bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain-Inspired Hardware Solutions for Inference in Bayesian Networks
Authors: Bagheriye Leila , Kwisthout Johan
Published: December 2021

The implementation of inference (i.e., computing posterior probabilities) in Bayesian networks using a conventional computing paradigm turns out to be inefficient in terms of energy, time, and space, due to the substantial resources required by floating-point operations. A departure from conventional computing systems to make use of the high parallelism of Bayesian inference has attracted recent attention, particularly in the hardware implementation of Bayesian networks. These efforts lead to several implementations ranging from digital circuits, mixed-signal circuits, to analog circuits by leveraging new emerging nonvolatile devices. Several stochastic computing architectures using Bayesian stochastic variables have been proposed, from FPGA-like architectures to brain-inspired architectures such as crossbar arrays. This comprehensive review paper discusses different hardware implementations of Bayesian networks considering different devices, circuits, and architectures, as well as a more futuristic overview to solve existing hardware implementation problems.
Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease
Authors: Kisby Glen E. , Spencer Peter S.
Published: December 2021

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex (ALS/PDC) is a disappearing prototypical neurodegenerative disorder (tau-dominated polyproteinopathy) linked with prior exposure to phytogenotoxins in cycad seed used for medicine and/or food. The principal cycad genotoxin, methylazoxymethanol (MAM), forms reactive carbon-centered ions that alkylate nucleic acids in fetal rodent brain and, depending on the timing of systemic administration, induces persistent developmental abnormalities of the cortex, hippocampus, cerebellum, and retina. Whereas administration of MAM prenatally or postnatally can produce animal models of epilepsy, schizophrenia or ataxia, administration to adult animals produces little effect on brain structure or function. The neurotoxic effects of MAM administered to rats during cortical brain development (specifically, gestation day 17) are used to model the histological, neurophysiological and behavioral deficits of human schizophrenia, a condition that may precede or follow clinical onset of motor neuron disease in subjects with sporadic ALS and ALS/PDC. While studies of migrants to and from communities impacted by ALS/PDC indicate the degenerative brain disorder may be acquired in juvenile and adult life, a proportion of indigenous cases shows neurodevelopmental aberrations in the cerebellum and retina consistent with MAM exposure in utero. MAM induces specific patterns of DNA damage and repair that associate with increased tau expression in primary rat neuronal cultures and with brain transcriptional changes that parallel those associated with human ALS and Alzheimer’s disease. We examine MAM in relation to neurodevelopment, epigenetic modification, DNA damage/replicative stress, genomic instability, somatic mutation, cell-cycle reentry and cellular senescence. Since the majority of neurodegenerative disease lacks a solely inherited genetic basis, research is needed to explore the hypothesis that early-life exposure to genotoxic agents may trigger or promote molecular events that culminate in neurodegeneration.
The Role of Central Command in the Increase in Muscle Sympathetic Nerve Activity to Contracting Muscle During High Intensity Isometric Exercise
Authors: Boulton Daniel , Taylor Chloe E. , Green Simon , Macefield Vaughan G.
Published: December 2021

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during high-intensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise ischemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensities.
Distribution of Large and Small Dorsal Root Ganglion Neurons in Common Marmosets
Authors: Kudo Moeko , Wupuer Sidikejiang , Kubota Shinji , Seki Kazuhiko
Published: December 2021

The aim of this study was to elucidate the size and distribution of dorsal root ganglion (DRG) neurons in non-human primates and to compare them with those of rodent DRG neurons. By measuring the size of NeuN-, NF200-, and peripherin-positive DRG neurons in the lumbar spinal cord of rats and marmosets, we found that the cell size distribution pattern was comparable in both species, although DRG neurons in marmosets were larger than those of rodents. This is the first demonstration that DRG neurons in marmosets have a bimodal size distribution, which has been well established in rodents and humans.
Marine Bioactive Compounds as Nutraceutical and Functional Food Ingredients for Potential Oral Health
Authors: Huang Yi-Zhen , Jin Zheng , Wang Zhe-Ming , Qi Li-Bo , Song Shuang , Zhu Bei-Wei , Dong Xiu-Ping
Published: December 2021

Oral diseases have received considerable attention worldwide as one of the major global public health problems. The development of oral diseases is influenced by socioeconomic, physiological, traumatic, biological, dietary and hygienic practices factors. Currently, the main prevention strategy for oral diseases is to inhibit the growth of biofilm-producing plaque bacteria. Tooth brushing is the most common method of cleaning plaque, aided by mouthwash and sugar-free chewing gum in the daily routine. As the global nutraceutical market grows, marine bioactive compounds are becoming increasingly popular among consumers for their antibacterial, anti-inflammatory and antitumor properties. However, to date, few systematic summaries and studies on the application of marine bioactive compounds in oral health exist. This review provides a comprehensive overview of different marine-sourced bioactive compounds and their health benefits in dental caries, gingivitis, periodontitis, halitosis, oral cancer, and their potential use as functional food ingredients for oral health. In addition, limitations and challenges of the application of these active ingredients are discussed and some observations on current work and future trends are presented in the conclusion section.
Relationships Among Pre-Pregnancy BMI, Gestational, and Postpartum Oral Glucose Tolerance Results in Women With Gestational Diabetes Mellitus
Authors: Mi Chunmei , Liu Hong , Peng Hongying , Cheng Chunxia , Wang Meng , Liu Hua , Feng Guo , Wu Jinru , Nie Hao , Liu Min
Published: December 2021

