bluuebunny/crossref_metadata_2025 huggingface dataset:
Joint optimization of dynamic resource allocation and packet scheduling for virtual switches in cognitive internet of vehicles
Authors: Wang Yang , Wang Xiong , Huang Zhuobin , Li Wei , Xu Shizhong
Published: April 2022

The rapidly evolving machine learning technologies have reshaped the transportation system and played an essential role in the Cognitive Internet of Vehicles (CIoV). Most of the cognitive services are computation-intensive or storage-intensive, and thus they are usually deployed in edge or cloud data centers. In today’s data center networks, the virtual machines hosted in a server are connected to a virtual switch responsible for forwarding all packets for the cognitive services deployed on the virtual machines. Therefore, the virtual switches will become a performance bottleneck for cognitive services without an efficient resource allocation and data scheduling strategy. However, the highly dynamic characteristics of cognitive services make the resource allocation and packet scheduling problem for virtual switches surprisingly challenging. To guarantee the performance of cognitive services, we investigate the joint optimization problem of dynamic resource allocation and packet scheduling for virtual switches. We first model the joint optimization problem of dynamic resource allocation and packet scheduling for virtual switches as a mathematical optimization problem. Then, we analyze the problem with Lyapunov Optimization Framework and derive efficient optimization algorithms with performance tradeoff bounds. At last, we evaluate these algorithms on a testbed and a network-wide simulation platform. Experiment results show that our algorithms outperform other designs and meet the theoretical performance bound.
Performance analysis of spatial multiplexing MIMO-MFSK based on energy detection for fast-fading environments
Authors: Li Shuaijun , Qiu Hongbing , Zheng Lin , Yang Chao
Published: April 2022

In fast-fading scattering environments such as high-speed rail and low-altitude communications, mobile communication systems need to quickly and robustly estimate and equalize fast-fading, time-varying channels. Under these circumstances, noncoherent multiple-input multiple-output (MIMO) has received attention in recent years, since it is less influenced by factors such as phase fluctuations and has fewer requirements for channel estimation and synchronization. Spatial multiplexing MIMO-MFSK based on energy detection is different from conventional noncoherent MIMO in that it can achieve higher spatial multiplexing gain in the independent distribution of channel fading statistics. At the receiver, partial real channel state information (CSI) is available, which can improve the capacity while ensuring the reliability of the link. With partial real CSI replacing instantaneous CSI, the system performance is inferior to conventional coherent MIMO under the influence of noise. As a result, it is necessary to analyze its theoretical detection performance. By energy detection, the noise of the MIMO-MFSK system conforms to the generalized gamma distribution. On the basis of this distribution, the optimal decision rule of the system and the symbol error rate (SER) formula are derived. Additionally, we investigate the signal-dependent noise problem of minimum Euclidean distance detection. Numerical results show that the SER formula fits well with the simulation results under the condition of a high signal-to-noise ratio.
Global well-posedness of the compressible quantum magnetohydrodynamic model with small initial energy
Authors: Yang Ying , Zhou Yu , Zhu Canze
Published: April 2022

In this paper, we investigate the three-dimensional Cauchy problem of the compressible quantum magnetohydrodynamic model. It is proved that the system admits a unique global solution, provided that the initial energy is suitably small. Furthermore, the large time behavior of the global solution is obtained.
The first case report of multiple thoracic vertebrae fractures caused by a low-voltage electric shock
Authors: Žatecký Jan , Peteja Matúš , Gawel Wladyslaw Bartosz , Lerch Milan
Published: April 2022

Background

This paper describes a unique case—the first case of multiple fractures of the thoracic vertebrae caused by a low-voltage electric shock.

Case presentation

A 22-year-old male patient was diagnosed with compression fractures of Th2–Th6 caused by a muscle spasm resulting from an electric shock. The patient was treated conservatively using a cervico-thoracic support corset. After rehabilitation, the patient has regained his physiological movement of the spine without any back pain.

Conclusions

Albeit vertebral fractures caused by electric shock injury are extremely rare, clinicians should always keep in mind this diagnosis, especially when clinical symptoms such as pain and limitation of movement are present.
Experimental Investigation on Flexural Capacity of Reinforced Concrete Beams Strengthened with 3D-Fiberglass, CFRP and GFRP
Authors: Vahidpour Mahdi , Kheyroddin Ali , Kioumarsi Mahdi
Published: April 2022

