bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Identification of Skull Fractures With Deep Learning: A Comparison Between Object Detection and Segmentation Approach
Authors: Shan Wei , Guo Jianwei , Mao Xuewei , Zhang Yulei , Huang Yikun , Wang Shuai , Li Zixiao , Meng Xia , Zhang Pingye , Wu Zhenzhou , Wang Qun , Liu Yaou , He Kunlun , Wang Yongjun
Published: October 2021

Objective: Skull fractures caused by head trauma can lead to life-threatening complications. Hence, timely and accurate identification of fractures is of great importance. Therefore, this study aims to develop a deep learning system for automated identification of skull fractures from cranial computed tomography (CT) scans.

Method: This study retrospectively analyzed CT scans of 4,782 patients (median age, 54 years; 2,583 males, 2,199 females; development set: n = 4,168, test set: n = 614) diagnosed with skull fractures between September 2016 and September 2020. Additional data of 7,856 healthy people were included in the analysis to reduce the probability of false detection. Skull fractures in all the scans were manually labeled by seven experienced neurologists. Two deep learning approaches were developed and tested for the identification of skull fractures. In the first approach, the fracture identification task was treated as an object detected problem, and a YOLOv3 network was trained to identify all the instances of skull fracture. In the second approach, the task was treated as a segmentation problem and a modified attention U-net was trained to segment all the voxels representing skull fracture. The developed models were tested using an external test set of 235 patients (93 with, and 142 without skull fracture).

Results: On the test set, the YOLOv3 achieved average fracture detection sensitivity and specificity of 80.64, and 85.92%, respectively. On the same dataset, the modified attention U-Net achieved a fracture detection sensitivity and specificity of 82.80, and 88.73%, respectively.

Conclusion: Deep learning methods can identify skull fractures with good sensitivity. The segmentation approach to fracture identification may achieve better results.
Discrete-Event Simulation to Model the Thrombolysis Process for Acute Ischemic Stroke Patients at Urban and Rural Hospitals
Authors: Bulmer Tessa , Volders David , Blake John , Kamal Noreen
Published: October 2021

Background: Effective treatment with tissue plasminogen activator (tPA) critically relies on rapid treatment. Door-to-needle time (DNT) is a key measure of hospital efficiency linked to patient outcomes. Numerous changes can reduce DNT, but they are difficult to trial and implement. Discrete-event simulation (DES) provides a way to model and determine the impact of process improvements.

Methods: A conceptual framework was developed to illustrate the thrombolysis process; allowing for treatment processes to be replicated using a DES model developed in ARENA. Activity time duration distributions from three sites (one urban and two rural) were used. Five scenarios, three process changes, and two reductions in activity durations, were simulated and tested. Scenarios were tested individually and in combinations. The primary outcome measure is median DNT. The study goal is to determine the largest improvement in DNT at each site.

Results: Administration of tPA in the imaging area resulted in the largest median DNT reduction for Site 1 and Site 2 for individual test scenarios (12.6%, 95% CI 12.4–12.8%, and 8.2%, 95% CI 7.5–9.0%, respectively). Ensuring that patients arriving via emergency medical services (EMS) remain on the EMS stretcher to imaging resulted in the largest median DNT improvement for Site 3 (9.2%, 95% CI 7.9–10.5%). Reducing both the treatment decision time and tPA preparation time by 35% resulted in a 11.0% (95% CI 10.0–12.0%) maximum reduction in median DNT. The lowest median and 90th percentile DNTs were achieved by combining all test scenarios, with a maximum reduction of 26.7% (95% CI 24.5–28.9%) and 17.1% (95% CI 12.5–21.7%), respectively.

Conclusions: The detailed conceptual framework clarifies the intra-hospital logistics of the thrombolysis process. The most significant median DNT improvement at rural hospitals resulted from ensuring patients arriving via EMS remain on the EMS stretcher to imaging, while urban sites benefit more from administering tPA in the imaging area. Reducing the durations of activities on the critical path will provide further DNT improvements. Significant DNT improvements are achievable in urban and rural settings by combining process changes with reducing activity durations.
Raloxifene Modulates Microglia and Rescues Visual Deficits and Pathology After Impact Traumatic Brain Injury
Authors: Honig Marcia G. , Del Mar Nobel A. , Henderson Desmond L. , O’Neal Dylan , Doty John B. , Cox Rachel , Li Chunyan , Perry Aaron M. , Moore Bob M. , Reiner Anton
Published: October 2021

