bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Mechanisms Thought to Govern Ice and Snow Friction and Their Interplay With Substrate Brittle Behavior
Authors: Lever James H. , Asenath-Smith Emily , Taylor Susan , Lines Austin P.
Published: June 2021

Sliding friction on ice and snow is characteristically low at temperatures common on Earth’s surface. This slipperiness underlies efficient sleds, winter sports, and the need for specialized tires. Friction can also play a micro-mechanical role affecting ice compressive and crushing strengths. Researchers have proposed several mechanisms thought to govern ice and snow friction, but directly validating the underlying mechanics has been difficult. This may be changing, as instruments capable of micro-scale measurements and imaging are now being brought to bear on friction studies. Nevertheless, given the broad regimes of practical interest (interaction length, temperature, speed, pressure, slider properties, etc.), it may be unrealistic to expect that a single mechanism accounts for why ice and snow are slippery. Because bulk ice, and the ice grains that constitute snow, are solids near their melting point at terrestrial temperatures, most research has focused on whether a lubricating water film forms at the interface with a slider. However, ice is extremely brittle, and dry-contact abrasion and wear at the front of sliders could prevent or delay a transition to lubricated contact. Also, water is a poor lubricant, and lubricating films thick enough to separate surface asperities may not form for many systems of interest. This article aims to assess our knowledge of the mechanics underlying ice and snow friction. We begin with a brief summary of the mechanical behavior of ice and snow substrates, behavior which perhaps has not received sufficient attention in friction studies. We then assess the strengths and weaknesses of five ice- and snow-friction hypotheses: pressure-melting, self-lubrication, quasi-liquid layers, abrasion, and ice-rich slurries. We discuss their assumptions and review evidence to determine whether they are consistent with the postulated mechanics. Lastly, we identify key issues that warrant additional research to resolve the specific mechanics and the transitions between them that control ice and snow friction across regimes of practical interest.
Patient Expectations of Assigned Treatments Impact Strength of Randomised Control Trials
Authors: Truzoli Roberto , Reed Phil , Osborne Lisa A.
Published: June 2021

Patient engagement with treatments potentially poses problems for interpreting the results and meaning of Randomised Control Trials (RCTs). If patients are assigned to treatments that do, or do not, match their expectations, and this impacts their motivation to engage with that treatment, it will affect the distribution of outcomes. In turn, this will impact the obtained power and error rates of RCTs. Simple Monto Carlo simulations demonstrate that these patient variables affect sample variance, and sample kurtosis. These effects reduce the power of RCTs, and may lead to false negatives, even when the randomisation process works, and equally distributes those with positive and negative views about a treatment to a trial arm.
SARS-CoV-2 Viral Shedding and Transmission Dynamics: Implications of WHO COVID-19 Discharge Guidelines
Authors: Badu Kingsley , Oyebola Kolapo , Zahouli Julien Z. B. , Fagbamigbe Adeniyi Francis , de Souza Dziedzom K. , Dukhi Natisha , Amankwaa Ebenezer F. , Tolba Mai F. , Sylverken Augustina A. , Mosi Lydia , Mante Priscilla Kolibea , Matoke-Muhia Damaris , Goonoo Nowsheen
Published: June 2021

The evolving nature of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated periodic revisions of COVID-19 patient treatment and discharge guidelines. Since the identification of the first COVID-19 cases in November 2019, the World Health Organization (WHO) has played a crucial role in tackling the country-level pandemic preparedness and patient management protocols. Among others, the WHO provided a guideline on the clinical management of COVID-19 patients according to which patients can be released from isolation centers on the 10th day following clinical symptom manifestation, with a minimum of 72 additional hours following the resolution of symptoms. However, emerging direct evidence indicating the possibility of viral shedding 14 days after the onset of symptoms called for evaluation of the current WHO discharge recommendations. In this review article, we carried out comprehensive literature analysis of viral shedding with specific focus on the duration of viral shedding and infectivity in asymptomatic and symptomatic (mild, moderate, and severe forms) COVID-19 patients. Our literature search indicates that even though, there are specific instances where the current protocols may not be applicable ( such as in immune-compromised patients there is no strong evidence to contradict the current WHO discharge criteria.
Remission Induced by TNF Inhibitors Plus Methotrexate is Associated With Changes in Peripheral Naïve B Cells in Patients With Rheumatoid Arthritis
Authors: Hernández-Breijo Borja , Plasencia-Rodríguez Chamaida , Navarro-Compán Victoria , García-Hoz Carlota , Nieto-Gañán Israel , Sobrino Cristina , Bachiller-Corral Javier , Díaz-Almirón Mariana , Martínez-Feito Ana , Jurado Teresa , Lapuente-Suanzes Paloma , Bonilla Gema , Pijoán-Moratalla Cristina , Roy Garbiñe , Vázquez-Díaz Mónica , Balsa Alejandro , Villar Luisa M. , Pascual-Salcedo Dora , Rodríguez-Martín Eulalia
Published: June 2021

