bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative profiling of extrachromosomal circular DNA in placenta and maternal plasma provides insights into the biology of fetal growth restriction and reveals potential biomarkers
Authors: Lin Minhuan , Chen Yiqing , Xia Shuting , He Zhiming , Yu Xuegao , Huang Linhuan , Lin Shaobin , Liang Binrun , Huang Ziliang , Mei Shiqiang , Liu Dong , Zheng Lingling , Luo Yanmin 
Published: July 2023

Introduction: Fetal growth restriction (FGR) is a placenta-mediated pregnancy complication that predisposes fetuses to perinatal complications. Maternal plasma cell-free DNA harbors DNA originating from placental trophoblasts, which is promising for the prenatal diagnosis and prediction of pregnancy complications. Extrachromosomal circular DNA (eccDNA) is emerging as an ideal biomarker and target for several diseases.Methods: We utilized eccDNA sequencing and bioinformatic pipeline to investigate the characteristics and associations of eccDNA in placenta and maternal plasma, the role of placental eccDNA in the pathogenesis of FGR, and potential plasma eccDNA biomarkers of FGR.Results: Using our bioinformatics pipelines, we identified multi-chromosomal-fragment and single-fragment eccDNA in placenta, but almost exclusively single-fragment eccDNA in maternal plasma. Relative to that in plasma, eccDNA in placenta was larger and substantially more abundant in exons, untranslated regions, promoters, repetitive elements [short interspersed nuclear elements (SINEs)/Alu, SINEs/mammalian-wide interspersed repeats, long terminal repeats/endogenous retrovirus-like elements, and single recognition particle RNA], and transcription factor binding motifs. Placental multi-chromosomal-fragment eccDNA was enriched in confident enhancer regions predicted to pertain to genes in apoptosis, energy, cell growth, and autophagy pathways. Placental eccDNA–associated genes whose abundance differed between the FGR and control groups were associated with immunity-related gene ontology (GO) terms. The combined analysis of plasma and placental eccDNA–associated genes in the FGR and control groups led to the identification of potential biomarkers that were assigned to the GO terms of the epigenetic regulation of gene expression and nutrient-related processes, respectively.Conclusion: Together, our results highlight links between placenta functions and multi-chromosomal-fragment and single-fragment eccDNA. The integrative analysis of placental and plasma eccDNA confirmed the potential of these molecules as disease-specific biomarkers of FGR.
Growth hormone remodels the 3D-structure of the mitochondria of inflammatory macrophages and promotes metabolic reprogramming
Authors: Soler Palacios Blanca , Villares Ricardo , Lucas Pilar , Rodríguez-Frade José Miguel , Cayuela Ana , Piccirillo Jonathan G. , Lombardía Manuel , Delgado Gestoso David , Fernández-García Miguel , Risco Cristina , Barbas Coral , Corrales Fernando , Sorzano Carlos Oscar S. , Martínez-Martín Nuria , Conesa José Javier , Iborra Francisco J. , Mellado Mario 
Published: July 2023

IntroductionMacrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming.MethodsHere we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy.ResultsWe demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae.ConclusionsOur data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases.
A network-based approach reveals long non-coding RNAs associated with disease activity in lupus nephritis: key pathways for flare and potential biomarkers to be used as liquid biopsies
Authors: Sentis George , Loukogiannaki Catherine , Malissovas Nikos , Nikolopoulos Dionysis , Manolakou Theodora , Flouda Sofia , Grigoriou Maria , Banos Aggelos , Boumpas Dimitrios T. , Filia Anastasia 
Published: July 2023