Background and Aims:To investigate the relationship among maternal demographic and clinical characteristics, gestational and postpartum oral glucose tolerance test (ppOGTT) results in patients with gestational diabetes mellitus (GDM).

Methods:Patients with gestational diabetes mellitus from January 1, 2016, to August 31, 2019, were enrolled. General characteristics, dietary energy intake, pre-gestational body mass index (BMI), gestational oral glucose tolerance test (gOGTT), and 42 days ppOGTT results of all participants were collected. The relationships among maternal clinical characteristics, fasting glucose of gOGTT (gOGTT-FPG), 1 h postprandial glucose of gOGTT (gOGTT-1h PG), 2 h postprandial glucose of gOGTT (gOGTT-2h PG), and maternal postpartum glucose outcomes were evaluated.

Results:A total of 156 patients with GDM were included in this study. Among them, 73.7% had inadequate daily total energy intake, an insufficient ratio of carbohydrates and protein, and an excessive fat ratio. Most of the patients (81.4%) were normal in their ppOGTT examination. Less than 20% of the patients (16.7%) were in the pre-diabetic situation, and 3 patients (1.9%) had diabetes. Pre-pregnancy BMI of patients with GDM was a risk factor for increased gOGTT-FPG levels. Those who were overweight before pregnancy had a greater risk for a higher gOGTT-FPG compared to those who had normal pre-pregnancy BMI (P= 0.021, odds ratio[OR] = 4.583). Abnormal gOGTT-2hPG was a risk factor for abnormal ppOGTT (P= 0.04). Those who had an elevated gOGTT-2hPG (≧8.5 mmol/L) had a 2.426 times higher risk for abnormal ppOGTT than those who had normal gOGTT-2hPG (<8.5 mmol/L) results.

Conclusion:For women who are overweight before pregnancy, it is better to control their BMI to normal before getting pregnant. Women who had abnormal gOGTT-2h PG should pay more attention to the ppOGTT results.
Relationship Between Dietary Patterns and Carotid Atherosclerosis Among People Aged 50 Years or Older: A Population-Based Study in China
Authors: Liu Yunyun , Wang Xuena , Zhang Qing , Meng Ge , Liu Li , Wu Hongmei , Gu Yeqing , Zhang Shunming , Wang Yawen , Zhang Tingjing , Górska Magdalena J. , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Tan Liping , Niu Kaijun
Published: December 2021

Background: The relationship between dietary patterns and atherosclerosis is inconclusive. Usually, diets vary greatly among different regions due to cultural differences and lifestyles. Few studies to date based on a Chinese population have investigated the relationship between dietary patterns and the formation of atherosclerosis in carotid arteries. We aimed to investigate whether dietary patterns were related to carotid atherosclerosis among an adult population in Tianjin, China.

Methods: This cross-sectional study included a total of 2,346 participants aged 50 years or older (mean: 59.7 ± 6.29 years). Dietary intakes were assessed using a validated 81-item semiquantitative food frequency questionnaire, and factor analysis was used to identify dietary patterns. Carotid atherosclerosis was defined as a common carotid artery intima-media thickness ≥1.0 mm or plaques, or a carotid bifurcation intima-media thickness ≥1.2 mm. Multiple logistic regression models were used to explore the relationship between dietary patterns and carotid atherosclerosis.

Results: Three factors were determined: “health” dietary pattern (factor 1), “traditional Tianjin” dietary pattern (factor 2), and “sweets” dietary pattern (factor 3). The multivariable-adjusted odds ratios (95% CI) of carotid atherosclerosis for the increasing quartiles of the sweets dietary pattern scores in women were as follows: 1.00 (reference), 1.33 (0.91, 1.97), 1.21 (0.82, 1.79), 1.64 (1.08, 2.51) (p for trend <0.05). No significant difference was found between any dietary pattern and carotid atherosclerosis in men.

Conclusion: Greater adherence to “sweets” dietary patterns was positively related to a higher prevalence of carotid atherosclerosis in women aged 50 or older. No relationship was found between any dietary pattern and carotid atherosclerosis in men. Further prospective studies are warranted to test this finding in other populations.
Dosimetric Comparison of Intraoperative Radiotherapy and SRS for Liver Metastases
Authors: Scafa Davide , Muedder Thomas , Holz Jasmin A. , Koch David , Nour Younéss , Garbe Stephan , Gonzalez-Carmona Maria A. , Feldmann Georg , Vilz Tim O. , Köksal Mümtaz , Giordano Frank A. , Schmeel Leonard Christopher , Sarria Gustavo R.
Published: December 2021

Purpose/Objectives

To perform a dosimetric comparison between kilovoltage intraoperative radiotherapy (IORT) and stereotactic radiosurgery (SRS) simulating both deep-inspiration breath-hold (DIBH) and free-breathing (FB) modalities for patients with liver metastases.

