Miracle-dz/UniFAR-FTUs huggingface dataset:
An In Silico Methodology That Facilitates Decision Making in the Engineering of Nanoscale Protein Materials

Under the need for new functional and biocompatible materials for biomedical applications, protein engineering allows the design of assemblable polypeptides, which, as convenient building blocks of supramolecular complexes, can be produced in recombinant cells by simple and scalable methodologies. However, the stability of such materials is often overlooked or disregarded, becoming a potential bottleneck in the development and viability of novel products. In this context, we propose a design strategy based on in silico tools to detect instability areas in protein materials and to facilitate the decision making in the rational mutagenesis aimed to increase their stability and solubility. As a case study, we demonstrate the potential of this methodology to improve the stability of a humanized scaffold protein (a domain of the human nidogen), with the ability to oligomerize into regular nanoparticles usable to deliver payload drugs to tumor cells. Several nidogen mutants suggested by the method showed important and measurable improvements in their structural stability while retaining the functionalities and production yields of the original protein. Then, we propose the procedure developed here as a cost-effective routine tool in the design and optimization of multimeric protein materials prior to any experimental testing.
The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal

Simple Summary An individualized treatment approach is necessary to improve survival and quality of life in rectal cancer. Tools to stratify patients are missing, but ctDNA seems to be a good candidate. Current results are sparse, conflicting and characterized by lack of a uniform approach. As the interpretation of results is dependent on the quality of reporting, we aimed to address this issue in our paper. Our results indicate an association between ctDNA status and outcome. In six out of nine papers, bias was low. However, a conclusion is dubious because of the heterogeneity among the studies and lack of standardized methods. Studies addressing these issues are warranted. Abstract The treatment of locally advanced rectal cancer (LARC) has evolved during the last decades, but recurrence remains a problem. Circulating tumor DNA (ctDNA) may result in an individualized treatment approach with improved survival and quality of life, but diverging results impede further development. In this systematic review, we addressed the quality of reporting and its impact on the interpretation of ctDNA results. We performed a systematic literature search using subject headings and search terms related to ctDNA and rectal cancer. The Quality of Prognostic Studies (QUIPS) tool was used to assess bias. Nine studies, with substantial heterogeneity, were included in the analysis. Three out of nine articles had moderate or high risk of bias. No association was found between treatment response and ctDNA status at baseline. There was a negative association between ctDNA positivity at baseline, before and after surgery and survival. The ctDNA status may be of importance to the long-term prognosis, but the area of research is new and is short of dedicated studies. There is an obvious need for standardization in ctDNA research, and the issue should be addressed in future research.
Antioxidant, Hypoglycemic and Molecular Docking Studies of Methanolic Extract, Fractions and Isolated Compounds from Aerial Parts of Cymbopogon citratus (DC.) Stapf

Traditionally, Cymbopogon citratus is used to treat a variety of ailments, including cough, indigestion, fever, and diabetes. The previous chemical and bioactive research on C. citratus mainly focused on its volatile oil. In this study, 20 non-volatile known compounds were isolated from the dried aerial part of C. citratus, and their structures were elucidated by MS, NMR spectroscopy, and comparison with the published spectroscopic data. Among them, 16 compounds were reported for the first time from this plant. The screening results for antioxidant and α-glucosidase inhibitory activities indicated that compounds caffeic acid (5), 1-O-p-coumaroyl-3-O-caffeoylglycerol (8), 1,3-O-dicaffeoylglycerol (9) and luteolin-7-O-β-D-glucopyranoside (12) had potent antioxidant capacities, with IC50 values from 7.28 to 14.81 μM, 1.70 to 2.15 mol Trolox/mol and 1.31 to 2.42 mol Trolox/mol for DPPH, ABTS, and FRAP, respectively. Meanwhile, compounds 8 and 9 also exhibited significant inhibitory activities against α-glucosidase, with IC50 values of 11.45 ± 1.82 μM and 5.46 ± 0.25 μM, respectively, which were reported for the first time for their α-glucosidase inhibitory activities. The molecular docking result provided a molecular comprehension of the interaction between compounds (8 and 9) and α-glucosidase. The significant antioxidant and α-glucosidase inhibitory activities of compounds 8 and 9 suggested that they could be developed into antidiabetic drugs because of their potential regulatory roles on oxidative stress and digestive enzyme.
Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process

Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft’s short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice.
Energy Balance Control for Improving Transient Performance of DC Bus Voltage in Power Electronic Transformer for the Voltage-Sensitive Loads

The power electronic transformer (PET), as a main topology for the energy router in the energy internet, consists of the rectifiers, the dual active bridge (DAB), and the inverter, and these three parts are connected by two dc buses. So, the performance of the dc bus voltages is very important because it can totally affect the output waveforms of the dc and ac voltage, especially for the voltage-sensitive loads. Compared with the proportion integration (PI) control scheme, the energy control method utilizes the energy as the control variable, and the control strategy derived from the energy relationship, including the passive elements and all the interfaces, is more direct and explicit. In this paper, considering the energy between the dc bus capacitors and the input inductor and the load and the source in the PET topology, the energy balance control (EBC) strategy is proposed. For the two dc bus voltages, the energy balance relationship of the different time scales is used to decouple the interaction in the control scheme. The EBC strategy can obviously reduce the fluctuation and the transient time of the two dc bus voltages when the load power or voltage reference is changed. Thus, under the limited voltage fluctuation, the EBC strategy can reduce the dc bus capacitance in order to reduce the volume and weight of the converter and enhance the reliability. The simulation and experimental results verify the effectiveness of the proposed control strategy.
The optimization of welding hardfacing on wear resistance of FC-25 grey cast iron steel substrate by response surface methodology (RSM)

This paper aimed to identify the optimal conditions for welding hardfacing by applying the Response Surface Methodology (RSM). The welding heat input, electrode type, and hardfacing layer on wear resistance of welding hardfacing were all optimized using the Box-Behnken experimental design. The findings revealed that these three variables had an impact on the volume loss of welding hardfacing. Because of the high coefficient of determination, the experimental data obtained were to a quadratic equation (96.90%). The ideal condition was determined using a 3D response surface plot and a contour map produced from mathematical models. The following were the ideal welding conditions: With a welding heat input of 1.58 J, a filler metal type of DFA2-600-B, and a third layer of hardfacing, the lower volume loss of the weld was 1.29 mm3.
Vitamin D Supplementation in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials

Randomized controlled trials (RCTs) have reported conflicting outcomes with the use of vitamin D in critically ill patients. With reporting of newer RCTs, we conducted this updated meta-analysis. Electronic databases were searched for RCTs comparing vitamin D with placebo in critically ill patients admitted to the intensive care unit (ICU). A random-effects meta-analysis was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI). Eleven RCTs with a total of 2,187 patients (vitamin D: n = 1,120; placebo: n = 1,067) were included. Vitamin D when compared to placebo was associated with the decreased duration of mechanical ventilation (SMD = -0.50; 95% CI = [-0.97, -0.03]; p = 0.04) and ICU stay (SMD = -0.60; 95% CI = [-1.03, -0.16]; p = 0.007) without any difference in the mortality (RR = 0.85; 95% CI = [0.68, 1.04]; p = 0.12) and length of hospital stay (SMD = -0.21; 95% CI = (-0.51, 0.09); p = 0.18]. Subgroup analysis showed that parenteral vitamin D may reduce the risk of mortality (RR = 0.54; 95% CI = [0.35, 0.83], p = 0.005). Vitamin D supplementation in critically ill patients decreases the duration of mechanical ventilation and ICU stay. Further studies should identify specific groups of patients who will derive the most benefit from vitamin D supplementation.
Rock engineering design — the importance of process, prediction of behaviour, choice of design criteria, review and consideration of risk

In this paper, a thorough design process is described briefly, highlighting the most important steps in the process. Several case studies are described illustrating non compliance with the design process, for the purpose of emphasising the critical steps in the process. The use of a risk approach in design is dealt with, showing that risk can be a satisfactory design criterion, and that identification of the consequences, and hence quantification of risk, can lead the way creation of value for a mining operation.
Reliability and Construct Validity on Undergraduate Geriatric Questionnaire