Mild traumatic brain injury (TBI) involves widespread axonal injury and activation of microglia, which initiates secondary processes that worsen the TBI outcome. The upregulation of cannabinoid type-2 receptors (CB2) when microglia become activated allows CB2-binding drugs to selectively target microglia. CB2 inverse agonists modulate activated microglia by shifting them away from the harmful pro-inflammatory M1 state toward the helpful reparative M2 state and thus can stem secondary injury cascades. We previously found that treatment with the CB2 inverse agonist SMM-189 after mild TBI in mice produced by focal cranial blast rescues visual deficits and the optic nerve axon loss that would otherwise result. We have further shown that raloxifene, which is Food and Drug Administration (FDA)-approved as an estrogen receptor modulator to treat osteoporosis, but also possesses CB2 inverse agonism, yields similar benefit in this TBI model through its modulation of microglia. As many different traumatic events produce TBI in humans, it is widely acknowledged that diverse animal models must be used in evaluating possible therapies. Here we examine the consequences of TBI created by blunt impact to the mouse head for visual function and associated pathologies and assess raloxifene benefit. We found that mice subjected to impact TBI exhibited decreases in contrast sensitivity and the B-wave of the electroretinogram, increases in light aversion and resting pupil diameter, and optic nerve axon loss, which were rescued by daily injection of raloxifene at 5 or 10 mg/ml for 2 weeks. Raloxifene treatment was associated with reduced M1 activation and/or enhanced M2 activation in retina, optic nerve, and optic tract after impact TBI. Our results suggest that the higher raloxifene dose, in particular, may be therapeutic for the optic nerve by enhancing the phagocytosis of axonal debris that would otherwise promote inflammation, thereby salvaging less damaged axons. Our current work, together with our prior studies, shows that microglial activation drives secondary injury processes after both impact and cranial blast TBI and raloxifene mitigates microglial activation and visual system injury in both cases. The results thus provide a strong basis for phase 2 human clinical trials evaluating raloxifene as a TBI therapy.
Recommendations of Choice of Head Coil and Prescan Normalize Filter Depend on Region of Interest and Task
Authors: Schmitt Tina , Rieger Jochem W.
Published: October 2021

The performance of MRI head coils together with the influence of the prescan normalize filter in different brain regions was evaluated. Functional and structural data were recorded from 26 participants performing motor, auditory, and visual tasks in different conditions: with the 20- and 64-channel Siemens head/neck coil and the prescan normalize filter turned ON or OFF. Data were analyzed with the MRIQC tool to evaluate data quality differences. The functional data were statistically evaluated by comparison of the β estimates and the time-course signal-to-noise ratio (tSNR) in four regions of interest, i.e., the auditory, visual, and motor cortices and the thalamus. The MRIQC tool indicated a better data quality for both functional and structural data with the prescan normalize filter, with an advantage for the 20-channel head coil in functional data and an advantage for the 64-channel head coil in structural measurements. Nevertheless, recommendations for the functional data regarding choice of head coils and prescan normalize filter depend on the brain regions of interest. Higher β estimates and tSNR values occurred in the auditory cortex and thalamus with the prescan normalize filter, whereas the contrary was true for the visual and motor cortices. Due to higher β estimates in the visual cortex in the 64-channel head coil, this head coil is recommended for studies investigating the visual cortex. For most of the research questions, the 20-channel head coil is better suited for functional experiments, with the prescan normalize filter, especially when investigating deep brain areas. For anatomical studies, the 64-channel head coil seemed to be the better choice.
Integrative Models of Brain Structure and Dynamics: Concepts, Challenges, and Methods
Authors: Venkadesh Siva , Van Horn John Darrell
Published: October 2021

The anatomical architecture of the brain constrains the dynamics of interactions between various regions. On a microscopic scale, neural plasticity regulates the connections between individual neurons. This microstructural adaptation facilitates coordinated dynamics of populations of neurons (mesoscopic scale) and brain regions (macroscopic scale). However, the mechanisms acting on multiple timescales that govern the reciprocal relationship between neural network structure and its intrinsic dynamics are not well understood. Studies empirically investigating such relationships on the whole-brain level rely on macroscopic measurements of structural and functional connectivity estimated from various neuroimaging modalities such as Diffusion-weighted Magnetic Resonance Imaging (dMRI), Electroencephalography (EEG), Magnetoencephalography (MEG), and functional Magnetic Resonance Imaging (fMRI). dMRI measures the anisotropy of water diffusion along axonal fibers, from which structural connections are estimated. EEG and MEG signals measure electrical activity and magnetic fields induced by the electrical activity, respectively, from various brain regions with a high temporal resolution (but limited spatial coverage), whereas fMRI measures regional activations indirectly via blood oxygen level-dependent (BOLD) signals with a high spatial resolution (but limited temporal resolution). There are several studies in the neuroimaging literature reporting statistical associations between macroscopic structural and functional connectivity. On the other hand, models of large-scale oscillatory dynamics conditioned on network structure (such as the one estimated from dMRI connectivity) provide a platform to probe into the structure-dynamics relationship at the mesoscopic level. Such investigations promise to uncover the theoretical underpinnings of the interplay between network structure and dynamics and could be complementary to the macroscopic level inquiries. In this article, we review theoretical and empirical studies that attempt to elucidate the coupling between brain structure and dynamics. Special attention is given to various clinically relevant dimensions of brain connectivity such as the topological features and neural synchronization, and their applicability for a given modality, spatial or temporal scale of analysis is discussed. Our review provides a summary of the progress made along this line of research and identifies challenges and promising future directions for multi-modal neuroimaging analyses.
Sensory Adaptation in the Whisker-Mediated Tactile System: Physiology, Theory, and Function
Authors: Adibi Mehdi , Lampl Ilan
Published: October 2021

