Miracle-dz/UniFAR-FTUs huggingface dataset:
Carfilzomib: A Promising Proteasome Inhibitor for the Treatment of Relapsed and Refractory Multiple Myeloma

The proteasome is crucial for the degradation of intracellular proteins and plays an important role in mediating a number of cell survival and progression events by controlling the levels of key regulatory proteins such as cyclins and caspases in both normal and tumor cells. However, compared to normal cells, cancer cells are more dependent on the ubiquitin proteasome pathway (UPP) due to the accumulation of proteins in response to uncontrolled gene transcription, allowing proteasome to become a potent therapeutic target for human cancers such as multiple myeloma (MM). Up to date, three proteasome inhibitors namely bortezomib (2003), carfilzomib (2012) and ixazomib (2015) have been approved by the US Food and Drug Administration (FDA) for the treatment of patients with relapsed and/or refractory MM. This review mainly focuses on the biochemical properties, mechanism of action, toxicity profile and pivotal clinical trials related to carfilzomib, a second-generation proteasome inhibitor that binds irreversibly with proteasome to overcome the major toxicities and resistance associated with bortezomib.
Just Do It: High Intensity Physical Activity Preserves Mental and Physical Health in Elite and Non-elite Athletes During COVID-19

Background: The COVID-19 pandemic forced most Italian athletes to cease their regular training activities, with possible consequences on both mental and physical health. The present study aimed at assessing changes in Physical Activity (PA) from pre- to lockdown, and examining the relationships among lockdown PA, quality of life (mental and physical health), motivation to exercise, psychological distress, intolerance of uncertainty, and body dissatisfaction. Methods: A total of 204 athletes of different sports (91 elite; 110 females; mean age = 22.55, SD = 5.76) answered an online survey investigating demographics, sport-related questions, PA (IPAQ-S), quality of life (SF-12), and psychological variables (BREQ-2, DASS-21, IUS-R, and EDI-3-Body dissatisfaction subscale). Results: Both elite and non-elite athletes significantly reduced their PA intensity and volume (p < 0.001). Elite athletes did not differ from non-elite in terms of total PA intensity and hours of training during lockdown (p > 0.05). Elite and individual athletes showed higher intrinsic motivation to exercise compared to non-elite and team sports (p < 0.01). Female athletes displayed higher distress, worse mental health, and higher body dissatisfaction than males (p < 0.05). Mediation models showed that vigorous PA positively affected both mental (p < 0.05) and physical (p < 0.001) health during lockdown, independently of distress and intolerance of uncertainty. Conclusion: The COVID-19 lockdown was taxing for athletes, particularly professionals; those who were able to practice PA at high intensity during lockdown reported better mental and physical health.
Understanding Continuance Usage of Mobile Learning Applications: The Moderating Role of Habit

This study explored the factors that affect the intention of users to continue using mobile learning (m-learning) applications (apps). The influence of habit on user behavior toward information systems has been extensively discussed in the literature, but its role in the continuance of users when it comes to their usage of apps, especially m-learning apps, has rarely been reported. To obtain a comprehensive understanding of behaviors regarding the use of m-learning apps, this study constructed a theoretical research framework based on expectation confirmation theory and flow theory by considering habit as a moderating variable. Online questionnaires were administered to users of m-learning apps in Taiwan and data were analyzed through a structural equation modeling approach. The results indicated that the intention of users to continue using m-learning apps was influenced by satisfaction, perceived usefulness, and flow experience. Expectation confirmation affected user satisfaction and perceived usefulness. Differences existed in the intention to continue usage between users with strong and weak habits. In addition, perceived usefulness, expectation confirmation, and flow experience had direct and positive effects on satisfaction. The implications of these findings were discussed.
Phospholipases and Reactive Oxygen Species Derived Lipid Biomarkers in Healthy and Diseased Humans and Animals – A Focus on Lysophosphatidylcholine

Phospholipids (PL) are converted into lipid biomarkers by the action of phospholipases and reactive oxygen species (ROS), which are activated or released under certain physiological and pathophysiological conditions. Therefore, the in vivo concentration of such lipid biomarkers [e.g., lysophospholipids (LPLs)] is altered in humans and animals under different conditions such as inflammation, stress, medication, and nutrition. LPLs are particularly interesting because they are known to possess pro- and anti-inflammatory properties and may be generated by two different pathways: either by the influence of phospholipase A2 or by different reactive oxygen species that are generated in significant amounts under inflammatory conditions. Both lead to the cleavage of unsaturated acyl residues. This review provides a short summary of the mechanisms by which lipid biomarkers are generated under in vitro and in vivo conditions. The focus will be on lysophosphatidylcholine (LPC) because usually, this is the LPL species which occurs in the highest concentration and is, thus, easily detectable by chromatographic and spectroscopic methods. Finally, the effects of lipid biomarkers as signaling molecules and their roles in different human and animal pathologies such as infertility, cancer, atherosclerosis, and aging will be shortly discussed.
Evolving to a "lighter" software process: a case study