Methods/Materials

Diagnostic computed tomographies (CT) of patients carrying one or two lesions <4 cm and who underwent surgery were retrospectively screened and randomly selected for the study. For DIBH-SRS, a gross target volume (GTV) plus planning target volume (PTV) were delineated. For FB-SRS, a GTV plus an internal target volume (ITV) and PTV were defined. Accounting for the maximal GTV diameters, a modified GTV (GTV-IORT) was expanded circumferentially to simulate a resection cavity. The best suitable round-applicator size was thereafter selected. All treatment plans were calculated homogeneously to deliver 40 Gy. Doses delivered to organs at risk (OAR) and target volumes were compared for IORT vs. both SRS modalities.

Results

Eight patients encompassing 10 lesions were included in the study. The mean liver volume was 2,050.97 cm3 (SD, 650.82), and the mean GTV volume was 12.23 cm3 (SD, 12.62). As for target structures, GTV-IORT [19.44 cm3 (SD, 17.26)] were significantly smaller than both PTV DIBH-SRS [30.74 cm3 (SD, 24.64), p = 0.002] and PTV FB-SRS [75.82 cm3 (SD, 45.65), p = 0.002]. The median applicator size was 3 cm (1.5–4.5), and the mean IORT simulated delivery time was 45.45 min (SD, 19.88). All constraints were met in all modalities. Liver V9.1 showed significantly smaller volumes with IORT [63.39 cm3 (SD, 35.67)] when compared to DIBH-SRS [150.12 cm3 (SD, 81.43), p = 0.002] or FB-SRS [306.13 cm3 (SD, 128.75), p = 0.002]. No other statistical or dosimetrically relevant difference was observed for stomach, spinal cord, or biliary tract. Mean IORT D90 was 85.3% (SD, 6.05), whereas D95 for DIBH-SRS and FB-SRS were 99.03% (SD, 1.71; p = 0.042) and 98.04% (SD, 3.46; p = 0.036), respectively.

Conclusion

Kilovoltage IORT bears the potential as novel add-on treatment for resectable liver metastases, significantly reducing healthy liver exposure to radiation in comparison to SRS. Prospective clinical evidence is required to confirm this hypothesis.
Automatic Sequence-Based Network for Lung Diseases Detection in Chest CT
Authors: Hao Jinkui , Xie Jianyang , Liu Ri , Hao Huaying , Ma Yuhui , Yan Kun , Liu Ruirui , Zheng Yalin , Zheng Jianjun , Liu Jiang , Zhang Jingfeng , Zhao Yitian
Published: December 2021

Objective

To develop an accurate and rapid computed tomography (CT)-based interpretable AI system for the diagnosis of lung diseases.

Background

Most existing AI systems only focus on viral pneumonia (e.g., COVID-19), specifically, ignoring other similar lung diseases: e.g., bacterial pneumonia (BP), which should also be detected during CT screening. In this paper, we propose a unified sequence-based pneumonia classification network, called SLP-Net, which utilizes consecutiveness information for the differential diagnosis of viral pneumonia (VP), BP, and normal control cases from chest CT volumes.

Methods

Considering consecutive images of a CT volume as a time sequence input, compared with previous 2D slice-based or 3D volume-based methods, our SLP-Net can effectively use the spatial information and does not need a large amount of training data to avoid overfitting. Specifically, sequential convolutional neural networks (CNNs) with multi-scale receptive fields are first utilized to extract a set of higher-level representations, which are then fed into a convolutional long short-term memory (ConvLSTM) module to construct axial dimensional feature maps. A novel adaptive-weighted cross-entropy loss (ACE) is introduced to optimize the output of the SLP-Net with a view to ensuring that as many valid features from the previous images as possible are encoded into the later CT image. In addition, we employ sequence attention maps for auxiliary classification to enhance the confidence level of the results and produce a case-level prediction.