ObjectiveA blood-based biomarker is needed to assess lupus nephritis (LN) disease activity, minimizing the need for invasive kidney biopsies. Long non-coding RNAs (lncRNAs) are known to regulate gene expression, appear to be stable in human plasma, and can serve as non-invasive biomarkers.MethodsTranscriptomic data of whole blood samples from 74 LN patients and 20 healthy subjects (HC) were analyzed to identify differentially expressed (DE) lncRNAs associated with quiescent disease and flares. Weighted gene co-expression network analysis (WGCNA) was performed to uncover lncRNAs with a central role (hub lncRNAs) in regulating key biological processes that drive LN disease activity. The association of hub lncRNAs with disease activity was validated using RT-qPCR on an independent cohort of 15 LN patients and 9 HC. cis- and trans-targets of validated lncRNAs were explored in silico to examine potential mechanisms of their action.ResultsThere were 444 DE lncRNAs associated with quiescent disease and 6 DE lncRNAs associated with flares (FDR &lt;0.05). WGCNA highlighted IFN signaling and B-cell activity/adaptive immunity as the most significant processes contributing to nephritis activity. Four disease-activity-associated lncRNAs, namely, NRIR, KLHDC7B-DT, MIR600HG, and FAM30A, were detected as hub genes and validated in an independent cohort. NRIR and KLHDC7B-DT emerged as potential key regulators of IFN-mediated processes. Network analysis suggests that FAM30A and MIR600HG are likely to play a central role in the regulation of B-cells in LN through cis-regulation effects and a competing endogenous RNA mechanism affecting immunoglobulin gene expression and the IFN-λ pathway.ConclusionsThe expression of lncRNAs NRIR, KLHDC7B-DT, FAM30A, and MIR600HG were associated with disease activity and could be further explored as blood-based biomarkers and potential liquid biopsy on LN.
Age-related effects on the modulation of gut microbiota by pectins and their derivatives: an in vitro study
Authors: Gu Fangjie , Larsen Nadja , Pascale Nélida , Petersen Sune Allan , Khakimov Bekzod , Respondek Frederique , Jespersen Lene 
Published: July 2023

IntroductionThe present study investigates whether supplementation with pectin-type polysaccharides has potential to improve aging-associated dysbiosis of the gut microbiota. The influence of different types of pectins on the gut microbiota composition and short-chain fatty acids (SCFAs) profiles of elderly was compared to younger adults.MethodsPectins studied included a pectin polysaccharide (PEC), a partially hydrolyzed pectin (PPH), and a pectin oligosaccharide (POS). Additionally, inulin was used as a reference prebiotic substrate. Individual fecal samples were collected from healthy elderly volunteers (70–75 years) and younger adults (30–35 years). In vitro fermentations were performed using the CoMiniGut model with controlled temperature and pH. Samples were withdrawn at baseline and after 24 h fermentation for measurement of SCFAs production and microbiota composition by 16S rRNA gene sequencing.Results and DiscussionThe results showed that fermentations with PEC and PPH resulted in a specific stimulation of Faecalibacterium prausnitzii regardless of the age groups. Collinsella aerofaciens became a dominating species in the young adult group with fermentations of all three pectins, which was not observed in the elderly group. No significant differences in SCFAs production were found among the pectins, indicating a high level of functional redundancy. Pectins boosted various bacterial groups differently from the reference prebiotic substrate (inulin). We also found inulin had reduced butyrogenic and bifidogenic effects in the elderly group compared to the younger adult group. In conclusion, the in vitro modulating effects of pectins on elderly gut microbiota showed potential of using pectins to improve age-related dysbiosis.
Effects of early postnatal hyperoxia exposure combined with early ovalbumin sensitization on lung inflammation and bacterial flora in a juvenile mouse model of asthma
Authors: Li Jingyan , Bao Tianping , Cao Linxia , Ma Mengmeng , Zhang Yuan , Tian Zhaofang 
Published: July 2023

