Miracle-dz/UniFAR-FTUs huggingface dataset:
Rhein Relieves Oxidative Stress in an Aβ1-42 Oligomer-Burdened Neuron Model by Activating the SIRT1/PGC-1α-Regulated Mitochondrial Biogenesis

Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.
Age at Disease Onset Associates With Oxidative Stress, Neuroinflammation, and Impaired Synaptic Plasticity in Relapsing-Remitting Multiple Sclerosis

Age at onset is the main risk factor for disease progression in patients with relapsing-remitting multiple sclerosis (RR-MS). In this cross-sectional study, we explored whether older age is associated with specific disease features involved in the progression independent of relapse activity (PIRA). In 266 patients with RR-MS, the associations between age at onset, clinical characteristics, cerebrospinal fluid (CSF) levels of lactate, and that of several inflammatory molecules were analyzed. The long-term potentiation (LTP)-like plasticity was studied using transcranial magnetic stimulation (TMS). Older age was associated with a reduced prevalence of both clinical and radiological focal inflammatory disease activity. Older patients showed also increased CSF levels of lactate and that of the pro-inflammatory molecules monocyte chemoattractant protein 1 (MCP-1)/CCL2, macrophage inflammatory protein 1-alpha (MIP-1α)/CCL3, and interleukin (IL)-8. Finally, TMS evidenced a negative correlation between age and LTP-like plasticity. In newly diagnosed RR-MS, older age at onset is associated with reduced acute disease activity, increased oxidative stress, enhanced central inflammation, and altered synaptic plasticity. Independently of their age, patients with multiple sclerosis (MS) showing similar clinical, immunological, and neurophysiological characteristics may represent ideal candidates for early treatments effective against PIRA.
Different Responses of Soil Bacterial Communities to Nitrogen Addition in Moss Crust

Bacterial communities in soil serve an important role in controlling terrestrial biogeochemical cycles and ecosystem processes. Increased nitrogen (N) deposition in Northwest China is generating quantifiable changes in many elements of the desert environment, but the impacts of N deposition, as well as seasonal variations, on soil bacterial community composition and structure are poorly understood. We used high-throughput sequencing of bacterial 16S rRNA genes from Gurbantünggüt Desert moss crust soils to study the impacts of N addition on soil bacterial communities in March, May, and November. In November, we discovered that the OTU richness and diversity of soil bacterial community dropped linearly with increasing N input. In November and March, the diversity of the soil bacterial community decreased significantly in the medium-N and high-N treatments. In May, N addition caused a substantial change in the makeup of the soil bacterial composition, while the impacts were far less apparent in November and March. Furthermore, the relative abundance of major bacterial phyla reacted non-linearly to N addition, with high-N additions decreasing the relative richness of Proteobacteria, Bacteroidetes, and Acidobacteria while increasing the relative abundance of Actinobacteria and Chloroflexi. We also discovered that seasonality, as characterized by changes in soil moisture, pH, SOC, and AK content, had a significant impact on soil bacterial communities. Significant variations in the makeup of the community were discovered at the phylum and genus levels throughout the various months. In May, the variety of soil bacterial community was at its peak. Further investigation showed that the decrease in soil bacterial diversity was mostly attributed to a drop in soil pH. These results indicated that the impact of N deposition on the soil bacterial community was seasonally dependent, suggesting that future research should evaluate more than one sample season at the same time.
Training Set Optimization for Sparse Phenotyping in Genomic Selection: A Conceptual Overview

Genomic selection (GS) is becoming an essential tool in breeding programs due to its role in increasing genetic gain per unit time. The design of the training set (TRS) in GS is one of the key steps in the implementation of GS in plant and animal breeding programs mainly because (i) TRS optimization is critical for the efficiency and effectiveness of GS, (ii) breeders test genotypes in multi-year and multi-location trials to select the best-performing ones. In this framework, TRS optimization can help to decrease the number of genotypes to be tested and, therefore, reduce phenotyping cost and time, and (iii) we can obtain better prediction accuracies from optimally selected TRS than an arbitrary TRS. Here, we concentrate the efforts on reviewing the lessons learned from TRS optimization studies and their impact on crop breeding and discuss important features for the success of TRS optimization under different scenarios. In this article, we review the lessons learned from training population optimization in plants and the major challenges associated with the optimization of GS including population size, the relationship between training and test set (TS), update of TRS, and the use of different packages and algorithms for TRS implementation in GS. Finally, we describe general guidelines to improving the rate of genetic improvement by maximizing the use of the TRS optimization in the GS framework.
Ultrasound-Assisted Production of Xylo-Oligosaccharides From Alkali-Solubilized Corncob Bran Using Penicillium janthinellum XAF01 Acidic Xylanase

