bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise improves subchondral bone microenvironment through regulating bone-cartilage crosstalk
Authors: Zhang Shihua , Li Tingting , Feng Yao , Zhang Keping , Zou Jun , Weng Xiquan , Yuan Yu , Zhang Lan
Published: May 2023

Articular cartilage degeneration has been proved to cause a variety of joint diseases, among which osteoarthritis is the most typical. Osteoarthritis is characterized by articular cartilage degeneration and persistent pain, which affects the quality of life of patients as well as brings a heavy burden to society. The occurrence and development of osteoarthritis is related to the disorder of the subchondral bone microenvironment. Appropriate exercise can improve the subchondral bone microenvironment, thus playing an essential role in preventing and treating osteoarthritis. However, the exact mechanism whereby exercise improves the subchondral bone microenvironment remains unclear. There is biomechanical interaction as well as biochemical crosstalk between bone and cartilage. And the crosstalk between bone and cartilage is the key to bone-cartilage homeostasis maintenance. From the perspective of biomechanical and biochemical crosstalk between bone and cartilage, this paper reviews the effects of exercise-mediated bone-cartilage crosstalk on the subchondral bone microenvironment, aiming to provide a theoretical basis for the prevention and treatment of degenerative bone diseases.
Case Report: Nine-year-old with parathyroid adenoma within the piriform sinus
Authors: Zenno Anna , Ramamoorthy Bhavishya , Hammoud Dima A. , Quezado Martha , Zeiger Martha A. , Jha Smita
Published: May 2023

We present the case of a 9-year-old girl who presented with symptomatic hypercalcemia from primary hyperparathyroidism (PHPT). Laboratory results revealed elevated serum calcium 12.1 mg/dl (ref: 9.1–10.4), elevated ionized calcium 6.8 (ref: 4.5–5.6) mg/dl, phosphorus 3.8 (ref: 3.3–5.1) mg/dl, 25-OH vitamin D 20.1 (30–100) ng/ml, and elevated intact PTH 70 (15-65) pg/ml, consistent with the diagnosis of PHPT. She had persistent hyperparathyroidism after bilateral neck exploration, left thyroid lobectomy, and transcervical thymectomy. Neither inferior gland was identified. No parathyroid tissue was seen on histology. Repeat preoperative imaging identified a 7-mm × 5-mm adenoma on 4DCT not seen on 99Tc-sestamibi parathyroid scan. The patient then underwent a successful redo parathyroidectomy with removal of a submucosal left parathyroid adenoma at the superior aspect of the thyroid cartilage in the piriform sinus. Her biochemical work-up remains consistent with surgical cure 6 months after surgery. Herein, we also review common locations for ectopic parathyroid adenomas.

Clinical Trial Registration

NCT04969926.
YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation
Authors: Wang Wei , Liu Ruixia , Zhu Yingying , Wang Lina , Tang Yu , Dou Baolei , Tian Shuo , Wang Furong
Published: May 2023

Introduction

Diabetic cardiomyopathy (DCM) is one of the most prevalent complications of diabetes with complex pathogenesis. YuNü-Jian (YNJ) is a traditional Chinese medicinal formula widely used for diabetes with hypoglycemic and cardioprotective effects. This study aims to investigate the actions and mechanisms of YNJ against DCM which has never been reported.

Methods

Network pharmacology approach was used to predict the potential pathways and targets of YNJ on DCM. Molecular docking between hub targets and active components of YNJ was performed and visualized by AutoDock Vina and PyMOL. Then type 2 diabetic model was employed and intervened with YNJ for 10 weeks to further validate these critical targets.

Results

First, a total of 32 main ingredients of YNJ were identified and 700 potential targets were screened to construct herb-compound-target network. Then 94 differentially expressed genes of DCM were identified from GEO database. After that, PPI network of DCM and YNJ were generated from which hub genes (SIRT1, Nrf2, NQO1, MYC and APP) were assessed by topology analysis. Next, functional and pathway analysis indicated that the candidate targets were enriched in response to oxidative stress and Nrf2 signaling pathway. Furthermore, molecular docking revealed strong affinity between core targets and active components of YNJ. Finally, in rats with type 2 diabetes, YNJ obviously attenuated cardiac collagen accumulation and degree of fibrosis. Meanwhile, YNJ significantly upregulated protein expression of SIRT1, Nrf2 and NQO1 in diabetic myocardium.

Discussion

Collectively, our findings suggested that YNJ could effectively ameliorate cardiomyopathy induced by diabetes possibly through SIRT1/Nrf2/NQO1 signaling.
Performance analysis of modeling scale on multiband oscillations in grid-connected wind farm
Authors: Zhu Lin , Chen Leke , Hu Peiyan , Wu Yue , Liao Mengjun , Xu Min
Published: May 2023