Biological therapies, such as TNF inhibitors (TNFi), are increasing remission (REM) rates in rheumatoid arthritis (RA) patients, although these are still limited. The aim of our study was to analyze changes in the profile of peripheral blood mononuclear cells (PBMC) in patients with RA treated with TNFi in relation to the clinical response. This is a prospective and observational study including 78 RA patients starting the first TNFi. PBMC were analyzed by flow cytometry both at baseline and at 6 months. Disease activity at the same time points was assessed by DAS28, establishing DAS28 ≤ 2.6 as the criteria for REM. Logistic regression models were employed to analyze the association between the changes in PBMC and REM. After 6 months of TNFi treatment, 37% patients achieved REM by DAS28. Patients who achieved REM showed a reduction in the percentage of naive B cells, but only when patients had received concomitant methotrexate (MTX) (OR: 0.59; 95% CI: 0.39–0.91). However, no association was found for patients who did not receive concomitant MTX (OR: 0.85; 95% CI: 0.63–1.16). In conclusion, PBMC, mainly the B-cell subsets, are modified in RA patients with TNFi who achieve clinical REM. A significant decrease in naive B-cell percentage is associated with achieving REM after 6 months of TNFi treatment in patients who received concomitant therapy with MTX.
Sulforaphane Alleviates Particulate Matter-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells
Authors: Sim Hyunchae , Lee Wonhwa , Choo Samyeol , Park Eui Kyun , Baek Moon-Chang , Lee In-Kyu , Park Dong Ho , Bae Jong-Sup
Published: June 2021

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 μm (PM2.5) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM2.5 exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM2.5-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM2.5 decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM2.5-induced oxidative stress in a dose-dependent manner. PM2.5-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM2.5 treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM2.5-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM2.5 exposure.
Diversity and Distribution of Uncultured and Cultured Gaiellales and Rubrobacterales in South China Sea Sediments
Authors: Chen Rou-Wen , He Yuan-Qiu , Cui Lin-Qing , Li Cun , Shi Song-Biao , Long Li-Juan , Tian Xin-Peng
Published: June 2021

Actinobacteria are ubiquitous in marine ecosystems, and they are regarded as an important, underexplored, potential pharmaceutical resource. The orders Gaiellales and Rubrobacterales are deep taxonomic lineages of the phylum Actinobacteria, both are represented by a single genus and contain only a few species. Although they have been detected frequently by high-throughput sequencing, their functions and characteristics in marine habitats remain unknown due to the lack of indigenous phenotypes. Here, we investigated the status of the orders in South China Sea (SCS) sediments using culture-independent and culture-dependent methods. Gaiellales is the second-most abundant order of Actinobacteria and was widely distributed in SCS sediments at water depths of 42–4,280 m, and four novel marine representatives in this group were successfully cultured. Rubrobacterales was present at low abundance in energy-limited marine habitats. An isolation strategy for Rubrobacterales from marine samples was proposed, and a total of 138 mesophilic Rubrobacterales strains were isolated under conditions of light and culture time combined with high-salinity or low-nutrient media. Marine representatives recovered in this study formed branches with a complex evolutionary history in the phylogenetic tree. Overall, the data indicate that both Gaiellales and Rubrobacterales can adapt to and survive in extreme deep-sea environments. This study lays the groundwork for further analysis of the distribution and diversity of the orders Gaiellales and Rubrobacterales in the ocean and provides a specific culture strategy for each group. The results open a window for further research on the ecological roles of the two orders in marine ecosystems.
Antibacterial Activity of a Fractionated Pistacia lentiscus Oil Against Pharyngeal and Ear Pathogens, Alone or in Combination With Antibiotics
Authors: Di Pierro Francesco , Sagheddu Valeria , Galletti Serena , Forti Mara , Elli Marina , Bertuccioli Alexander , Gaeta Simone
Published: June 2021

Previous studies have clearly demonstrated that the addition of lentisk oil (LO) to streptococcal cultures makes it possible to differentiate Streptococcus spp. into three categories with Streptococcus mitis and Streptococcus intermedius sensitive, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus mutans partially sensitive, and Streptococcus salivarius insensitive to the product. We have investigated here whether the winterization of LO, an easy and cheap procedure that removes some of the fatty substances contained within, resulted in a better antimicrobial effect on human pathogens affecting the pharyngeal mucosa and middle ear such as S. pyogenes, S. pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae, without affecting, or minimally affecting, S. salivarius strains, oral probiotics commonly used to reduce oral and middle ear infection recurrence, especially in children. Our results not only demonstrated a stronger antimicrobial action of winterized LO (WLO) on S. pyogenes, compared to what was seen with LO, but also demonstrated a strong antimicrobial action vs. S. pneumoniae and M. catarrhalis and a very limited effect on S. salivarius (strains K12 and M18). Moreover, WLO demonstrated a co-acting action when tested along with the antibiotics amoxicillin (A) and amoxicillin clavulanate (AC), effects clearly visible also on H. influenzae. Our results also showed that at least part of the antimicrobial effect observed was due to the presence of anacardic acids (AAs). Finally, WLO, when tested with human peripheral blood mononuclear cells (h-PBMCs), reduced the release of IL-6 and TNF-α and, in the case of cells stimulated by LPS, the release of IFN-γ. In conclusion, our study highlights an enhanced antimicrobial role for LO when winterized, suggests a co-acting effect of this when given with antibiotics, identifies AAs as possible active ingredients, and proposes a possible anti-inflammatory role for it.
RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains
Authors: Zhou Yong , Gorfe Alemayehu A. , Hancock John F.
Published: June 2021

