Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Epidemiology of Staphylococcus aureus Lineages in Wild Animals in Europe: A Review

Staphylococcus aureus is an opportunist pathogen that is responsible for numerous types of infections. S. aureus is known for its ability to easily acquire antibiotic resistance determinants. Methicillin-resistant S. aureus (MRSA) is a leading cause of infections both in humans and animals and is usually associated with a multidrug-resistant profile. MRSA dissemination is increasing due to its capability of establishing new reservoirs and has been found in humans, animals and the environment. Despite the fact that the information on the incidence of MRSA in the environment and, in particular, in wild animals, is scarce, some studies have reported the presence of these strains among wildlife with no direct contact with antibiotics. This shows a possible transmission between species and, consequently, a public health concern. The aim of this review is to better understand the distribution, prevalence and molecular lineages of MRSA in European free-living animals.
A PSMA-Targeting CD3 Bispecific Antibody Induces Antitumor Responses that Are Enhanced by 4-1BB Costimulation

A CD3 bispecific antibody that targets a prostate tumor antigen elicits effective antitumor responses against smaller, but not larger, solid tumors. Addition of 4-1BB controls tumors through enhanced T-cell responses, T-cell memory formation, and response persistence. Patients with hematologic cancers have improved outcomes after treatment with bispecific antibodies that bind to CD3 on T cells and that redirect T cells toward cancer cells. However, clinical benefit against solid tumors remains to be shown. We made a bispecific antibody that targets both the common prostate tumor–specific antigen PSMA and CD3 (PMSAxCD3) and provide evidence for tumor inhibition in several preclinical solid tumor models. Mice expressing the human extracellular regions of CD3 and PSMA were generated to examine antitumor efficacy in the presence of an intact immune system and PSMA expression in normal tissues. PSMAxCD3 accumulated in PSMA-expressing tissues and tumors as detected by immuno-PET imaging. Although PSMAxCD3 induced T-cell activation and showed antitumor efficacy in mice with low tumor burden, PSMAxCD3 lost efficacy against larger solid tumors, mirroring the difficulty of treating solid tumors in the clinic. Costimulatory receptors can enhance T-cell responses. We show here that costimulation can enhance the antitumor efficacy of PSMAxCD3. In particular, 4-1BB stimulation in combination with PSMAxCD3 enhanced T-cell activation and proliferation, boosted efficacy against larger tumors, and induced T-cell memory, leading to durable antitumor responses. The combination of CD3 bispecific antibodies and anti-4-1BB costimulation represents a therapeutic approach for the treatment of solid tumors.
Diagnostic accuracy of ultrasonography and scoring systems: The effects on the negative appendectomy rate and gender.

BACKGROUND Despite the development of clinical, laboratory, and imaging methods, the diagnosis of acute appendicitis is not always easy, and negative appendectomy rates are still high. This study aims to reveal the effects of different scoring systems on the diagnostic accuracy of acute appendicitis and negative appendectomy rates, alone or when evaluated together with ultrasonography. METHODS In this study, 202 consecutive patients who underwent emergency appendectomy for acute appendicitis were included. Clinical scores of all patients were preoperatively calculated using Ohmann, Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA), Lintula, Eskelinen, and Alvarado scoring systems. Abdominal ultrasonography (USG) was performed randomly in all cases. The sensitivity and specificity of scoring systems were calculated according to the threshold values. The area under the curve (AUC) was calculated using ROC analysis. In the regression model, histological diagnosis of appendicitis was used as the dependent variable, while scoring systems and USG were preferred as independent variables. RESULTS The negative appendectomy rate was 15.8%. In the diagnosis of acute appendicitis, Ohmann was the most predictive for both genders (DOR=24.2, 95% CI 6.98-84.44). Similarly, the lowest negative appendectomy rates were obtained with the Ohmann score as 6.9% in females and 3.4% in males. When the scores were combined with USG, the rate of diagnostic accuracy for acute appendicitis was not increased. However, when Ohmann and USG were combined, negative appendectomy rates were further reduced for women from 6.9% to 4%. CONCLUSION In addition to being a good diagnostic predictor of acute appendicitis in male and female patients, Ohmann score provides the best negative appendectomy rates. The combination of USG and scoring systems does not increase the diagnostic accuracy of acute appendicitis. However, negative appendectomy rates are significantly reduced when the USG and Ohmann scale are used together in females, while this reduction is minimal in men.
The GDSL Lipase MHZ11 Modulates Ethylene Signaling in Rice Roots[OPEN]