Grid-connected permanent magnet synchronous generator (PMSG) wind farms may be susceptible to oscillation when connected to weak grids. This paper explores the root causes of the oscillations from two perspectives: the model and the oscillation frequency band. First, the small signal model of PMSG wind farm grid-side system is established, and the small disturbance comparison with the PMSGA full-order electromagnetic transient model in MATLAB/Simulink is carried out. Then, we calculatue the eigenvalues of the small signal model and use model analysis techniques such as participation factors calculation and root locus method to identify the critical factors that cause the oscillation modes to be dominant. Finally, time-domain simulation is used to verify the theoretical analysis. Two dominant modes are identified: the subsynchronous oscillation mode and the low-frequency oscillation mode. The subsynchronous oscillation mode is closely related to the direct current (DC) voltage control and the dynamics of DC link. The low-frequency oscillation is significantly weakened with the decrease in grid strength, and it is closely related to the phase-locked loop (PLL) control. The conclusions can provide a reference for tuning the control parameters of PMSG converter.
Diabetic macrophage small extracellular vesicles-associated miR-503/IGF1R axis regulates endothelial cell function and affects wound healing
Authors: Wang Jianqiang , Han Yuanshan , Huang Fang , Tang Liuhuan , Mu Jianfei , Liang Ying
Published: May 2023

Diabetic foot ulcer (DFU) is a break in the skin of the foot caused by diabetes. It is one of the most serious and debilitating complications of diabetes. The previous study suggested that dominant M1 polarization during DFU could be the leading reason behind impaired wound healing. This study concluded that macrophage M1 polarization predominates in DFU skin tissue. iNOS was increased in HG-induced M1-polarized macrophages; conversely, Arg-1 was decreased. Macrophage pellets after HG stimulation can impair endothelial cell (EC) function by inhibiting cell viability, tube formation and cell migration, indicating M1 macrophage-derived small extracellular vesicles (sEVs) -mediated HUVEC dysfunction. sEVs miR-503 was significantly upregulated in response to HG stimulation, but inhibition of miR-503 in HG-stimulated macrophages attenuated M1 macrophage-induced HUVEC dysfunction. ACO1 interacted with miR-503 and mediated the miR-503 package into sEVs. Under HG stimulation, sEVs miR-503 taken in by HUVECs targeted IGF1R in HUVECs and inhibited IGF1R expression. In HUVECs, miR-503 inhibition improved HG-caused HUVEC dysfunction, whereas IGF1R knockdown aggravated HUVEC dysfunction; IGF1R knockdown partially attenuated miR-503 inhibition effects on HUVECs. In the skin wound model in control or STZ-induced diabetic mice, miR-503-inhibited sEVs improved, whereas IGF1R knockdown further hindered wound healing. Therefore, it can be inferred from the results that the M1 macrophage-derived sEVs miR-503 targets IGF1R in HUVECs, inhibits IGF1R expression, leads to HUVEC dysfunction, and impedes wound healing in diabetic patients, while packaging miR-503 as an M1 macrophage-derived sEVs may be mediated by ACO1.
Elevated serum levels of human epididymis protein 4 in adult patients with proliferative lupus nephritis
Authors: Li Liubing , Xu Huiya , Le Yuting , Li Runzhao , Shi Qiong , Zhu Hongji , Xu Hongxu , Li Laisheng , Liu Min , Wang Fen , Zhang Hui
Published: May 2023

Background

This study aimed to access whether serum human epididymis protein 4 (HE4) level could identify lupus nephritis (LN) pathological classes in adults and children.

Methods

The serum HE4 levels of 190 healthy subjects and 182 patients with systemic lupus erythematosus (SLE) (61 adult-onset LN [aLN], 39 childhood-onset LN [cLN], and 82 SLE without LN) were determined using Architect HE4 kits and an Abbott ARCHITECT i2000SR Immunoassay Analyzer.

Results

Serum HE4 level was significantly higher in the aLN patients (median, 85.5 pmol/L) than in the patients with cLN (44 pmol/L, P < 0.001) or SLE without LN (37 pmol/L, P < 0.001), or the healthy controls (30 pmol/L, P < 0.001). Multivariate analysis showed that serum HE4 level was independently associated with aLN. Stratified by LN class, serum HE4 level was significantly higher in the patients with proliferative LN (PLN) than in those with non-PLN, and this difference was found only in aLN (median, 98.3 versus 49.3 pmol/L, P = 0.021) but not in cLN. Stratified by activity (A) and chronicity (C) indices, the aLN patients with class IV (A/C) possessed significantly higher serum HE4 levels than those with class IV (A) (median, 195.5 versus 60.8 pmol/L, P = 0.006), and this difference was not seen in the class III aLN or cLN patients.

Conclusion

Serum HE4 level is elevated in patients with class IV (A/C) aLN. The role of HE4 in the pathogenesis of chronic lesions of class IV aLN needs further investigation.
Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA
Authors: Sun Weijie , Wang Jue , Wang Zhiqiang , Xu Ming , Lin Quanjun , Sun Peng , Yuan Yihang
Published: May 2023