In the natural environment, organisms are constantly exposed to a continuous stream of sensory input. The dynamics of sensory input changes with organism's behaviour and environmental context. The contextual variations may induce >100-fold change in the parameters of the stimulation that an animal experiences. Thus, it is vital for the organism to adapt to the new diet of stimulation. The response properties of neurons, in turn, dynamically adjust to the prevailing properties of sensory stimulation, a process known as “neuronal adaptation.” Neuronal adaptation is a ubiquitous phenomenon across all sensory modalities and occurs at different stages of processing from periphery to cortex. In spite of the wealth of research on contextual modulation and neuronal adaptation in visual and auditory systems, the neuronal and computational basis of sensory adaptation in somatosensory system is less understood. Here, we summarise the recent finding and views about the neuronal adaptation in the rodent whisker-mediated tactile system and further summarise the functional effect of neuronal adaptation on the response dynamics and encoding efficiency of neurons at single cell and population levels along the whisker-mediated touch system in rodents. Based on direct and indirect pieces of evidence presented here, we suggest sensory adaptation provides context-dependent functional mechanisms for noise reduction in sensory processing, salience processing and deviant stimulus detection, shift between integration and coincidence detection, band-pass frequency filtering, adjusting neuronal receptive fields, enhancing neural coding and improving discriminability around adapting stimuli, energy conservation, and disambiguating encoding of principal features of tactile stimuli.
Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility
Authors: Victor A. Kaitlyn , Donaldson Martin , Johnson Daniel , Miller Winston , Reiter Lawrence T.
Published: October 2021

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk.

Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings.

Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons.

Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.
The Association of Dietary Energy Density and Body Composition Components in a Sample of Iranian Adults
Authors: Bazshahi Elham , Pourreza Sanaz , Imani Hossein , Azadbakht Leila , Ebaditabar Mojdeh , Davarzani Samira , Babaei Nadia , Naghshi Sina , Djafarian Kurosh , Shab-Bidar Sakineh
Published: October 2021

Background: We aimed to investigate the association between the energy density (ED) of diet and body composition components in Iranian adults.

Methods: We conducted a cross-sectional study on 267 adults in Tehran. We obtained ED (kcal/g) using the two most common methods: ED1, ED from foods only with the exclusion of all beverages and ED2, from foods and all beverages. Body composition was measured using a multifrequency bio-impedance analysis. To find a strong association, we used both the linear and binary regression analysis in the three adjusted models.

Results: The mean of ED1 and ED2 was 1.34 ± 0.23 and 0.89 ± 0.20 kcal/g, respectively. Increasing the ED of diet in both methods was associated with a high intake of dietary fat, of saturated fatty acid (SFA), of monounsaturated fatty acid (MUFA), of polyunsaturated fatty acid (PUFA), of oleic and linoleic acids, accompanied by a low intake of fruits, vegetables, and some vitamins and minerals. There was a significant positive relationship between fat-free mass index (FFMI) and ED1 (β = 4.44, p = 0.02). However, we found no significant association between the consumption of ED1 and fat mass index (FMI) (0.28; 95% CI 0.08, 0.98; p = 0.07), and abdominal obesity (0.91; 95% CI 0.43, 1.94; p = 0.82). Also, ED2 had no association with FMI (0.86; 95% CI 0.26, 2.80; p = 0.81) and abdominal obesity (0.78; 95% CI 0.35, 1.72; p = 0.54). No significant associations were found between ED and other anthropometric indices and body composition components after considering the confounders.

Conclusion: This study supports the positive association between ED and poor dietary quality. However, our findings did not show significant associations of dietary energy density (DED) with anthropometric indices and body composition components. Further well-designed studies are required to investigate the exact link between DED and body composition.
Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study
Authors: Salvador Christina , Salvador Robert , Willeit Peter , Kuntner Christine , Haid Alexandra , Müller Thomas , Kropshofer Gabriele , Crazzolara Roman
Published: October 2021

Background

Hyponatremia is a well-known adverse event of repeated therapy with vincristine in oncological patients. However, to date, data in pediatric patients with malignant diseases other than acute lymphoblastic leukemia (ALL) are sparse or lacking.

Materials and Methods

A retrospective study of 98 pediatric patients was conducted to analyze the incidence of hyponatremia in a Caucasian cohort of newly diagnosed ALL. For comparison, we further examined five other pediatric oncological cohorts (Hodgkin’s disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes.

Results

We found a high incidence of hyponatremia (14.7%) in our ALL cohort with a trend toward male patients of elementary school age. None of the affected patients showed neurological symptoms. By comparison, patients from other malignancy groups did not show significant hyponatremia, regardless of their comparable therapy with alkaloids. We here show a noticeable coincidence of hyponatremia and hypertriglyceridemia in ALL patients, indicating a possible role of L-asparaginase-related hypertriglyceridemia in the development of severe hyponatremia in such patients.

