Miracle-dz/UniFAR-FTUs huggingface dataset:
T Lymphocytes +Cytolytic Effector Molecules in Human CD8 Functional Heterogeneity of Cytokines and

CD8 1 T cells use a number of effector mechanisms to protect the host against infection. We have studied human CD8 1 T cells speciﬁc for CMV pp65 495–503 epitope, or for staphylococcal enterotoxin B, for the expression patterns of ﬁve cytokines and cytolytic effector molecules before and after antigenic stimulation. Ex vivo, the cytolytic molecule granzyme B was detected in a majority of circulating CMV-speciﬁc CD8 1 T cells, whereas perforin was rarely expressed. Both were highly expressed after Ag-speciﬁc activation accompanied by CD45RO up-regulation. TNF- a , IFN g , and IL-2 were sequentially acquired on recognition of Ag, but surprisingly, only around half of the CMV-speciﬁc CD8 1 T cells responded to antigenic stimuli with production of any cytokine measured. A dominant population coexpressed TNF- a and IFN- g , and cells expressing TNF- a only, IFN- g only, or all three cytokines together also occurred at lower but clearly detectable frequencies. Interestingly, perforin expression and production of IFN- g and TNF- a in CD8 1 T cells responding to staphylococcal enterotoxin B appeared to be largely segregated, and no IL-2 was detected in perforin-positive cells. Together, these data indicate that human CD8 1 T cells can be functionally segregated in vivo and have implications for the understanding of human CD8 1 T cell differentiation and specialization and regulation of effector mechanisms. The Journal of Immunology, 2001, 167: 181–187.
Systematic generation of biophysically detailed models with generalization capability for non-spiking neurons

Unlike spiking neurons which compress continuous inputs into digital signals for transmitting information via action potentials, non-spiking neurons modulate analog signals through graded potential responses. Such neurons have been found in a large variety of nervous tissues in both vertebrate and invertebrate species, and have been proven to play a central role in neuronal information processing. If general and vast efforts have been made for many years to model spiking neurons using conductance-based models (CBMs), very few methods have been developed for non-spiking neurons. When a CBM is built to characterize the neuron behavior, it should be endowed with generalization capabilities (i.e. the ability to predict acceptable neuronal responses to different novel stimuli not used during the model’s building). Yet, since CBMs contain a large number of parameters, they may typically suffer from a lack of such a capability. In this paper, we propose a new systematic approach based on multi-objective optimization which builds general non-spiking models with generalization capabilities. The proposed approach only requires macroscopic experimental data from which all the model parameters are simultaneously determined without compromise. Such an approach is applied on three non-spiking neurons of the nematode Caenorhabditis elegans (C. elegans), a well-known model organism in neuroscience that predominantly transmits information through non-spiking signals. These three neurons, arbitrarily labeled by convention as RIM, AIY and AFD, represent, to date, the three possible forms of non-spiking neuronal responses of C. elegans.
A Retrospective Analysis of 10 Years of Liver Surveillance Undertaken in Uveal Melanoma Patients Treated at the Supraregional “Liverpool Ocular Oncology Centre”, UK

Simple Summary Around 45% of patients with uveal melanoma (UM) develop liver metastases on average 3 years after diagnosis of the primary tumour. After clinical detection of metastases, median patient survival is approximately one year. Early identification of metastases through liver surveillance is important so that targeted treatment can benefit affected patients, aiming to prolong their survival. The aim of our retrospective study was to investigate and correlate the characteristics of UM patients diagnosed and treated at a UK supraregional referral center, the Liverpool Ocular Oncology Centre (LOOC), and who were included in the Centre’s liver screening programs for screening for liver metastases. “Real-world” data on the frequency of liver screening in patients after diagnosis and treatment of primary UM are lacking. Through the liver screening program, we found that metastases were detected in 37% of the 615 UM patients studied. A new output based on the prognostic indices of the Liverpool Uveal Melanoma Prognosticator Online version 3 (LUMPO3) model was fitted to the dataset of these patients and accurately estimated the time of onset of metastases. Abstract Purpose: To determine liver screening frequency and modality in UM patients following primary treatment, and the characteristics of detected metastases. Methods: A 10-year retrospective study of 615 UM patients undergoing liver surveillance in Liverpool. Information was collected from liver scan reports of these patients. Results: Of 615 UM patients analyzed, there were 337 men (55%) and 278 women (45%). Median age at primary treatment was 61 years (range, 22–94). At study end, median follow-up was 5.1 years, with 375 patients (61%) alive and 240 deceased (39%). Of the deceased patients, 187 (78%) died due to metastatic UM; 24 (10%) deaths were due to other causes; and 29 (12%) patients died of unknown conditions. In total, 3854 liver scans were performed in the 615 UM patients, with a median of 6.2 scans per patient (range, 1–40). Liver MRI was most frequently performed (62.8%). In total, 229 (37%) UM patients developed metastases during the study period: 150 were detected via liver surveillance and 79 were observed post-mortem. Conclusions: Metastatic UM onset is related to the size and genetic profiles of the primary UM, and can be predicted using the model LUMPO3. Regular liver surveillance allowed for timely detection of metastases, and through metastasectomy can lead to prolongation of life in some patients.
Targeting Sphingolipid Metabolism as a Therapeutic Strategy in Cancer Treatment