Many new development processes that characterize themselves as lightweight or agile have become fashionable, e.g. Extreme Programming (XP) (Beck, 2000; Cockburn, 2000; Rising and Janoff, 2000). Each of these processes is focused on maximizing the effectiveness of a small team of developers while anticipating changes in the development environment. These processes are mainly focused on the coding phase of the process and require strict adherence to the techniques set forth (Beck, 1999). Since most of these processes have at least some aspects that might seem radical to a more traditional process, e.g. pair programming (Williams et al., 2000), an issue arises of how to integrate a lightweight process into an existing development/maintenance effort without stalling the effort for retraining in the new techniques? How do we evolve a traditional process to a lighter one? This paper describes the experiences of a development effort within an organization of the United States government as it tried to evolve to a lighter process. The project was subjected to both organizational and technical changes that required the project to be able to adapt rapidly to new development landscapes.
Barrier Island Sediments Reveal Storm Surge and Fluvial Flood Events in the Past Centuries at Thua Thien Hue, Central Vietnam

Sedimentary evidence of storms and fluvial floods (FFs) is crucial for a better understanding of such events in coastal zones. In this study, we analyzed the sedimentary characteristics of the coastal storm and FF deposits at the Hoa Duan barrier, Thua Thien Hue, central Vietnam. Analyses of the sedimentary structures and properties (grain size distribution, composition, roundness, and sphericity) and loss on ignition revealed that the storm sediments were comprised of coarser grains with a low organic and carbonated content, and with sedimentary structures, including parallel and inclined landward lamination, multiple sets of normal and reverse grading, mud rip-up clasts, and sharp and erosional contacts (both top and bottom) with finer-grain layers. Conversely, the FF sediments had only fine to very fine grains, with dominant high organic and carbonate contents, and only exhibited sedimentary structures of sharp erosional top and bottom contacts with coarser-grained layers. The clearest differentiation to distinguish coastal storm layers from inland FF layers was obtained by plotting the mean grain size against the sorting. The results of optically stimulated luminescence dating suggested that two storm layers and one FF layer were deposited during the last 130 ± 10 years. Moreover, two layers were deposited by storms and one by a FF prior to that (>130 ± 10 years). The identification of the sedimentary diagnostic key of these two hazards can help to improve the understanding of the geomorphological evolution of the studied site and the other parts of this coastal region in order to remind the coastal community to prepare for future coastal hazards well.
Oyster Biodeposition Alleviates Sediment Nutrient Overload: A Case Study at Shenzhen Bay, China

Oysters are ecological engineers, and previous studies have examined their role as competent facilitators of ecological restoration. However, the decisive role of oysters in the aquatic environment is still debatable because oyster biodeposition (OBD) may also increase the nutrients enriched in sediments. In order to better interpret this problem, we sampled sediment cores from representative oyster culture areas and uncultured areas in Shenzhen Bay. The results have shown that the TOC (total organic carbon) and TN (total nitrogen) decreased significantly (p < 0.05) at the surface sediment layer (0–20-cm deep) and the sediment layer (20–40-cm deep) of the oyster site compared with the reference site. The decreased TOC and TN were also observed at 60- to 100-cm sediment depth in the oyster site. This indicated that the OBD significantly impacted the concentration of TOC and TN in the sediment. To confirm the alleviative role of OBD, we conducted stable isotope (δ13C and δ15N) analyses, which further demonstrated the presence of heavier and less lighter forms of organic carbon and nitrogen sediment. The surface sediment layer (0–20 cm) at the oyster site showed 8% more δ13C‰ compared with the control site (p < 0.05), reflecting the reduction in the TOC. In order to reveal the potential microbial mechanisms involved in OBD, we performed a functional analysis using the Geochip5 advanced microarray technology. Regarding carbon metabolism, we observed that genes (encoding pullulanase, glucoamylase, exoglucanase, cellobiase, and xylanase) involved in the degradation of relatively labile C-based molecules (e.g., starch, cellulose, and hemicellulose) were highly represented in an experimental area (p < 0.05). In addition, microbes in the experimental area exhibited a greater capacity for degrading recalcitrant C (e.g., lignin), which involves glyoxal oxidase (glx), manganese peroxidase (mnp), and phenol oxidase. Among the genes controlling nitrogen metabolism, the genes involved in denitrification, assimilation, ammonification, and nitrification were differentially expressed compared with the control area. These results indicated that microbial metabolic roles might have enhanced the C/N-flux speed and reduced the overall nutrient status. We concluded that OBD alleviates sediment nutrient overload under oyster farming from a microbial ecological perspective in a rapidly urbanized coastal area. Graphical Abstract
Families Affected by Parental Cancer: Quality of Life, Impact on Children and Psychosocial Care Needs