The main objective of this study is to investigate the structural performance of reinforced concrete (RC) beam specimens strengthened with 3D-fiberglass as compared with fiber-reinforced polymers (FRP) sheets. For this purpose, six RC beams were fabricated, strengthened, and tested under a four-point bending machine. One of the beams served as the control beam (REF), while the others were strengthened with carbon FRP (RCFRP), glass FRP (RGFRP), 3D-fiberglass and epoxy resin (R3DTR), 3D-fiberglass and epoxy resin extended to the sides (R3DTRB), and 3D-fiberglass and concrete repair (R3DTG). Failure mode, crack development, flexural capacity, ductility, the effectiveness of wrapping configurations, and the performance of epoxy resin in comparison with concrete repairer were studied between various beams. The results attest to the better performance and effectiveness of 3D-fiberglass over FRP in terms of flexural capacity, crack pattern, and ductility. The R3DTR and RGFRP specimens, compared to the control specimen, had the highest and lowest flexural capacity growth, with 19% and 8.4%, respectively. In addition, the failure modes observed in this study were in good agreement with the failure modes present in ACI.440.2R-17. Moreover, finite element (FE) models were proposed to predict the residual capacity of the specimens strengthened with FRP, using Abaqus software.
Physical activity improves outcomes of combined lenvatinib plus anti-PD-1 therapy in unresectable hepatocellular carcinoma: a retrospective study and mouse model
Authors: Liu Xue-Feng , Zhu Xiao-Dong , Feng Long-Hai , Li Xiao-Long , Xu Bin , Li Kang-Shuai , Xiao Nan , Lei Ming , Sun Hui-Chuan , Tang Zhao-You
Published: April 2022

Background

Physical activity is known to have anti-cancer effects, including immunomodulatory actions. This study investigated the hypothesis that physical activity synergizes with combined lenvatinib plus anti-PD-1 therapy to enhance efficacy in patients with unresectable HCC.

Methods

The physical activity levels of patients with unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy were recorded by questionnaire. Patients were categorized according to physical activity levels (active vs. sedentary). The primary outcome was overall survival (OS). Secondary outcomes included objective response rate (ORR) and progression-free survival (PFS). A subcutaneous syngeneic HCC model was generated in C57BL/6 mice. Mice were randomized to receive placebo, combined lenvatinib plus anti-PD-1 antibodies or combination therapy plus physical activity. Tumors were measured every 3 days and harvested for immunohistochemistry analysis at 20 mm maximum diameter.

Results

Fifty-nine patients with unresectable HCC were categorized to active (n = 28) or sedentary (n = 31) groups. The active group had higher albumin and des-γ-carboxy prothrombin levels and lower hepatitis B virus load at baseline; other clinical and oncologic characteristics were comparable between the two groups. Patients in the active group had significantly longer OS (HR = 0.220, 95% CI 0.060–0.799) and PFS (HR = 0.158, 95% CI 0.044–0.562) and higher ORR (OR = 4.571, 95% CI 1.482–14.102) than patients in the sedentary group. Regular physical activity was independently associated with OS, PFS and ORR. The mouse model showed that physical activity significantly suppressed tumor growth and prolonged survival of tumor-bearing mice. Furthermore, physical activity inhibited Treg cell infiltration and immune checkpoint expression (including CTLA4, TIGIT and TIM3) induced by long-term combined lenvatinib plus anti-PD-1 therapy, improving efficacy.

Conclusions

Regular physical activity was associated with improved outcomes in unresectable HCC receiving combined lenvatinib plus anti-PD-1 therapy. Physical activity may improve therapeutic efficacy by reprograming the tumor microenvironment from an immunosuppressive to immunostimulatory phenotype.
Identification of novel lipid biomarkers in xmrk- and Myc-induced models of hepatocellular carcinoma in zebrafish
Authors: Monroe Jerry D. , Fraher Daniel , Huang Xiaoqian , Mellett Natalie A. , Meikle Peter J. , Sinclair Andrew J. , Lirette Seth T. , Maihle Nita J. , Gong Zhiyuan , Gibert Yann
Published: April 2022

Background

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is accompanied by complex dysregulation of lipids. Increasing evidence suggests that particular lipid species are associated with HCC progression. Here, we aimed to identify lipid biomarkers of HCC associated with the induction of two oncogenes, xmrk, a zebrafish homolog of the human epidermal growth factor receptor (EGFR), and Myc, a regulator of EGFR expression during HCC.

Methods

We induced HCC in transgenic xmrk, Myc, and xmrk/Myc zebrafish models. Liver specimens were histologically analyzed to characterize the HCC stage, Oil-Red-O stained to detect lipids, and liquid chromatography/mass spectrometry analyzed to assign and quantify lipid species. Quantitative real-time polymerase chain reaction was used to measure lipid metabolic gene expression in liver samples. Lipid species data was analyzed using univariate and multivariate logistic modeling to correlate lipid class levels with HCC progression.

Results

We found that induction of xmrk, Myc and xmrk/Myc caused different stages of HCC. Lipid deposition and class levels generally increased during tumor progression, but triglyceride levels decreased. Myc appears to control early HCC stage lipid species levels in double transgenics, whereas xmrk may take over this role in later stages. Lipid metabolic gene expression can be regulated by either xmrk, Myc, or both oncogenes. Our computational models showed that variations in total levels of several lipid classes are associated with HCC progression.

Conclusions

These data indicate that xmrk and Myc can temporally regulate lipid species that may serve as effective biomarkers of HCC progression.
Disordered eating behaviour in adolescents with type 1 diabetes on continuous subcutaneous insulin infusion; relation to body image, depression and glycemic control
Authors: Salah Nouran Yousef , Hashim Mostafa Ahmad , Abdeen Mai Seif ElDin
Published: April 2022

Background

Disordered eating behaviour (DEB) represents a significant morbidity among people with type-1 diabetes (T1D). Continuous-subcutaneous insulin infusion (CSII) improves glycemic control and psychological wellbeing in those with T1D. However, its relation to DEB remains obscure.