Results

For evaluation, we constructed a dataset of 258 chest CT volumes with 153 VP, 42 BP, and 63 normal control cases, for a total of 43,421 slices. We implemented a comprehensive comparison between our SLP-Net and several state-of-the-art methods across the dataset. Our proposed method obtained significant performance without a large amount of data, outperformed other slice-based and volume-based approaches. The superior evaluation performance achieved in the classification experiments demonstrated the ability of our model in the differential diagnosis of VP, BP and normal cases.
The Effect of Radiation and Chemoradiation Therapy on the Head and Neck Mucosal Microbiome: A Review
Authors: Zagury-Orly Ivry , Khaouam Nader , Noujaim Jonathan , Desrosiers Martin Y. , Maniakas Anastasios
Published: December 2021

Radiation (RT) and chemoradiation therapy (CRT) play an essential role in head and neck cancer treatment. However, both cause numerous side effects in the oral cavity, paranasal sinuses, and pharynx, having deleterious consequences on patients’ quality of life. Concomitant with significant advances in radiation oncology, much attention has turned to understanding the role of the microbiome in the pathogenesis of treatment-induced tissue toxicity, to ultimately explore microbiome manipulation as a therapeutic intervention. This review sought to discuss current publications investigating the impact of RT and CRT-induced changes on the head and neck microbiome, using culture-independent molecular methods, and propose opportunities for future directions. Based on 13 studies derived from a MEDLINE, EMBASE, and Web of Science search on November 7, 2021, use of molecular methods has uncovered various phyla and genera in the head and neck microbiome, particularly the oral microbiome, not previously known using culture-based methods. However, limited research has investigated the impact of RT/CRT on subsites other than the oral cavity and none of the studies aimed to examine the relationship between the head and neck microbiome and treatment effectiveness. Findings from this review provide helpful insights on our current understanding of treatment-induced oral mucositis, dental plaque, and caries formation and highlight the need for future research to examine the effect of RT/CRT on the sinonasal and oropharyngeal microbiome. In addition, future research should use larger cohorts, examine the impact of the microbiome on treatment response, and study the effect of manipulating the microbiome to overcome therapy resistance.
Case Report: Clostridium neonatale Bacteremia in a Preterm Neonate With Necrotizing Enterocolitis
Authors: Cassir Nadim , Grandvuillemin Isabelle , Boxberger Manon , Jardot Priscilla , Boubred Farid , La Scola Bernard
Published: December 2021

Necrotizing enterocolitis is a life-threatening acquired gastrointestinal disorder among preterm neonates and is associated with a high mortality rate and long-term neurodevelopmental morbidity. No etiologic agent has been definitively established; nonetheless, the most implicated bacteria include members of the Clostridium genus. We reported here on a case of Clostridium neonatale bacteremia in a preterm neonate with necrotizing enterocolitis, providing more information regarding the potential role of this bacterium in pathogenesis of necrotizing enterocolitis. We emphasized the sporulating form of C. neonatale that confers resistance to disinfectants usually applied for the hospital environmental cleaning. Further works are needed to establish the causal relationship between the occurrence of NEC and the isolation of C. neonatale, with promising perspectives in terms of diagnostic and therapeutic management.
Inhibition of Sirt2 Alleviates Fibroblasts Activation and Pulmonary Fibrosis via Smad2/3 Pathway
Authors: Gong Hui , Zheng Chenyi , Lyu Xing , Dong Lini , Tan Shengyu , Zhang Xiangyu
Published: December 2021

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with unknown cause and limited treatment options. Its mechanism needs to be further explored. Sirtuin2 (Sirt2), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, has been proved to be involved in the fibrosis and inflammation in the liver, kidney and heart. In this study, we aimed to evaluate the role of Sirt2 in pulmonary fibrosis. We found that Sirt2 expression was upregulated in transforming growth factor-β1 (TGF-β1) treated human embryonic lung fibroblasts. Sirt2 inhibitor AGK2 or the knockdown of Sirt2 expression by targeting small interfering RNA (siRNA) suppressed the fibrogenic gene α-SMA and Fibronectin expression in TGF-β1 treated fibroblasts and primary lung fibroblasts derived from patients with IPF. In addition, Sirt2 inhibition suppresses the phosphorylation of Smad2/3. Co-immunoprecipitation (Co-IP) showed that there is interaction between Sirt2 and Smad3 in the TGF-β1 treated lung fibroblasts. In bleomycin-induced pulmonary fibrosis in mice, AGK2 treatment significantly mitigated the degree of fibrosis and decreased the phosphorylation of Smad2/3. These data suggest that Sirt2 may participate in the development of IPF via regulating the Smad2/3 pathway. Inhibition of Sirt2 would provide a novel therapeutic strategy for this disease.
Peiminine Induces G0/G1-Phase Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells in Vitro and in Vivo
Authors: Yu Lei , Chen Yuxi , Yuan Shaohui , Cao Yang , Bi Zhenggang
Published: December 2021

Aims: Peiminine has been reported to have various pharmacological properties, including anticancer activity. In this study, we investigated the effect of this alkaloid on osteosarcoma and explored the underlying mechanisms.

