main clinical manifestations of DD-1 such as high levels of urinary b2-microglobulin, phosphate and calcium. Mutation p.Val523del causes partial ClC-5 retention in the endoplasmic reticulum. Additionally, we assessed the ability of sodium 4-phenylbutyrate, a small chemical chaperone, to ameliorate DD-1 symptoms in this mouse model. The proposed model would be of significant value in the investigation of the fundamental pathological processes underlying DD-1 and in the development of effective therapeutic strategies for this rare condition.
The Role of Changes in the Expression of Inflammation-Associated Genes in the Variants of Cerebral Small Vessel Disease
Authors: Dobrynina Larisa A. , Makarova Angelina G. , Shabalina Alla A. , Burmak Anastasiia G. , Shlapakova Polina S. , Shamtieva Kamila V. , Tsypushtanova Maria M. , Kremneva Elena I. , Zabitova Maryam R. , Filatov Alexey S. , Gnedovskaya Elena V.
Published: July 2024

Age-dependent cerebral small vessel disease (CSVD) is a common disease with a high social burden characterized by heterogeneity of forms and frequent comorbidity with Alzheimer’s disease (AD). Previously, we identified two MRI types of CSVD with specific clinical presentation and, probably, different mechanisms. The present study included 34 patients with CSVD and white matter hyperintensity (WMH) of stage Fazekas (F) 3 (mean age 61.7 ± 8.9) and 11 volunteers (mean age 57.3 ± 9.7). Total RNA was isolated from peripheral blood leukocytes. The expression of 58 protein-coding genes associated with CSVD and/or AD and 4 reference genes were assessed as part of the original panel for the NanoString nCounter analyzer. Testing results were validated by real-time PCR. There was a significant decrease in the expression levels of the ACOX1, CD33, CD2AP, TNFR1, and VEGFC genes in MRI type 2 relative to the control group as well as a decrease in the expression level of the CD33 gene in MRI type 2 compared to MRI type 1. Processes associated with inflammatory pathways with decreased expression of the identified genes are important in the development of MRI type 2 of CSVD. Given the direct connection of the established genes with AD, the importance of this form of CSVD in comorbidity with AD has been assumed.
Alzheimer’s Disease Neuropathological Change in Aged Non-Primate Mammals
Authors: Ferrer Isidro
Published: July 2024

Human brain aging is characterized by the production and deposition of β-amyloid (Aβ) in the form of senile plaques and cerebral amyloid angiopathy and the intracellular accumulation of hyper-phosphorylated tau (Hp-tau) to form neurofibrillary tangles (NFTs) and dystrophic neurites of senile plaques. The process progresses for years and eventually manifests as cognitive impairment and dementia in a subgroup of aged individuals. Aβ is produced and deposited first in the neocortex in most aged mammals, including humans; it is usually not accompanied by altered behavior and cognitive impairment. Hp-tau is less frequent than Aβ pathology, and NFTs are rare in most mammals. In contrast, NFTs are familiar from middle age onward in humans; NFTs first appear in the paleocortex and selected brain stem nuclei. NFTs precede for decades or years Aβ deposition and correlate with dementia in about 5% of individuals at the age of 65 and 25% at the age of 85. Based on these comparative data, (a) Aβ deposition is the most common Alzheimer’s disease neuropathological change (ADNC) in the brain of aged mammals; (b) Hp-tau is less common, and NFTs are rare in most aged mammals; however, NFTs are the principal cytoskeletal pathology in aged humans; (c) NFT in aged humans starts in selected nuclei of the brain stem and paleocortical brain regions progressing to the most parts of the neocortex and other regions of the telencephalon; (d) human brain aging is unique among mammalian species due to the early appearance and dramatic progression of NFTs from middle age onward, matching with cognitive impairment and dementia in advanced cases; (e) neither mammalian nor human brain aging supports the concept of the amyloid cascade hypothesis.
COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer
Authors: Ho Chih-Ming , Yen Ting-Lin , Chang Tzu-Hao , Huang Shih-Hung
Published: July 2024

Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival among EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, p <0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibited reduced invasion ability (p < 0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p < 0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p = 0.007) or SKOV3/COL6A3 cells and PBS (p = 0.039). Knockdown of COL6A3 or treatment with EX inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness of EOC.
Get Spliced: Uniting Alternative Splicing and Arthritis
Authors: van Haaren Maurice J. H. , Steller Levina Bertina , Vastert Sebastiaan J. , Calis Jorg J. A. , van Loosdregt Jorg
Published: July 2024

Immune responses demand the rapid and precise regulation of gene protein expression. Splicing is a crucial step in this process; ~95% of protein-coding gene transcripts are spliced during mRNA maturation. Alternative splicing allows for distinct functional regulation, as it can affect transcript degradation and can lead to alternative functional protein isoforms. There is increasing evidence that splicing can directly regulate immune responses. For several genes, immune cells display dramatic changes in isoform-level transcript expression patterns upon activation. Recent advances in long-read RNA sequencing assays have enabled an unbiased and complete description of transcript isoform expression patterns. With an increasing amount of cell types and conditions that have been analyzed with such assays, thousands of novel transcript isoforms have been identified. Alternative splicing has been associated with autoimmune diseases, including arthritis. Here, GWASs revealed that SNPs associated with arthritis are enriched in splice sites. In this review, we will discuss how alternative splicing is involved in immune responses and how the dysregulation of alternative splicing can contribute to arthritis pathogenesis. In addition, we will discuss the therapeutic potential of modulating alternative splicing, which includes examples of spliceform-based biomarkers for disease severity or disease subtype, splicing manipulation using antisense oligonucleotides, and the targeting of specific immune-related spliceforms using antibodies.
Genome-Wide Association and RNA-Seq Analyses Reveal a Potential Candidate Gene Related to Oil Content in Soybean Seeds
Authors: Jia Hongchang , Han Dezhi , Yan Xiaofei , Zhang Lei , Liang Jili , Lu Wencheng
Published: July 2024

Soybean is a crucial crop globally, serving as a significant source of unsaturated fatty acids and protein in the human diet. However, further enhancements are required for the related genes that regulate soybean oil synthesis. In this study, 155 soybean germplasms were cultivated under three different environmental conditions, followed by phenotypic identification and genome-wide association analysis using simplified sequencing data. Genome-wide association analysis was performed using SLAF-seq data. A total of 36 QTLs were significantly associated with oil content (−log10(p) > 3). Out of the 36 QTLs associated with oil content, 27 exhibited genetic overlap with previously reported QTLs related to oil traits. Further transcriptome sequencing was performed on extreme high–low oil soybean varieties. Combined with transcriptome expression data, 22 candidate genes were identified (|log2FC| ≥ 3). Further haplotype analysis of the potential candidate genes showed that three potential candidate genes had excellent haplotypes, including Glyma.03G186200, Glyma.09G099500, and Glyma.18G248900. The identified loci harboring beneficial alleles and candidate genes likely contribute significantly to the molecular network’s underlying marker-assisted selection (MAS) and oil content.
Buckling Instability of Monopiles in Liquefied Soil via Structural Reliability Assessment Framework
Authors: Bachinilla Brian , Siddhpura Milind , Evangelista Ana , Hammad Ahmed WA , Haddad Assed N.
Published: July 2024