ObjectiveThe aim of this study is to explore the effects of early postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization on lung inflammation and bacterial flora in neonatal mice on a juvenile mouse model of asthma.MethodsThirty-two newborn female C57BL/6 J mice were randomly divided into four groups, which including room air+phosphate-buffered saline (PBS) group, hyperoxia+PBS group, room air+OVA group, and hyperoxia+OVA group, according to the hyperoxia exposure and/or OVA induction. Mice were exposed to either 95% O2 or room air for 7 days after birth; after 7 days, they were exposed to air and received an intraperitoneal injection of OVA suspension or PBS solution on postnatal days 21 (P21) and 28 (P28). From P36 to P42, the mice were allowed to inhale of 1% OVA or 0.9% NaCl solution. The mice were observed after the last excitation. HE staining was performed to observe the pathological changes in lung tissues. Wright-Giemsa staining was used to perform bronchoalveolar lavage fluid (BALF) leukocyte sorting. Enzyme-linked immunosorbent assay was used to determined the cytokines levels of interleukin (IL)-2, IL-5, IL-13, IL-17A, and IL-10 and serum IgE levels in BALF. Additionally, 16S rRNA sequencing was used to analyze the characteristics of lung microbiota.ResultsMice in the hyperoxia+OVA group showed asthma-like symptoms. HE staining results revealed a significant thickening of the airway wall and airway inflammation. BALF analysis of cellular components showed significant increases in total leukocyte and eosinophil counts and the levels of cytokines related to Th2 (IL-5 and IL-13) and Th17 (IL-17A); 16S rRNA sequencing revealed that the main members of the pulmonary microflora were Actinobacteriota, Proteobacteria, Firmicutes, and Bacteroidota at the phylum level. In addition, the bacteria with a major role were Acinetobacter and Moraxellaceae in the O2 + OVA group.ConclusionThe mouse suffering from postnatal hyperoxia exposure and early OVA sensitization, changes in symptoms, pathology, leukocyte and eosinophil counts, and levels of different T-cell cytokines in BALF and lung microbiota, which may provide a basis for the establishment of a juvenile mouse model of asthma.
Ionizing radiation alters functional neurotransmission in Drosophila larvae
Authors: Zhang Yi , Zhang Yihao , Shen Cong , Hao Shun , Duan Wenlan , Liu Li , Wei Hongying 
Published: July 2023

IntroductionPatients undergoing cranial ionizing radiation therapy for brain malignancies are at increased risk of long-term neurocognitive decline, which is poorly understood and currently untreatable. Although the molecular pathogenesis has been intensively researched in many organisms, whether and how ionizing radiation alters functional neurotransmission remains unknown. This is the first study addressing physiological changes in neurotransmission after ionizing radiation exposure.MethodsTo elucidate the cellular mechanisms of radiation damage, using calcium imaging, we analyzed the effects of ionizing radiation on the neurotransmitter-evoked responses of prothoracicotropic hormone (PTTH)-releasing neurons in Drosophila larvae, which play essential roles in normal larval development.ResultsThe neurotransmitters dopamine and tyramine decreased intracellular calcium levels of PTTH neurons in a dose-dependent manner. In gamma irradiated third-instar larvae, a dose of 25 Gy increased the sensitivity of PTTH neurons to dopamine and tyramine, and delayed development, possibly in response to abnormal functional neurotransmission. This irradiation level did not affect the viability and arborization of PTTH neurons and successful survival to adulthood. Exposure to a 40-Gy dose of gamma irradiation decreased the neurotransmitter sensitivity, physiological viability and axo-dendritic length of PTTH neurons. These serious damages led to substantial developmental delays and a precipitous reduction in the percentage of larvae that survived to adulthood. Our results demonstrate that gamma irradiation alters neurotransmitter-evoked responses, indicating synapses are vulnerable targets of ionizing radiation.DiscussionThe current study provides new insights into ionizing radiation-induced disruption of physiological neurotransmitter signaling, which should be considered in preventive therapeutic interventions to reduce risks of neurological deficits after photon therapy.
Sex differences concerning the effects of ankle muscle fatigue on static postural control and spinal proprioceptive input at the ankle
Authors: Jo Donguk , Bilodeau Martin 
Published: July 2023