The GDSL lipase MHZ11 affects OsCTR2 phosphorylation status to facilitate ethylene signaling partially through modulating sterol homeostasis. Ethylene plays important roles in plant growth and development, but the regulation of ethylene signaling is largely unclear, especially in crops such as rice (Oryza sativa). Here, by analysis of the ethylene-insensitive mutant mao huzi 11 (mhz11), we identified the GDSL lipase MHZ11, which modulates ethylene signaling in rice roots. MHZ11 localized to the endoplasmic reticulum membrane and has acyl-hydrolyzing activity. This activity affects the homeostasis of sterols in rice roots and is required for root ethylene response. MHZ11 overexpression caused constitutive ethylene response in roots. Genetically, MHZ11 acts with the ethylene receptor ETHYLENE RESPONSE SENSOR2 (OsERS2) upstream of CONSTITUTIVE TRIPLE RESPONSE2 (OsCTR2) and ETHYLENE INSENSITIVE2 (OsEIN2). The mhz11 mutant maintains more OsCTR2 in the phosphorylated form whereas MHZ11 overexpression promotes ethylene-mediated inhibition of OsCTR2 phosphorylation. MHZ11 colocalized with the ethylene receptor OsERS2, and its effect on OsCTR2 phosphorylation requires ethylene perception and initiation of ethylene signaling. The mhz11 mutant overaccumulated sterols and blocking sterol biosynthesis partially rescued the mhz11 ethylene response, likely by reducing receptor-OsCTR2 interaction and OsCTR2 phosphorylation. We propose that MHZ11 reduces sterol levels to impair receptor-OsCTR2 interactions and OsCTR2 phosphorylation for triggering ethylene signaling. Our study reveals a mechanism by which MHZ11 participates in ethylene signaling for regulation of root growth in rice.
Analyzing the Importance of Driver Behavior Criteria Related to Road Safety for Different Driving Cultures

Driver behavior has been considered as the most critical and uncertain criteria in the study of traffic safety issues. Driver behavior identification and categorization by using the Fuzzy Analytic Hierarchy Process (FAHP) can overcome the uncertainty of driver behavior by capturing the ambiguity of driver thinking style. The main goal of this paper is to examine the significant driver behavior criteria that influence traffic safety for different traffic cultures such as Hungary, Turkey, Pakistan and China. The study utilized the FAHP framework to compare and quantify the driver behavior criteria designed on a three-level hierarchical structure. The FAHP procedure computed the weight factors and ranked the significant driver behavior criteria based on pairwise comparisons (PCs) of driver’s responses on the Driver Behavior Questionnaire (DBQ). The study results observed “violations” as the most significant driver behavior criteria for level 1 by all nominated regions except Hungary. While for level 2, “aggressive violations” is observed as the most significant driver behavior criteria by all regions except Turkey. Moreover, for level 3, Hungary and Turkey drivers evaluated the “drive with alcohol use” as the most significant driver behavior criteria. While Pakistan and China drivers evaluated the “fail to yield pedestrian” as the most significant driver behavior criteria. Finally, Kendall’s agreement test was performed to measure the agreement degree between observed groups for each level in a hierarchical structure. The methodology applied can be easily transferable to other study areas and our results in this study can be helpful for the drivers of each region to focus on highlighted significant driver behavior criteria to reduce fatal and seriously injured traffic accidents.
Role of 3-Mercaptopyruvate Sulfurtransferase in the Regulation of Proliferation, Migration, and Bioenergetics in Murine Colon Cancer Cells

3-mercaptopyruvate sulfurtransferase (3-MST) has emerged as one of the significant sources of biologically active sulfur species in various mammalian cells. The current study was designed to investigate the functional role of 3-MST’s catalytic activity in the murine colon cancer cell line CT26. The novel pharmacological 3-MST inhibitor HMPSNE was used to assess cancer cell proliferation, migration and bioenergetics in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux analysis). 3-MST expression was detected by Western blotting; H2S production was measured by the fluorescent dye AzMC. The results show that CT26 cells express 3-MST protein and mRNA, as well as several enzymes involved in H2S degradation (TST, ETHE1). Pharmacological inhibition of 3-MST concentration-dependently suppressed H2S production and, at 100 and 300 µM, attenuated CT26 proliferation and migration. HMPSNE exerted a bell-shaped effect on several cellular bioenergetic parameters related to oxidative phosphorylation, while other bioenergetic parameters were either unaffected or inhibited at the highest concentration of the inhibitor tested (300 µM). In contrast to 3-MST, the expression of CBS (another H2S producing enzyme which has been previously implicated in the regulation of various biological parameters in other tumor cells) was not detectable in CT26 cells and pharmacological inhibition of CBS exerted no significant effects on CT26 proliferation or bioenergetics. In summary, 3-MST catalytic activity significantly contributes to the regulation of cellular proliferation, migration and bioenergetics in CT26 murine colon cancer cells. The current studies identify 3-MST as the principal source of biologically active H2S in this cell line.
Secrecy Performance Analysis of Wireless Powered Sensor Networks Under Saturation Nonlinear Energy Harvesting and Activation Threshold