Conclusion

We report a higher incidence of hyponatremia following vincristine therapy in Caucasian children with ALL than published before. This hyponatremia could not be demonstrated in other oncologic cohorts treated with alkaloids. L-Asparaginase-induced hypertriglyceridemia may play a role in the certainly multifactorial development of hyponatremia in childhood leukemia.
Encouraging Early Outcomes of Treatment With Arsenic Trioxide Combined With Chemotherapy for Alveolar Rhabdomyosarcoma in Children: 4 Case Reports
Authors: Peng Xiaomin , Xiong Xilin , Li Yang , Feng Chuchu , Liu Hongyan , Wu Pingping , Li Chunmou , Weng Wenjun
Published: October 2021

Background

Alveolar rhabdomyosarcoma (ARMS) is a subtype of rhabdomyosarcoma characterized by its aggressive behavior and poor prognosis, highlighting the need for novel treatment options. Arsenic trioxide (ATO) has been shown to specifically inhibit tumor growth and the metastasis of ARMS in vitro by acting on the hedgehog pathway. Here we report on a pilot clinical study to evaluate the activity of an ATO-combined chemotherapy approach for the treatment of ARMS patients.

Methods

We designed a therapeutic schedule of an ATO-combined chemotherapy, incorporating comprehensive management according to the Intergroup Rhabdomyosarcoma Study Group protocol. ATO was administered at 0.16 mg/kg per day over 8 h via an IV for 10 days combined with a chemotherapeutic regimen of vincristine, actinomycin, and cyclophosphamide (VAC regimen) on the third day, which was repeated every 21 days. A total of eight cycles of ATO-combined chemotherapy were applied throughout the entire scheme.

Results

A total of three refractory/recurrent and one untreated ARMS patient, three male and one female, with a median age of 5.8 years (range, 5.1 to 12.5 years), were enrolled in the present study. All patients were sensitive to combined chemotherapy with ATO and achieved partial or complete remission during treatment. Except for reversible gastrointestinal reaction and myelosuppression, no other adverse events were observed during the process of treatment.

Conclusions

The combined chemotherapy of ATO and the VAC regimen exhibited beneficial activities against ARMS in pediatrics and was well tolerated, but prospective large-scale clinical trials are warranted to determine the long-term efficacy, optimal courses, and late toxicity in this population.
Case Report: Oculomotor Palsy With Cyclic Spasms in a Patient With Charcot-Marie-Tooth Disease Type 1
Authors: Weber Konrad P. , Bockisch Christopher J. , Landau Klara
Published: October 2021

Oculomotor palsy with cyclic spasms is an extremely rare condition whose exact pathophysiology remains a mystery. We followed a boy from the onset of symptoms at the age of ten months until 15 years and documented the case with video oculography. In addition, he was diagnosed with hereditary motor and sensory neuropathy (Charcot-Marie-Tooth disease type 1). Although a pure coincidence cannot be ruled out, it is conceivable that the underlying demyelinating neuropathy of this patient rendered the oculomotor nerve more susceptible to damage.
Estimated Manipulation of Tablets and Capsules to Meet Dose Requirements for Chinese Children: A Cross-Sectional Study
Authors: Zhang Liwen , Hu Yan , Pan Panpan , Hong Chengtao , Fang Luo
Published: October 2021

Objectives: To estimate the frequency of manipulations of all tablets and capsules prescribed for children in a teaching and tertiary children's hospital in China over the course of 1 month. Moreover, hypothetical reduction of manipulation according to the availability of low-strength tablets/capsules licensed by the Chinese National Medical Products Administration (CNMPA) was evaluated.

Methods: Information on all tablets and capsules prescribed in the hospital from March 17 to April 16, 2019 was collected. It was assumed that tablets or capsules were manipulated if the prescribed dose would have required only a proportion of the intact dose form. Manipulation typically includes splitting or crushing tablets, opening capsules and dispersing in water, or combinations of these method. Moreover, we defined an “avoidable manipulation,” when the dose could be rounded and/or when alternative products with a reduced strength or in liquid formulation were available in the hospital, and a “inappropriate manipulation,” which involved manipulated medications with a direct contraindication for any manipulation, such as those with a narrow therapeutic index or hazardous ingredients, or modified release dosage-forms. The frequencies of total, avoidable, and inappropriate manipulation were estimated, along with the hypothetical reduction of manipulation according to the availability of CNMPA-approved drug doses.

Results: A total of 17,123 prescriptions for 142 medications were identified to have required a manipulation among 78,366 prescriptions administered during the study period, with 43 different proportions of subdivisions, ranging from a 19/20 to 1/180 product strength reduction. Half, quarter, and trisection were the most common subdivisions administered. Overall, 19% of the manipulated prescriptions were determined to be avoidable, and 19% of the manipulations involved medications with a clear recommendation to not manipulate. In addition, 21% of the manipulated prescriptions could have been potentially avoided if all of the approved preparations with the lowest strength would have been available at the hospital. Any manipulations undertaken were carried out by pharmacists and family care givers.