Objectives

To compare DEB among adolescents with T1D on CSII versus basal-bolus regimen and correlate it with body image, HbA1C and depression.

Methods

Sixty adolescents with T1D (30 on CSII and 30 on basal-bolus regimen), aged 12–17 years were studied focusing on diabetes-duration, insulin therapy, exercise, socioeconomic standard, hypoglycemic attacks/week and family history of psychiatric illness. Anthropometric measures, HbA1C, binge eating scale (BES), body image tool, patient health questionnaire-9 (PHQ9) and the Mini-KID depression scale were assessed.

Results

Among the studied adolescents with T1D, six had DEB (10%), 14 had poor body-image perception (23.3%), 42 had moderate body-image perception (70%) and 22 had depression (36.7%). Adolescents with T1D on CSII had significantly lower BES (p = 0.022), Mini-KID depression (p = 0.001) and PHQ9 (p = 0.02) than those on basal-bolus regimen. BES was positively correlated to depression (p < 0.001), HbA1C (p = 0.013) and diabetes-duration (p = 0.009) and negatively correlated to body-image (p = 0.003).

Conclusion

DEB is a prevalent comorbidity among adolescents with T1D, with higher frequency in those on basal-bolus regimen than CSII.
Evaluating the quality, safety, and functionality of commonly used smartphone apps for bipolar disorder mood and sleep self-management
Authors: Morton Emma , Nicholas Jennifer , Yang Linda , Lapadat Laura , Barnes Steven J. , Provencher Martin D. , Depp Colin , Chan Michelle , Kulur Rhea , Michalak Erin E.
Published: April 2022

Background

Individuals with bipolar disorder (BD) are increasingly turning to smartphone applications (apps) for health information and self-management support. While reviews have raised concerns regarding the effectiveness and safety of publicly available apps for BD, apps surveyed may not reflect what individuals with BD are using. The present study had two aims: first, to characterize the use of health apps to support mood and sleep amongst people with BD, and second, to evaluate the quality, safety and functionality of the most commonly used self-management apps.

Methods

A web-based survey was conducted to explore which apps people with BD reported using to support self-management of mood and sleep. The characteristics of the most commonly nominated apps were described using a standardized framework, including their privacy policy, clinical foundations, and functionality.

Results

Respondents (n = 919) were 77.9% female with a mean age of 36.9 years. 41.6% of participants (n = 382) reported using a self-management app to support mood or sleep. 110 unique apps were nominated in relation to mood, and 104 unique apps nominated in relation to sleep; however, most apps were only mentioned once. The nine most frequently nominated apps related to mood and sleep were subject to further evaluation. All reviewed apps offered a privacy policy, however user control over data was limited and the complexity of privacy policies was high. Only one app was developed for BD populations. Half of reviewed apps had published peer-reviewed evidence to support their claims of efficacy, but little research was specific to BD.

Conclusion

Findings illustrate the potential of smartphone apps to increase the reach of psychosocial interventions amongst people with BD. Apps were largely created by commercial developers and designed for the general population, highlighting a gap in the development and dissemination of evidence-informed apps for BD. There may be risks in using generic health apps for BD self-management; clinicians should enquire about patients’ app use to foster conversations about their particular benefits and limitations.
Mical modulates Tau toxicity via cysteine oxidation in vivo
Authors: Prifti Engie , Tsakiri Eleni N. , Vourkou Ergina , Stamatakis George , Samiotaki Martina , Skoulakis Efthimios M. C. , Papanikolopoulou Katerina
Published: April 2022

Tau accumulation is clearly linked to pathogenesis in Alzheimer’s disease and other Tauopathies. However, processes leading to Tau fibrillization and reasons for its pathogenicity remain largely elusive. Mical emerged as a novel interacting protein of human Tau expressed in Drosophila brains. Mical is characterized by the presence of a flavoprotein monooxygenase domain that generates redox potential with which it can oxidize target proteins. In the well-established Drosophila Tauopathy model, we use genetic interactions to show that Mical alters Tau interactions with microtubules and the Actin cytoskeleton and greatly affects Tau aggregation propensity and Tau-associated toxicity and dysfunction. Exploration of the mechanism was pursued using a Mical inhibitor, a mutation in Mical that selectively disrupts its monooxygenase domain, Tau transgenes mutated at cysteine residues targeted by Mical and mass spectrometry analysis to quantify cysteine oxidation. The collective evidence strongly indicates that Mical’s redox activity mediates the effects on Tau via oxidation of Cys322. Importantly, we also validate results from the fly model in human Tauopathy samples by showing that MICAL1 is up-regulated in patient brains and co-localizes with Tau in Pick bodies. Our work provides mechanistic insights into the role of the Tau cysteine residues as redox-switches regulating the process of Tau self-assembly into inclusions in vivo, its function as a cytoskeletal protein and its effect on neuronal toxicity and dysfunction.
Zika virus vertical transmission in interferon receptor1-antagonized Rag1−/− mice results in postnatal brain abnormalities and clinical disease
Authors: Winkler Clayton W. , Clancy Chad S. , Rosenke Rebecca , Peterson Karin E.
Published: April 2022