The number of elderly people in Malaysia is increasing in trend due to better healthcare services provided by the government and increased awareness of the community towards disease prevention. Therefore, the knowledge of future medical doctors towards geriatric care should be upgraded at par to fulfill the needs of the older population. As a result, their level of knowledge should be assessed, particularly in terms of the fundamental concept of geriatrics. A new, invented, reliable and valid questionnaire is needed. This study aimed to develop and validate a newly developed questionnaire to assess the knowledge of medical students in geriatrics. The 23 items consist of true-false questions and one-based answer responses based on five domains of Giant I’s geriatric, namely immobility, instability, incontinence, cognition, and iatrogenic. The sample size is calculated using a five-to-one item ratio. The questionnaires were distributed to 143 medical students. Reliability was determined using Cronbach’s alpha for internal consistency, while construct validity was assessed using factor analysis. An acceptable internal consistency was observed (Cronbach’s alpha = 0.62). Factor analysis showed two meaningful finalized components, which represent the geriatric general knowledge and the Giant I’s. According to the findings of this study, this questionnaire is a reliable and valid tool for assessing medical students' knowledge of geriatric. Keywords: Geriatric, Reliability, Construct Validity, Undergraduate Geriatric, Questionnaire
Factors related to survival time in dogs with pulmonary hypertension secondary to degenerative mitral valve disease stage C

ABSTRACT Pulmonary hypertension (PH) is a common complication in dogs with degenerative mitral valve disease (DMVD). The aim of this study was to determine the survival time and to determine factors related to the survival time of dogs with PH secondary to DMVD stage C. A retrospective study was conducted in 37 dogs with PH secondary to DMVD stage C to analyse the median survival time and associated factors such as age, sex, breed, body weight, the presence of syncope, heart rate, systolic blood pressure, manifestation of congestive heart failure (CHF), vertebral heart score (VHS), the presence of left or right heart enlargement, probability of PH and medication. Data were analysed using the Log-Rank test and plotted with the Kaplan-Meier curve. The results showed that the median survival time of dogs with PH secondary to DMVD stage C was 368 days, and factors that shortened the median survival time of dogs with PH secondary to DMVD stage C were mixed breeds, VHS > 11.5, the presence of right heart enlargement, ascites and high probability of PH. Factors associated with an increased hazard of death were mixed breed dogs, dogs with right heart enlargement and ascites. These findings may be useful for the prognosis and management of dogs with PH secondary to DMVD stage C.
Challenges and Support in Article Publication: Perspectives of Non-Native English Speaking Doctoral Students in a “Publish or No Degree” Context

Article publication as a requirement for graduation appears to be the most compelling challenge for doctoral candidates, especially for the non-English speaking ones. In order to contribute to this topic of growing interest, we aimed to investigate the key challenges to doctoral student research publication and develop an understanding of support they needed to ease the publication process. To this end, we conducted semi-structured interviews with 19 non-English speaking doctoral students in varied science and social science programs at an international university in north Cyprus. The findings revealed that the participants supported the “publish or no degree” policy as a condition for their graduation despite several challenges it created for them, such as lack of publication experience, weaknesses in the article composition, tough criteria of journals, and inadequate support from the instructors at the course phase. Peer-support community among the doctoral students lacked in the examined context and promoting it might yield positive results.
Continuing Professional Development (CPD) Practices Among Basic School Teachers in the Central Region of Ghana

This paper reports on an exploratory study regarding the current continuing professional development (CPD) situation of basic schoolteachers in Ghana. The study investigates the teachers’ CPD needs, frequency and nature of CPD provisions, and barriers to teachers’ participation in CPD activities. Using a cross-sectional survey involving 456 teachers, the study found that teachers required to be developed in areas of “ICT skills for teaching,” “research and dissemination,” and “teaching students with special learning needs. ” It was also revealed that the predominant CPD practices were workshops, in-service training, and continuing education. However, these practices were seldom provided and rarely met the development needs of the teachers. Teachers’ participation in CPD activities were also found to be minimal due to factors such as non-available CPD offerings, lack of pre-requisite information on CPD activities and lack of schools’ support. The study concludes that the current CPD situation of teachers in Ghana reflects a lack of implemented CPD policy framework. There is therefore the need for a broader CPD policy framework that will guide the provision, participation, and CPD practices of teachers in Ghana.
Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges

Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.
Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology

Selenium (Se) role in obesity is not clear. In addition, information on Se’s role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.
The Multiple Pharmacologic Functions and Mechanisms of Action of Guizhi Fuling Formulation

Objectives Guizhi Fuling Formulation (GZFL), a traditional Chinese medical formulation, consists of Cinnamomi Ramulus, Paeoniae Radix Alba (or Paeoniae Radix Rubra), Moutan Cortex, Persicae Semen, and Poria, with multiple therapeutic functions such as sedation, antitumor activity, anti-inflammation, and neuroprotection. However, its clinical applications remain relatively fragmented, and the underlying mechanisms of GZFL in different diseases are still not very certain. Further research and summary in both application and mechanisms remain to be needed for human health and the best use of GZFL. Therefore, we summarized the multiple pharmacologic effects and possible mechanisms of action of GZFL according to recent 17 years of research. Methods We retrieved four English and two Chinese databases using these keywords (the formulation name or its synonyms) and searched articles written in English from January 2006 up to February 2022. Key Findings. GZFL exhibits multiple pharmacologic advantages in gynecologic diseases and other expanding diseases such as cancer, blood, and vascular disease, renal failure, inflammation, and brain injury. Possibly due to its diverse bioactive components and pharmacologic activities, GZFL could target the multiple signaling pathways involved in regulating blood circulation, inflammatory and immune factors, proliferation, apoptosis, and so on. Conclusion This review suggests that GZFL displays promising therapeutic effects for many kinds of diseases, which have been beyond the scope of the original prescription for gynecologic diseases. In this way, we wish to provide a reference and recommendation for further preclinic and clinic studies.
Foliar Infiltration of Virus-Derived Small Hairpin RNAs Triggers the RNAi Mechanism against the Cucumber Mosaic Virus

Post-transcriptional gene silencing (PTGS) is an evolutionarily conserved plant defense mechanism against viruses. This paper aimed to evaluate a dsDNA construct (77 bp) as a template for in vitro production of virus-derived artificial small hairpin RNAs (shRNAs) and test for their potential to trigger the RNAi mechanism in Nicotiana benthamiana plants against CMV after their foliar infiltration. This approach allowed for the production of significant amounts of shRNAs (60-mers) quickly and easily. The gene silencing was confirmed using polymerase chain reaction (PCR), immunological-based assays, and real-time PCR (qPCR). The highest levels of gene silencing were recorded for mRNAs coding for replication protein (ORF1a), the viral suppressor of RNA silencing (ORF2b), and the capsid protein (ORF3b), with 98, 94, and 70% of total transcript silencing, respectively. This protocol provides an alternative to producing significant shRNAs that can effectively trigger the RNAi mechanism against CMV.
A Multi-Granular Aggregation-Enhanced Knowledge Graph Representation for Recommendation

Knowledge graph (KG) helps to improve the accuracy, diversity, and interpretability of a recommender systems. KG has been applied in recommendation systems, exploiting graph neural networks (GNNs), but most existing recommendation models based on GNNs ignore the influence of node types and the loss of information during aggregation. In this paper, we propose a new model, named A Multi-Granular Aggregation-Enhanced Knowledge Graph Representation for Recommendation (MAKR), that relieves the sparsity of the network and overcomes the limitation of information loss of the traditional GNN recommendation model. Specifically, we propose a new graph, named the Improved Collaborative Knowledge Graph (ICKG), that integrates user–item interaction and a knowledge graph into a huge heterogeneous network, divides the nodes in the heterogeneous network into three categories—users, items, and entities, and connects the edges according to the similarity between the users and items so as to enhance the high-order connectivity of the graph. In addition, we used attention mechanisms, the factorization machine (FM), and transformer (Trm) algorithms to aggregate messages from multi-granularity and different types to improve the representation ability of the model. The empirical results of three public benchmarks showed that MAKR outperformed state-of-the-art methods such as Neural FM, RippleNet, and KGAT.