RAS proteins are lipid-anchored small GTPases that switch between the GTP-bound active and GDP-bound inactive states. RAS isoforms, including HRAS, NRAS and splice variants KRAS4A and KRAS4B, are some of the most frequently mutated proteins in cancer. In particular, constitutively active mutants of KRAS comprise ∼80% of all RAS oncogenic mutations and are found in 98% of pancreatic, 45% of colorectal and 31% of lung tumors. Plasma membrane (PM) is the primary location of RAS signaling in biology and pathology. Thus, a better understanding of how RAS proteins localize to and distribute on the PM is critical to better comprehend RAS biology and to develop new strategies to treat RAS pathology. In this review, we discuss recent findings on how RAS proteins sort lipids as they undergo macromolecular assembly on the PM. We also discuss how RAS/lipid nanoclusters serve as signaling platforms for the efficient recruitment of effectors and signal transduction, and how perturbing the PM biophysical properties affect the spatial distribution of RAS isoforms and their functions.
Prospective Use of Brown Spider Venom Toxins as Therapeutic and Biotechnological Inputs
Authors: Gremski Luiza Helena , Matsubara Fernando Hitomi , Polli Nayanne Louise Costacurta , Antunes Bruno Cesar , Schluga Pedro Henrique de Caires , Justa Hanna Câmara da , Minozzo João Carlos , Wille Ana Carolina Martins , Senff-Ribeiro Andrea , Veiga Silvio Sanches
Published: June 2021

Brown spider (genus Loxosceles) venoms are mainly composed of protein toxins used for predation and defense. Bites of these spiders most commonly produce a local dermonecrotic lesion with gravitational spread, edema and hemorrhage, which together are defined as cutaneous loxoscelism. Systemic loxoscelism, such as hematological abnormalities and renal injury, are less frequent but more lethal. Some Loxosceles venom toxins have already been isolated and extensively studied, such as phospholipases D (PLDs), which have been recombinantly expressed and were proven to reproduce toxic activities associated to the whole venom. PLDs have a notable potential to be engineered and converted in non-toxic antigens to produce a new generation of antivenoms or vaccines. PLDs also can serve as tools to discover inhibitors to be used as therapeutic agents. Other Loxosceles toxins have been identified and functionally characterized, such as hyaluronidases, allergen factor, serpin, TCTP and knottins (ICK peptides). All these toxins were produced as recombinant molecules and are biologically active molecules that can be used as tools for the potential development of chemical candidates to tackle many medical and biological threats, acting, for instance, as antitumoral, insecticides, analgesic, antigens for allergy tests and biochemical reagents for cell studies. In addition, these recombinant toxins may be useful to develop a rational therapy for loxoscelism. This review summarizes the main candidates for the development of drugs and biotechnological inputs that have been described in Brown spider venoms.
Regional Spontaneous Neural Activity Alterations in Type 2 Diabetes Mellitus: A Meta-Analysis of Resting-State Functional MRI Studies
Authors: Liu Jieke , Li Yong , Yang Xi , Xu Hao , Ren Jing , Zhou Peng
Published: June 2021

Objective: Resting-state functional magnetic resonance imaging (rs-fMRI) studies have revealed inconsistent regional spontaneous neural activity alterations in patients with type 2 diabetes mellitus (T2DM). The aim of our meta-analysis was to identify concordant regional spontaneous neural activity abnormalities in patients with T2DM.

Methods: A systematic search was conducted to identify voxel-based rs-fMRI studies comparing T2DM patients with healthy controls. The permutation of subject images seed-based d mapping (SDM) was used to quantitatively estimate the regional spontaneous neural activity abnormalities in patients with T2DM. Metaregression was conducted to examine the associations between clinical characteristics and functional alterations.

Results: A total of 16 studies with 19 datasets including 434 patients with T2DM and 391 healthy controls were included. Patients with T2DM showed hypoactivity in the right medial superior frontal gyrus, right superior temporal gyrus, and left lingual gyrus, whereas hyperactivity in the right cerebellum. Metaregression analysis identified negative correlation between regional activity in the medial superior frontal and anterior cingulate gyri and illness duration of patients with T2DM.

Conclusion: The patterns of regional spontaneous neural activity alterations, characterized by hypoactivity in the medial pre-frontal cortex, visual cortex, and superior temporal gyrus, whereas hyperactivity in the cerebellum, might represent the underlying neuropathological mechanisms of T2DM.
Early Prediction of Refractory Epilepsy in Children Under Artificial Intelligence Neural Network
Authors: Huang Yueyan , Li Qingfeng , Yang Qian , Huang Zhijing , Gao Hongbo , Xu Yunan , Liao Lianghua
Published: June 2021