In this paper, we investigate the impact of saturation nonlinear energy harvesting (EH) and activation threshold on the multiuser wireless powered sensor networks (WPSNs) from the physical layer security (PLS) perspective. In particular, for improving the secrecy performance, the generalized multiuser scheduling (GMS) scheme is exploited, in which the Kth strongest sensor is chosen based on the legitimate link. For evaluating the impact of various key parameters on the security of system, we obtain the exact closed-form expressions for secrecy outage probability (SOP) under linear EH (LEH), saturation nonlinear EH (SNEH) and saturation nonlinear EH with activation threshold (SNAT), respectively, and solve the maximization problem of secure energy efficiency (SEE). Simulation results demonstrate that: (1) the number of source sensors, the EH efficiency and the transmit power of power beacon (PB) all have positive impact on SOP, and the smaller generalized selection coefficient is advantageous for secrecy performance; (2) LEH is an ideal situation for SNEH when the saturation threshold is large enough and SNEH is a special situation for SNAT when the activation threshold is low enough; (3) the time-switching factor and the activation threshold both have an important impact on the secrecy performance, which are worth considering carefully.
EML4–ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7

ABSTRACT EML4–ALK is an oncogenic fusion present in ∼5% of non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants of EML4–ALK with different patient outcomes. Here, we show that, in cell models, EML4–ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. EML4–ALK V3 also recruits the NEK9 and NEK7 kinases to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4, as well as constitutive activation of NEK9, also perturbs cell morphology and accelerates migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but does not require ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4–ALK patients. Hence, we propose that EML4–ALK V3 promotes microtubule stabilization through NEK9 and NEK7, leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4–ALK lung cancer. Summary: EML4–ALK fusions are major drivers of lung cancer. Particular fusion variants act through a novel actionable pathway involving NEK7 and NEK9, promoting cell migration and potentially influencing metastatic progression.
Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)-containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells.
The Rural Pharmacy Practice Landscape: Challenges and Motivators

Background Health outcome delivery for rural and remote Australian communities is challenged by the maldistribution of the pharmacy workforce. High staff turnover rates, reduced pharmacist numbers, and reliance on temporary staff have placed great strain on both state health services and rural community pharmacies. However, recent changes to the demographic profile of the rural pharmacist including a lower average age and increased time spent in rural practice highlights a more positive future for the delivery of better health outcomes for rural communities. The aim of this study was to investigate the factors that motivate and challenge pharmacists’ choice to practice rurally. Methods Rural pharmacists were invited to participate in semi-structured interviews using purposive non-probability sampling. Twelve pharmacists were interviewed with early-, middle- and late-career pharmacists represented. Participants described their experiences of working and living in rural and remote locations. Three themes emerged: workforce, practice environment and social factors, which were examined to determine the underlying challenges and motivators impacting rural and remote pharmacy practice. Results Lack of staff presented a workforce challenge, while motivators included potential for expanded scope of practice and working as part of a multidisciplinary team. While social isolation has often been presented as a challenge, an emerging theme highlighted that this may no longer be true, and that notions of “rural and remote communities as socially isolated was a stigma that needed to be stopped”. Conclusion This study highlights that despite the challenges rural pharmacists face, there is a shift happening that could deliver better health outcomes for isolated communities. However, for this to gain momentum, it is important to examine both the challenges and motivators of rural pharmacy practice to provide a platform for the development and implementation of appropriate frameworks and programs to better support the rural pharmacy workforce.
Selective Extraction of Cannabinoid Compounds from Cannabis Seed Using Pressurized Hot Water Extraction