Hepatocellular carcinoma (HCC) is a malignant tumor with high recurrence and metastasis rates and poor prognosis. Basement membrane is a ubiquitous extracellular matrix and is a key physical factor in cancer metastasis. Therefore, basement membrane-related genes may be new targets for the diagnosis and treatment of HCC. We systematically analyzed the expression pattern and prognostic value of basement membrane-related genes in HCC using the TCGA-HCC dataset, and constructed a new BMRGI based on WGCNA and machine learning. We used the HCC single-cell RNA-sequencing data in GSE146115 to describe the single-cell map of HCC, analyzed the interaction between different cell types, and explored the expression of model genes in different cell types. BMRGI can accurately predict the prognosis of HCC patients and was validated in the ICGC cohort. In addition, we also explored the underlying molecular mechanisms and tumor immune infiltration in different BMRGI subgroups, and confirmed the differences in response to immunotherapy in different BMRGI subgroups based on the TIDE algorithm. Then, we assessed the sensitivity of HCC patients to common drugs. In conclusion, our study provides a theoretical basis for the selection of immunotherapy and sensitive drugs in HCC patients. Finally, we also considered CTSA as the most critical basement membrane-related gene affecting HCC progression. In vitro experiments showed that the proliferation, migration and invasion abilities of HCC cells were significantly impaired when CTSA was knocked down.
Biosonar activity of the Indo-Pacific humpback dolphin (Sousa chinensis) near the tunnel section of the world’s longest cross-sea bridge—the Hong Kong-Zhuhai-Macao Bridge—is negatively correlated with underwater noise
Authors: An Xue , Duan Pengxiang , Li Weilun , Yuan Jing , Chen Yuwei , Fan Fei , Deng Xiaojun , Xiao Yousheng , Chen Xi , Wang Ding , Wang Zhitao , Wang Kexiong
Published: May 2023

Underwater noise pollution from the world’s longest cross-sea bridge—the Hong Kong-Zhuhai-Macao Bridge (HZMB)—which stretches across the Chinese White Dolphin National Nature Reserve (of the People’s Republic of China, PRC) in the Pearl River Estuary may affect the distribution of local humpback dolphins. In this study, static passive acoustic monitoring was applied to monitor biosonar activity of humpback dolphins and underwater noise adjacent to the tunnel section of the HZMB for more than one year. During the monitoring period, dolphin biosonar signals were detected on 88.5% of days. A significant temporal pattern occurred in dolphin biosonar activity and in anthropogenic noise. Biosonar activity was significantly higher at night than during the day, whereas underwater noise occurred more in the day than at night. Significantly more echolocation signals were detected in winter-spring than in summer-autumn, and highest acoustic activity occurred significantly more during high tide than at other tidal periods. In addition, the negative correlation between elevated underwater noise and dolphin sonar activity in winter suggests that dolphins may avoid noisy waters for short periods, perhaps due to auditory stress, but fish prey movement cannot be ruled out. These findings facilitate understanding activity patterns of humpback dolphins in the Pearl River Estuary and may contribute to conservation efforts.
Chondrinema litorale gen. nov., sp. nov., of the phylum Bacteroidota, carrying multiple megaplasmids isolated from a tidal flat in the West Sea, Korea
Authors: Muhammad Neak , Avila Forbes , Lee Yong-Jae , Han Ho Le , Kim Kyoung-Ho , Kim Song-Gun
Published: May 2023

A Gram-stain-negative, long rod, oxidase and catalase-positive strain WSW3-B12T was isolated from red algae on tidal flats in the West Sea, Korea. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the strain WSW3-B12T had the highest sequence similarity, 92.7%, to Flexithrix dorotheae DSM 6795T, followed by Rapidithrix thailandica TISTR 1750T at 90.8% in the family Flammeovirgaceae of the phylum Bacteroidota. The whole genome sequence determined using both the Nanopore and Illumina platforms revealed that the complete genome consists of 29 contigs, among which contig 1 was a circular chromosome, while the remaining 28 contigs were plasmids. The size of the genome was 10.1 Mbp and the G+C content was 34.1%. The average nucleotide identity (ANI), digital DNA–DNA hybridization (dDDH), average amino acid identity (AAI), and percentage of conserved proteins (POCP), phylogenomic-related indexes between the strain WSW3-B12T and the closest strain Flexithrix dorotheae DSM 6795T, were 76.6%, 19.9%, 57.2%, and 55.6%, respectively, which were all lower than the threshold values to support the creation of a novel genus. A comprehensive genome analysis revealed that the strain WSW3-B12T harbored many of the key genes involved in central metabolism in the main chromosome and also carried important genes for the production of vitamins, quinone, and antimicrobial resistance on the plasmids. The strain also carried genes that are involved in the metabolism of heavy metals such as arsenic, cobalt, copper, and iron on both the chromosome and plasmids. Furthermore, the genome of the strain was highly enriched with carbohydrate-active enzymes (CAZymes), carrying a total of 241 CAZymes. Moreover, a complete CRISPR/Cas system was detected on plasmid 20. The major fatty acids of the strain were iso-C15:0 and C16:1 ω5. The polar lipids contained phosphatidylethanolamine, four unidentified lipids, and four glycolipids. The respiratory quinone was menaquinone 7. Based on the phenotypic, chemotaxonomic, and genomic analyses, the strain WSW3-B12T could be assigned to a novel species and novel genus within the family Flammeovirgaceae, for which the name Chondrinema litorale gen. nov., sp. nov. (type strain WSW3-B12T = KCTC 82707T = GDMCC 1.3198T) is proposed.
Spike count and morphology in the classification of epileptiform discharges
Authors: Aanestad Eivind , Gilhus Nils Erik , Olberg Henning Kristian , Kural Mustafa Aykut , Beniczky Sándor , Brogger Jan
Published: May 2023

Purpose

The purpose of this study is to investigate the impact of Bergen Epileptiform Morphology Score (BEMS) and interictal epileptiform discharge (IED) candidate count in EEG classification.