A novel treatment involving enzymatic hydrolysis using an acidic xylanase coupled with ultrasound was performed to improve the xylo-oligosaccharides (XOS) yield from corncob bran. The acidic xylanase (XynB) was purified to a most suitable pH, temperature, and operational parameters for ultrasound-assisted hydrolysis were determined. A preliminary mechanistic investigation was performed through circular dichroism (CD) spectroscopy, scanning electron microscope (SEM) and a laser particle size analyzer, and the effects of ultrasound on enzyme (XynB) and substrate (corncob bran) were assessed. The results show that the maximum XOS yield was 20.71% when the reaction pH and temperature were 4.3 and 50°C, the ultrasonic parameters were 50 kHz and 0.40 W/cm2, which was 2.55 fold higher than that obtained using a non-ultrasound-assisted enzymatic preparation. Mechanism studies indicated that ultrasonic pretreatment could reduce the β-fold content and increase the random coil content. Changes in structure and size of substrate were observed. The specific surface area of the XAC molecules is easy to carry out enzymatic reaction, which is beneficial to the production of XOS.
Salvage Reirradiation Options for Locally Recurrent Prostate Cancer: A Systematic Review

Background Reirradiation using brachytherapy (BT) and external beam radiation therapy (EBRT) are salvage strategies with locally radiorecurrent prostate cancer. This systematic review describes the oncologic and toxicity outcomes for salvage BT and EBRT [including Stereotactic Body Radiation Therapy (SBRT)]. Methods An International Prospective Register of Systematic Reviews (PROSPERO) registered (#211875) study was conducted using Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. EMBASE and MEDLINE databases were searched from inception to December 2020. For BT, both low dose rate (LDR) and high dose rate (HDR) BT techniques were included. Two authors independently assessed study quality using the 18-item Modified Delphi technique. Results A total of 39 eligible studies comprising 1967 patients were included (28 BT and 11 SBRT). In 35 studies (90%), the design was single centre and/or retrospective and no randomised prospective studies were found. Twelve BT studies used LDR only, 11 HDR only, 4 LDR or HDR and 1 pulsed-dose rate only. All EBRT studies used SBRT exclusively, four with Cyberknife alone and 7 using both Cyberknife and conventional linear accelerator treatments. Median (range) modified Delphi quality score was 15 (6-18). Median (range) follow-up was 47.5 months (13-108) (BT) and 25.4 months (21-44) (SBRT). For the LDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 71% (48-89.5) and 52.5% (20-79). For the HDR-BT studies, the median (range) 2-year and 5-year bRFS rates were 74% (63-89) and 51% (45-65). For the SBRT studies, the median (range) 2-year bRFS for the SBRT group was 54.9% (40-80). Mean (range) acute and late grade≥3 GU toxicity rates for LDR-BT/HDR-BT/SBRT were 7.4%(0-14)/2%(0-14)/2.7%(0-8.7) and 13.6%(0-30)/7.9%(0-21.3%)/2.7%(0-8%). Mean (range) acute and late grade≥3 GI toxicity rates for LDR-BT/HDR-BT/SBRT were 6.5%(0-19)/0%/0.5%(0-4%) and 6.4%(0-20)/0.1%(0-0.9)/0.2%(0-1.5). One third of studies included Patient Reported Outcome Measures (PROMs). Conclusions Salvage reirradiation of radiorecurrent prostate cancer using HDR-BT or SBRT provides similar biochemical control and acceptable late toxicity. Salvage LDR-BT is associated with higher late GU/GI toxicity. Challenges exist in comparing BT and SBRT from inconsistencies in reporting with missing data, and prospective randomised trials are needed.
MRI-Based Radiomics Nomogram for Selecting Ovarian Preservation Treatment in Patients With Early-Stage Endometrial Cancer