Conclusions: More than 20% of tablets and capsules prescriptions need manipulated, included a high incidence of avoidable and inappropriate manipulation.
Saikosaponin A, a Triterpene Saponin, Suppresses Angiogenesis and Tumor Growth by Blocking VEGFR2-Mediated Signaling Pathway
Authors: Zhang Pan , Lai Xing , Zhu Mao-Hua , Long Mei , Liu Xue-Liang , Wang Zi-Xiang , Zhang Yifan , Guo Run-Jie , Dong Jing , Lu Qin , Sun Peng , Fang Chao , Zhao Mei
Published: October 2021

Saikosaponin A (SSA), a main triterpenoid saponin component from Radix Bupleurum, has been revealed to have a variety of pharmacological activities. However, whether SSA can inhibit angiogenesis, a key step in solid tumor progression, remains unknown. In this study, we demonstrated that SSA could powerfully suppress the proliferation, migration, and tube formation of human umbilical vein endothelial cells. SSA also significantly inhibited angiogenesis in the models of the chick embryo chorioallantoic membrane and Matrigel plugs. Moreover, SSA was found to inhibit tumor growth in both orthotopic 4T1 breast cancer and subcutaneous HCT-15 colorectal tumor by the inhibition of tumor angiogenesis. Western blot assay indicated the antiangiogenic mechanism of SSA in the suppression of the protein phosphorylation of VEGFR2 and the downstream protein kinase including PLCγ1, FAK, Src, and Akt. In summary, SSA can suppress angiogenesis and tumor growth by blocking the VEGFR2-mediated signaling pathway.
SC75741, A Novel c-Abl Inhibitor, Promotes the Clearance of TDP25 Aggregates via ATG5-Dependent Autophagy Pathway
Authors: Zhou Dongheng , Yan Huanhuan , Yang Shuying , Zhang Yuhong , Xu Xiaoyan , Cen Xufeng , Lei Kai , Xia Hongguang
Published: October 2021

Abnormal accumulation of TDP43-related mutant proteins in the cytoplasm causes amyotrophic lateral sclerosis (ALS). Herein, unbiased drug screening approaches showed that SC75741, a multi-target inhibitor, inhibited inflammation-induced aggregation by inhibiting NF-κB and also degraded already aggregated proteins by inhibiting c-Abl mediated autophagy-lysosomal pathway. We delineate the mechanism that SC75741 could markedly enhance TFEB nuclear translocation by an mTORC1-independent TFEB regulatory pathway. In addition, SC75741 enhanced the interaction between p62 with TDP25 and LC3C, thus promoting TDP25 degradation. Taken together, these findings show that SC75741 has beneficial neuroprotective effects in ALS. Our study elucidates that dual-targeted inhibition of c-Abl and NF-κB may be a potential treatment for TDP43 proteinopathies and ALS.
The Impact of Inflammatory Immune Reactions of the Vascular Niche on Organ Fibrosis
Authors: Zhou Hong-Yan , Sui Hua , Zhao Yang-Jianing , Qian Hong-Jie , Yang Nan , Liu Lu , Guan Qing , Zhou Yue , Lin Hong-Li , Wang Da-Peng
Published: October 2021

Inflammation is a type of defense response against tissue damage, and can be mediated by lymphocytes and macrophages. Fibrosis is induced by tissue injury and inflammation, which leads to an increase in fibrous connective tissue in organs and a decrease in organ parenchyma cells, finally leading to organ dysfunction or even failure. The vascular niche is composed of endothelial cells, pericytes, macrophages, and hematopoietic stem cells. It forms a guiding microenvironment for the behavior of adjacent cells, and mainly exists in the microcirculation, including capillaries. When an organ is damaged, the vascular niche regulates inflammation and affects the repair of organ damage in a variety of ways, such as via its angiocrine function and transformation of myofibroblasts. In this paper, the main roles of vascular niche in the process of organ fibrosis and its mechanism of promoting the progress of fibrosis through inflammatory immunoregulation are summarized. It was proposed that the vascular niche should be regarded as a new therapeutic target for organ fibrosis, suggesting that antifibrotic effects could be achieved by regulating macrophages, inhibiting endothelial-mesenchymal transition, interfering with the angiocrine function of endothelial cells, and inhibiting the transformation of pericytes into myofibroblasts, thus providing new ideas for antifibrosis drug research.
Quantifying Fatigue in the Rugby Codes: The Interplay Between Collision Characteristics and Neuromuscular Performance, Biochemical Measures, and Self-Reported Assessments of Fatigue
Authors: Naughton Mitchell , McLean Scott , Scott Tannath J. , Weaving Dan , Solomon Colin
Published: October 2021

