Miracle-dz/UniFAR-FTUs huggingface dataset:
Endoscopic 1½-transseptal approach for pituitary surgery

Background We previously introduced the one-and-a-half (1½) nostril endoscopic transsphenoidal approach (OETA) to reduce the damage to the nasal structures. Here, we reported the modified approach which is called the endoscopic 1½-transseptal approach (EOTA) for pituitary surgery by combining the OETA and the microscopic transseptal approach to simplify intranasal procedures and protect nasal mucosa. In EOTA, we removed the sellar lesions in a corridor that is composed of the right submucosal space and the anterior left ½ nasal cavity. Methods We introduced EOTA with a detailed technical description and preliminary clinical outcomes. A total of 128 patients who underwent EOTA for pituitary surgery from July 2018 to September 2020 were reviewed for evaluation of the safety and efficacy of this approach. Results EOTA had a high gross total resection (GTR) rate and a 1ow complication rate. GTR was achieved in 106 (82.8%) patients, with 81.4% for pituitary adenomas and 93.3% for other non-adenomatous lesions. Post-operative complications included 3 patients (2.3%) with postoperative cerebrospinal fluid leak, 3 patients (2.3%) with diabetes insipidus, 5 patients (3.9%) with anterior pituitary insufficiency and 2 patients (1.6%) with meningitis. In addition, EOTA simplified the intranasal procedures, which led to shortened operation time (67.8 minutes). The results of ASK nasal-12, the Lund-Kennedy score, and the odor identification test showed that patients who underwent EOTA recovered quickly after surgery and the nasal cavity returned to the preoperative condition both apparently and physiologically one month after surgery. Conclusions EOTA is a simple, safe and effective approach for pituitary lesions, which provides not only a sufficient surgical corridor for 2-surgeon/4- or 3-hands technique but also minimally invasive access to the sellar region.
Metabolic dysregulation and decreased capillarization in skeletal muscles of male adolescent offspring rats exposed to gestational intermittent hypoxia

Gestational intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea that occurs frequently during pregnancy, and effects caused by this environmental change during pregnancy may be transmitted to the offspring. In this study, we aimed to clarify the effects of IH in pregnant rats on the skeletal muscle of adolescent offspring rats. Mother rats underwent IH from gestation day 7–21, and their 5-weeks-old male offspring were analyzed. All male offspring rats were born and raised under normoxia conditions. Although no general growth retardation was observed, we found that exposure to gestational IH reduces endurance running capacity of adolescent offspring rats. Both a respiratory muscle (diaphragm; DIA) and a limb muscle (tibialis anterior; TA) showed no histological abnormalities, including fiber size and fiber type distribution. To identify the possible mechanism underlying the reduced running capacity, regulatory factors associated with energy metabolism were analyzed in different parts of skeletal muscles. Compared with rats born under conditions of gestational normoxia, gestational IH offspring rats showed significantly lower expression of genes associated with glucose and lipid metabolism, and lower protein levels of phosphorylated AMPK and AKT. Furthermore, gene expression of adiponectin receptors one and two was significantly decreased in the DIA and TA muscles. In addition, the DIA muscle from adolescent rats had significantly decreased capillary density as a result of gestational IH. However, these changes were not observed in a sucking muscle (geniohyoid) and a masticating muscle (masseter) of these rats. These results suggest that respiratory and limb muscles are vulnerable to gestational IH, which induces altered energy metabolism with decreased aerobic motor function. These changes were partially owing to the decreased expression of adiponectin receptors and decreased capillary density in adolescent offspring rats.
Integrated analysis of transcription factor-mRNA-miRNA regulatory network related to immune characteristics in medullary thyroid carcinoma