AimsThe main aim of this study was to determine sex differences in postural control changes with ankle muscle fatigue during a standing forward leaning (FL) task under different vision conditions. The secondary aim was to examine sex differences in the effect of fatigue on soleus (SOL) H-reflex amplitude, a measure of motoneuron excitability with activation of Ia afferents.MethodsFifteen healthy young adult males (mean age: 28.0 years) and 16 healthy young adult females (mean age: 26.1 years) were asked to perform four consecutive FL tasks [30 s; two with eyes open (EO) and two with eyes closed (EC)] before, and immediately following a fatiguing exercise consisting of alternating ankle plantarflexion (6 s) and dorsiflexion (2 s) maximal isometric contractions, and at 5 and 10 min of recovery. Center of pressure (COP) sway variables (mean position, standard deviation, ellipse area, average velocity, and frequency), an ankle co-contraction index, and a ratio of SOL H-reflex to the maximum amplitude of the compound muscle action potential (M-max) were obtained during the FL tasks. A rating of perceived fatigue (RPF) was also documented at the different time points.ResultsTime to task failure (reduction of 50% in maximal voluntary isometric contraction torque of ankle plantar flexors) and the increase in RPF value were not significantly different between males and females. Both sex groups showed similar and significant increases (p &lt; 0.05) in mean COP sway velocity with no significant changes in co-contraction indices. No significant effects of fatigue and related interactions were found for SOL H/M-max ratio.DiscussionThe absence of a significant sex difference in postural control change (sway and co-contraction) with fatigue could be explained by similar perceived (RPF) and performance fatigability (exercise duration) between males and females in the present study. Fatigue did not lead to significant changes in SOL spinal motoneuron excitability with activation of Ia afferents.
Relationship between Mediterranean diet and depression in South Korea: the Korea National Health and Nutrition Examination Survey
Authors: Hwang Yeong-Geon , Pae Chongwon , Lee Sang-Hyuk , Yook Ki-Hwan , Park Chun Il 
Published: July 2023

BackgroundSeveral studies have shown that adherence to the Mediterranean diet is associated with a lower risk of depression; however, little is known about the Asian population. This study investigated the relationship between adherence to the Mediterranean diet and depression in a sample of the South Korean population.MethodsIn total, 5,849 adults from the 2014 and 2016 Korea National Health and Nutrition Examination Surveys were included in the study. The Mediterranean diet adherence was measured using a modified alternate Mediterranean diet score (mMED) developed to adjust for Korean dietary patterns. The mMED scores using the Food Frequency Questionnaire were divided into four categories (0–2, 3–4, 5–6, and 7–9 points). Subjects with depression were defined as having moderate-to-severe depressive symptoms using the Patient Health Questionnaire-9, with a cutoff value of 10. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A subgroup analysis was performed based on sex.ResultsThe results of logistic regression analysis indicated that individuals with higher mMED were 42–73% less likely to report depression compared to individuals with the lowest mMED [ORs (95% CIs) =0.58 (0.37–0.90), 0.50 (0.31–0.80), 0.27 (0.15–0.47)] after adjusting for socio-demographic and health-related variables. In women, individuals with mMED of 7–9 had 71% lower odds of depression [ORs (95% CIs): 0.29 (0.13–0.64)]. In men, individuals with mMED of 5–9 had 55% [ORs (95% CIs): 0.45 (0.23–0.91)] to 79% [ORs (95% CIs): 0.21 (0.08–0.57)] lower odds of depression.ConclusionThis study suggests that adherence to the Mediterranean diet is inversely associated with depression in both men and women among Korean adults. This study provides evidence that a Mediterranean diet is crucial in preventing depressive symptoms in Asian populations.
Ceruminous adenoma of the external auditory canal: 9 cases series with imaging and pathologic findings
Authors: Yang Yifan , Liu Honggang , Fang Jugao , Li Yongxin , Chen Shubin 
Published: July 2023

