Miracle-dz/UniFAR-FTUs huggingface dataset:
Activated Regulatory T-Cells, Dysfunctional and Senescent T-Cells Hinder the Immunity in Pancreatic Cancer

Simple Summary Pancreatic cancer has the worst survival of any human cancer. Checkpoint blockade has not yielded much benefit in pancreatic cancer. We explored immune cell phenotypes with this disease to identify new targets for checkpoint blockade therapy. We created a checkpoint-focused panel to analyse immune cells from eight pancreatic cancer patients. This showed us the majority of T-cells are senescent. Further T-cell investigation demonstrated the majority of cytotoxic T-cells have intermediate to low PD1 expression suggesting why PD1 may not work as a pancreatic cancer therapy strategy. Our data has also highlighted a regulatory T-cell population which is highly activated and can mediate immunosuppression. The checkpoints that are highly expressed on these cells are TIGIT, ICOS and CD39, suggesting inhibition of these may be a viable therapeutic strategy. Furthermore, we showed that Tregs were retained amongst the fibroblast stroma of the tumour. Our work suggests there are key checkpoints on Tregs that may help guide therapeutic strategies in pancreatic cancer. Abstract Pancreatic cancer has one of the worst prognoses of any human malignancy and leukocyte infiltration is a major prognostic marker of the disease. As current immunotherapies confer negligible survival benefits, there is a need to better characterise leukocytes in pancreatic cancer to identify better therapeutic strategies. In this study, we analysed 32 human pancreatic cancer patients from two independent cohorts. A multi-parameter mass-cytometry analysis was performed on 32,000 T-cells from eight patients. Single-cell RNA sequencing dataset analysis was performed on a cohort of 24 patients. Multiplex immunohistochemistry imaging and spatial analysis were performed to map immune infiltration into the tumour microenvironment. Regulatory T-cell populations demonstrated highly immunosuppressive states with high TIGIT, ICOS and CD39 expression. CD8+ T-cells were found to be either in senescence or an exhausted state. The exhausted CD8 T-cells had low PD-1 expression but high TIGIT and CD39 expression. These findings were corroborated in an independent pancreatic cancer single-cell RNA dataset. These data suggest that T-cells are major players in the suppressive microenvironment of pancreatic cancer. Our work identifies multiple novel therapeutic targets that should form the basis for rational design of a new generation of clinical trials in pancreatic ductal adenocarcinoma.
Development and Investigation of PEDOT:PSS Composition Coated Fabrics Intended for Microwave Shielding and Absorption

This study presents the investigation of the electromagnetic properties and resistance performance of electrically conductive fabrics coated with composition containing the conjugated polymer system poly(3,4-ethylenedioxythiophene)-polystyrene sulfonate (PEDOT:PSS). The developed fabrics were intended for electromagnetic radiation (EMR) shielding in microwave range and for absorbing microwaves in radar operating range, so as to act as radar absorbing materials (RAM). The measurements of reflection and transmission of the developed fabrics were performed in a frequency range of 2–18 GHz, which covers the defined frequencies relevant to the application. Four types of fabrics with different fiber composition (polyamide; polyamide/cotton; wool and para-aramid/viscose) were selected and coated with conductive paste using screen printing method. It was found that EMR shielding effectiveness (SE) as well as absorption properties depend not only the amount of conductive paste topped on the fabric, but also resides in the construction parameters of fabrics. Depending on such fabric structural parameters as density, mass per unit area, type of weave, a layer of shield (or coating) just sticks on the fabric surface or penetrates into fabric, changing the shield thickness and herewith turning SE results. Meanwhile, the fiber composition of fabrics influences mostly bonding between fibers and polymer coating. To improve the resistance performance of the developed samples, a conventional textile surface modification technique, atmospheric plasma treatment, was applied. Initially, before plasma treatment and after treatment the fabrics were evaluated regarding an aqueous liquid repellency test, measuring the contact angles for the water solvent. The influence of plasma treatment on resistance performance of coated fabrics was evaluated by subjecting the plasma treated samples and untreated samples to abrasion in the Martindale abrasion apparatus and to multiplex washing cycles. These investigations revealed that applied plasma treatment visibly improved abrasion resistance as a result of better adhesion of the coating. However, washing resistance increased not so considerably.
Pelvic Radiation Therapy Induced Vaginal Stenosis: A Review of Current Modalities and Recent Treatment Advances