Parental cancer poses major challenges for families with minor children. Due to diagnosis and treatment family life is disrupted. To prevent long-term consequences in all family members and to design needs-oriented family-centered interventions, further understanding of the family's situation including the impact on the children, quality of life levels and the parental psychosocial needs is necessary. This study aims at investigating the impact of parental cancer on the minor children, family-specific psychosocial needs and quality of life levels of parents and children. Cancer patients parenting at least 1 minor child (<18 years) were eligible for study participation. In total, n=86 cancer patients under treatment participated in the study. After excluding participants without a minor child, 78 patients remained for analyses. We assessed children's quality of life using the parent proxy version of the KIDSCREEN-10 and parental quality of life using the EORTC QLQ C30 quality of life questionnaire. Additionally, the questionnaire comprised open questions about positive and negative changes parents perceived in their children as well as questions on specific family- and child-related psychosocial needs. The majority of participants were mothers (91%), mainly diagnosed with breast cancer (59%). The participating parents provided data on 117 minor children. Parents mentioned positive changes in 38% of the children (e.g., being more attentive and helpful). Negative changes were reported in 37% of the children (e.g., being more anxious and clingy). Parents reported family-specific psychosocial supportive care needs for themselves as a parent (e.g., support regarding parenting concerns), support needs for the partner or the children. Moreover, parents expressed family-related information needs and needs regarding practical aspects (e.g., childcare, household help). Global quality of life was M = 55.7 (SD = 23.4) for parents and M = 57.5 (SD = 15.5) for children. Pearson's correlation coefficient between parental and children's quality of life was 0.377 (p < 0.001). To identify parents with cancer and children in need for additional support, health care providers should proactively inquire about the impact of the disease on the children. In terms of a comprehensive cancer care, the direct assessment of family impact and family-specific support needs in cancer patients with minor children allows for needs-based allocation to support offers.
Basic Predictive Risk Factors for Cytokine Storms in COVID-19 Patients

Objective A critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as “a cytokine storm” (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice. Materials and Methods The authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer. Results The basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.
A Transcriptional Signature of IL-2 Expanded Natural Killer Cells Predicts More Favorable Prognosis in Bladder Cancer

Activation of natural killer (NK) cell function is regulated by cytokines, such as IL-2, and secreted factors upregulated in the tumor microenvironment, such as platelet-derived growth factor D (PDGF-DD). In order to elucidate a clinical role for these important regulators of NK cell function in antitumor immunity, we generated transcriptional signatures representing resting, IL-2-expanded, and PDGF-DD-activated, NK cell phenotypes and established their abundance in The Cancer Genome Atlas bladder cancer (BLCA) dataset using CIBERSORT. The IL-2-expanded NK cell phenotype was the most abundant in low and high grades of BLCA tumors and was associated with improved prognosis. In contrast, PDGFD expression was associated with numerous cancer hallmark pathways in BLCA tumors compared with normal bladder tissue, and a high tumor abundance of PDGFD transcripts and the PDGF-DD-activated NK cell phenotype were associated with a poor BLCA prognosis. Finally, high tumor expression of transcripts encoding the activating NK cell receptors, KLRK1 and the CD160–TNFRSF14 receptor–ligand pair, was strongly correlated with the IL-2-expanded NK cell phenotype and improved BLCA prognosis. The transcriptional parameters we describe may be optimized to improve BLCA patient prognosis and risk stratification in the clinic and potentially provide gene targets of therapeutic significance for enhancing NK cell antitumor immunity in BLCA.
SLC13A4 Might Serve as a Prognostic Biomarker and be Correlated with Immune Infiltration into Head and Neck Squamous Cell Carcinoma

SLC13A4 is a sodium sulfate co-transporter, which is expressed in brains, placentas, thymes and other tissues, plays an essential role in maintaining the metabolic balance of sulfate in vivo. The TCGA database shows that it is differentially expressed in a variety of tumors, but its prognostic value in tumors has not been clarified. TCGA, Oncomine and Timer databases were used to analyze SLC13A4 mRNA expression in cancer tissues and normal tissues, and its correlation with clinical prognosis in head and neck tumor. The CIBERSORT database was used to analyze the correlation between SLC13A4 expression and the infiltration of immune cells. SLC13A4 enrichment analysis was carried out by GSEA. SLC13A4 mRNA levels were significantly lower in head and neck tumors than in paracancer tissues. SLC13A4 expression in Head and neck squamous cell carcinoma (HNSCC) was closely related to tumor pathological grade and clinical stage. Decreased SLC13A4 expression was associated with poor overall survival (OS), progression free survival (PFS), disease specific survival (DSS) and recurrence free survival (RFS) in HNSCC patients. The expression of SLC13A4 was negatively correlated with Monocytes, M1 macrophages, M2 macrophages, resting CD4+ memory T cells, resting NK cells and activated NK cells, but positively correlated with neutrophils, plasma cells, T follicular helper cells, gamma delta T cells, regulatory T cells and naive B cells. In addition, the genes in SLC13A4 low-expression group were mainly concentrated in immunity-related activities, viral diseases, typical tumor pathways and metabolism. The SLC13A4 high expression group was mainly enriched in metabolic pathways. These suggest that SLC13A4 may be a potential prognostic biomarker in HNSC and correlated with immune infiltrates.
E2 Site Mutations in S Protein Strongly Affect Hepatitis B Surface Antigen Detection in the Occult Hepatitis B Virus