Background Medullary thyroid carcinoma (MTC), a thyroid C cell-derived malignancy, is poorly differentiated and more aggressive than papillary, follicular and oncocytic types of thyroid cancer. The current therapeutic options are limited, with a third of population suffering resistance. The differential gene expression pattern among thyroid cancer subtypes remains unclear. This study intended to explore the exclusive gene profile of MTC and construct a comprehensive regulatory network via integrated analysis, to uncover the potential key biomarkers. Methods Multiple datasets of thyroid and other neuroendocrine tumors were obtained from GEO and TCGA databases. Differentially expressed genes (DEGs) specific in MTC were identified to construct a transcription factor (TF)-mRNA-miRNA network. The impact of the TF-mRNA-miRNA network on tumor immune characteristics and patient survival was further explored by single-sample GSEA (ssGSEA) and ESTIMATE algorithms, as well as univariate combined with multivariate analyses. RT-qPCR, cell viability and apoptosis assays were performed for in vitro validation. Results We identified 81 genes upregulated and 22 downregulated in MTC but not in other types of thyroid tumor compared to the normal thyroid tissue. According to the L1000CDS2 database, potential targeting drugs were found to reverse the expressions of DEGs, with panobinostat (S1030) validated effective for tumor repression in MTC by in vitro experiments. The 103 DEGs exclusively seen in MTC were involved in signal release, muscle contraction, pathways of neurodegeneration diseases, neurotransmitter activity and related amino acid metabolism, and cAMP pathway. Based on the identified 15 hub genes, a TF-mRNA-miRNA linear network, as well as REST-cored coherent feed-forward loop networks, namely REST-KIF5C-miR-223 and REST-CDK5R2-miR-130a were constructed via online prediction and validation by public datasets and our cohort. Hub-gene, TF and miRNA scores in the TF-mRNA-miRNA network were related to immune score, immune cell infiltration and immunotherapeutic molecules in MTC as well as in neuroendocrine tumor of lung and neuroblastoma. Additionally, a high hub-gene score or a low miRNA score indicated good prognoses of neuroendocrine tumors. Conclusion The present study uncovers underlying molecular mechanisms and potential immunotherapy-related targets for the pathogenesis and drug discovery of MTC.
Mesenchymal stem cells express epidermal markers in an in vitro reconstructed human skin model

Introduction: In skin traumas, such as burns, epidermal homeostasis is affected, often requiring clinical approaches. Different therapeutic strategies can be used including transplantation, besides the use of synthetic or natural materials with allogeneic cells. In this context, tissue engineering is an essential tool for skin regeneration, and using mesenchymal stem cells (MSC) from the umbilical cord appears to be a promising strategy in regenerative medicine due to its renewal and differentiation potential and hypo immunogenicity. We evaluated the transdifferentiation of MSC from umbilical cord into keratinocytes in three-dimensional (3D) in vitro skin models, using dermal equivalents composed by type I collagen with dermal fibroblasts and a commercial porcine skin decellularized matrix, both cultured at air-liquid interface (ALI). Methods: The expression of epidermal proteins cytokeratins (CK) 5, 14 and 10, involucrin and filaggrin was investigated by real-time PCR and immunofluorescence, in addition to the activity of epidermal kallikreins (KLK) on the hydrolysis of fluorogenic substrates. Results and discussion: The cultivation of MSCs with differentiation medium on these dermal supports resulted in organotypic cultures characterized by the expression of the epidermal markers CK5, CK14, CK10 and involucrin, mainly on the 7th day of culture, and filaggrin at 10th day in ALI. Also, there was a 3-fold increase in the KLK activity in the epidermal equivalents composed by MSC induced to differentiate into keratinocytes compared to the control (MSC cultivated in the proliferation medium). Specifically, the use of collagen and fibroblasts resulted in a more organized MSC-based organotypic culture in comparison to the decellularized matrix. Despite the non-typical epithelium structure formed by MSC onto dermal equivalents, the expression of important epidermal markers in addition to the paracrine effects of these cells in skin may indicate its potential use to produce skin-based substitutes.
The art of combining neuroanatomy and microsurgical skills in modern neurosurgery