The mechanisms by which vertically transmitted Zika virus (ZIKV) causes postnatal brain development abnormalities and congenital disease remain poorly understood. Here, we optimized the established anti-IFNAR1 treated, Rag1−/− (AIR) mouse model of ZIKV infection to examine the consequence of vertical transmission on neonate survival and postnatal brain development. We found that modulating the infectious dose and the frequency of anti-IFNAR1 treatment of pregnant mice (termed AIRlow mice) prolonged neonatal survival allowing for pathogenesis studies of brain tissues at critical postnatal time points. Postnatal AIRlow mice all had chronic ZIKV infection in the brain that was associated with decreased cortical thickness and cerebellar volume, increased gliosis, and higher levels of cell death in many brain areas including cortex, hippocampus and cerebellum when compared to controls. Interestingly, despite active infection and brain abnormalities, the neurodevelopmental program remained active in AIRlow mice as indicated by elevated mRNA expression of critical neurodevelopmental genes in the brain and enlargement of neural-progenitor rich regions of the cerebellum at a developmental time point analogous to birth in humans. Nevertheless, around the developmental time point when the brain is fully populated by neurons, AIRlow mice developed neurologic disease associated with persistent ZIKV infection in the brain, gliosis, and increased cell death. Together, these data show that vertically transmitted ZIKV infection in the brain of postnatal AIRlow mice strongly influences brain development resulting in structural abnormalities and cell death in multiple regions of the brain.
A Sui-Tang dynasty woman’s crown: analyzing form, glass and class
Authors: Du Jingnan , Eckfeld Tonia , Yang Junchang , Jiang Fengrui , Zhang Quanmin , Shao Yanbing
Published: April 2022

A woman’s crown made of fine gilt bronze with refined glass inlay work was excavated from a Sui-Tang tomb called Kunlun M2 in Xi’an, Shaanxi Province, China. Very few female crowns and crown ornaments have been excavated in China thus far, and there has been a lack of systematic research into the technologies used to manufacture them. Importantly, this paper uses the M2 crown to investigate its surface inlays and overall shape, then conducts a comparative analysis of women's crown ornaments of the same type, providing a reference for study of the crown. Non-invasive and micro-destructive analysis including optical microscopy (OM), optical coherence tomography (OCT), micro X-ray fluorescence imagery (XRF), and Raman spectroscopy were applied. These identified the crown’s inlays as potash-lime glass, composed mainly of the raw materials: vein quartz or quartzite with potassium nitrate as flux. The inlays were sintered before embedding into gilt copper wire filigree. In comparison to the composition proportions in other ancient potash-lime glass, there is no specific percentage of the raw materials in Chinese potash-lime glass, where the ingredients were likely determined by the experience of the craftsman. Compared with existing research on other crowns and their inlays, this study speculates that the crown dates from the Sui dynasty (581–618) or early Tang dynasty (618–649), was made locally by Chinese craftsmen and belonged to the wife of a high official.
Defining user spectra to classify Ethereum users based on their behavior
Authors: Bonifazi Gianluca , Corradini Enrico , Ursino Domenico , Virgili Luca
Published: April 2022

Purpose

In this paper, we define the concept of user spectrum and adopt it to classify Ethereum users based on their behavior.

Design/methodology/approach

Given a time period, our approach associates each user with a spectrum showing the trend of some behavioral features obtained from a social network-based representation of Ethereum. Each class of users has its own spectrum, obtained by averaging the spectra of its users. In order to evaluate the similarity between the spectrum of a class and the one of a user, we propose a tailored similarity measure obtained by adapting to this context some general measures provided in the past. Finally, we test our approach on a dataset of Ethereum transactions.

Findings

We define a social network-based model to represent Ethereum. We also define a spectrum for a user and a class of users (i.e., token contract, exchange, bancor and uniswap), consisting of suitable multivariate time series. Furthermore, we propose an approach to classify new users. The core of this approach is a metric capable of measuring the similarity degree between the spectrum of a user and the one of a class of users. This metric is obtained by adapting the Eros distance (i.e., Extended Frobenius Norm) to this scenario.