In order to realize the early prediction of refractory epilepsy in children, data preprocessing technology was used to improve the data quality, and the detection model of refractory epilepsy in children based on convolutional neural network (CNN) was established. Then, the data in the epilepsy electroencephalography (EEG) signal public data set was used for model training and the diagnosis of refractory epilepsy in children. Moreover, back propagation neural network (BPNN), support vector machine (SVM), XGBoost, gradient boosting decision tree (GBDT), AdaBoost algorithm were introduced for comparison. The results showed that the early prediction accuracy of BP, SVM, XGBoost, GBDT, AdaBoost, and the algorithm in this study for refractory epilepsy in children were 0.745, 0.778, 0.885, 0.846, 0.874, and 0.941, respectively. The sensitivities were 0.81, 0.826, 0.822, 0.84, 0.859, and 0.918, respectively. The specificities were 0.683, 0.696, 0.743, 0.792, 0.84, and 0.905, respectively. The accuracy was 0.707, 0.732, 0.765, 0.802, 0.839, and 0.881, respectively. The recall rates were 0.69, 0.716, 0.753, 0.784, 0.813, and 0.877, respectively. F1 scores were 0.698, 0.724, 0.759, 0.793, 0.826, and 0.879, respectively. Through the comparisons of the above six indicators, the algorithm proposed in this study was significantly higher than other algorithms, suggesting that the proposed algorithm was more accurate in early prediction of refractory epilepsy in children. Analysis of the EEG characteristics and magnetic resonance imaging (MRI) images of refractory epilepsy in children suggested that the MRI images of patients' brains under this algorithm had obvious characteristics. The reason for the prediction error of the algorithm was that the duration of epilepsy was too short or the EEG of the patient didn't change notably during the epileptic seizure. In summary, the prediction method of refractory epilepsy in children based on CNN was accurate, which had broad adoption prospects in assisting clinicians in the examination and diagnosis of refractory epilepsy in children.
Lipid Levels and 3-Month Prognosis After Spontaneous Intracerebral Hemorrhage in Women
Authors: Feng Hao , Wang Xin , Wang Wenjuan , Zhao Xingquan
Published: June 2021

Background: The relationship between serum lipids levels and prognosis after spontaneous intracerebral hemorrhage (ICH) is still unclear. We aim to examine the association between lipid levels and 3-month ICH prognosis in women.

Method: We went through a registry of spontaneous ICH cases and selected female patients to study according to our criteria. We collected demographic, clinical, and laboratory information and evaluated serum triglyceride (TG) levels, total cholesterol (TC) levels, low-density cholesterol (LDLC) levels, high-density cholesterol (HDLC) levels, non-high-density cholesterol (non-HDLC) levels, and 3-month modified Rankin Scale (mRS). Multivariate logistic regression was performed, and receiver operating characteristic (ROC) curves were plotted to explore the relationship between serum lipid levels and 3-month ICH clinical outcomes.

Results: Two hundred six female patients were included in this study, and 96 (46.6%) of them had poor functional outcomes. In the univariate analysis, low TG (p = 0.006), TC (p = 0.025), LDLC (p = 0.001), non-HDLC (p < 0.001) levels, and high HDL (p = 0.036) levels were associated with poor 3-month clinical outcomes in women. In the multivariate logistic regression, low levels of TG (OR = 0.711, 95% CI = 0.542–0.933, p = 0.014), TC (OR = 0.523, 95% CI = 0.304–0.903, p = 0.020), LDLC (OR = 0.538, 95% CI = 0.307–0.942, p = 0.030), non-HDLC (OR = 0.327, 95% CI = 0.177–0.603, p < 0.001), and a high level of HDLC (OR = 2.075, 95% CI = 1.064–4.047, p = 0.032) with area under the curve (AUC) of 0.610, 0.590, 0.630, 0.645, and 0.415, respectively, remained as independent indicators of poor prognosis at 3 months after adjusting for confounding factors.

Conclusion: Low levels of TG, TC, LDLC, non-HDLC, and high levels of HDLC were independently associated with poor prognosis of spontaneous ICH in women.
Dual Task Effects on Speed and Accuracy During Cognitive and Upper Limb Motor Tasks in Adults With Stroke Hemiparesis
Authors: Kim Hogene , Kim Hyun-Ki , Kim Nayoung , Nam Chang S.
Published: June 2021

Background

Adults with stroke need to perform cognitive–motor dual tasks during their day-to-day activities. However, they face several challenges owing to their impaired motor and cognitive functions.

Objective

This case-controlled pilot study investigates the speed and accuracy tradeoffs in adults with stroke while performing cognitive–upper limb motor dual tasks.

Methods

Ten adults with stroke and seven similar-aged controls participated in this study. The participants used a robotic arm for the single motor task and participated in either the serial sevens (S7) or the controlled oral word association test (COWAT) for single-cognitive task. For the dual task, the participants performed the motor and cognitive components simultaneously. Their speed and accuracy were measured for the motor and cognitive tasks, respectively.

Results

Two-sample t-statistics indicated that the participants with stroke exhibited a lower motor accuracy in the cross task than in the circle task. The cognitive speed and motor accuracy registered by the subjects with stroke in the dual task significantly decreased. There was a negative linear correlation between motor speed and accuracy in the subjects with stroke when the COWAT task was performed in conjunction with the cross task (ρ = −0.6922, p = 0.0388).