Simple Summary Sphingolipids, which are important cell membrane components, have critical roles in regulating cancer cell signaling to control pro-tumoral or antitumoral functions. Ceramide, which is the central sphingolipid, facilitates cancer cell death, while sphingosine-1-phosphate (S1P) induces tumor growth/metastasis and confers resistance to chemo-, immuno-, or radiotherapies. The aim of this review is to highlight the mechanistic strategies of targeting sphingolipid metabolism for cancer therapeutics. Abstract Sphingolipids are bioactive molecules that have key roles in regulating tumor cell death and survival through, in part, the functional roles of ceramide accumulation and sphingosine-1-phosphate (S1P) production, respectively. Mechanistic studies using cell lines, mouse models, or human tumors have revealed crucial roles of sphingolipid metabolic signaling in regulating tumor progression in response to anticancer therapy. Specifically, studies to understand ceramide and S1P production pathways with their downstream targets have provided novel therapeutic strategies for cancer treatment. In this review, we present recent evidence of the critical roles of sphingolipids and their metabolic enzymes in regulating tumor progression via mechanisms involving cell death or survival. The roles of S1P in enabling tumor growth/metastasis and conferring cancer resistance to existing therapeutics are also highlighted. Additionally, using the publicly available transcriptomic database, we assess the prognostic values of key sphingolipid enzymes on the overall survival of patients with different malignancies and present studies that highlight their clinical implications for anticancer treatment.
Development of a Novel Coaching Platform to Improve Tackle Technique in Youth Rugby Players: A Proof of Concept

Rugby union is a field sport that is played at amateur and professional levels by male and female players globally. One of the most prevalent injury risks associated with the sport involves tackle collisions with opposition players. This suggests that a targeted injury reduction strategy could focus on the tackle area in the game. In amateur rugby union, injuries to the head, face and shoulder are the most common injury sites in youth rugby playing populations. A suboptimal tackle technique may contribute to an increased injury risk in these populations. One proposed mitigation strategy to reduce tackle-related injuries in youth populations may be to increase tackle proficiency by coaching an effective tackle technique. The present study aimed to demonstrate a proof of concept for a tackle technique coaching platform using inertial measurement units (IMUs) and a bespoke mobile application developed for a mobile device (i.e., a mobile phone). The test battery provided a proof of concept for the primary objective of modelling the motion of a player in a tackle event. The prototype (bespoke mobile application) modelled the IMU in a 3D space and demonstrated the orientation during a tackle event. The participants simulated ten tackle events that were ten degrees above and ten degrees below the zero degree of approach, and these (unsafe tackles) were indicated by a red light on the mobile display unit. The parameters of ten degrees above and below the zero angle of approach were measured using an inclinometer mobile application. These tackle event simulations provided a real-time stream of data that displayed the angle of tackles on a mobile device. The novel coaching platform could therefore constitute part of an injury reduction strategy for amateur or novice coaches to instruct safer tackle practice in youth rugby playing populations.
New Panx-1 Blockers: Synthesis, Biological Evaluation and Molecular Dynamic Studies

The channel protein Panx-1 is involved in some pathologies, such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. These observations make Panx-1 an interesting biological target. We previously published some potent indole derivatives as Panx-1 blockers, and as continuation of the research in this field we report here the studies on additional chemical scaffolds, naphthalene and pyrazole, appropriately substituted with those functions that gave the best results as in our indole series (sulphonamide functions and one/two carboxylic groups) and in Panx-1 blockers reported in the literature (sulphonic acid). Compounds 4 and 13, the latter being an analogue of the drug Probenecid, are the most potent Panx-1 blockers obtained in this study, with I = 97% and I = 93.7% at 50 µM, respectively. Both compounds, tested in a mouse model of oxaliplatin-induced neuropathic pain, showed a similar anti-hypersensitivity profile and are able to significantly increase the mouse pain threshold 45 min after the injection of the doses of 1 nmol and 3 nmol. Finally, the molecular dynamic studies and the PCA analysis have made it possible to identify a discriminating factor able to separate active compounds from inactive ones.
Overcoming Therapy Resistance in Colon Cancer by Drug Repurposing