Originality/value

This paper introduces the concept of spectrum of a user and a class of users, which is new for blockchains. Differently from past models, which represented user behavior by means of univariate time series, the user spectrum here proposed exploits multivariate time series. Moreover, this paper shows that the original Eros distance does not return satisfactory results when applied to user and class spectra, and proposes a modified version of it, tailored to the reference scenario, which reaches a very high accuracy. Finally, it adopts spectra and the modified Eros distance to classify Ethereum users based on their past behavior. Currently, no multi-class automatic classification approach tailored to Ethereum exists yet, albeit some single-class ones have been recently proposed. Therefore, the only way to classify users in Ethereum are online services (e.g., Etherscan), where users are classified after a request from them. However, the fraction of users thus classified is low. To address this issue, we present an automatic approach for a multi-class classification of Ethereum users based on their past behavior.
Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock
Authors: Dyer Wayne B. , Simonova Gabriela , Chiaretti Sara , Bouquet Mahe , Wellburn Rebecca , Heinsar Silver , Ainola Carmen , Wildi Karin , Sato Kei , Livingstone Samantha , Suen Jacky Y. , Irving David O. , Tung John-Paul , li Bassi Gianluigi , Fraser John F.
Published: April 2022

Background

Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.

Methods

A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.

Results

Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034).

Conclusions

Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.
Investigation of enzymatic hydrolysis kinetics of soy protein isolate: laboratory and semi-industrial scale
Authors: Pozdnyakov Nikita , Shilov Sergey , Lukin Alexander , Bolshakov Maxim , Sogorin Evgeny
Published: April 2022

Using parameters of optimal conditions from laboratory experiments often results in the loss of significant time and resources when trying to scale up the process. In this study, the comparison of results of laboratory and semi-industrial experiments of enzymatic hydrolysis of soy protein isolate is considered. The kinetics of peptides accumulation was investigated by colorimetric method in both microtube (volume reaction is 0.7 ml, 7.14 mg/ml of substrate, incubation in solid state thermostat) and industrial homogenizer (volume reaction is 4,000 ml, 100 mg/ml of substrate, rotor–stator type mixer). The enzyme preparation Protosubtilin G3x (main component is subtilisin) was used as an analogue of the Alcalase preparation, which is already widely used in the food industry. It was found that the pH and the number of proteolytic units in the reaction mixture of both scales had slightly different results of the kinetics, while the temperature showed significantly one. The laboratory scale of the reaction had a wide range of optimal temperature (40–60 $$^{\circ }$$

∘

C, 30 $$^{\circ }$$

∘

C showed slowest rate of kinetics reaction), whereas the semi-industrial scale had 50 $$^{\circ }$$

∘

C of optimal temperature (30, 40, 60 $$^{\circ }$$

∘

C had the same kinetics). It also was found that maintaining the pH value of the reaction mixture was not mandatory. The obtained results indicate the need to refine the process conditions using semi-industrial experiments before attracting industrial-scale resources. In the case of selection of conditions for the hydrolysis of soy protein isolate in production, it is necessary first of all to take into account the reaction temperature as the most irreproducible parameter when scaling.

Graphical Abstract
Directed evolution driving the generation of an efficient keratinase variant to facilitate the feather degradation
Authors: Zhang Jing , Su Chang , Kong Xiao-Li , Gong Jin-Song , Liu Yan-Lin , Li Heng , Qin Jiufu , Xu Zheng-Hong , Shi Jin-Song
Published: April 2022

Keratinases can specifically degrade keratins, which widely exist in hair, horns, claws and human skin. There is a great interest in developing keratinase to manage keratin waste generated by the poultry industry and reusing keratin products in agriculture, medical treatment and feed industries. Degradation of keratin waste by keratinase is more environmentally friendly and more sustainable compared with chemical and physical methods. However, the wild-type keratinase-producing strains usually cannot meet the requirements of industrial production, and some are pathogenic, limiting their development and utilization. The main purpose of this study is to improve the catalytic performance of keratinase via directed evolution technology for the degradation of feathers. We first constructed a mutant library through error-prone PCR and screened variants with enhanced enzyme activity. The keratinase activity was further improved through fermentation conditions optimization and fed-batch strategies in a 7-L bioreactor. As a result, nine mutants with enhanced activity were identified and the highest enzyme activity was improved from 1150 to 8448 U/mL finally. The mutant achieved efficient biodegradation of feathers, increasing the degradation rate from 49 to 88%. Moreover, a large number of amino acids and soluble peptides were obtained as degradation products, which were excellent protein resources to feed. Therefore, the study provided a keratinase mutant with application potential in the management of feather waste and preparation of protein feed additive.

Graphical Abstract
Identification and characterization of immunomodulatory peptides from pepsin–soy protein hydrolysates
Authors: Hsieh Lu-Sheng , Lu Ming-Shing , Chiang Wen-Dee
Published: April 2022

To obtain immunomodulatory peptides from isolated soy protein (ISP), pepsin was selected to prepare hydrolysates and 4-h treatment (Pepsin-ISPH4h) showed the highest yield and immunomodulatory activities. The Pepsin-ISPH4h was sequentially fractionated by 30, 10 and 1-kDa molecular weight cut-off (MWCO) membranes, in which 1-kDa MWCO permeate (1P) exhibited the most significant enhancement of phagocytosis activity without causing excessive inflammation as compared with Pepsin-ISPH4h. To further purify and enhance the immunomodulatory activity, 1P was distinct by high-performance liquid chromatography equipped with a reverse-phase column and in vivo immunomodulatory activity of fractions was examined in mice. Fraction 1 (F1) significantly elevated phagocytosis activity of mice spleen macrophages and neutrophils. However, increase of phagocytosis activity did not result from the induction of macrophages M1 or M2 polarization. The immunomodulatory peptide sequence, EKPQQQSSRRGS, from F1 was identified by LC–MS/MS. Phagocytosis activity and macrophage M1 polarization were elevated by synthetic peptide treatment. Hence, our results indicated that isolated soy protein hydrolysates prepared by pepsin could provide a source of peptides with immunomodulatory effects.