Conclusions

This study proves the existence of cognitive–upper limb motor interference in adults with stroke while performing dual tasks, based on the observation that their performance during one or both dual tasks deteriorated compared to that during the single task. Both speed and accuracy were complementary parameters that may indicate clinical effectiveness in motor and cognitive outcomes in individuals with stroke.
Naturalistic Stimuli in Affective Neuroimaging: A Review
Authors: Saarimäki Heini
Published: June 2021

Naturalistic stimuli such as movies, music, and spoken and written stories elicit strong emotions and allow brain imaging of emotions in close-to-real-life conditions. Emotions are multi-component phenomena: relevant stimuli lead to automatic changes in multiple functional components including perception, physiology, behavior, and conscious experiences. Brain activity during naturalistic stimuli reflects all these changes, suggesting that parsing emotion-related processing during such complex stimulation is not a straightforward task. Here, I review affective neuroimaging studies that have employed naturalistic stimuli to study emotional processing, focusing especially on experienced emotions. I argue that to investigate emotions with naturalistic stimuli, we need to define and extract emotion features from both the stimulus and the observer.
DeepNavNet: Automated Landmark Localization for Neuronavigation
Authors: Edwards Christine A. , Goyal Abhinav , Rusheen Aaron E. , Kouzani Abbas Z. , Lee Kendall H.
Published: June 2021

Functional neurosurgery requires neuroimaging technologies that enable precise navigation to targeted structures. Insufficient image resolution of deep brain structures necessitates alignment to a brain atlas to indirectly locate targets within preoperative magnetic resonance imaging (MRI) scans. Indirect targeting through atlas-image registration is innately imprecise, increases preoperative planning time, and requires manual identification of anterior and posterior commissure (AC and PC) reference landmarks which is subject to human error. As such, we created a deep learning-based pipeline that consistently and automatically locates, with submillimeter accuracy, the AC and PC anatomical landmarks within MRI volumes without the need for an atlas. Our novel deep learning pipeline (DeepNavNet) regresses from MRI scans to heatmap volumes centered on AC and PC anatomical landmarks to extract their three-dimensional coordinates with submillimeter accuracy. We collated and manually labeled the location of AC and PC points in 1128 publicly available MRI volumes used for training, validation, and inference experiments. Instantiations of our DeepNavNet architecture, as well as a baseline model for reference, were evaluated based on the average 3D localization errors for the AC and PC points across 311 MRI volumes. Our DeepNavNet model significantly outperformed a baseline and achieved a mean 3D localization error of 0.79 ± 0.33 mm and 0.78 ± 0.33 mm between the ground truth and the detected AC and PC points, respectively. In conclusion, the DeepNavNet model pipeline provides submillimeter accuracy for localizing AC and PC anatomical landmarks in MRI volumes, enabling improved surgical efficiency and accuracy.
Maturation of Heterogeneity in Afferent Synapse Ultrastructure in the Mouse Cochlea
Authors: Payne Shelby A. , Joens Matthew S. , Chung Heather , Skigen Natalie , Frank Adam , Gattani Sonali , Vaughn Kya , Schwed Allison , Nester Matt , Bhattacharyya Atri , Iyer Guhan , Davis Bethany , Carlquist Jason , Patel Honey , Fitzpatrick James A. J. , Rutherford Mark A.
Published: June 2021

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured the size, shape, vesicle content, and position of 70 ribbon synapses from the mid-cochlea. Several features matured over late postnatal development. From p17 to p34, presynaptic densities (PDs) and post-synaptic densities (PSDs) became smaller on average (PDs: 0.75 to 0.33; PSDs: 0.58 to 0.31 μm2) and less round as their short axes shortened predominantly on the modiolar side, from 770 to 360 nm. Membrane-associated synaptic vesicles decreased in number from 53 to 30 per synapse from p17 to p34. Anatomical coupling, measured as PSD to ribbon distance, tightened predominantly on the pillar side. Ribbons became less spherical as long-axes lengthened only on the modiolar side of the IHC, from 372 to 541 nm. A decreasing gradient of synaptic ribbon size along the modiolar-pillar axis was detected only at p34 after aligning synapses of adjacent IHCs to a common reference frame (median volumes in nm3 × 106: modiolar 4.87; pillar 2.38). The number of ribbon-associated synaptic vesicles scaled with ribbon size (range 67 to 346 per synapse at p34), thus acquiring a modiolar-pillar gradient at p34, but overall medians were similar at p17 (120) and p34 (127), like ribbon surface area (0.36 vs. 0.34 μm2). PD and PSD morphologies were tightly correlated to each other at individual synapses, more so at p34 than p17, but not to ribbon morphology. These observations suggest that PDs and PSDs mature according to different cues than ribbons, and that ribbon size may be more influenced by cues from the IHC than the surrounding tissue.
Application of Visible/Infrared Spectroscopy and Hyperspectral Imaging With Machine Learning Techniques for Identifying Food Varieties and Geographical Origins
Authors: Feng Lei , Wu Baohua , Zhu Susu , He Yong , Zhang Chu
Published: June 2021

Food quality and safety are strongly related to human health. Food quality varies with variety and geographical origin, and food fraud is becoming a threat to domestic and global markets. Visible/infrared spectroscopy and hyperspectral imaging techniques, as rapid and non-destructive analytical methods, have been widely utilized to trace food varieties and geographical origins. In this review, we outline recent research progress on identifying food varieties and geographical origins using visible/infrared spectroscopy and hyperspectral imaging with the help of machine learning techniques. The applications of visible, near-infrared, and mid-infrared spectroscopy as well as hyperspectral imaging techniques on crop food, beverage, fruits, nuts, meat, oil, and some other kinds of food are reviewed. Furthermore, existing challenges and prospects are discussed. In general, the existing machine learning techniques contribute to satisfactory classification results. Follow-up researches of food varieties and geographical origins traceability and development of real-time detection equipment are still in demand.
MRI Features of Hepatic Sarcomatoid Carcinoma Different From Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
Authors: Zhang Hongbin , Chai Siyuan , Chen Lintao , Wang Yubizhuo , Cheng Yongna , Fang Quan , Wu Guosen , Wang Xiangming , Liang Wenjie , Xiao Wenbo
Published: June 2021

Introduction

Hepatic sarcomatoid carcinoma (HSC) is a rare type of liver cancer with a high malignant grade and poor prognosis. This study compared the clinical characteristics and magnetic resonance imaging (MRI) features of HSCs with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), aiming to identify valuable features for HSC diagnosis.