ObjectivesCeruminous adenoma is a rare benign tumor of the external auditory canal. This study aimed to present the clinical characteristics, imaging findings, pathological results and the management outcomes of the ceruminous adenoma.Study designRetrospective case series review.SettingTertiary referral center.Patients and methodsPatients undergoing surgery for ceruminous adenoma of the external auditory canal between the years 2004 to 2018. All patients with ceruminous adenoma were analyzed for demographic, clinical, radiological features and pathologic findings. The outcomes of the management were also evaluated.ResultsNine patients with ceruminous adenoma were included in the study. Hearing loss was the most common complaint (5/9, 56%), followed by otalgia (4/9, 44%), pruritus (4/9, 44%), and otorrhea (2/9, 22%). The tumors originated mostly from the cartilaginous portion of the external auditory canal (8/9, 89%) and merely from the bony portion of the external auditory canal (1/9, 11%). Pathohistological study indicated that the ceruminous adenomas were divided into three types: the ceruminous gland adenoma (6/9, 67%), the ceruminous pleomorphic adenoma (2/9, 22%) and the ceruminous syringocystadenoma papilliferum (1/9, 11%). No recurrence was found during follow-up for two to fifteen years after surgical resection.ConclusionCeruminous adenomas are rare entities. They originate mainly from the cartilaginous portion of the EAC, but occasionally from the bony portion of the EAC. The surgical section with enough margin is adequate for management of these tumors.
Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis
Authors: Kempska Joanna , Oliveira-Ferrer Leticia , Grottke Astrid , Qi Minyue , Alawi Malik , Meyer Felix , Borgmann Kerstin , Hamester Fabienne , Eylmann Kathrin , Rossberg Maila , Smit Daniel J. , Jücker Manfred , Laakmann Elena , Witzel Isabell , Schmalfeldt Barbara , Müller Volkmar , Legler Karen 
Published: July 2023

IntroductionThe PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases.MethodsThe impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed.ResultsPharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR.DiscussionCollectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.
Cadaveric analysis of transcranial versus endoscopic transorbital petrosectomy: comparison of surgical maneuverability and brainstem exposure
Authors: Kwon Sae Min , Na Min Kyun , Choi Kyu-Sun , Byoun Hyoung Soo , Nam Yong Seok 
Published: July 2023

IntroductionWhile accessing the posterior fossa, the anterior transpetrosal approach (ATPA) and endoscopic transorbital approach (ETOA) use the same bony landmarks during petrous apex drilling. However, owing to their contrasting surgical axes, they are expected to show differences in surgical view, maneuverability, and clinical implications. This study aimed to investigate the feasibility of ETOA in accessing the brainstem and to compare the surgical view and maneuverability of each approach.MethodsATPA and ETOA were performed in four human cadaveric heads (eight sides and four sides in each procedure). The angle of attack (AOA) and surgical depth were measured at the target of interest (root exit zone [REZ] of cranial nerve [CN] V, VI, and VII). When measuring the area of exposure, the brainstem was divided into two areas (anterior and lateral brainstem) based on the longitudinal line crossing the entry zone of the trigeminal root, and the area of each was measured.ResultsATPA showed significantly greater value at the trigeminal REZ in both vertical (31.8 ± 6.7° vs. 14.3 ± 5.3°, p=0.006) and horizontal AOA (48.5 ± 2.9° vs. 15.0 ± 5.2°, p&lt;0.001) than ETOA. The AOA at facial REZ was also greater in ATPA than ETOA (vertical, 27.5 ± 3.9° vs. 8.3 ± 3.3°, p&lt;0.001; horizontal, 33.8 ± 2.2° vs. 11.8 ± 2.9°, p&lt;0.001). ATPA presented significantly shorter surgical depth (CN V, 5.8 ± 0.5 cm vs. 9.0 ± 0.8, p&lt;0.001; CN VII, 6.3 ± 0.5 cm vs. 9.5 ± 1.0, p=0.001) than ETOA. The mean area of brainstem exposure did not differ between the two approaches. However, ATPA showed significantly better exposure of anterior brainstem than ETOA (240.7 ± 9.6 mm2 vs. 171.7 ± 15.0 mm2, p&lt;0.001), while ETOA demonstrated better lateral brainstem exposure (174.2 ± 29.1 mm2 vs. 231.1 ± 13.6 mm2, p=0.022).ConclusionsETOA could be a valid surgical option, in selected cases, that provides a direct ventral route to the brainstem. Compared with ATPA, ETOA showed less surgical maneuverability, AOA and longer surgical depth; however, it presented comparable brainstem exposure and better exposure of the lateral brainstem.