Methods

We included 400 consecutive patients from a clinical SCORE EEG database during 2013–2017 who had focal sharp discharges in their EEG, but no previous diagnosis of epilepsy. Three blinded EEG readers marked all IED candidates. BEMS and IED candidate counts were combined to classify EEGs as epileptiform or non-epileptiform. Diagnostic performance was assessed and then validated in an external dataset.

Results

Interictal epileptiform discharge (IED) candidate count and BEMS were moderately correlated. The optimal criteria to classify an EEG as epileptiform were either one spike at BEMS > = 58, two at > = 47, or seven at > = 36. These criteria had almost perfect inter-rater reliability (Gwet’s AC1 0.96), reasonable sensitivity of 56–64%, and high specificity of 98–99%. The sensitivity was 27–37%, and the specificity was 93–97% for a follow-up diagnosis of epilepsy. In the external dataset, the sensitivity for an epileptiform EEG was 60–70%, and the specificity was 90–93%.

Conclusion

Quantified EEG spike morphology (BEMS) and IED candidate count can be combined to classify an EEG as epileptiform with high reliability but with lower sensitivity than regular visual EEG review.
Quantifying evoked responses through information-theoretical measures
Authors: Fuhrer Julian , Glette Kyrre , Llorens Anaïs , Endestad Tor , Solbakk Anne-Kristin , Blenkmann Alejandro Omar
Published: May 2023

Information theory is a viable candidate to advance our understanding of how the brain processes information generated in the internal or external environment. With its universal applicability, information theory enables the analysis of complex data sets, is free of requirements about the data structure, and can help infer the underlying brain mechanisms. Information-theoretical metrics such as Entropy or Mutual Information have been highly beneficial for analyzing neurophysiological recordings. However, a direct comparison of the performance of these methods with well-established metrics, such as the t-test, is rare. Here, such a comparison is carried out by evaluating the novel method of Encoded Information with Mutual Information, Gaussian Copula Mutual Information, Neural Frequency Tagging, and t-test. We do so by applying each method to event-related potentials and event-related activity in different frequency bands originating from intracranial electroencephalography recordings of humans and marmoset monkeys. Encoded Information is a novel procedure that assesses the similarity of brain responses across experimental conditions by compressing the respective signals. Such an information-based encoding is attractive whenever one is interested in detecting where in the brain condition effects are present.
Stimulation enhancement effect of the combination of exoskeleton-assisted hand rehabilitation and fingertip haptic stimulation
Authors: Li Min , Chen Jing , He Bo , He Guoying , Zhao Chen-Guang , Yuan Hua , Xie Jun , Xu Guanghua , Li Jichun
Published: May 2023

Introduction

Providing stimulation enhancements to existing hand rehabilitation training methods may help stroke survivors achieve better treatment outcomes. This paper presents a comparison study to explore the stimulation enhancement effects of the combination of exoskeleton-assisted hand rehabilitation and fingertip haptic stimulation by analyzing behavioral data and event-related potentials.

Methods

The stimulation effects of the touch sensations created by a water bottle and that created by cutaneous fingertip stimulation with pneumatic actuators are also investigated. Fingertip haptic stimulation was combined with exoskeleton-assisted hand rehabilitation while the haptic stimulation was synchronized with the motion of our hand exoskeleton. In the experiments, three experimental modes, including exoskeleton-assisted grasping motion without haptic stimulation (Mode 1), exoskeleton-assisted grasping motion with haptic stimulation (Mode 2), and exoskeleton-assisted grasping motion with a water bottle (Mode 3), were compared.

Results

The behavioral analysis results showed that the change of experimental modes had no significant effect on the recognition accuracy of stimulation levels (p = 0.658), while regarding the response time, exoskeleton-assisted grasping motion with haptic stimulation was the same as grasping a water bottle (p = 0.441) but significantly different from that without haptic stimulation (p = 0.006). The analysis of event-related potentials showed that the primary motor cortex, premotor cortex, and primary somatosensory areas of the brain were more activated when both the hand motion assistance and fingertip haptic feedback were provided using our proposed method (P300 amplitude 9.46 μV). Compared to only applying exoskeleton-assisted hand motion, the P300 amplitude was significantly improved by providing both exoskeleton-assisted hand motion and fingertip haptic stimulation (p = 0.006), but no significant differences were found between any other two modes (Mode 2 vs. Mode 3: p = 0.227, Mode 1 vs. Mode 3: p = 0.918). Different modes did not significantly affect the P300 latency (p = 0.102). Stimulation intensity had no effect on the P300 amplitude (p = 0.295, 0.414, 0.867) and latency (p = 0.417, 0.197, 0.607).

Discussion

Thus, we conclude that combining exoskeleton-assisted hand motion and fingertip haptic stimulation provided stronger stimulation on the motor cortex and somatosensory cortex of the brain simultaneously; the stimulation effects of the touch sensations created by a water bottle and that created by cutaneous fingertip stimulation with pneumatic actuators are similar.
Triple-network analysis of Alzheimer’s disease based on the energy landscape
Authors: Li Youjun , An Simeng , Zhou Tianlin , Su Chunwang , Zhang Siping , Li Chenxi , Jiang Junjie , Mu Yunfeng , Yao Nan , Huang Zi-Gang ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2023

Introduction

Research on the brain activity during resting state has found that brain activation is centered around three networks, including the default mode network (DMN), the salient network (SN), and the central executive network (CEN), and switches between multiple modes. As a common disease in the elderly, Alzheimer’s disease (AD) affects the state transitions of functional networks in the resting state.