Methods

In total, 17 pathologically confirmed HSC cases, 50 HCC cases and 50 common ICC cases were enrolled from two hospitals. The clinical characteristics and MRI features of all cases were summarized and statistically analyzed.

Results

On the one hand, the incidence rates of elevated carbohydrate antigen (CA) 19-9 and elevated carcinoembryonic antigen (CEA) were significantly higher in the HSC cases than in the HCC cases (29.4% vs. 0%; 17.6% vs. 0%). The HSC enhancement patterns, primarily including progressive enhancement, were also significantly different from HCC cases. The incidence rates of heterogeneous signals on T2-weighted imaging and during the arterial phase were significantly higher in the HSC cases than in the HCC cases (94.1% vs. 66.0%; 100.0% vs. 72.0%). The diameter of HSCs was significantly larger than that in the HCC cases (6.12 cm vs. 4.21 cm), and the incidence rates of adjacent cholangiectasis, intrahepatic metastasis and lymph node enlargement were considerably higher in the HSC cases than in the HCC cases (52.9% vs. 6.0%; 47.1% vs. 12.0%; 41.2% vs. 2.0%). On the other hand, the incidence rate of elevated CA199 was significantly lower in the HSC cases than in the ICC cases (29.4% vs. 60.0%). The incidence rates of intratumoral necrosis and pseudocapsules were significantly higher in the HSC cases than in the HCC cases (35.3% vs. 8.0%; 47.1% vs. 12.0%). However, the incidence rates of target signs were significantly lower in the HSC cases than in the HCC cases (11.8% vs. 42.0%). In addition, there was no significant difference in the enhancement patterns between HSC cases and ICC cases.

Conclusions

HSCs were frequently seen in elderly men with clinical symptoms and elevated CA199 levels. The MRI features, including large size, obvious heterogeneity, hemorrhage, progressive enhancement, pseudocapsule and lymph node enlargement, contributed to the diagnosis of HSC.
Barrett’s Esophagus and Intestinal Metaplasia
Authors: Zhang Lu , Sun Binyu , Zhou Xi , Wei QiongQiong , Liang Sicheng , Luo Gang , Li Tao , Lü Muhan
Published: June 2021

Intestinal metaplasia refers to the replacement of the differentiated and mature normal mucosal epithelium outside the intestinal tract by the intestinal epithelium. This paper briefly describes the etiology and clinical significance of intestinal metaplasia in Barrett’s esophagus. This article summarizes the impact of intestinal metaplasia on the diagnosis, monitoring, and treatment of Barrett’s esophagus according to different guidelines. We also briefly explore the basis for the endoscopic diagnosis of intestinal metaplasia in Barrett’s esophagus. The identification techniques of goblet cells in Barrett’s esophagus are also elucidated by some scholars. Additionally, we further elaborate on the current treatment methods related to Barrett’s esophagus.
Preoperative Fibrosis-4 (FIB-4) Evaluation May Be Helpful to Evaluate Prognosis of Gastric Cancer Patients Undergoing Operation: A Retrospective Study
Authors: Xu Ke , Shi Mingming , Zhang Weiteng , Shi Yiyi , Dong Qiantong , Shen Xian , Chen Xiaolei , Lin Ji
Published: June 2021

Background

Liver dysfunction and chronic inflammation influence the prognosis of many tumors and surgical outcomes. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, originally defined as a noninvasive fibrosis marker, can predict the prognosis of patients with gastric cancer undergoing radical gastric cancer surgery.

Methods

We have retrospectively analyzed 594 consecutive patients with gastric cancer who underwent gastrectomy in our database. The FIB-4 index was calculated using laboratory data and age before gastrectomy. The clinical utility of FIB-4 was evaluated by X-tile. Patients were divided into two groups (high and low FIB-4 index groups), and their overall survival (OS) was investigated. Cox regression analysis was used to identify the independent parameters associated with prognosis. Finally, we developed a prognostic prediction model by using R statistical software.

Results

A total of 556 patients, including 422 men and 134 women, were enrolled. Of these, 61 (11.0%) and 495 (89.0%) patients had low and FIB-4 indexes, respectively. In addition to the indicators of FIB-4, preoperative age, tumor site, surgical procedure, TNM stage, and postoperative complications were found to be independent predictors of prognosis (P < 0.05). Among patients, the FIB-4 index group had significantly shorter OS (log-rank P = 0.01) than the low FIB-4 index group. This association was also confirmed in the multivariate analysis (hazard ratio, 4.65; 95% confidence interval, 1.07-4.29; P = 0.031).