Simple Summary Despite improvements in standardized screening methods and the development of promising therapies for colorectal cancer (CRC), survival rates are still low. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC. In this review, we summarize the current data supporting drug repurposing as a feasible option for patients with CRC. Abstract Colorectal cancer (CRC) is the third most common cancer in the world. Despite improvement in standardized screening methods and the development of promising therapies, the 5-year survival rates are as low as 10% in the metastatic setting. The increasing life expectancy of the general population, higher rates of obesity, poor diet, and comorbidities contribute to the increasing trends in incidence. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC with the advantage of treating underlying comorbidities and decreasing chemotherapy toxicity. This review elaborates on the current data that supports drug repurposing as a feasible option for patients with CRC with a focus on the evidence and mechanism of action promising repurposed candidates that are widely used, including but not limited to anti-malarial, anti-helminthic, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic agents.
Dietary Supplements for Weight Management: A Narrative Review of Safety and Metabolic Health Benefits

Dietary supplements for weight management include myriad ingredients with thermogenic, lipotropic, satiety, and other metabolic effects. Recently, the safety of this product category has been questioned. In this review, we summarize the safety evidence as well as relevant clinical findings on weight management and metabolic effects of six representative dietary supplement ingredients: caffeine, green tea extract (GTE), green coffee bean extract (GCBE), choline, glucomannan, and capsaicinoids and capsinoids. Of these, caffeine, GTE (specifically epigallocatechin gallate [EGCG]), and choline have recommended intake limits, which appear not to be exceeded when used according to manufacturers’ instructions. Serious adverse events from supplements with these ingredients are rare and typically involve unusually high intakes. As with any dietary component, the potential for gastrointestinal intolerance, as well as possible interactions with concomitant medications/supplements exist, and the health status of the consumer should be considered when consuming these components. Most of the ingredients reviewed also improved markers of metabolic health, such as glucose, lipids, and blood pressure, although the data are limited for some. In summary, weight management supplements containing caffeine, GTE, GCBE, choline, glucomannan, and capsaicinoids and capsinoids are generally safe when taken as directed and demonstrate metabolic health benefits for overweight and obese people.
Analyzing Consumer Perception on Quality and Safety of Frozen Foods in Emerging Economies: Evidence from Albania and Kosovo

Freezing technology is one of the most well established long-term preservation techniques for producing high-quality, nutritious foods with prolonged shelf-life. Frozen foods (FFs) are a significant section of the global food market experiencing rapid growth. It also represents an alternative to small producers in developing countries to add value to their products in a competitive market. However, unfairly, FFs are often perceived as less qualitative than fresh produce, although studies have shown that some FFs have higher nutritional values than fresh products. This study’s aim is to analyze consumers’ perceptions in the two Balkan countries towards FFs. A total of 380 questionnaires were completed in both countries (182 in Kosovo and 198 in Albania). Consumers’ perceptions towards FFs were measured through eleven items using a five-point Likert scale. The items addressed issues related to the quality and safety of FFs, information on FFs, and the impact of origin on the perception of FFs. The differences between populations were tested with the t-test and correlation analysis with the bootstrapping method for sociodemographic factors. The results show that Kosovo consumers generally show a higher positive attitude toward FFs than Albanian consumers. Albanian consumers prefer fresh foods over FFs. The lack of trust in food safety institutions was expressed with concern for the conditions of the frozen chain applied both on the imported and domestic frozen products. Similarly, the findings show that Albanian consumers are willing to pay more than the baseline price to obtain fresh products instead of frozen compared with Kosovo consumers. Additional studies are needed to explore whether the lack of trust in food safety institutions inhibits the successful development of FFs in Albania and Kosovo. In both countries, responsible authorities should help consumers to have a more profound knowledge of the quality of FFs and boost these activities to increase farmers’ incomes and play an active role in reducing food loss and waste.
Linoleic Acid Attenuates Denervation-Induced Skeletal Muscle Atrophy in Mice through Regulation of Reactive Oxygen Species-Dependent Signaling