Neurosurgical training outside the operating room has become a priority for all neurosurgeons around the world. The exponential increase in the number of publications on training in neurosurgery reflects changes in the environment that future neurosurgeons are expected to work in. In modern practice, patients and medicolegal experts demand objective measures of competence and proficiency in the growing list of techniques available to treat complex neurosurgical conditions. It is important to ensure the myriad of training models available lead to tangible improvements in the operating room. While neuroanatomy textbooks and atlases are continually revised to teach the aspiring surgeon anatomy with a three-dimensional perspective, developing technical skills are integral to the pursuit of excellence in neurosurgery. Parapharsing William Osler, one of the fathers of neurosurgical training, without anatomical knowledge we are lost, but without the experience and skills from practice our journey is yet to begin. It is important to constantly aspire beyond competence to mastery, as we aim to deliver good outcomes for patients in an era of declining case volumes. In this article, we discuss, based on the literature, the most commonly used training models and how they are integrated into the treatment of some surgical brain conditions.
Formaldehyde and methylamine reactivity in interstellar ice analogues as a source of molecular complexity at low temperature

Context. Laboratory simulations on interstellar or cometary ice analogues are crucial to understand the formation of complex organic molecules that are detected in the interstellar medium (ISM). Results from this work give hints on physical and chemical processes occurring in space and can serve as a benchmark for dedicated space missions. Aims. The aim of this work is to consolidate the knowledge of ice evolution during the star formation process by investigating the influence of thermal reactions as a source of molecular complexity in the ISM. In this study, we are interested in the thermal reactivity between two interstellar molecules, formaldehyde (H2CO) and methylamine (CH3NH2) in water ice analogues. Methods. We used Fourier transform infrared spectroscopy, mass spectrometry, and B3LYP calculations to investigate the thermal reaction between formaldehyde and methylamine (14N and 15N) at low temperature in water ice analogues. Results. We demonstrate that methylamine and formaldehyde quickly react in water ice analogues for astronomically relevant temperatures and form N-methylaminomethanol CH3NHCH2OH. The measured activation energy of this reaction, 1.1 ± 0.05 kJ mol−1 (1.8 ± 0.08 kJ mol−1 with methylamine 15N), allows the reaction to proceed in interstellar ices, when the ices are gently warmed, as it occurs in young stellar objects, in photo-dissociation regions, or in comets. Therefore, CH3NHCH2OH is likely to be found in these objects. This hypothesis is confirmed by numerical simulations that clearly show that the formation of N-methylaminomethanol is likely at low temperature. Isotopic experiments as well as photochemical studies have also been performed to better characterise the ice evolution induced by heat and ultraviolet radiation during star formation.
Steering thermal photoassociation of magnesium atoms by two time-delayed femtosecond laser pulses

By solving the full-dimensional time-dependent Schrödinger equation with the thermal-random-phase wavepacket method, we investigate the photoassociation (PA) process of hot (1000 K) magnesium atoms induced by two time-delayed femtosecond laser pulses. Driven by the 840 nm fs laser pulses, the Mg2 molecules can be formed on the four excited states, (1)1Π g , (1)1Π u , (2)1Π u , and ( 2 ) 1 Σ u + , from the initial electronic ground state X 1 Σ g + . It is found that the three-photon couplings between X 1 Σ g + and the three ungerade states [(1)1Π u (2)1Π u , and ( 2 ) 1 Σ u + ], play dominant roles in the population transfer process. By scanning the pulse duration τ from 50 to 200 fs, and varying the delay time δt 0 from 0 to 2τ fs, we find that the final PA population is strongly dependent on the two parameters. For a given δt 0, the parameter τ can induce a significant variation (2 ∼ 6.8 times) for the final PA population transfer, and for a given τ, one can also obtain a significant variation (2.7 ∼ 3.5 times) of the final PA population by varying δt 0. Additionally, the dynamics of the coherently vibrational wavepackets of the four excited states are also influenced by the two parameters.
Bifurcation and chaos of direct radiation loudspeaker

The bifurcation and chaos of an 8" cone loudspeaker from its radiation in axial direction have been investigated by adopting an experimental setup quite similar to that of measuring frequency response in an anechois room. Experiments show that lower order and more fractional subharmonics of the fed-in signal begin to appear with increasing input voltage and eventually a chaotic state is reached.
Isolation of high-purity and high-stability exosomes from ginseng