Conclusions

Preoperative FIB-4 index can predict long-term outcomes of gastric cancer patients who had undergone gastrectomy.
Association of the 12-Gene Breast DCIS Score® Assay With Local Recurrence in Patients With Ductal Carcinoma In Situ Treated on Accelerated Partial Breast Radiotherapy Protocols
Authors: Leonard Charles E. , Tole Shannon P. , Turner Michelle P. , Bennett John P. , Howell Kathryn T. , Carter Dennis L.
Published: June 2021

Background

The following analysis explores clinicopathologic factors and the 12-gene Breast DCIS Score test result in order to better define an appropriate DCIS (ductal carcinoma in situ) population eligible for APBI (accelerated partial breast radiotherapy).

Methods

This exploratory analysis aimed to retrospectively measure the association between the 12-gene Oncotype DX Breast DCIS Score® assay (Redwood City, CA) and relevant clinicopathologic factors with locoregional recurrence in a pooled cohort of women treated with local excision and APBI on prospective phase II (NCT01185145) and phase III (NCT01185132) clinical trials. Univariable Cox proportional hazards regression was used to determine whether there was an association between local recurrence and DCIS Score result risk group (≥ 39 vs < 39) and clinicopathologic factors.

Results

This analysis included 104 evaluable patients (n = 18 from NCT01185145 and n = 86 from NCT01185132). The median age was 60 years (range: 40-79). Seventy-nine percent of patients were postmenopausal. The median span of DCIS was 10 mm (range 2-45 mm). Two-thirds of the cohort presented with necrosis (71%). The distribution of DCIS Score® results ranged from 0 to 82, with 69% of patients having a DCIS Score result < 39. The median follow-up time was 8.2 years in NCT01185145 versus 3.0 years in NCT01185132. There were 6 local ipsilateral breast recurrences. DCIS Score result was significantly associated with local recurrence in univariable modeling, hazard ratio = 10.3 (95% CI 1.7, 198.4); p = 0.010. None of the clinicopathologic characteristics resulted in any significant association with locoregional recurrence.

Conclusion

The Breast DCIS Score assay demonstrated risk stratification in this cohort of patients treated with local excision and APBI pooled from two clinical trials. These results are consistent with those recently published utilizing whole breast radiotherapy. Due to the small number of local recurrence events and limited follow-up time, further investigations are needed to confirm findings.
Berberine Sensitizes Human Hepatoma Cells to Regorafenib via Modulating Expression of Circular RNAs
Authors: Wang Kunyuan , Yu Ganxiang , Lin Jiaen , Wang Zhilei , Lu Qianting , Gu Chengxin , Yang Tao , Liu Shiming , Yang Hui
Published: June 2021

Regorafenib resistance is a key limiting factor in the treatment of advanced hepatocellular carcinoma (HCC). Increasing evidence has demonstrated that Berberine (BBR) can synergistically enhance the therapeutic effect of various chemotherapeutic agents. However, the contribution of BBR on regorafenib therapy remains unclear. The purpose of this study was to explore the combined treatment effect of berberine and regorafenib in HCC. We found that BBR enhanced the cytotoxicity of regorafenib in HCC cells. Compared with regorafenib alone, the combined treatment of BBR and regorafenib significantly inhibited the proliferation of HCC cells and induced cellular apoptosis. Meanwhile, the combined treatment group with BBR (10mg/kg/day) and regorafenib (5mg/kg/day) had a dramatic inhibitory effect on the growth of HCC xenograft tumors in nude mice. The increased apoptosis of xenograft tumors was seen in the combined treatment group. Moreover, a comprehensive circular RNA sequencing was performed to identify differentially expressed circRNAs in HCC cells after exposure to 100µM BBR and 5µM regorafenib. The volcano plot and scatter plot analyses revealed that there were 58 up-regulated and 19 down-regulated differentially expressed circRNAs between the combination treatment and control groups. Among them, the expression of hsa_circ_0032029 and hsa_circ_0008928 were up-regulated in HCC cells after treatment with 100µM BBR and 5µM regorafenib. Taken together, this study demonstrated that BBR enhanced the anti-HCC effect of regorafenib both in vitro and in vivo. The synergistic anti-tumor effect of BBR and regorafenib might be related to the up-regulation of hsa_circ_0032029 and hsa_circ_0008928 in HCC cells.
Partially Coherent Optical Diffraction Tomography Toward Practical Cell Study
Authors: Soto Juan M. , Rodrigo José A. , Alieva Tatiana
Published: June 2021

Optical diffraction tomography (ODT) is a computational imaging technique based on refractive index (RI) contrast. Its application for microscopic imaging of weakly absorbing and scattering samples has been demonstrated by using a specially designed holographic microscope with angular scanning of the coherent sample illumination direction. Recently, an alternative low cost technique based on partially coherent sample illumination (PC-ODT), which is compatible with the conventional wide-field transmission microscope, has been established. In this case, the 3D refractive index distribution of the sample is obtained by deconvolution from a single stack of through-focus intensity images. The performance of PC-ODT has been successfully tested on various fixed specimens (diatom frustule and biological cells) and moving bacteria. Here, we demonstrate that the PC-ODT is an efficient tool for the analysis of living eukaryotic cell dynamics at short- and long-term periods. The COS-7 cells, which hail from the African green monkey kidney, have been chosen for this study. A fast data acquisition setup comprising an optical scanning module can be easily attached to the microscope, and it allows observing cell 3D organelle movements and RI variations, with the required temporal resolution. In particular, a more rapid nucleoli rotation than previously reported has been found. The long-term cell monitoring during necrosis reveals significant changes in cell dry mass concentration obtained from recovered RI contrast.
A Bistable Phenomena Induced by a Mean-Field SIS Epidemic Model on Complex Networks: A Geometric Approach
Authors: Wang Xiaoyan , Yang Junyuan
Published: June 2021