Methods: To evaluate the antiosteosarcoma effects of peiminine in vitro, cell viability was assessed by CCK-8 and live/dead assays; the effects of the drug on apoptosis and the cell cycle were examined by flow cytometry; the effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively, while its effects on autophagy were observed by transmission electron microscopy and an LC3 fluorescent puncta formation assay. The role of autophagy in the peiminine-mediated effects in osteosarcoma cells was evaluated by CCK-8 assay and western blotting after the application of the autophagy inhibitor chloroquine. The effect of peiminine on reactive oxygen species (ROS) production was analyzed using fluorescence confocal microscopy and spectrophotometry. Additionally, peiminine-treated osteosarcoma cells were exposed to SP600125, a JNK inhibitor, and N-acetylcysteine, a ROS scavenger, after which the contribution of the ROS/JNK signaling pathway to osteosarcoma was assessed using cell viability and LC3 fluorescent puncta formation assays, flow cytometry, and western blotting. A xenograft mouse model of osteosarcoma was generated to determine the antitumor effects of peiminine in vivo.

Results: Peiminine suppressed proliferation and metastasis and induced cell cycle arrest, apoptosis, and autophagy in osteosarcoma cells. These anticancer effects of peiminine were found to be dependent on intracellular ROS generation and activation of the JNK pathway. In line with these results, peiminine significantly inhibited xenograft tumor growth in vivo.

Conclusions: Peiminine induced G0/G1-phase arrest, apoptosis, and autophagy in human osteosarcoma cells via the ROS/JNK signaling pathway both in vitro and in vivo. Our study may provide an experimental basis for the evaluation of peiminine as an alternative drug for the treatment of osteosarcoma.
A Study on the Drug Concentration in Fellow Eyes After Unilateral Intravitreal Injection of Conbercept Into New Zealand Rabbit Eyes
Authors: Di Yu , Xu Haiyan , Ye Junjie , Guo Zijian
Published: December 2021

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) have become increasingly popular in the treatment of ocular diseases. However, few studies have determined the efficiency of unilateral intravitreal anti-VEGF injection in the fellow eye. Herein, we performed a study to investigate the drug concentration in fellow eyes and venous serum after unilateral intravitreal injection of conbercept into rabbit eyes. This is an experimental animal study. Thirty male New Zealand rabbits (60 eyes) were used. One eye of each rabbit was intravitreally injected with 0.5 mg of conbercept. Both eyes from six rabbits were enucleated on days 1, 3, 7, 14, and 30. Conbercept concentrations were measured in the serum, aqueous humor, and vitreous humor. We found conbercept was detected in the fellow eyes and serum of rabbits. Conbercept concentrations in the vitreous humor of the fellow eyes increased from 74.11 ng/ml on day 1 to 246.69 ng/ml on day 3 and then declined to 69.11 ng/ml after 30 days. The concentration in the aqueous humor peaked on day 1 with a concentration of 244.82 ng/ml and declined to 40.13 ng/ml after 30 days. The maximum conbercept concentrations in the aqueous humor and vitreous humor of fellow eyes were similar, which were 0.2 and 1.3% of those of the injected eye, respectively. A peak concentration of 102.49 ng/ml was achieved in the venous serum 1 day after intravitreal injection of conbercept, which was 0.08 and 0.5% of those of the maximum conbercept concentrations in the vitreous humor and aqueous humor of the injected eye, respectively, and 41.5 and 41.8% of the maximum conbercept concentrations in the vitreous humor and aqueous humor of the non-injected eye, respectively. In conclusion, after intravitreal injection of 0.5 mg of conbercept into rabbit eyes, very small amounts of conbercept were detected in the fellow non-injected eyes and venous serum.
Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
Authors: Zhang Ni , Zhu Lichong , Ouyang Qiuhong , Yue Saisai , Huang Yichun , Qu Shuang , Li Runwei , Qiao Yuanyuan , Xu Man , He Fangfei , Zhao Bin , Wei Lai , Wu Xiaoai , Zhang Peisen
Published: December 2021

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.
The L1624Q Variant in SCN1A Causes Familial Epilepsy Through a Mixed Gain and Loss of Channel Function
Authors: Jones Laura B. , Peters Colin H. , Rosch Richard E. , Owers Maxine , Hughes Elaine , Pal Deb K. , Ruben Peter C.
Published: December 2021

Variants of the SCN1A gene encoding the neuronal voltage-gated sodium channel NaV1.1 cause over 85% of all cases of Dravet syndrome, a severe and often pharmacoresistent epileptic encephalopathy with mostly infantile onset. But with the increased availability of genetic testing for patients with epilepsy, variants in SCN1A have now also been described in a range of other epilepsy phenotypes. The vast majority of these epilepsy-associated variants are de novo, and most are either nonsense variants that truncate the channel or missense variants that are presumed to cause loss of channel function. However, biophysical analysis has revealed a significant subset of missense mutations that result in increased excitability, further complicating approaches to precision pharmacotherapy for patients with SCN1A variants and epilepsy. We describe clinical and biophysical data of a familial SCN1A variant encoding the NaV1.1 L1624Q mutant. This substitution is located on the extracellular linker between S3 and S4 of Domain IV of NaV1.1 and is a rare case of a familial SCN1A variant causing an autosomal dominant frontal lobe epilepsy. We expressed wild-type (WT) and L1642Q channels in CHO cells. Using patch-clamp to characterize channel properties at several temperatures, we show that the L1624Q variant increases persistent current, accelerates fast inactivation onset and decreases current density. While SCN1A-associated epilepsy is typically considered a loss-of-function disease, our results put L1624Q into a growing set of mixed gain and loss-of-function variants in SCN1A responsible for epilepsy.
Ultrasmall PEI-Decorated Bi2Se3 Nanodots as a Multifunctional Theranostic Nanoplatform for in vivo CT Imaging-Guided Cancer Photothermal Therapy
Authors: Zhang Peng , Wang Lei , Chen Xiuying , Li Xiang , Yuan Qinghai
Published: December 2021