Methods

Energy landscape, as a new method, can intuitively and quickly grasp the statistical distribution of system states and information related to state transition mechanisms. Therefore, this study mainly uses the energy landscape method to study the changes of the triple-network brain dynamics in AD patients in the resting state.

Results

AD brain activity patterns are in an abnormal state, and the dynamics of patients with AD tend to be unstable, with an unusually high flexibility in switching between states. Also , the subjects’ dynamic features are correlated with clinical index.

Discussion

The atypical balance of large-scale brain systems in patients with AD is associated with abnormally active brain dynamics. Our study are helpful for further understanding the intrinsic dynamic characteristics and pathological mechanism of the resting-state brain in AD patients.
Systems-level analysis of local field potentials reveals differential effects of lysergic acid diethylamide and ketamine on neuronal activity and functional connectivity
Authors: Nasretdinov Azat , Barrientos Sebastian A. , Brys Ivani , Halje Pär , Petersson Per
Published: May 2023

Psychedelic substances have in recent years attracted considerable interest as potential treatments for several psychiatric conditions, including depression, anxiety, and addiction. Imaging studies in humans point to a number of possible mechanisms underlying the acute effects of psychedelics, including changes in neuronal firing rates and excitability as well as alterations in functional connectivity between various brain nodes. In addition, animal studies using invasive recordings, have suggested synchronous high-frequency oscillations involving several brain regions as another key feature of the psychedelic brain state. To better understand how the imaging data might be related to high-resolution electrophysiological measurements, we have here analyzed the aperiodic part of the local field potential (LFP) in rodents treated with a classic psychedelic (LSD) or a dissociative anesthetic (ketamine). In addition, functional connectivity, as quantified by mutual information measures in the LFP time series, has been assessed with in and between different structures. Our data suggest that the altered brain states of LSD and ketamine are caused by different underlying mechanisms, where LFP power shifts indicate increased neuronal activity but reduced connectivity following ketamine, while LSD also leads to reduced connectivity but without an accompanying change in LFP broadband power.
Circulating hsa-miR-5096 predicts 18F-FDG PET/CT positivity and modulates somatostatin receptor 2 expression: a novel miR-based assay for pancreatic neuroendocrine tumors
Authors: Bocchini Martine , Tazzari Marcella , Ravaioli Sara , Piccinini Filippo , Foca Flavia , Tebaldi Michela , Nicolini Fabio , Grassi Ilaria , Severi Stefano , Calogero Raffaele Adolfo , Arigoni Maddalena , Schrader Joerg , Mazza Massimiliano , Paganelli Giovanni
Published: May 2023

Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are rare diseases encompassing pancreatic (PanNETs) and ileal NETs (SINETs), characterized by heterogeneous somatostatin receptors (SSTRs) expression. Treatments for inoperable GEP-NETs are limited, and SSTR-targeted Peptide Receptor Radionuclide Therapy (PRRT) achieves variable responses. Prognostic biomarkers for the management of GEP-NET patients are required. 18F-FDG uptake is a prognostic indicator of aggressiveness in GEP-NETs. This study aims to identify circulating and measurable prognostic miRNAs associated with 18F-FDG-PET/CT status, higher risk and lower response to PRRT.

Methods

Whole miRNOme NGS profiling was conducted on plasma samples obtained from well-differentiated advanced, metastatic, inoperable G1, G2 and G3 GEP-NET patients enrolled in the non-randomized LUX (NCT02736500) and LUNET (NCT02489604) clinical trials prior to PRRT (screening set, n= 24). Differential expression analysis was performed between 18F-FDG positive (n=12) and negative (n=12) patients. Validation was conducted by Real Time quantitative PCR in two distinct well-differentiated GEP-NET validation cohorts, considering the primary site of origin (PanNETs n=38 and SINETs n=30). The Cox regression was applied to assess independent clinical parameters and imaging for progression-free survival (PFS) in PanNETs. In situ RNA hybridization combined with immunohistochemistry was performed to simultaneously detect miR and protein expression in the same tissue specimens. This novel semi-automated miR-protein protocol was applied in PanNET FFPE specimens (n=9). In vitro functional experiments were performed in PanNET models.

Results

While no miRNAs emerged to be deregulated in SINETs, hsa-miR-5096, hsa-let-7i-3p and hsa-miR-4311 were found to correlate with 18F-FDG-PET/CT in PanNETs (p-value:<0.005). Statistical analysis has shown that, hsa-miR-5096 can predict 6-month PFS (p-value:<0.001) and 12-month Overall Survival upon PRRT treatment (p-value:<0.05), as well as identify 18F-FDG-PET/CT positive PanNETs with worse prognosis after PRRT (p-value:<0.005). In addition, hsa-miR-5096 inversely correlated with both SSTR2 expression in PanNET tissue and with the 68Gallium-DOTATOC captation values (p-value:<0.05), and accordingly it was able to decrease SSTR2 when ectopically expressed in PanNET cells (p-value:<0.01).