Locomotor and collision actions that rugby players complete during match-play often lead to substantial fatigue, and in turn, delays in recovery. The methods used to quantify post-match fatigue and recovery can be categorised as subjective and objective, with match-related collision characteristics thought to have a primary role in modulating these recovery measures. The aim of this review was to (1) evaluate how post-match recovery has been quantified in the rugby football codes (i.e., rugby league, rugby union, and rugby sevens), (2) to explore the time-course of commonly used measures of fatigue post-match, and (3) to investigate the relationships between game-related collisions and fatigue metrics. The available evidence suggests that upper-, and lower-body neuromuscular performance are negatively affected, and biomarkers of muscular damage and inflammation increase in the hours and days following match-play, with the largest differences being at 12–36 h post-match. The magnitude of such responses varies within and between neuromuscular performance (Δ ≤ 36%,n= 13 studies) and tissue biomarker (Δ ≤ 585%,n= 18 studies) measures, but nevertheless appears strongly related to collision frequency and intensity. Likewise, the increase in perceived soreness in the hours and days post-match strongly correlate to collision characteristics across the rugby football codes. Within these findings, there are specific differences in positional groups and recovery trajectories between the codes which relate to athlete characteristics, and/or locomotor and collision characteristics. Finally, based on these findings, we offer a conceptual model of fatigue which details the multidimensional latent structure of the load to fatigue relationship contextualised to rugby. Research to date has been limited to univariate associations to explore relationships between collision characteristics and recovery, and multivariate methods are necessary and recommended to account for the latent structures of match-play external load and post-match fatigue constructs. Practitioners should be aware of the typical time windows of fatigue recovery and utilise both subjective and objective metrics to holistically quantify post-match recovery in rugby.
The Glycine-Rich Domain Protein GRDP2 Regulates Ovule Development via the Auxin Pathway in Arabidopsis
Authors: Wang Lulu , Liu Yanhui , Aslam Mohammad , Jakada Bello Hassan , Qin Yuan , Cai Hanyang
Published: October 2021

The glycine-rich domain proteins (GRDP) have been functionally implicated in the cell wall structure, biotic, and abiotic stress responses. However, little is known about GRDP genes in female gametophyte development of Arabidopsis. This study shows that GRDP2, a GRDP, plays a crucial role in female gametophyte development. In GRDP2 overexpression lines, grdp2-3, the embryo sacs were arrested at FG1 and no nucleus stages. Furthermore, callose staining shows that cell plate formation during megasporogenesis is disturbed in grdp2-3. In contrast, the pollen development is not affected in grdp2-3. The expression patterns of auxin-specific marker lines in female gametophytes showed that the auxin distribution and transport were significantly changed during megagametogenesis in grdp2-3. In addition, compared with the membrane-localized pattern of PIN1, PIN2, and PIN7 in WT, the signals were detected in the cytoplasm in grdp2-3. Together, our data suggest that GRDP2 plays an essential role in auxin-mediated female gametophyte development.
Remote vs. In-person Delivery of LearningRx One-on-One Cognitive Training During the COVID-19 Pandemic: A Non-inferiority Study
Authors: Moore Amy Lawson , Miller Terissa Michele , Ledbetter Christina
Published: October 2021

The COVID-19 pandemic challenged in-person delivery of cognitive training. Some clinics pivoted to remote delivery for those impacted by lockdowns, illness, or fear of exposure to the virus. However, it was unknown if remote delivery using teleconferencing technology was as effective as in-person delivery. The current study compared the outcomes of remote delivery to in-person delivery of ThinkRx cognitive training during 2020. The sample included 381 child and adult clients from 18 cognitive training centers. One group (n = 178, mean age = 12.3) received traditional in-person delivery of cognitive training. The second group (n = 203, mean age = 11.7) received remote delivery of one-on-one cognitive training via Zoom teleconferencing. Each client was assessed before and after the intervention using the Woodcock Johnson IV Tests of Cognitive Abilities. Clients completed an average of 112 h of cognitive training delivered by a clinician in 90-min sessions 3 or 4 days per week. Paired samples t-tests revealed significant differences from pretest to post-test across all constructs for both groups. After Bonferroni correction, MANOVA revealed no significant difference in changes scores between the two intervention groups on any of the subtests. With very small effect sizes, linear regression analyses indicated that age was a significant predictor of change in working memory and processing speed for the in-person group, and a significant predictor of change in overall IQ score for the teletherapy group. Non-inferiority analyses indicated remote delivery is not inferior to in-person delivery on the primary outcome measure of overall IQ score along with processing speed, fluid reasoning, long-term memory, and visual processing. Although in-person training results were slightly higher than remote training results, the current study reveals remote delivery of cognitive training during COVID-19 was a viable alternative to in-person delivery of cognitive training with little practical differences based on the age of client.
Exploring the Conceptual Constructs of Learners’ Goal Commitment, Grit, and Self-Efficacy
Authors: Han Zhong
Published: October 2021

Although learners’ success in learning has generally been attributed to cognitive factors, non-cognitive issues in education should be taken into consideration in the process of learning which affects learners’ achievement. One of these issues, which become popular among researchers in the previous decade is grit, that is, posited as passion and perseverance thanks to its enduring quality and the other is self-efficacy. Another factor is goal commitment that talks about the way to reach a goal or insistent determinations to achieve a goal. The proposed review attempts to focus on these three factors in regulating students’ learning achievement. Accordingly, some educational suggestions are offered for teachers, students, and syllabus designers.
Circadian Functioning and Quality of Life in Substance Use Disorder Patients With and Without Comorbid Major Depressive Disorder
Authors: Hashemzadeh Iman , Marquez-Arrico Julia E. , Hashemzadeh Kosar , Navarro José Francisco , Adan Ana
Published: October 2021

Aim: Although a relationship between circadian disruption and development of several psychiatric disorders, such as major depressive disorder (MDD) and substance use disorder (SUD), has been observed, knowledge on this area is scarce yet. Therefore, this study aims to analyze the circadian functioning and quality of life (QOL) in SUD patients with and without comorbid MDD, two highly prevalent clinical entities with difficult therapeutic management.