Exosomes are nano-sized extracellular vesicles that regulate cell growth and defense by delivering bioactive cellular constituents. They are a promising material for biomedical and cosmetic utilization, especially in medicinal crops such as ginseng. One main hurdle to their usage is the need for a method to isolate stable exosomes with high purity. In this study, we first tested two methods to isolate exosomes from ginseng: ultracentrifugation, the most widely used method; and the ExoQuick system, a polymer-based exosome precipitation approach. We also designed and tested a third method in which we combined ultracentrifugation and ExoQuick methods. Size distribution analysis revealed that the exosome isolation purity by the ultracentrifugation and ExoQuick methods alone were 34.1% and 59.7%, respectively, while the combination method greatly improved exosome isolation purity (83.3%). Furthermore, we found that the combination method also increases the colloidal stability of isolated ginseng exosomes, and the increase was almost double that of the ultracentrifugation method. Lastly, we showed that the combination method can also be used to isolate high-purity and high-stability exosomes from the model plant Arabidopsis. Overall, our findings indicate that the combination method is suitable to isolate high-purity and high-stability exosomes from plants including ginseng.
Regionally restricted modulation of Sam68 expression and Arhgef9 alternative splicing in the hippocampus of a murine model of multiple sclerosis

Multiple sclerosis (MS) and its preclinical models are characterized by marked changes in neuroplasticity, including excitatory/inhibitory imbalance and synaptic dysfunction that are believed to underlie the progressive cognitive impairment (CI), which represents a significant clinical hallmark of the disease. In this study, we investigated several parameters of neuroplasticity in the hippocampus of the experimental autoimmune encephalomyelitis (EAE) SJL/J mouse model, characterized by rostral inflammatory and demyelinating lesions similar to Relapsing–Remitting MS. By combining morphological and molecular analyses, we found that the hippocampus undergoes extensive inflammation in EAE-mice, more pronounced in the CA3 and dentate gyrus (DG) subfields than in the CA1, associated with changes in GABAergic circuitry, as indicated by the increased expression of the interneuron marker Parvalbumin selectively in CA3. By laser-microdissection, we investigated the impact of EAE on the alternative splicing of Arhgef9, a gene encoding a post-synaptic protein playing an essential role in GABAergic synapses and whose mutations have been related to CI and epilepsy. Our results indicate that EAE induces a specific increase in inclusion of the alternative exon 11a only in the CA3 and DG subfields, in line with the higher local levels of inflammation. Consistently, we found a region-specific downregulation of Sam68, a splicing-factor that represses this splicing event. Collectively, our findings confirm a regionalized distribution of inflammation in the hippocampus of EAE-mice. Moreover, since neuronal circuit rearrangement and dynamic remodeling of structural components of the synapse are key processes that contribute to neuroplasticity, our study suggests potential new molecular players involved in EAE-induced hippocampal dysfunction.
Fast cycling of intermittent hypoxia in a physiomimetic 3D environment: A novel tool for the study of the parenchymal effects of sleep apnea

Background: Patients with obstructive sleep apnea (OSA) experience recurrent hypoxemic events with a frequency sometimes exceeding 60 events/h. These episodic events induce downstream transient hypoxia in the parenchymal tissue of all organs, thereby eliciting the pathological consequences of OSA. Whereas experimental models currently apply intermittent hypoxia to cells conventionally cultured in 2D plates, there is no well-characterized setting that will subject cells to well-controlled intermittent hypoxia in a 3D environment and enable the study of the effects of OSA on the cells of interest while preserving the underlying tissue environment. Aim: To design and characterize an experimental approach that exposes cells to high-frequency intermittent hypoxia mimicking OSA in 3D (hydrogels or tissue slices). Methods: Hydrogels made from lung extracellular matrix (L-ECM) or brain tissue slices (300–800-μm thickness) were placed on a well whose bottom consisted of a permeable silicone membrane. The chamber beneath the membrane was subjected to a square wave of hypoxic/normoxic air. The oxygen concentration at different depths within the hydrogel/tissue slice was measured with an oxygen microsensor. Results: 3D-seeded cells could be subjected to well-controlled and realistic intermittent hypoxia patterns mimicking 60 apneas/h when cultured in L-ECM hydrogels ≈500 μm-thick or ex-vivo in brain slices 300–500 μm-thick. Conclusion: This novel approach will facilitate the investigation of the effects of intermittent hypoxia simulating OSA in 3D-residing cells within the parenchyma of different tissues/organs.
Existing knowledge on Zn status biomarkers (1963–2021) with a particular focus on FADS1 and FADS2 diagnostic performance and recommendations for further research