Conclusions

hsa-miR-5096 well performs as a biomarker for 18F-FDG-PET/CT and as independent predictor of PFS. Moreover, exosome-mediated delivery of hsa-miR-5096 may promote SSTR2 heterogeneity and thus resistance to PRRT.
How well are Brazilian mastologists (breast surgeons) trained in breast reconstruction and oncoplastic surgery? A study of the impact of a breast reconstruction and oncoplastic surgery improvement course
Authors: Businaro Fernandes João Thais , de Oliveira Vilmar Marques , Bagnoli Fábio , Bastos Maria Carolina Soliani , Rinaldi José Francisco , Brenelli Fabrício Palermo , Mateus Evandro Fallaci
Published: May 2023

Introduction

The breasts are a female symbol, impacts self-image and self-esteem. Breast reconstructive and oncoplastic surgeries have an important role in minimizing injuries. In Brazil less than a third of public health system (SUS) users have access to immediate reconstructive surgery. The low rate of breast reconstructions has multiple causes and the deficiency in availability and surgeons’ technical qualification play a role. In 2010, the Breast Reconstruction and Oncoplastic Surgery Improvement Course was created by professors of the Mastology Department of Santa Casa de São Paulo and State University of Campinas (UNICAMP). The objectives of this study were to evaluate the impact of the techniques learned on patients’ management by the surgeons enrolled in the Course, as well as to characterize their profile.

Methods

All students enrolled in the Improvement Course between 2010 and 2018 were invited to answer an online questionnaire. Students who did not agree to answer the questionnaire or answered them incompletely were excluded.

Results

Total students included: 59. The mean age: 48.9 years, male (72%) with more than 5 years of Mastology practice (82.2%), from all regions of Brazil, 1.7% from the North, 33.9% from the Northeast, 44.1% from the Southeast, and 12% from the South. Most of the students considered they had little or no knowledge of breast reconstruction (74.6%) and 91,5% did not consider they had enough aptitude to perform breast reconstructions after finishing residency. After the Course, 96.6% considered themselves apt to perform such surgeries. Over 90% of the students considered the Course had impacted their practice and changed their surgical strategy view. Before the Course, 84.8% of the students stated that less than half of their patients who were operated on for breast cancer had breast reconstruction, compared to 30.5% after the Course.

Conclusion

The Breast Reconstruction and Oncoplastic Surgery Improvement Course studied here positively impacted the mastologists’ management of patients. New training centers worldwide can help a lot of women with breast cancer.
Development of an AI based automated analysis of pediatric Apple Watch iECGs
Authors: Teich L. , Franke D. , Michaelis A. , Dähnert I. , Gebauer R. A. , Markel F. , Paech C.
Published: May 2023

Introduction

The Apple Watch valuably records event-based electrocardiograms (iECG) in children, as shown in recent studies by Paech et al. In contrast to adults, though, the automatic heart rhythm classification of the Apple Watch did not provide satisfactory results in children. Therefore, ECG analysis is limited to interpretation by a pediatric cardiologist. To surmount this difficulty, an artificial intelligence (AI) based algorithm for the automatic interpretation of pediatric Apple Watch iECGs was developed in this study.

Methods

A first AI-based algorithm was designed and trained based on prerecorded and manually classified i.e., labeled iECGs. Afterward the algorithm was evaluated in a prospectively recruited cohort of children at the Leipzig Heart Center. iECG evaluation by the algorithm was compared to the 12-lead-ECG evaluation by a pediatric cardiologist (gold standard). The outcomes were then used to calculate the sensitivity and specificity of the Apple Software and the self-developed AI.

Results

The main features of the newly developed AI algorithm and the rapid development cycle are presented. Forty-eight pediatric patients were enrolled in this study. The AI reached a specificity of 96.7% and a sensitivity of 66.7% for classifying a normal sinus rhythm.

Conclusion

The current study presents a first AI-based algorithm for the automatic heart rhythm classification of pediatric iECGs, and therefore provides the basis for further development of the AI-based iECG analysis in children as soon as more training data are available. More training in the AI algorithm is inevitable to enable the AI-based iECG analysis to work as a medical tool in complex patients.
Phosphatidylethanolamine aggravates Angiotensin II-induced atrial fibrosis by triggering ferroptosis in mice
Authors: Huang Fangze , Liu Ximao , Liu Junjie , Xie Yu , Zhao Li , Liu Deshen , Zeng Zifeng , Liu Xiu , Zheng Shaoyi , Xiao Zezhou
Published: May 2023

As atrial fibrosis is the main feature of atrial structural remodeling, inhibiting atrial fibrosis is crucial to the prevention of atrial fibrillation (AF) progression. Research has shown the correlation between abnormal lipid metabolism and AF progression. However, the effect of specific lipids on atrial fibrosis remains unclear. In the present study, we applied ultra-high-performance lipidomics to analyze the lipid profiles in patients with AF and identify phosphatidylethanolamine (PE) as the differential lipid associated with AF. To detect the effect of the differential lipid on atrial fibrosis, we performed the intraperitoneal injection of Angiotensin II (Ang II) to mice to induce atrial fibrosis and supplemented PE in diets. We also treated atrial cells with PE to evaluate the cellular effect of PE. We found that PE supplementation aggravated atrial fibrosis and increased the expression of the fibrosis-related protein in vitro and in vivo. Moreover, we detected the effect of PE on the atrium. We found that PE increased oxidation products and regulated the expression of ferroptosis-related proteins, which could be alleviated by a ferroptosis inhibitor. PE increased peroxidation and mitochondrial damage in vitro, which promoted cardiomyocyte death induced by Ang II. Examination of protein expression in cardiomyocytes indicated that PE triggered ferroptosis and caused cell death to participate in myocardium fibrosis. In summary, our findings demonstrated the differential lipid profiles of AF patients and revealed the potential effect of PE on atrial remodelling, suggesting that inhibition of PE and ferroptosis might serve as a potential therapy to prevent AF progression.
High-Q transmission characteristics in terahertz guided-mode magnetic resonance system
Authors: Yan Fei , Li Qi , Wang Ze Wen
Published: May 2023