Methods: One hundred sixty-three male patients under treatment, 81 with SUD and 82 with SUD comorbid major depressive disorder (SUD + MDD), were evaluated. For the circadian functioning assessment, we calculated Social Jet Lag (SJL) and used the reduced Morningness–Eveningness Questionnaire (rMEQ) and the Pittsburgh Sleep Quality Index (PSQI). QOL was measured using the shortened version of the World Health Organization's Quality of Life Questionnaire (WHOQOL-BREF). We collected sociodemographic and clinical variables to evaluate their possible influence on the circadian functioning. Intergroup differences among the variables were examined by different analyses of covariance (ANCOVA and MANCOVA). The possible relationships of quantitative clinical variables with rMEQ, PSQI, and WHOQOL-BREF were explored using bivariate correlation analysis.

Results: Lower SJL appears in the SUD + MDD group compared with SUD. The intermediate-type was more prevalent in the SUD group, while a higher percentage of morning-type patients was found in the SUD + MDD. Sleep quality (including latency and daytime dysfunction) was worse for SUD + MDD patients than for SUD even after controlling age and age of SUD onset variables. Last, QOL was poorer in patients with SUD + MDD and, for them, psychological health had a negative relationship with SJL and severity of depression.

Conclusions: Our data support and extend previous findings indicating that SUD + MDD is associated with worse clinical characteristics, more sleep problems, and poorer QOL than SUD patients. These results underline the importance of a precise assessment of these measurements in future studies conducted in SUD patients with/without MDD comorbidity that could be considered from a therapeutic point of view.
Burnout Among Healthcare Workers in the COVID 19 Era: A Review of the Existing Literature
Authors: Leo Carlo Giacomo , Sabina Saverio , Tumolo Maria Rosaria , Bodini Antonella , Ponzini Giuseppe , Sabato Eugenio , Mincarone Pierpaolo
Published: October 2021

In the current period of global public health crisis due to the COVID-19, healthcare workers are more exposed to physical and mental exhaustion – burnout – for the torment of difficult decisions, the pain of losing patients and colleagues, and the risk of infection, for themselves and their families. The very high number of cases and deaths, and the probable future “waves” raise awareness of these challenging working conditions and the need to address burnout by identifying possible solutions. Measures have been suggested to prevent or reduce burnout at individual level (physical activity, balanced diet, good sleep hygiene, family support, meaningful relationships, reflective practices and small group discussions), organizational level (blame-free environments for sharing experiences and advices, broad involvement in management decisions, multi-disciplinary psychosocial support teams, safe areas to withdraw quickly from stressful situations, adequate time planning, social support), and cultural level (involvement of healthcare workers in the development, implementation, testing, and evaluation of measures against burnout). Although some progress has been made in removing the barrier to psychological support to cope with work-related stress, a cultural change is still needed for the stigma associated with mental illness. The key recommendation is to address the challenges that the emergency poses and to aggregate health, well-being and behavioral science expertise through long term researches with rigorous planning and reporting to drive the necessary cultural change and the improvement of public health systems.
The Effect of Commercial Activity Tracker Based Physical Activity Intervention on Body Composition and Cardiometabolic Health Among Recent Retirees
Authors: Leskinen Tuija , Suorsa Kristin , Heinonen Ilkka HA , Löyttyniemi Eliisa , Pentti Jaana , Vahtera Jussi , Stenholm Sari
Published: October 2021

The REACT is a commercial activity tracker based intervention, which primarily aimed to increase physical activity. This study examines the secondary outcomes of the physical activity intervention on body composition and cardiometabolic health indicators. Overall 231 recently retired Finnish men and women [65.2 (SD 1.1) years, 83% women] took part to the study. The participants were randomized into intervention (n = 117) and control (n = 114) groups. The intervention group members used a commercial activity tracker (Polar Loop 2, Polar, Kempele, Finland) with a daily activity goal and inactivity alerts every day for 12 months. Controls received no intervention. Secondary health outcomes included body weight, fat mass, fat free mass, waist circumference, blood pressure, indicators of glucose and lipid metabolisms, and high-sensitivity C-reactive protein, and they were measured at baseline and at 12-months end point. Hierarchical linear mixed models were used to examine the differences between the groups over time, and no differences in the mean changes of the body composition and cardiometabolic health indicators between the groups were found (group*time interaction >0.20 for all measures). Fat free mass, waist circumference, blood pressure, and low density lipoprotein levels decreased in both groups over the 12 months. These findings state that 1-year daily use of commercial activity tracker does not induce different cardiometabolic health effects when compared to the non-user controls among general population of recent retirees.
Effectiveness of the Conservative Surgical Management of the Ameloblastomas: A Cross-Sectional Study
Authors: Rocha André Caroli , Fonseca Felipe Paiva , Santos-Silva Alan Roger , Lourenço Silvia Vanessa , Ceccheti Marcelo Minharro , Júnior Jayro Guimarães
Published: October 2021