Muscle atrophy is a major muscle disease, the symptoms of which include decreased muscle volume leading to insufficient muscular support during exercise. One cause of muscle atrophy is the induction of oxidative stress by reactive oxygen species (ROS). This study aimed to identify the antioxidant mechanism of linoleic acid (LA) in muscle atrophy caused by oxidative stress. H2O2 has been used to induce oxidative stress in myoblasts in vitro. C2C12 myoblasts treated with H2O2 exhibited decreased viability and increased ROS synthesis. However, with LA treatment, the cells tended to recover from oxidative effects similar to those of the control groups. At the molecular level, the expression of superoxide dismutase 1 (SOD1), Bax, heat shock protein 70 (HSP70), and phosphorylated forkhead box protein O1 was increased by oxidative stress, causing apoptosis. LA treatment suppressed these changes. In addition, the expression of MuRF1 and Atrogin-1/MAFbx mRNA increased under oxidative stress but not in the LA-treated group. Sciatic denervation of C57BL/6 mice manifested as atrophy of the skeletal muscle in micro-computed tomography (micro-CT). The protein expression levels of SOD1, HSP70, and MuRF1 did not differ between the atrophied muscle tissues and C2C12 myoblasts under oxidative stress. With LA treatment, muscle atrophy recovered and protein expression was restored to levels similar to those in the control. Therefore, this study suggests that LA may be a candidate substance for preventing muscle atrophy.
Pengaruh Brand Equity terhadap Loyalitas Konsumen Produk Air Minum dalam Kemasan (AMDK) Merk Aqua di Bandar Lampung

The purpose of this research is to know the consumer’s loyalty of AMDK product branded AQUA in Bandar Lampung. The research problems are: 1) Is there any individual influence of product, image, and visual to consumer’s loyalty AQUA product in Bandar Lampung? 2) Is there simultaneous influence of product, image, and visual to consumer’s loyalty AQUA product in Bandar Lampung. The research used double linear regression. In this model, product, image, and visual as independent variables and consumer’s loyalty as dependent variable. To analyze independent variables influence to dependent variable individually, is used t test. On the other hand, to analyze the influence of independent variables to dependent variable simultaneously, is used F test. 100 samples were collected by judgement sampling and data were collected by questionnaire. The result of this research showed that product, image and visual individually influence consumer’s loyalty of AQUA product in Bandar Lampung positively and significantly, it’s proved by t significant value 0,000, and t coefficient values of the third independent variables are 6,615, 7,468, and 6,276. Product, image, and visual also simultaneously influence consumer’s loyalty of AQUA product in Bandar Lampung positively and significantly with F coefficients value 90,424, and significant value 0,000. 0,739 R square mean that 73,9% of AMDK AQUA consumer’s loyalty is defined by product, image and visual, while the rest are defined by other variable.
Synthesis of High Surface Area—Group 13—Metal Oxides via Atomic Layer Deposition on Mesoporous Silica

The atomic layer deposition of gallium and indium oxide was investigated on mesoporous silica powder and compared to the related aluminum oxide process. The respective oxide (GaOx, InOx) was deposited using sequential dosing of trimethylgallium or trimethylindium and water at 150 °C. In-situ thermogravimetry provided direct insight into the growth rates and deposition behavior. The highly amorphous and well-dispersed nature of the oxides was shown by XRD and STEM EDX-mappings. N2 sorption analysis revealed that both ALD processes resulted in high specific surface areas while maintaining the pore structure. The stoichiometry of GaOx and InOx was suggested by thermogravimetry and confirmed by XPS. FTIR and solid-state NMR were conducted to investigate the ligand deposition behavior and thermogravimetric data helped estimate the layer thicknesses. Finally, this study provides a deeper understanding of ALD on powder substrates and enables the precise synthesis of high surface area metal oxides for catalytic applications.
Application of Fungal Biomass for the Development of New Polylactic Acid-Based Biocomposites

Fungal biomass (FB), a by-product of the fermentation processes produced in large volumes, is a promising biomaterial that can be incorporated into poly(lactic acid) (PLA) to develop enhanced biocomposites that fully comply with the biobased circular economy concept. The PLA/FB composites, with the addition of triethyl citrate (TEC) as a biobased plasticizer, were fabricated by a microcompounder at 150 °C followed by injection molding. The effects of FB (10 and 20 wt %) and TEC (5, 10, and 15 wt %) contents on the mechanical, thermal and surface properties of the biocomposites were analyzed by several techniques. The PLA/FB/TEC composites showed a rough surface in their fracture section. A progressive decrease in tensile strength and Young’s modulus was observed with increasing FB and TEC, while elongation at break and impact strength started to increase. The neat PLA and biocomposite containing 10% FB and 15% TEC exhibited the lowest (3.84%) and highest (224%) elongation at break, respectively. For all blends containing FB, the glass transition, crystallization and melting temperatures were shifted toward lower values compared to the neat PLA. The incorporation of FB to PLA thus offers the possibility to overcome one of the main drawbacks of PLA, which is brittleness.