The role of Zn in human health was discovered 60 years ago, and despite remarkable research efforts, a sufficiently sensitive and specific biomarker of Zn status is still lacking. Plasma/serum Zn, currently the best available and most accepted population Zn status indicator, responds well to severe Zn deficiency, yet, mild to moderate Zn deficiency states usually remain unrecognized. Identifying early-stage Zn deficiency requires additional robust markers of Zn status. This paper discusses the sensitivity, specificity, and responsiveness of plasma Zn concentrations to Zn interventions. It describes the biochemical and dietary basis for the causal association between Zn and fatty acid desaturases activity, FADS1 and FADS2, based on data collected through studies performed in animals and/or humans. The influence of potential confounders and covariates on the observed relationships is considered. Additional potential Zn biomarkers are discussed and suggestions for further research in this area are provided.
Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia

Background White matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer’s disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research. Methods We used a pseudo-randomly selected dataset (n = 50) from the DZNE-multicenter observational Longitudinal Cognitive Impairment and Dementia Study (DELCODE) that included 3D fluid-attenuated inversion recovery (FLAIR) images from participants across the cognitive continuum. Performances of top-rated algorithms for automated WMH segmentation [Brain Intensity Abnormality Classification Algorithm (BIANCA), lesion segmentation toolbox (LST), lesion growth algorithm (LGA), LST lesion prediction algorithm (LPA), pgs, and sysu_media] were compared to manual reference segmentation (RS). Results Across tools, segmentation performance was moderate for global WMH volume and number of detected lesions. After retraining on a DELCODE subset, the deep learning algorithm sysu_media showed the highest performances with an average Dice’s coefficient of 0.702 (±0.109 SD) for volume and a mean F1-score of 0.642 (±0.109 SD) for the number of lesions. The intra-class correlation was excellent for all algorithms (>0.9) but BIANCA (0.835). Performance improved with high WMH burden and varied across brain regions. Conclusion To conclude, the deep learning algorithm, when retrained, performed well in the multicenter context. Nevertheless, the performance was close to traditional methods. We provide methodological recommendations for future studies using automated WMH segmentation to quantify and assess WMH along the continuum of cognitive impairment and AD dementia.
Tire appearance defect detection method via combining HOG and LBP features

Tire appearance defect detection based on machine vision is an effective technology to improve the tire production quality. The detection process can be completed by the way of non-destructive testing. Therefore, more and more researchers are paying attention to this technology. However, tires are characterized by single block colors and various defects. It is a great challenge to accurately detect tire appearance defects. To complete the task of detecting tire defects, this paper presents a novel tire appearance defect detection method via combining histogram of oriented gradients (HOG) and local binary pattern (LBP) features. First, we construct a tire image dataset to provide defective and normal tire images. Then, histogram of oriented gradients and local binary pattern features of tire images are, respectively, extracted and used to train the support vector machine (SVM) classifier. Finally, the support vector machine classifier calculates the prediction scores of the test images via combining the histogram of oriented gradients and local binary pattern features. These scores can be utilized to determine whether the test image is a defective or a normal tire image, and the goal of tire appearance defect detection is achieved. Conducted on the tire image dataset, our method has verified the effectiveness of detecting tire detects, and the mean accuracy is improved more than 1.6% than the algorithm that only uses the histogram of oriented gradients or local binary pattern feature. The experimental results demonstrate that the combination of HOG and LBP features can increase tire appearance defect detection accuracy.