In this paper, we propose a degree-based mean-field SIS epidemic model with a saturated function on complex networks. First, we adopt an edge-compartmental approach to lower the dimensions of such a proposed system. Then we give the existence of the feasible equilibria and completely study their stability by a geometric approach. We show that the proposed system exhibits a backward bifurcation, whose stabilities are determined by signs of the tangent slopes of the epidemic curve at the associated equilibria. Our results suggest that increasing the management and the allocation of medical resources effectively mitigate the lag effect of the treatment and then reduce the risk of an outbreak. Moreover, we show that decreasing the average of a network sufficiently eradicates the disease in a region or a country.
High Reflectivity and Low Reflectivity Properties on OCTA Influence the Detection of Macular Neovascularization in AMD
Authors: Arrigo Alessandro , Aragona Emanuela , Bordato Alessandro , Amato Alessia , Saladino Andrea , Bandello Francesco , Parodi Maurizio Battaglia
Published: June 2021

Background: In this study, we aimed to discriminate high reflectivity and low reflectivity macular neovascularization (MNV) lesions secondary to age-related macular degeneration (AMD)and to assess the influence of blood flow features on the amount of MNV detected by optical coherence tomography angiography (OCTA).

Methods: The study was designed as observational, cross-sectional. Type 1 and type 2 MNV lesions were included. All the patients underwent fluorescein angiography (FA), indocyanine green angiography (ICGA) and OCTA. MNV size was calculated on early FA for type 2 MNV and on both early and late phases of ICGA for type 1 lesions. From OCTA, we calculated both MNV size and MNV reflectivity. We assessed the agreement between FA/ICGA and OCTA MNV sizes. Moreover, we studied the relationship between MNV reflectivity properties and MNV OCTA detection.

Results: Fifty eyes (50 patients) were included. MNV was identified as follows: 35 /70%) type 1 and 15 (30%) type 2. We found a good agreement between early ICGA size and OCTA size for type 1 MNV (2.10 ± 1.91 mm2 vs 2.09 ± 1.87 mm2; p > 0.05), whereas MNV lesions turned out to be remarkably bigger on late ICGA phase (3.41 ± 2.87 mm2; p < 0.01). Interestingly, OCTA well-matched with FA in terms of MNV size for type 2 lesions (2.36 ± 2.15 mm2 vs 2.37 ± 2.25 mm2). MNV reflectivity was higher in type 2 MNV and it was strongly associated with the OCTA ability to reconstruct the neovascular network.

Conclusion: Our study quantitatively showed that MNV filling pattern and MNV blood flow reflectivity features influence the OCTA detection of the MNV in its entirety.
Selective β2-Adrenoceptor Blockade Rescues Mandibular Growth Retardation in Adolescent Rats Exposed to Chronic Intermittent Hypoxia
Authors: Hong Haixin , Hosomichi Jun , Maeda Hideyuki , Ishida Yuji , Usumi-Fujita Risa , Yoshida Ken-ichi , Ono Takashi
Published: June 2021

Activation of the sympathoadrenal system is associated with sleep apnea-related symptoms and metabolic dysfunction induced by chronic intermittent hypoxia (IH). IH can induce hormonal imbalances and growth retardation of the craniofacial bones. However, the relationship between IH and β2-adrenergic receptor signaling in the context of skeletal growth regulation is unclear. This study aimed to investigate the role of β2-adrenergic receptors in IH-induced mandibular growth retardation and bone metabolic alterations. Male 7-week-old Sprague–Dawley rats were subjected to IH for 3 weeks. IH conditions were established using original customized hypoxic chambers; IH was induced at a rate of 20 cycles per hour (oxygen levels changed from 4 to 21% in one cycle) for 8 h per day during the 12 h “lights on” period. The rats received intraperitoneal administration of a β2-adrenergic antagonist (butoxamine) or saline. To exclude dietary effects on general growth, the normoxic rats with saline, normoxic rats with butoxamine, and IH rats with butoxamine were subjected to food restriction to match the body weight gains between IH and other three groups. Body weight, heart rate, blood pressure, and plasma concentrations of leptin, serotonin, and growth hormone were measured. Bone growth and metabolism were evaluated using radiography, microcomputed tomography, and immunohistochemical staining. Plasma leptin levels were significantly increased, whereas that of serotonin and growth hormone were significantly decreased following IH exposure. Leptin levels recovered following butoxamine administration. Butoxamine rescued IH-induced mandibular growth retardation, with alterations in bone mineral density at the condylar head of the mandible. Immunohistochemical analysis revealed significantly lower expression levels of receptor activator of nuclear factor-kappa B ligand (RANKL) in the condylar head of IH-exposed rats. Conversely, recovery of RANKL expression was observed in IH-exposed rats administered with butoxamine. Collectively, our findings suggest that the activation of β2-adrenergic receptors and leptin signaling during growth may be involved in IH-induced skeletal growth retardation of the mandible, which may be mediated by concomitant changes in RANKL expression at the growing condyle.