Graphical Abstract
Cytochrome C catalyzed oxygen tolerant atom-transfer radical polymerization
Authors: Xie Peng-Cheng , Guo Xue-Qing , Yang Fu-Qiao , Xu Nuo , Chen Yuan-Yuan , Wang Xing-Qiang , Wang Hongcheng , Yong Yang-Chun
Published: April 2022

Atom-transfer radical polymerization (ATRP) is a well-known technique for controlled polymer synthesis. However, the ATRP usually employed toxic heavy metal ionas as the catalyst and was susceptible to molecular oxygen, which made it should be conducted under strictly anoxic condition. Conducting ATRP under ambient and biocompatible conditions is the major challenge. In this study, cytochrome C was explored as an efficient biocatalyst for ATRP under biocompatible conditions. The cytochrome C catalyzed ATRP showed a relatively low polymer dispersity index of 1.19. More interestingly, the cytochrome C catalyzed ATRP showed superior oxygen resistance as it could be performed under aerobic conditions with high dissolved oxygen level. Further analysis suggested that the Fe(II) embed in the cytochrome C might serve as the catalytic center and methyl radical was responsible for the ATRP catalysis. This work explored new biocompatible catalyst for aerobic ATRP, which might open new dimension for practical ATRP and application of cytochrome C protein.

Graphical Abstract
Dynamic contrast-enhanced MRI radiomics nomogram for predicting axillary lymph node metastasis in breast cancer
Authors: Song Deling , Yang Fei , Zhang Yujiao , Guo Yazhe , Qu Yingwu , Zhang Xiaochen , Zhu Yuexiang , Cui Shujun
Published: April 2022

Purpose

The goal of this study is to develop and validate a radiomics nomogram integrating the radiomics features from DCE-MRI and clinical factors for the preoperative diagnosis of axillary lymph node (ALN) metastasis in breast cancer patients.

Procedures

A total of 432 patients with breast cancer were enrolled in this retrospective study and divided into a training cohort (n = 296) and a validation cohort (n = 136). Radiomics features were extracted from the second phase of dynamic contrast enhanced (DCE) MRI images. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen optimal features and construct a radiomics signature in the training cohort. Multivariable logistic regression analysis was used to establish a radiomics nomogram model based on the radiomics signature and clinical factors. The predictive performance of the nomogram was quantified with respect to discrimination and calibration, which was further evaluated in the independent validation cohort.

Results

Fourteen ALN metastasis-related features were selected to construct the radiomics signature, with an area under the curve (AUC) of 0.847 and 0.805 in the training and validation cohorts, respectively. The nomogram was established by incorporating the histological grade, multifocality, MRI report lymph node status and radiomics signature and showed good calibration and excellent performance for ALN detection (AUC of 0.907 and 0.874 in the training and validation cohorts, respectively). The decision curve, which demonstrated the radiomics nomogram, displayed promising clinical utility.

Conclusions

The radiomics nomogram can be used as a noninvasive and reliable tool to assist clinicians in accurately predicting ALN metastasis in breast cancer preoperatively.
Hybrid kernelised expectation maximisation for Bremsstrahlung SPECT reconstruction in SIRT with 90Y micro-spheres
Authors: Deidda Daniel , Denis-Bacelar Ana M. , Fenwick Andrew J. , Ferreira Kelley M. , Heetun Warda , Hutton Brian F. , Robinson Andrew P. , Scuffham James , Thielemans Kris
Published: April 2022

Background

Selective internal radiation therapy with Yttrium-90 microspheres is an effective therapy for liver cancer and liver metastases. Yttrium-90 is mainly a high-energy beta particle emitter. These beta particles emit Bremsstrahlung radiation during their interaction with tissue making post-therapy imaging of the radioactivity distribution feasible. Nevertheless, image quality and quantification is difficult due to the continuous energy spectrum which makes resolution modelling, attenuation and scatter estimation challenging and therefore the dosimetry quantification is inaccurate. As a consequence a reconstruction algorithm able to improve resolution could be beneficial.

Methods

In this study, the hybrid kernelised expectation maximisation (HKEM) is used to improve resolution and contrast and reduce noise, in addition a modified HKEM called frozen HKEM (FHKEM) is investigated to further reduce noise. The iterative part of the FHKEM kernel was frozen at the 72nd sub-iteration. When using ordered subsets algorithms the data is divided in smaller subsets and the smallest algorithm iterative step is called sub-iteration. A NEMA phantom with spherical inserts was used for the optimisation and validation of the algorithm, and data from 5 patients treated with Selective internal radiation therapy were used as proof of clinical relevance of the method.