Background Ovarian preservation treatment (OPT) was recommended in young women with early-stage endometrial cancer [superficial myometrial invasion (MI) and grades (G) 1/2-endometrioid adenocarcinoma (EEC)]. A radiomics nomogram was developed to assist radiologists in assessing the depth of MI and in selecting eligible patients for OPT. Methods From February 2014 to May 2021, 209 G 1/2-EEC patients younger than 45 years (mean 39 ± 4.3 years) were included. Of them, 104 retrospective patients were enrolled in the primary group, and 105 prospective patients were enrolled in the validation group. The radiomics features were extracted based on multi-parametric magnetic resonance imaging, and the least absolute shrinkage and selection operator algorithm was applied to reduce the dimensionality of the data and select the radiomics features that correlated with the depth of MI in G 1/2-EEC patients. A radiomics nomogram for evaluating the depth of MI was developed by combing the selected radiomics features with the cancer antigen 125 and tumor size. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the radiomics nomogram and of radiologists without and with the aid of the radiomics nomogram. The net reclassification index (NRI) and total integrated discrimination index (IDI) based on the total included patients to assess the clinical benefit of radiologists with the radiomics nomogram were calculated. Results In the primary group, for evaluating the depth of MI, the AUCs were 0.96 for the radiomics nomogram; 0.80 and 0.86 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.98 and 0.98 for radiologists 1 and 2 with the aid of the nomogram, respectively. In the validation group, the AUCs were 0.88 for the radiomics nomogram; 0.82 and 0.83 for radiologists 1 and 2 without the aid of the nomogram, respectively; and 0.94 and 0.94 for radiologists 1 and 2 with the aid of the nomogram, respectively. The yielded NRI and IDI values were 0.29 and 0.43 for radiologist 1 and 0.23 and 0.37 for radiologist 2, respectively. Conclusions The radiomics nomogram outperformed radiologists and could help radiologists in assessing the depth of MI and selecting eligible OPTs in G 1/2-EEC patients.
CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.
Design, Implementation, and Evaluation of a Distance Learning Framework to Adapt to the Changing Landscape of Anatomy Instruction in Medical Education During COVID-19 Pandemic: A Proof-of-Concept Study

This study presents the design of a DL-framework to deliver anatomy teaching that provides a microfiche of the onsite anatomy learning experience during the mandated COVID-19 lockdown. First, using nominal-group technique, we identified the DL learning theories to be employed in blueprinting the DL-framework. Effectiveness of the designed DL-framework in anatomy teaching was demonstrated using the exemplar of the Head and Neck (H&N) course during COVID-19 lockdown, in the pre-clerkship curriculum at our medical school. The dissemination of the DL-framework in the anatomy course was informed by the Analyse, Design, Develop, Implement, and Evaluate (ADDIE) model. The efficiency of the DL-framework was evaluated using the first two levels of Kirkpatrick's model. Versatility of the DL-framework was demonstrated by aligning its precepts with individual domains of key learning outcomes framework. The framework's blueprint was designed amalgamating principles of: Garrison's community inquiry, Siemens' connectivism and Harasim's online-collaborative-learning; and improved using Anderson's DL-model. Following the implementation of the DL-framework in the H&N course informed by ADDIE, the framework's efficiency was evaluated. In total, 70% students responded to the survey assessing perception toward DL (Kirkpatrick's Level: 1). Descriptive analysis of the survey results showed that the DL-framework was positively received by students and attested that students had an enriched learning experience, which promoted collaborative-learning and student-autonomy. For, Kirkpatrick's Level: 2 i.e., cognitive development, we compared the summative assessment performance in the H&N course across three cohort of students. The results show that the scores of the cohort, which experienced the course entirely through DL modality was statistically higher (P < 0.01) than both the other cohorts, indicating that shift to DL did not have an adverse effect on students' learning. Using Bourdieu's Theory of Practice, we showed that the DL-framework is an efficient pedagogical approach, pertinent for medical schools to adopt; and is versatile as it attests to the key domains of students' learning outcomes in the different learning outcomes framework. To our knowledge this is the first-study of its kind where a rationale and theory-guided approach has been availed not only to blueprint a DL framework, but also to implement it in the MBBS curriculum.
Interference Alignment Inspired Opportunistic Communications in Multi-Cluster MIMO Networks with Wireless Power Transfer