Ameloblastoma is a benign, but locally aggressive odontogenic neoplasm, whose appropriate therapeutic management remains highly debatable. The aim of this study was to evaluate the reliability and effectiveness of the two conservative surgical therapeutic protocols (curettage with peripheral ostectomy only and curettage plus cryotherapy) for the management of ameloblastomas. About 53 cases of the ameloblastomas treated in 9 years were retrospectively analyzed regarding their clinical, histopathologic, radiographic, and therapeutic data. The results and the postoperative complications related to both the therapeutic protocols were also statistically investigated. A slight female preponderance was seen (1.12:1.0) with a mean age of 27.1 years. The posterior mandible was the most affected site and dental involvement was frequently found. Multilocular lesions causing the alterations of the bone cortices were the most common radiographic findings. Recurrences were seen in 9.4% of the cases and although the patients submitted to curettage plus cryotherapy have shown an increased incidence of wound dehiscence, infection, and paresthesia, only bone sequestration proved to be significantly more frequent in this group compared to the patients treated by curettage with peripheral ostectomy only. The incidence of the recurrences following the conservative management is low and cryotherapy use as an adjuvant tool must be rationally considered.
Methodologies of Stigma-Related Research Amongst Men Who Have Sex With Men (MSM) and Transgender People in Asia and the Pacific Low/Middle Income Countries (LMICs): A Scoping Review
Authors: Septarini Ni Wayan , Hendriks Jacqueline , Maycock Bruce , Burns Sharyn
Published: October 2021

Much stigma-related research focuses on marginalized populations, including men who have sex with men (MSM) and transgender people. The importance of research in this area is widely recognized, however methodologies and measures vary between studies. This scoping review will collate existing information about how stigma-related research has been conducted in low/middle income countries (LMICs) within the Asia Pacific region, and will compare research designs, sampling frameworks, and measures. Strengths and limitations of these studies will inform recommendations for future stigma-related health research. A methodological framework for scoping studies was applied. Searches of Psych INFO, Scopus, ProQuest, Global Health and PubMed were used to identify articles. Stigma-related research amongst MSM and transgender communities, published between 2010 and 2019 in LMICs within the Asia Pacific region were included. A total of 129 articles based on 123 different studies were included. Of the 129 articles 51.19% (n = 66) were quantitative; 44.96% (n = 57) were qualitative and 3.88% (n = 5) were mixed methods studies. The majority of studies (n = 57; 86.36%) implemented a cross sectional survey. In-depth interviews (n = 20, 34.48%) were also common. Only 3.88% of studies utilized mixed-methods design. Non-probabilistic and probabilistic sampling methods were employed in 99.22 and 0.78% of studies respectively. The most common measures used in quantitative studies were the Center for Epidemiological Study on Depression (CES-D) (n = 18) and the Self Stigma Scale (SSS) (n = 6). Strengths and limitations proposed by researchers included in this review are summarized as lesson learnt and best practices in stigma-related research.
Performances of Hybridized-, Embedded-, and Weighted-Interior Penalty Discontinuous Galerkin Methods for Heterogeneous and Anisotropic Diffusion Problems
Authors: Etangsale Grégory , Fontaine Vincent , Rajaonison Nalitiana
Published: October 2021

The present paper discusses families of Interior Penalty Discontinuous Galerkin (IP) methods for solving heterogeneous and anisotropic diffusion problems. Specifically, we focus on distinctive schemes, namely the Hybridized-, Embedded-, and Weighted-IP schemes, leading to final matrixes of different sizes and sparsities. Both the Hybridized- and Embedded-IP schemes are eligible for static condensation, and their degrees of freedom are distributed on the mesh skeleton. In contrast, the unknowns are located inside the mesh elements for the Weighted-IP variant. For a given mesh, it is well-known that the number of degrees of freedom related to the standard Discontinuous Galerkin methods increases more rapidly than those of the skeletal approaches (Hybridized- and Embedded-IP). We then quantify the impact of the static condensation procedure on the computational performances of the different IP classes in terms of robustness, accuracy, and CPU time. To this aim, numerical experiments are investigated by considering strong heterogeneities and anisotropies. We analyze the fixed error tolerance versus the run time and mesh size to guide our performance criterion. We also outlined some relationships between these Interior Penalty schemes. Eventually, we confirm the superiority of the Hybridized- and Embedded-IP schemes, regardless of the mesh, the polynomial degree, and the physical properties (homogeneous, heterogeneous, and/or anisotropic).