Results

The results suggest a maximum improvement of 56% for region of interest mean recovery coefficient at fixed coefficient of variation and better identification of the hot volumes in the NEMA phantom. Similar improvements were achieved with patient data, showing 47% mean value improvement over the gold standard used in hospitals.

Conclusions

Such quantitative improvements could facilitate improved dosimetry calculations with SPECT when treating patients with Selective internal radiation therapy, as well as provide a more visible position of the cancerous lesions in the liver.
A community-based survey to assess risk for one health challenges in rural Philippines using a mobile application
Authors: Kim Tae Youn , Baldrias Loinda , Papageorgiou Sophia , Aguilar Edna , Tee Michael , Kelly Terra , Hill Jim , Wilkes Michael
Published: April 2022

Background

Recent emerging and re-emerging diseases in animals and humans show the vulnerability of humans, animals, and crops to disease outbreaks and the large potential impact on health, food security, and economies worldwide. A technology-enabled One Health (OH) surveillance program offers an opportunity for early detection and response as well as prevention of disease outbreaks in resource-limited settings. As an initial step toward developing the surveillance program, we aimed to identify at-risk groups of households for potential shared health challenges at the human-animal-environmental interface in a rural community of the Philippines.

Methods

A cross-sectional household survey was conducted in the municipality of Los Baños in proximity (63 kilometers south) to Metro Manila by enumerators living in the same community. Twenty-four enumerators conducted household interviews asking a) household characteristics including ownership of animals and crops; b) awareness, beliefs and knowledge about OH; c) family-level health practices related to sanitation, hygiene, and food safety; and d) risk factors for potential OH issues. All data collection and transferring process were streamlined using a mobile application.

Results

Of 6,055 participating households, 68% reported having one or more of gardens, farms, and animals for various reasons. While only 2% of the households have heard about OH, 97% believed they can get disease from animals, plants or the environment. A latent class analysis with nine risk factors for potential OH issues suggested that 46% of the households were at moderate to high risk for exposure to zoonotic pathogens and environmental contaminants.

Conclusion

Our findings indicate that there are unaddressed threats to human, animal, and plant health. Given the importance of the interconnections between the health of humans, animals, and plants, further evaluations of the at-risk households would be necessary to mitigate potential shared health threats in the community. Further, our study demonstrates that mHealth technology can provide an opportunity to systematically assess potential one health problems in the rural communities with limited internet connection.
Student interest, concerns, and information-seeking behaviors related to COVID-19
Authors: Elsner Jamie N. , Sadler Troy D. , Zangori Laura , Friedrichsen Patricia J. , Ke Li
Published: April 2022

COVID-19 creates an opportunity for science classrooms to relate content about viruses to students’ personal experiences with the pandemic. Previous researchers have shown that students are interested in crisis situations like disease outbreaks; however, they primarily acquire information about these events through internet sources which are often biased. We argue that it is important to understand student interest, concerns, and information-seeking behaviors related to COVID-19 to support science classroom learning and engagement about the virus and other potential outbreaks. We surveyed 224 high school students and analyzed their responses to six open-ended questions. We found that students expressed the most interest in topics related to the origin of COVID-19 and vaccines. Their greatest concerns included contracting the virus or someone they know contracting the virus and vaccine distribution. Of our sample, only 6.7% reported using their teachers as their source of COVID-19 information. Science classrooms have the potential to pique students’ situational interest by discussing COVID-19 topics that are important to students, which can increase their academic performance, content knowledge, attention, and engagement in learning about viruses. Moreover, classroom instruction about COVID-19 by teachers has shown to alleviate students’ stress and anxiety. We provide key areas of student interest about COVID-19 to help educators address students’ questions and improve curricular resources on viral pandemics.
Obesity and male infertility: multifaceted reproductive disruption
Authors: Chaudhuri Gargi Ray , Das Arnab , Kesh Swaraj Bandhu , Bhattacharya Koushik , Dutta Sulagna , Sengupta Pallav , Syamal Alak Kumar
Published: April 2022

Background

The global prevalence of obesity has soared to a concerning height in the past few decades. Interestingly, the global decline in semen quality is a parallel occurrence that urges researchers to evaluate if obesity is among the most essential causatives of male infertility or subfertility.

Main body

Obesity may alter the synchronized working of the reproductive-endocrine milieu, mainly the hypothalamic-pituitary-gonadal (HPG) axis along with its crosstalks with other reproductive hormones. Obesity-mediated impairment in semen parameters may include several intermediate factors, which include physical factors, essentially increased scrotal temperature due to heavy adipose tissue deposits, and systemic inflammation and oxidative stress (OS) initiated by various adipose tissue-derived pro-inflammatory mediators. Obesity, via its multifaceted mechanisms, may modulate sperm genetic and epigenetic conformation, which severely disrupt sperm functions. Paternal obesity reportedly has significant adverse effects upon the outcome of assisted reproductive techniques (ARTs) and the overall health of offspring. Given the complexity of the underlying mechanisms and rapid emergence of new evidence-based hypotheses, the concept of obesity-mediated male infertility needs timely updates and pristine understanding.