Bi-based nanomaterials, such as Bi2Se3, play an important part in biomedicine, such as photothermal therapy (PTT) and computed tomography (CT) imaging. Polyethylenimine (PEI)-modified ultrasmall Bi2Se3 nanodots were prepared using an ultrafast synthetic method at room temperature (25°C). Bi2Se3 nanodots exhibited superior CT imaging performance, and could be used as effective photothermal reagents owing to their broad absorption in the ultraviolet–visible–near infrared region. Under irradiation at 808 nm, PEI-Bi2Se3 nanodots exhibited excellent photothermal-conversion efficiency of up to 41.3%. Good biocompatibility and significant tumor-ablation capabilities were demonstrated in vitro and in vivo. These results revealed that PEI-Bi2Se3 nanodots are safe and a good nanotheranostic platform for CT imaging-guided PTT of cancer.
Perinatal Food Deprivation Modifies the Caloric Restriction Response in Adult Mice Through Sirt1
Authors: Peña-Villalobos Isaac , Otárola Fabiola A. , Casas Bárbara S. , Sabat Pablo , Palma Verónica
Published: December 2021

Variations in the availability of nutritional resources in animals can trigger reversible adjustments, which in the short term are manifested as behavioral and physiological changes. Several of these responses are mediated by Sirt1, which acts as an energy status sensor governing a global genetic program to cope with changes in nutritional status. Growing evidence suggests a key role of the response of the perinatal environment to caloric restriction in the setup of physiological responses in adulthood. The existence of adaptive predictive responses has been proposed, which suggests that early nutrition could establish metabolic capacities suitable for future food-scarce environments. We evaluated how perinatal food deprivation and maternal gestational weight gain impact the transcriptional, physiological, and behavioral responses in mice, when acclimated to caloric restriction in adulthood. Our results show a strong predictive capacity of maternal weight and gestational weight gain, in the expression of Sirt1 and its downstream targets in the brain and liver, mitochondrial enzymatic activity in skeletal muscle, and exploratory behavior in offspring. We also observed differential responses of both lactation and gestational food restriction on gene expression, thermogenesis, organ masses, and behavior, in response to adult caloric restriction. We conclude that the early nutritional state could determine the magnitude of responses to food scarcity later in adulthood, mediated by the pivotal metabolic sensor Sirt1. Our results suggest that maternal gestational weight gain could be an important life history trait and could be used to predict features that improve the invasive capacity or adjustment to seasonal food scarcity of the offspring.
Diagnosis of Typical Apple Diseases: A Deep Learning Method Based on Multi-Scale Dense Classification Network
Authors: Tian Yunong , Li En , Liang Zize , Tan Min , He Xiongkui
Published: December 2021

Disease has always been one of the main reasons for the decline of apple quality and yield, which directly harms the development of agricultural economy. Therefore, precise diagnosis of apple diseases and correct decision making are important measures to reduce agricultural losses and promote economic growth. In this paper, a novel Multi-scale Dense classification network is adopted to realize the diagnosis of 11 types of images, including healthy and diseased apple fruits and leaves. The diagnosis of different kinds of diseases and the same disease with different grades was accomplished. First of all, to solve the problem of insufficient images of anthracnose and ring rot, Cycle-GAN algorithm was applied to achieve dataset expansion on the basis of traditional image augmentation methods. Cycle-GAN learned the image characteristics of healthy apples and diseased apples to generate anthracnose and ring rot lesions on the surface of healthy apple fruits. The diseased apple images generated by Cycle-GAN were added to the training set, which improved the diagnosis performance compared with other traditional image augmentation methods. Subsequently, DenseNet and Multi-scale connection were adopted to establish two kinds of models, Multi-scale Dense Inception-V4 and Multi-scale Dense Inception-Resnet-V2, which facilitated the reuse of image features of the bottom layers in the classification neural networks. Both models accomplished the diagnosis of 11 different types of images. The classification accuracy was 94.31 and 94.74%, respectively, which exceeded DenseNet-121 network and reached the state-of-the-art level.
Network Analysis of Different Exogenous Hormones on the Regulation of Deep Sowing Tolerance in Maize Seedlings
Authors: Chen Fenqi , Ji Xiangzhuo , Bai Mingxing , Zhuang Zelong , Peng Yunling
Published: December 2021