During devastating earthquakes, soil liquefaction has disastrous outcomes on bridge foundations, as mentioned in books and published research. To avoid foundation failure when the surrounding soil is fully liquefied, a bridge’s pile foundation design could be such that the bridge pier is directly resting on the top of a large-diameter monopile instead of the traditional multiple small-diameter piles. This paper discusses the gap of insufficient studies on large-diameter monopiles to support railway bridges subjected to buckling instability and the lack of simplified tools to quickly assess structural reliability. A framework could quickly assess the structural reliability by formulating a simplified reliability analysis. This study focused on pure buckling with shear deformation and reliability assessment to calculate a monopile’s failure probability in fully liquefied soils. In reliability assessment, with the critical pile length (Lcrit) and the unsupported pile length (Luns), the limit state function g(x) = [Lcrit − Luns] thus forms the basis for assessing the safety and reliability of a structure, indicating the state of success or failure. The Lcrit formulation is accomplished with a differential equation. Here, Luns assumes various depths of liquefied soil. The reliability index’s (β) formulation is achieved through the Hasofer–Lind concept and then double-checked through a normal or Gaussian distribution. A case study was conducted using a high-speed railway bridge model from a published research to demonstrate the application of the proposed methodology. To validate the minimum pile diameter for buckling instability when a fully liquefied soil’s thickness reaches the condition that Lcrit = Luns, this study applies the published research of Bhattacharya and Tokimatsu. The validation results show good agreement for 0.85–0.90 m monopile diameters. With a monopile diameter smaller than 0.85 m, the Lcrit = Luns limit was at lesser depths, while with a monopile diameter larger than 0.90 m, the Lcrit = Luns limit was at deeper depths. A load increase notably affected the large-diameter monopiles because the Lcrit movement required a longer range. In fully liquefied soil, buckling will likely happen in piles with a diameter between 0.50 m and 1.60 m because the calculated probability of failure (Pf) value is nearly one. Conversely, buckling instability will likely not happen in monopiles with a diameter of 1.80–2.20 m because the Pf value is zero. Hence, the outcome of this case study suggests that the reliable monopile minimum diameter is 1.80 m for supporting a high-speed railway bridge. Lastly, this paper analyzed the shear deformation effect on large-diameter monopiles, the result of which was 0.30% of Lcrit. Shear deformation makes minimal contributions to large-diameter monopile buckling.
Comparative Population Biology and Related Gene Expression in the Beta-Cypermethrin-Resistant Strains of Bactrocera dorsalis (Hendel)
Authors: Li Doudou , Chen Langjie , Cai Xinyan , Qi Yixiang , Lu Yongyue
Published: July 2024

Diptera and Lepidoptera species have the highest levels of insecticide resistance, and the mechanism of drug resistance has been studied in detoxification metabolism genes such as P450, GST, EST, and ABC. Since Bactrocera dorsalis are resistant to a variety of chemicals, the pattern and mechanism of resistance in Bactrocera dorsalis have been investigated from a variety of aspects such as detoxification metabolism genes, detoxification enzymes, intestinal symbiotic bacteria, and synergists in the world. In this study, 51 species and 149 detoxification metabolism genes were annotated in the Suppression Subtractive Hybridization (SSH) library, and 12 candidate genes related to beta-cypermethrin resistance were screened and quantitatively expressed in this library. Two genes were found to be upregulated in the egg stage, three genes in the larval stage, one gene in the pupal stage, and five genes in the adult stage, and four genes were found to be upregulated in the midgut and the malacca ducts in the midgut. The expression of cyp6g1, cyp6a22, GST-Epsilon9, and Trypsin-4 genes was upregulated in resistant strains, with the most obvious upregulation occurring in the midgut and the Malpighian tubules. These results provide new insights into the study of pesticide resistance in quarantine insects.
Aircraft Innovation Trends Enabling Advanced Air Mobility
Authors: Bridgelall Raj
Published: July 2024