In this work, we jointly investigate the issues of node scheduling and transceiver design in a sensor network with multiple clusters, which is endowed with simultaneous wireless information and power transfer. In each cluster of the observed network, S out of N nodes are picked, each of which is capable of performing information transmission (IT) via uplink communications. As for the remaining idle nodes, they can harvest energy from radio-frequency signals around their ambient wireless environments. Aiming to boost the intra-cluster performance, we advocate an interference alignment enabled opportunistic communication (IAOC) scheme. This scheme can yield better tradeoffs between IT and wireless power transfer (WPT). With the aid of IAOC scheme, the signal projected onto the direction of the receive combining vector is adopted as the accurate measurement of effective signal strength, and then the high-efficiency scheduling metric for each node can be accordingly obtained. Additionally, an algorithm, based on alternative optimization and dedicated for transceiver design, is also put forward, which is able to promote the achievable sum rate performance as well as the total harvested power. Our simulation results verify the effectiveness of the designed IAOC scheme in terms of improving the performance of IT and WPT in multi-cluster scenarios.
Employee Well-Being and Digital Work during the COVID-19 Pandemic

The digitalisation of work is resulting in a transformation in the relationship between employees and employers as well as the perception of quality of life. Under the conditions of the COVID-19 pandemic, individuals whose work could be done with digital tools were directed to work remotely. Performing work duties at a distance from the workplace, colleagues, and supervisors affects the workplace resources available to employees and can have an impact on employee well-being. The main purpose of this paper is to analyse the relationship between remote working and employee well-being. The research hypothesis was that there is a relationship between employee well-being and the level of digitisation of work performed, as measured by the frequency of remote working. This article presents the results of empirical research conducted in January 2021, using the CAWI method, on a representative sample of Polish workers (n = 1000). An exploratory factor analysis and logistic regression were carried out. The results point to the three-dimensional nature of employee well-being, which includes workplace relationships, health, and work–life balance. Based on the results, working exclusively remotely was shown to negatively affect well-being in terms of workplace relationships and work–life balance. There was no statistically significant association between remote working and subjective health assessment. The results have important implications for the management of employee well-being in remote working settings. Originality/value lies in the fact that the article provides practical guidance in planning hybrid work arrangements.
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This review provides a comprehensive overview on the biomedical applications of electrical stimulation (EStim). EStim has a wide range of direct effects on both biomolecules and cells. These effects have been exploited to facilitate proliferation and functional development of engineered tissue constructs for regenerative medicine applications. They have also been tested or used in clinics for pain mitigation, muscle rehabilitation, the treatment of motor/consciousness disorders, wound healing, and drug delivery. However, the research on fundamental mechanism of cellular response to EStim has fell behind its applications, which has hindered the full exploitation of the clinical potential of EStim. Moreover, despite the positive outcome from the in vitro and animal studies testing the efficacy of EStim, existing clinical trials failed to establish strong, conclusive supports for the therapeutic efficacy of EStim for most of the clinical applications mentioned above. Two potential directions of future research to improve the clinical utility of EStim are presented, including the optimization and standardization of the stimulation protocol and the development of more tissue-matching devices. Footnote Abstract This review provides a comprehensive overview on the biomedical applications of electrical stimulation (EStim). EStim has a wide range of direct efects on both biomolecules and cells. These efects have been exploited to facilitate proliferation and functional development of engineered tissue constructs for regenerative medicine applications. They have also been tested or used in clinics for pain mitigation, muscle rehabilitation, the treatment of motor/consciousness disorders, wound healing, and drug delivery. However, the research on fundamental mechanism of cellular response to EStim has fell behind its applications, which has hindered the full exploitation of the clinical potential of EStim. Moreover, despite the positive outcome from the in vitro and animal studies testing the eicacy of EStim, existing clinical trials failed to establish strong, conclusive supports for the therapeutic eicacy of EStim for most of the clinical applications mentioned above. Two potential directions of future research to improve the clinical utility of EStim are presented, including the optimization and standardization of the stimulation protocol and the development of more tissue-matching devices.
Autotuning LLVM OptimizationPasses for Matrix Multiplication in Rust

The LLVM compiler framework transforms its Intermediate Representation (IR) to optimize code. These transformations are controlled by flags which interfere on metrics such as the execution time. Selecting flags to improve the execution time of a program is difficult, and requires expert knowledge. Autotuning methods can automate parts of this process and help understanding the underlying search spaces. This paper describes ongoing work, showing that LLVM flags can impact the execution time of a Rust matrix multiplication algorithm, and planning future autotuning experiments for flag selection.