Phytochemicals of Cannabis sativa mainly for the use in the different industries are that of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Pressurized hot water extraction (PHWE) is seen as an efficient, fast, green extraction technique for the removal of polar and semi-polar compounds from plant materials. The PHWE technique was applied to extract cannabinoid compounds from Cannabis sativa seed. Response surface methodology was used to investigate the influence of extraction time (5–60 min), extraction temperature (50–200 °C) and collector vessel temperature (25–200 °C) on the recovery of delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), cannabichromene (CBG) and cannabigerol (CBC) from Cannabis sativa seed by PHWE. The identification and semi quantification of cannabinoid compounds were determined using GCXGC-TOFMS. The results obtained from different extractions show that the amount of THC and CBN was drastically decreasing in the liquid extract when the temperature rose from 140 to 160 °C in the extraction cell and the collector′s vessel. The optimal conditions to extract more CBD, CBC, and CBG than THC and CBN were set at 150 °C, 160 °C and 45 min as extraction temperature, the temperature at collector vessel, and the extraction time, respectively. At this condition, the predicted and experimental ratio of THCt (THC + CBN)/CBDt (CBD + CBC+ CBG) was found to be 0.17 and 0.18, respectively. Therefore, PHWE can be seen as an alternative to the classic extraction approach as the efficiency is higher and it is environmentally friendly.
The Added Value of In-Hospital Tracking of the Efficacy of Decongestion Therapy and Prognostic Value of a Wearable Thoracic Impedance Sensor in Acutely Decompensated Heart Failure With Volume Overload: Prospective Cohort Study

Background Incomplete relief of congestion in acute decompensated heart failure (HF) is related to poor outcomes. However, congestion can be difficult to evaluate, stressing the urgent need for new objective approaches. Due to its inverse correlation with tissue hydration, continuous bioimpedance monitoring might be an effective method for serial fluid status assessments. Objective This study aimed to determine whether in-hospital bioimpedance monitoring can be used to track fluid changes (ie, the efficacy of decongestion therapy) and the relationships between bioimpedance changes and HF hospitalization and all-cause mortality. Methods A wearable bioimpedance monitoring device was used for thoracic impedance measurements. Thirty-six patients with signs of acute decompensated HF and volume overload were included. Changes in the resistance at 80 kHz (R80kHz) were analyzed, with fluid balance (fluid in/out) used as a reference. Patients were divided into two groups depending on the change in R80kHz during hospitalization: increase in R80kHz or decrease in R80kHz. Clinical outcomes in terms of HF rehospitalization and all-cause mortality were studied at 30 days and 1 year of follow-up. Results During hospitalization, R80kHz increased for 24 patients, and decreased for 12 patients. For the total study sample, a moderate negative correlation was found between changes in fluid balance (in/out) and relative changes in R80kHz during hospitalization (rs=-0.51, P<.001). Clinical outcomes at both 30 days and 1 year of follow-up were significantly better for patients with an increase in R80kHz. At 1 year of follow-up, 88% (21/24) of patients with an increase in R80kHz were free from all-cause mortality, compared with 50% (6/12) of patients with a decrease in R80kHz (P=.01); 75% (18/24) and 25% (3/12) were free from all-cause mortality and HF hospitalization, respectively (P=.01). A decrease in R80kHz resulted in a significant hazard ratio of 4.96 (95% CI 1.82-14.37, P=.003) on the composite endpoint. Conclusions The wearable bioimpedance device was able to track changes in fluid status during hospitalization and is a convenient method to assess the efficacy of decongestion therapy during hospitalization. Patients who do not show an improvement in thoracic impedance tend to have worse clinical outcomes, indicating the potential use of thoracic impedance as a prognostic parameter.
Current Trends and Confounding Factors in Myoelectric Control: Limb Position and Contraction Intensity

This manuscript presents a hybrid study of a comprehensive review and a systematic (research) analysis. Myoelectric control is the cornerstone of many assistive technologies used in clinical practice, such as prosthetics and orthoses, and human-computer interaction, such as virtual reality control. Although the classification accuracy of such devices exceeds 90% in a controlled laboratory setting, myoelectric devices still face challenges in robustness to variability of daily living conditions. The intrinsic physiological mechanisms limiting practical implementations of myoelectric devices were explored: the limb position effect and the contraction intensity effect. The degradation of electromyography (EMG) pattern recognition in the presence of these factors was demonstrated on six datasets, where classification performance was 13% and 20% lower than the controlled setting for the limb position and contraction intensity effect, respectively. The experimental designs of limb position and contraction intensity literature were surveyed. Current state-of-the-art training strategies and robust algorithms for both effects were compiled and presented. Recommendations for future limb position effect studies include: the collection protocol providing exemplars of at least 6 positions (four limb positions and three forearm orientations), three-dimensional space experimental designs, transfer learning approaches, and multi-modal sensor configurations. Recommendations for future contraction intensity effect studies include: the collection of dynamic contractions, nonlinear complexity features, and proportional control.