This study presents a comprehensive exploration of vertical take-off and landing (VTOL) aircraft within advanced air mobility (AAM), examining the crucial challenges of integrating these innovative technologies into transportation systems. AAM promises transformational social change by enhancing transportation energy efficiency, safety, and operational effectiveness. This research utilizes a methodical approach that juxtaposes a systematic review of patents with an extensive analysis of the academic literature to map the innovation landscape of VTOL technology. This dual analysis reveals a dynamic progression in VTOL advancements, highlighting significant strides in aerodynamic optimization, propulsion technology, and control systems. The novelty of this study lies in its dual-method approach, combining patent analysis with the academic literature to provide a holistic view of VTOL technological evolution. The patent analysis reveals that companies have been most productive on innovations relating to VTOL aircraft transition efficiency, control enhancement, and energy management. The literature review identifies key trends such as the rise in electric propulsion technologies and the integration of AI-driven control mechanisms. These results provide new engineering knowledge that can guide future VTOL development and policy formulation. The original contributions include a detailed mapping of VTOL innovation trends, identification of key technological advancements, and a predictive lens into future directions. These findings offer a valuable resource for aerospace engineers, policymakers, and urban planners. This study contributes a detailed assessment of both theoretical foundations and practical applications, fostering a holistic view of the challenges and innovations shaping the future of AAM. By connecting research and practical development, this study serves as a critical tool for strategic decision making and policy formulation towards advancing the integration of VTOL aircraft into sustainable urban transportation networks.
Hearing Screening for Congenital CytoMegaloVirus—Exploring Parents’ Experiences of Completing Targeted Congenital Cytomegalovirus Screening at the Time of Their Infants’ Newborn Hearing Screening
Authors: Webb Emma , Hodgson Jan , Gillespie Alanna N. , Jones Cheryl A. , Poulakis Zeffie , Wong Janis , Sung Valerie
Published: July 2024

Background/Objectives: Congenital cytomegalovirus (cCMV) is the leading infectious cause of sensorineural hearing loss and neurodevelopmental disabilities, with prompt detection (<21 days of life) required to enable accurate diagnosis and anti-viral treatment where clinically appropriate. International guidelines recommend cCMV screening for infants who do not pass their Universal Newborn Hearing Screening (UNHS). This study aimed to explore parental experiences of targeted cCMV screening through the UNHS in Victoria, Australia between 2019 and 2020 (HearS-cCMV study). Methods: A qualitative study comprising 18 semi-structured interviews with parents who took saliva swabs from their infants who did not pass their UNHS. A maximum variation sampling strategy was used with data analysed using thematic analysis. Results: Four themes described 18 parents’ experiences of cCMV screening: (1) parents’ lack of CMV awareness prior to cCMV screening; (2) overall positive experience; (3) varied understanding of CMV post screening; and (4) parents were glad to screen their infant for cCMV. Enablers of targeted cCMV screening included the swab being simple and non-invasive, being easier to complete in the hospital than at home, and the screening being well delivered by the staff. Barriers included a potential increase in anxiety, especially with false positives, and the timing of cCMV screening coinciding with their infant not passing UNHS being difficult for some parents. Conclusions: Parent experiences of targeted cCMV screening were positive. Increasing public knowledge of cCMV and training staff members to complete the CMV swab would reduce the risk of false positives and associated parental anxiety. This would facilitate successful routine targeted cCMV screening.
Autologous Fat Grafting (AFG): A Systematic Review to Evaluate Oncological Safety in Breast Cancer Patients
Authors: Lo Torto Federico , Patanè Luca , Abbaticchio Donato , Pagnotta Alessia , Ribuffo Diego
Published: July 2024

Background: Autologous fat grafting (AFG) has emerged as a useful technique in breast reconstruction. Utilizing a patient’s own fat from areas like the abdomen or thighs, AFG serves various reconstruction needs. Nevertheless, the oncological safety of AFG in breast cancer patients has become a contentious issue. Concerns about its influence on cancer recurrence and detention have led to significant clinical debate and the need for thorough investigation. Methods: To determine the impact of autologous fat grafting (AFG) on loco-regional recurrence (LRR) in breast cancer survivors undergoing reconstruction, a comprehensive search of databases including PubMed, Medline, Web of Science, and Cochrane libraries was conducted from November 2023 through March 2024. This search adhered to the PRISMA guidelines and aimed to identify all the relevant studies on AFG in the context of breast reconstruction post cancer treatment. A meta-analysis was performed. Results: Out of the studies reviewed, 40 met the inclusion criteria, with a total patient cohort of 14,078. The analysis revealed that AFG had no significant association with increased rates of LRR. Conclusions: According to the available literature, AFG is a safe reconstructive option for breast cancer patients and does not increase the risk of loco-regional recurrence. Nevertheless, further well-structured long-term prospective studies are required, since heterogeneity of available studies is high and requires standardization.
Minimally Invasive Plasma Device Management of Multiple Benign Skin Cancers Associated with Rare Genodermatoses—Case Series and Review of the Therapeutic Methods
Authors: Płatkowska Anna , Słowińska Monika , Zalewska Joanna , Swacha Zbigniew , Szumera-Ciećkiewicz Anna , Wągrodzki Michał , Patera Janusz , Łapieńska-Rey Katarzyna , Lorent Małgorzata , Ługowska Iwona , Rutkowski Piotr , Owczarek Witold
Published: July 2024