Introduction: Guided mode resonance is generated by coupling wave diffractions with the waveguided mode. The guided mode resonances provide narrow-linewidth and resonance intensity for high quality factor (Q-factor) optical resonators.

Methods: we demonstrate the high-Q guided mode resonances propagating on a low-loss, terahertz guided-mode magnetic resonance system, which are periodic square lattices of U-shaped split ring resonators (SRRs) on quartz substrates.

Results: By choosing a judicious array period, two distinct frequency guided mode resonances and a magnetic dipole resonance with high Q-factor are observed. The interaction of the two resonances at similar frequencies produces a total transmission peak.

Discussion: The dependences of the magnetic dipole resonance on the lattice period and structural parameters are investigated and discussed. The frequency difference between these two guided mode resonances widens with increasing Lattice period. The sharp spectral feature of each resonance results in the abrupt degradation of the spectral edge transmission. The proposed scheme is promising for efficient THz sensing, THz switching, and slow-light devices.
Unsupervised classification of plethysmography signals with advanced visual representations
Authors: Germain Thibaut , Truong Charles , Oudre Laurent , Krejci Eric
Published: May 2023

Ventilation is a simple physiological function that ensures the vital supply of oxygen and the elimination of CO2. The recording of the airflow through the nostrils of a mouse over time makes it possible to calculate the position of critical points, based on the shape of the signals, to compute the respiratory frequency and the volume of air exchanged. These descriptors only account for a part of the dynamics of respiratory exchanges. In this work we present a new algorithm that directly compares the shapes of signals and considers meaningful information about the breathing dynamics omitted by the previous descriptors. The algorithm leads to a new classification of inspiration and expiration, which reveals that mice respond and adapt differently to inhibition of cholinesterases, enzymes targeted by nerve gas, pesticide, or drug intoxication.
Pelvic floor dysfunction and electrophysiology in postpartum women at 6–8 weeks
Authors: Wu Jia-Cong , Yu Xiao-Li , Ji Hui-Jing , Lou Hai-Qin , Gao Hong-Ju , Huang Guo-Qin , Zhu Xiao-Li
Published: May 2023

Objective: To investigate the incidence of pelvic floor dysfunction (PFD) and electrophysiological indicators in postpartum women at 6–8 weeks and explore the influence of demographic characteristics and obstetric factors.

Methods: A survey questionnaire collected information about the conditions of women during their pregnancy and puerperal period and their demographic characteristics; pelvic organ prolapse quantitation (POP-Q) and pelvic floor muscle electrophysiology (EP) examination were conducted in postpartum women at 6–8 weeks.

Results: Vaginal delivery was a risk factor for anterior pelvic organ prolapse (POP) (OR 7.850, 95% confidence interval (CI) 5.804–10.617), posterior POP (OR 5.990, 95% CI 3.953–9.077), anterior and posterior stage II POP (OR 6.636, 95% CI 3.662–15.919), and postpartum urinary incontinence (UI) (OR 6.046, 95% CI 3.894–9.387); parity was a risk factor for anterior POP (OR 1.397,95% CI 0.889–2.198) and anterior and posterior stage II POP (OR 4.162, 95% CI 2.125–8.152); age was a risk factor for anterior POP (OR 1.056, 95% CI 1.007–1.108) and postpartum UI (OR 1.066, 95% CI 1.014–1.120); body mass index (BMI) was a risk factor for postpartum UI (OR 1.117, 95% CI 1.060–1.177); fetal birth weight was a risk factor for posterior POP (OR 1.465, 95% CI 1.041–2.062); and the frequency of pregnancy loss was a risk factor for apical POP (OR 1.853, 95% CI 1.060–3.237).

Conclusion: Pelvic floor muscle EP is a sensitive index of early pelvic floor injury. The changes in muscle strength and fatigue degree coexist in different types of postpartum PFD, and each has its own characteristics.
Cerebral hemodynamics comparison using transcranial doppler ultrasound and 4D flow MRI
Authors: Fico Brandon G. , Miller Kathleen B. , Rivera-Rivera Leonardo A. , Corkery Adam T. , Pearson Andrew G. , Loggie Nicole A. , Howery Anna J. , Rowley Howard A. , Johnson Kevin M. , Johnson Sterling C. , Wieben Oliver , Barnes Jill N.
Published: May 2023

Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI).

Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI.

Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513).

Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.
Betula mcallisteri sp. nov. (sect. Acuminatae, Betulaceae), a new diploid species overlooked in the wild and in cultivation, and its relation to the widespread B. luminifera
Authors: Zhang Huayu , Ding Junyi , Holstein Norbert , Wang Nian
Published: May 2023

Taxa are traditionally identified using morphological proxies for groups of evolutionarily isolated populations. These proxies are common characters deemed by taxonomists as significant. However, there is no general rule on which character or sets of characters are appropriate to circumscribe taxa, leading to discussions and uncertainty. Birch species are notoriously hard to identify due to strong morphological variability and factors such as hybridization and the existence of several ploidy levels. Here, we present evidence for an evolutionarily isolated line of birches from China that are not distinguishable by traditionally assumed taxon recognition proxies, such as fruit or leaf characters. We have discovered that some wild material in China and some cultivated in the Royal Botanic Gardens Edinburgh, formerly recognized as Betula luminifera, differ from other individuals by having a peeling bark and a lack of cambial fragrance. We use restriction site-associated DNA sequencing and flow cytometry to study the evolutionary status of the unidentified Betula samples to assess the extent of hybridization between the unidentified Betula samples and typical B. luminifera in natural populations. Molecular analyses show the unidentified Betula samples as a distinct lineage and reveal very little genetic admixture between the unidentified samples and B. luminifera. This may also be facilitated by the finding that B. luminifera is tetraploid, while the unidentified samples turned out to be diploid. We therefore conclude that the samples represent a yet unrecognized species, which is here described as Betula mcallisteri.
Unravelling the molecular mechanism underlying drought stress response in chickpea via integrated multi-omics analysis
Authors: Singh Vikram , Gupta Khushboo , Singh Shubhangi , Jain Mukesh , Garg Rohini
Published: May 2023

Drought stress affects growth and productivity significantly in chickpea. An integrated multi-omics analysis can provide a better molecular-level understanding of drought stress tolerance. In the present study, comparative transcriptome, proteome and metabolome analyses of two chickpea genotypes with contrasting responses to drought stress, ICC 4958 (drought-tolerant, DT) and ICC 1882 (drought-sensitive, DS), was performed to gain insights into the molecular mechanisms underlying drought stress response/tolerance. Pathway enrichment analysis of differentially abundant transcripts and proteins suggested the involvement of glycolysis/gluconeogenesis, galactose metabolism, and starch and sucrose metabolism in the DT genotype. An integrated multi-omics analysis of transcriptome, proteome and metabolome data revealed co-expressed genes, proteins and metabolites involved in phosphatidylinositol signaling, glutathione metabolism and glycolysis/gluconeogenesis pathways, specifically in the DT genotype under drought. These stress-responsive pathways were coordinately regulated by the differentially abundant transcripts, proteins and metabolites to circumvent the drought stress response/tolerance in the DT genotype. The QTL-hotspot associated genes, proteins and transcription factors may further contribute to improved drought tolerance in the DT genotype. Altogether, the multi-omics approach provided an in-depth understanding of stress-responsive pathways and candidate genes involved in drought tolerance in chickpea.
Genetic mapping identified three hotspot genomic regions and candidate genes controlling heat tolerance-related traits in groundnut
Authors: Sharma Vinay , Gangurde Sunil S. , Nayak Spurthi N. , Gowda Anjan S. , Sukanth B.S. , Mahadevaiah Supriya S. , Manohar Surendra S. , Choudhary Rakeshkumar S. , Anitha T. , Malavalli Sachin S. , Srikanth S.N. , Bajaj Prasad , Sharma Shailendra , Varshney Rajeev K. , Latha Putta , Janila Pasupuleti , Bhat Ramesh S. , Pandey Manish K.
Published: May 2023

Groundnut productivity and quality have been impeded by rising temperatures in semi-arid environments. Hence, understanding the effects and molecular mechanisms of heat stress tolerance will aid in tackling yield losses. In this context, a recombinant inbred line (RIL) population was developed and phenotyped for eight seasons at three locations for agronomic, phenological, and physiological traits under heat stress. A genetic map was constructed using genotyping-by-sequencing with 478 single-nucleotide polymorphism (SNP) loci spanning a map distance of 1,961.39 cM. Quantitative trait locus (QTL) analysis using phenotypic and genotypic data identified 45 major main-effect QTLs for 21 traits. Intriguingly, three QTL clusters (Cluster-1-Ah03, Cluster-2-Ah12, and Cluster-3-Ah20) harbor more than half of the major QTLs (30/45, 66.6%) for various heat tolerant traits, explaining 10.4%–38.6%, 10.6%–44.6%, and 10.1%–49.5% of phenotypic variance, respectively. Furthermore, important candidate genes encoding DHHC-type zinc finger family protein (arahy.J0Y6Y5), peptide transporter 1 (arahy.8ZMT0C), pentatricopeptide repeat-containing protein (arahy.4A4JE9), Ulp1 protease family (arahy.X568GS), Kelch repeat F-box protein (arahy.I7X4PC), FRIGIDA-like protein (arahy.0C3V8Z), and post-illumination chlorophyll fluorescence increase (arahy.92ZGJC) were the underlying three QTL clusters. The putative functions of these genes suggested their involvement in seed development, regulating plant architecture, yield, genesis and growth of plants, flowering time regulation, and photosynthesis. Our results could provide a platform for further fine mapping, gene discovery, and developing markers for genomics-assisted breeding to develop heat-tolerant groundnut varieties.