The mechanism of occult hepatitis B infection (OBI) has not yet been fully clarified. Our previous research found that novel OBI-related mutation within S protein, E2G, could cause the hepatitis B surface antigen (HBsAg) secretion impairment, which resulted in intracellular accumulation in OBI of genotype B. Here, to further explore the role of E2 site mutations in the occurrence of OBI, we analyzed these site mutations among 119 OBI strains identified from blood donors. Meanwhile, 109 wild-type HBV strains (HBsAg positive/HBV DNA positive) were used as control group. Furthermore, to verify the E2 site mutations, two conservative 1.3-fold full-gene expression vectors of HBV genotype B and C (pHBV1.3B and pHBV1.3C) were constructed. Then, the E2 mutant plasmids on the basis of pHBV1.3B or pHBV1.3C were constructed and transfected into HepG2 cells, respectively. The extracellular and intracellular HBsAg were analyzed by electrochemical luminescence and cellular immunohistochemistry. The structural characteristics of S proteins with or without E2 mutations were analyzed using relevant bioinformatics software. E2 mutations (E2G/A/V/D) existed in 21.8% (26/119) of OBIs, while no E2 mutations were found in the control group. E2G/A/V/D mutations could strongly affect extracellular and intracellular level of HBsAg (p < 0.05). Notably, unlike E2G in genotype B that could cause HBsAg intracellular accumulation and secretion decrease (p < 0.05), E2G in genotype C could lead to a very significant HBsAg decrease both extracellularly (0.46% vs. pHBV1.3C) and intracellularly (11.2% vs. pHBV1.3C) (p < 0.05). Meanwhile, for E2G/A mutations, the relative intracellular HBsAg (110.7–338.3% vs. extracellular) and its fluorescence intensity (1.5–2.4-fold vs. with genotype-matched pHBV1.3B/C) were significantly higher (p < 0.05). Furthermore, N-terminal signal peptides, with a typical cleavage site for peptidase at positions 27 and 28, were exclusively detected in S proteins with secretion-defective mutants (E2G/A). Our findings suggest that: (1) E2G/A/V/D mutations were confirmed to significantly influence the detection of HBsAg, (2) the underlying mechanism of OBI caused by E2G mutation is quite different between genotype B and genotype C, and (3) E2G/A could produce a N-terminal truncated S protein, which might attribute to the HBsAg secretion impairment in the OBIs.
Trajectory generation for lane-change maneuver of autonomous vehicles

Goswami, Ashesh M.S.E.C. E, Purdue University, May 2015. Trajectory Generation for Lane-change Maneuver of Autonomous Vehicles. Major Professor: C. S. George Lee. Lane-change maneuver is one of the most thoroughly investigated automatic driving operations that can be used by an autonomous self-driving vehicle as a primitive for performing more complex operations like merging, entering/exiting highways or overtaking another vehicle. This thesis focuses on two coherent problems that are associated with the trajectory generation for lane-change maneuvers of autonomous vehicles in a highway scenario: (i) an effective velocity estimation of neighboring vehicles under different road scenarios involving linear and curvilinear motion of the vehicles, and (ii) trajectory generation based on the estimated velocities of neighboring vehicles for safe operation of self-driving cars during lane-change maneuvers. We first propose a two-stage, interactive-multiple-model-based estimator to perform multi-target tracking of neighboring vehicles in a lane-changing scenario. The first stage deals with an adaptive window based turn-rate estimation for tracking maneuvering target vehicles using Kalman filter. In the second stage, variable-structure models with updated estimated turn-rate are utilized to perform data association followed by velocity estimation. Based on the estimated velocities of neighboring vehicles, piecewise Bezier-curve-based methods that minimize the safety/collision risk involved and maximize the comfort ride have been developed for the generation of desired trajectory for lane-change maneuvers. The proposed velocity-estimation and trajectory-generation algorithms have been validated experimentally using Pioneer3DX mobile robots in a simulated lane-change environment as well as validated by computer simulations.