Background: Non-melanocytic benign skin tumours encompass a diverse group of lesions, classified based on their cellular origin, such as epidermal, vascular, fibrous, neural, muscle, and adnexal tumours. Though they often reveal solitary lesions, multiple skin tumours focus on genodermatoses. Each syndrome exhibits distinct clinical characteristics and potential complications, including cutaneous and extra-cutaneous malignancies, some of which are potentially life-threatening. Diagnosing genetic syndromes is complex and requires numerous histopathological and immunohistochemistry tests due to similarities between the adnexal tumours and basal cell carcinoma upon pathology. Methods: To illustrate the clinical practice, we conducted a retrospective case study that included eleven patients with genodermatoses referred to a tertiary dermatology clinic from September 2018 to April 2024. We have also conducted a research study on available treatment modalities in this setting. Results: Five patients with excellent aesthetic results were treated using a recently approved FDA plasma device. After searching SCOPUS and PubMed database records, we assessed 96 original articles to present current knowledge regarding the dermato-surgical approach. Conclusions: Multiple skin tumours, especially on the face, may significantly affect patients’ quality of life and have psychological consequences. An appropriate treatment selection tailored to the patient’s needs should be provided. There is no standardised treatment for multiple benign tumours in genodermatoses, and selected methods with varying efficacy are employed. We presented the utility of a new plasma device in these settings.
Spontaneous Non-Aneurysmal Convexity Subarachnoid Hemorrhage: A Scoping Review of Different Etiologies beyond Cerebral Amyloid Angiopathy
Authors: Zedde Marialuisa , Grisendi Ilaria , Assenza Federica , Napoli Manuela , Moratti Claudio , Pavone Claudio , Bonacini Lara , Cecco Giovanna Di , D’Aniello Serena , Pezzella Francesca Romana , Merlino Giovanni , Piazza Fabrizio , Pezzini Alessandro , Morotti Andrea , Fainardi Enrico , Toni Danilo , Valzania Franco , Pascarella Rosario
Published: July 2024

Spontaneous convexity subarachnoid hemorrhage (cSAH) is a vascular disease different from aneurysmal SAH in neuroimaging pattern, causes, and prognosis. Several causes might be considered in individual patients, with a limited value of the patient’s age for discriminating among these causes. Cerebral amyloid angiopathy (CAA) is the most prevalent cause in people > 60 years, but reversible cerebral vasoconstriction syndrome (RCVS) has to be considered in young people. CAA gained attention in the last years, but the most known manifestation of cSAH in this context is constituted by transient focal neurological episodes (TFNEs). CAA might have an inflammatory side (CAA-related inflammation), whose diagnosis is relevant due to the efficacy of immunosuppression in resolving essudation. Other causes are hemodynamic stenosis or occlusion in extracranial and intracranial arteries, infective endocarditis (with or without intracranial infectious aneurysms), primary central nervous system angiitis, cerebral venous thrombosis, and rarer diseases. The diagnostic work-up is fundamental for an etiological diagnosis and includes neuroimaging techniques, nuclear medicine techniques, and lumbar puncture. The correct diagnosis is the first step for choosing the most effective and appropriate treatment.