Conclusions

The present review comprehensively explains the possible obesity-mediated mechanisms, especially via physical factors, OS induction, endocrine modulation, immune alterations, and genetic and epigenetic changes, which may culminate in perturbed spermatogenesis, disrupted sperm DNA integrity, compromised sperm functions, and diminished semen quality, leading to impaired male reproductive functions.
Partial splenic artery embolization (PSE) in a patient with grey platelet syndrome (GPS): a case report
Authors: Zaitoun Mohamed M. A. , Abdullah Rania Mohammad , Zaitoun Nahla A. , Shahin Shahenda , Basha Mohammad Abd Alkhalik
Published: April 2022

Background

Grey platelet syndrome (GPS) is a rare cause of mild-to-severe bleeding. Up till now, there has been no definite treatment for GPS.

Case presentation

We reported a case diagnosed as GPS and presented with menorrhagia, metrorrhagia, gingival bleeding, and left hypochondrial pain. The platelet count was 18 thousand/cmm. Ultrasound splenic diameter was 22.0 cm. The multidisciplinary team decided to perform splenectomy; however, the patient was unfit for surgery. Partial splenic artery embolization (PSE) was performed. Follow-up after 24 months showed a normal menstrual cycle and absent pain. Platelet count rise to 70, 55, and 51 thousand/cmm after 1, 12, and 24 months, respectively. Splenic diameter showed a significant decrease to 11.2 cm after 24 months.

Conclusion

PSE is effective and safe in symptomatic patients with GPS.
Spontaneous perforation of common hepatic duct: an intraoperative surprise
Authors: Kerkeni Y. , Thamri F. , Zouaoui A. , Aziza B. , Jouini R.
Published: April 2022

Background

Pediatric spontaneous bile duct perforation is one of the rare causes of acute abdomen in infants. With a highly variable presentation, diagnosis and treatment can prove challenging. We report a case of spontaneous common hepatic duct perforation mistaken for appendicular peritonitis.

Case presentation

An otherwise healthy 3-year-old boy presented to the emergency department with complaints of abdominal pain, distention, bilious vomiting, and fever evolving for 4 days. Preoperative ultrasound was suggestive of appendicular peritonitis. Laparotomy revealed abundant biliary fluid, a distended gallbladder with thickened and inflammatory wall, and a macroscopically normal appendix. Intraoperative cholangiography showed a leak of contrast from the anterior wall of the common hepatic duct, 2–3 mm below the upper biliary confluence and 2 cm above the junction of the cystic duct to the common hepatic duct. A cholecystostomy was performed, and two external intraabdominal drains were placed. A retrograde cholangiogram was performed on postoperative day 21 showing no extravasation of contrast product. The patient was discharged on postoperative day 25.

Conclusion

Spontaneous perforation of the common hepatic duct is a rare phenomenon. It should be considered as a differential diagnosis in pediatric patients that present with unexplained peritonitis. The optimal method of diagnosis and management remains controversial.
Recent advances in the psychopharmacology of major depressive disorder
Authors: Alexander Laith , Young Allan H.
Published: April 2022

This review highlights some of the recent advances in the psychopharmacology of major depressive disorder (MDD). We synthesise evidence on emerging pharmacological therapies targeting the serotonergic system, before exploring several novel treatment targets: the glutamatergic system, the GABAergic system and inflammation. When describing new treatment avenues, we examine the evidence base and how far these new treatments are from routine practice.
The impact of shielding during the COVID-19 pandemic on mental health: evidence from the English Longitudinal Study of Ageing
Authors: Di Gessa Giorgio , Price Debora
Published: April 2022

Background

During the COVID-19 pandemic, older and clinically vulnerable people were instructed to shield or stay at home. Policies restricting social contact and human interaction pose a risk to mental health, but we know very little about the impact of shielding and stay-at-home orders on the mental health of older people.

Aims

To understand the extent to which shielding contributes to poorer mental health.

Method

We used longitudinal data from wave 9 (2018/2019) and two COVID-19 sub-studies (June/July 2020; November/December 2020) of the English Longitudinal Study of Ageing, and constructed logistic and linear regression models to investigate associations between patterns of shielding during the pandemic and mental health, controlling for sociodemographic characteristics, pre-pandemic physical and mental health, and social isolation measures.

Results

By December 2020, 70% of older people were still shielding or staying at home, with 5% shielding throughout the first 9 months of the pandemic. Respondents who shielded experienced worse mental health. Although prior characteristics and lack of social interactions explain some of this association, even controlling for all covariates, those shielding throughout had higher odds of reporting elevated depressive symptoms (odds ratio 1.87, 95% CI 1.22–2.87) and lower quality of life (β = −1.28, 95% CI −2.04 to −0.52) than those who neither shielded nor stayed at home. Shielding was also associated with increased anxiety.

Conclusions

Shielding seems associated with worse mental health among older people, highlighting the need for policy makers to address the mental health needs of those who shielded, both in the current pandemic and for the future.