The planting method of deep sowing can make the seeds make full use of water in deep soil, which is considered to be an effective way to respond to drought stress. However, deep sowing will affect the growth and development of maize (Zea mays L.) at seedling stage. To better understand the response of maize to deep sowing stress and the mechanism of exogenous hormones [Gibberellin (GA3), Brassinolide (BR), Strigolactone (SL)] alleviates the damaging effects of deep-sowing stress, the physiological and transcriptome expression profiles of seedlings of deep sowing sensitive inbred line Zi330 and the deep-tolerant inbred line Qi319 were compared under deep sowing stress and the conditions of exogenous hormones alleviates stress. The results showed that mesocotyl elongated significantly after both deep sowing stress and application of exogenous hormones, and its elongation was mainly through elongation and expansion of cell volume. Hormone assays revealed no significant changes in zeatin (ZT) content of the mesocotyl after deep sowing and exogenous hormone application. The endogenous GA3 and auxin (IAA) contents in the mesocotyl of the two inbred lines increased significantly after the addition of exogenous GA3, BR, and SL under deep sowing stress compared to deep sowing stress, while BR and SL decreased significantly. Transcriptome analysis showed that the deep seeding stress was alleviated by GA3, BR, and SLs, the differentially expressed genes (DEGs) mainly included cellulose synthase, expansin and glucanase, oxidase, lignin biosynthesis genes and so on. We also found that protein phosphatase 2C and GA receptor GID1 enhanced the ability of resist deep seeding stress in maize by participating in the abscisic acid (ABA) and the GA signaling pathway, respectively. In addition, we identified two gene modules that were significantly related to mesocotyl elongation, and identified some hub genes that were significantly related to mesocotyl elongation by WGCNA analysis. These genes were mainly involved in transcription regulation, hydrolase activity, protein binding and plasma membrane. Our results from this study may provide theoretical basis for determining the maize deep seeding tolerance and the mechanism by which exogenous hormones regulates deep seeding tolerance.
Being There: Exploring Virtual Symphonic Experience as a Salutogenic Design Intervention for Older Adults
Authors: Faw Meara H. , Buley Taylor , Malinin Laura Healey
Published: December 2021

This co-design study examined salutogenic potential of mobile virtual reality (VR) experiences as an alternative to participation in a community-based symphonic engagement program (B Sharp), previously found to benefit people with dementia (PWD) and their informal caregivers. Six focus groups were conducted with sixteen adults aged 76–90; three participants had dementia, and two were informal spousal caregivers. No participants had prior VR experience. The study assessed the feasibility of replicating the community-based-arts program in VR, with the goal of enhancing its salutogenic qualities (e.g., positive distraction, engagement, and social connection). Video-recordings of participants while using a mobile head-mounted display (HMD) were analyzed using qualitative thematic analysis to compare perceptions of different virtual experiences, including replication or enhancement of B Sharp and a campus tour. Findings suggest participants had positive perceptions of enhanced VR experiences with no adverse effects, although PWD were less enthusiastic and HMD usability was complicated by eyewear use and comfort with technology. Participants reacted most favorably to the enhanced symphonic experience, where they were “virtually” onstage during the performance, suggesting unique experiences beyond what is possible in the real world have the greatest potential for deep immersion for older adults. Results suggest VR has strong potential to replicate and enhance salutogenic qualities of community-based programming by enabling greater access to experiences for older adults and by increasing enjoyment and engagement through experiences not otherwise feasible. Furthermore, this study illuminates advantages of a user-centered, co-design approach when developing VR experiences with community partners and older adults.
Reading Comprehension Predictors in European Portuguese Adults
Authors: Gonçalves Fábio , Reis Alexandra , Inácio Filomena , Morais Inês Salomé , Faísca Luís
Published: December 2021

Research on the predictors of reading comprehension has been largely focused on school-aged children and mainly in opaque orthographies, hindering the generalization of the results to adult populations and more transparent orthographies. In the present study, we aim to test two versions of the Simple View of Reading (SVR): the original model and an extended version, including reading fluency and vocabulary. Additional mediation models were analyzed to verify if other reading comprehension predictors (rapid automatized naming, phonological decoding, phonological awareness, morphological awareness, and working memory) have direct effects or if they are mediated through word reading and reading fluency. A sample of 67 typical adult Portuguese readers participated in this study. The SVR model accounted for 27% of the variance in reading comprehension, with oral language comprehension displaying a larger contribution than word reading. In the extended SVR model, reading fluency and vocabulary provided an additional and significant contribution of 7% to the explained variance. Moreover, vocabulary influenced reading comprehension directly and indirectly, via oral language comprehension. In the final mediation model, the total mediation hypothesis was rejected, and only morphological awareness showed a direct effect on reading comprehension. These results provide preliminary evidence that the SVR (with the possible addition of vocabulary) might be a reliable model to explain reading comprehension in adult typical readers in a semitransparent orthography. Furthermore, oral language comprehension and vocabulary were the best predictors in the study, suggesting that remediation programs addressing reading comprehension in adults should promote these abilities.
Altered Functional Connectivity in a Triple-Network Model in Autism With Co-occurring Attention Deficit Hyperactivity Disorder
Authors: Wang Kai , Li Ke , Niu Xiaoyu
Published: December 2021

Purpose: This study aimed to explore alterations in functional connectivity (FC) within and between default mode network (DMN), central executive network, and salience network in autism spectrum disorder (ASD) with co-occurring attention deficit hyperactivity disorder (ADHD).

Method: A total of 135 individuals' date of the Autism Brain Imaging Data Exchange II was used to compare the ASD+ADHD group with the ASD group in relation to the abnormal within-network and between-network connectivity of the ASD group relative to the TD group; consequently, the correlation analysis between abnormal FC and behavior was performed.

Results: The ASD+ADHD group exhibited decreased within-network connectivity in the precuneus of the ventral DMN compared with the ASD group. Among the three groups, the ASD+ADHD group showed lower connectivity, whereas the ASD group had higher connectivity than the TD group, although the effect of the separate post hoc test was not significant. Meanwhile, the ASD+ADHD group showed increased between-network connectivity between the ventral DMN and dorsal DMN and between the ventral DMN and left executive control network, compared with the ASD and TD groups.

Conclusion: Dysfunction of DMN in the “triple-network model” is the core evidence for ASD with co-occurring ADHD.
Implementation of Video Feedback Within a Community Based Naturalistic Developmental Behavioral Intervention Program for Toddlers With ASD: Pilot Study
Authors: Klein Claire B. , Swain Deanna M. , Vibert Bethany , Clark-Whitney Elysha , Lemelman Amy R. , Giordano Jennifer A. , Winter Jamie , Kim So Hyun
Published: December 2021

Video feedback (VF) is an intervention delivery technique that complements naturalistic developmental behavioral interventions (NDBI) and parent-mediated interventions (PMI) by using caregiver-child interaction videos reviewed with a clinician to facilitate behavioral change in caregivers. Although VF has been implemented in PMI with young children with ASD, examinations of feasibility and acceptability, as well as the potential effectiveness of VF in community settings, have been limited. In this pilot randomized control trial (NCT03397719; https://clinicaltrials.gov/ct2/show/NCT03397719), families were randomized into a state-funded Early Intervention (EI) NDBI program or the NDBI program augmented with VF. Results demonstrated high levels of implementation and acceptability of VF augmenting the community-based EI program in caregivers and clinicians. Both groups showed significant improvements after 6 months in social communication symptoms and some areas of developmental and adaptive skills.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03397719, identifier: NCT03397719.
Health Systems Responsiveness in Addressing Indigenous Residents' Health and Mental Health Needs Following the 2016 Horse River Wildfire in Northern Alberta, Canada: Perspectives From Health Service Providers
Authors: Fitzpatrick Kayla M. , Wild T. Cameron , Pritchard Caillie , Azimi Tara , McGee Tara , Sperber Jodi , Albert Lorraine , Montesanti Stephanie
Published: December 2021

Following the 2016 Horse River Wildfire in northern Alberta, the provincial health authority, the ministry of health, non-profit and charitable organizations, and regional community-based service agencies mobilized to address the growing health and mental health concerns among Indigenous residents and communities through the provision of services and supports. Among the communities and residents that experienced significant devastation and loss were First Nation and Métis residents in the region. Provincial and local funding was allocated to new recovery positions and to support pre-existing health and social programs. The objective of this research was to qualitatively describe the health systems response to the health impacts following the wildfire from the perspective of service providers who were directly responsible for delivering or organizing health and mental wellness services and supports to Indigenous residents. Semi-structured qualitative interviews were conducted with 15 Indigenous and 10 non-Indigenous service providers from the Regional Municipality of Wood Buffalo (RMWB). Interviews were transcribed verbatim and a constant comparative analysis method was used to identify themes. Following service provider interviews, a supplemental document review was completed to provide background and context for the qualitative findings from interviews. The document review allowed for a better understanding of the health systems response at a systems level following the wildfire. Triangulation of semi-structured interviews and organization report documents confirmed our findings. The conceptual framework by Mirzoev and Kane for understanding health systems responsiveness guided our data interpretation. Our findings were divided into three themes (1) service provision in response to Indigenous mental health concerns (2) gaps in Indigenous health-related services post-wildfire and (3) adopting a health equity lens in post-disaster recovery. The knowledge gained from this research can help inform future emergency management and assist policy and decision makers with culturally safe and responsive recovery planning. Future recovery and response efforts should consider identifying and addressing underlying health, mental health, and emotional concerns in order to be more effective in assisting with healing for Indigenous communities following a public health emergency such as a wildfire disaster.