Radiation-induced vaginal stenosis (VS) is a common side effect of pelvic radiotherapy (RT). RT-induced VS may have various negative effects on women’s quality of life, in particular dyspareunia, decreased vaginal lubrication and difficulties in sexual intercourse. This narrative review provides the aspects of RT-induced VS pathogenesis, incidence, evaluation and associated risk factors. Available treatment modalities are discussed in the article, putting the focus on preliminary, although promising, experience in the use of hyaluronic acid and laser therapy in cancer survivors after pelvic RT.
Differential Influence of Age on the Relationship between Genetic Mismatch and A(H1N1)pdm09 Vaccine Effectiveness

Assessment of influenza vaccine effectiveness (VE) and identification of relevant influencing factors are the current priorities for optimizing vaccines to reduce the impacts of influenza. To date, how the difference between epidemic strains and vaccine strains at genetic scale affects age-specific vaccine performance remains ambiguous. This study investigated the association between genetic mismatch on hemagglutinin and neuraminidase genes and A(H1N1)pdm09 VE in different age groups with a novel computational approach. We found significant linear relationships between VE and genetic mismatch in children, young adults, and middle-aged adults. In the children’s group, each 3-key amino acid mutation was associated with an average of 10% decrease in vaccine effectiveness in a given epidemic season, and genetic mismatch exerted no influence on VE for the elderly group. We demonstrated that present vaccines were most effective for children, while protection for the elderly was reduced and indifferent to vaccine component updates. Modeling such relationships is practical to inform timely evaluation of VE in different groups of populations during mass vaccination and may inform age-specific vaccination regimens.
Successful Direct Acting Antiviral Therapy in Chronic Hepatitis C Normalizes IFNγ and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells

Chronic hepatitis C infection (HCV) activates a systemic cell-mediated immune response characterized by the production of IFNγ and an innate immune response addressed by the activation of TLR signaling. We aimed to investigate whether HCV eradication by direct acting antivirals (DAA) leads to a recovery in cell-mediated immune response and TLR expression and functionality. Blood samples were obtained in HCV infected patients before DAA treatment and at week +48 after the end of treatment. Results were compared to healthy controls. Cell surface expression of TLR8 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated PBMCs were cultured with specific TLR8 agonists and intracellular production of cytokines was determined by flow-cytometry after ex vivo TLR8 activation with ssRNA 40. Production of IFNγ, IL2 and IL17 was assessed by flow cytometry in T cells after polyclonal activation. Included were 50 HCV-infected patients and 15 controls. TLR8 expression in PBMCs was significantly increased before treatment and recovered normal levels at week +48. Production of IL1b, IL6 and TNFα dependent on the activation of TLR8 in PBMCs was also increased in patients before DAA treatment, with a significant reduction at week +48. Combined expression of IFNγ and IL2 in CD4+ T cells in HCV-infected patients was significantly increased compared to controls and recovered normal levels at week +48. DAA-mediated clearance of HCV is associated with a decreased expression and activation of TLR8 in PBMCs until healthy control levels which is accompanied by a reduction in the Th1 response.
Retrieval of Vegetation Indices Related to Leaf Water Content from a Single Index: A Case Study of Eucalyptus globulus (Labill.) and Pinus radiata (D. Don.)

The vegetation indices derived from spectral reflectance have served as an indicator of vegetation’s biophysical and biochemical parameters. Some of these indices are capable of characterizing more than one parameter at a time. This study examines the feasibility of retrieving several spectral vegetation indices from a single index under the assumption that all these indices are correlated with water content. The models used are based on a linear regression adjusted with least squares. The spectral signatures of Eucalyptus globulus and Pinus radiata, which constitute 97.5% of the forest plantation in Valparaiso region in Chile, have been used to test and validate the proposed approach. The linear models were fitted with an independent data set from which their performance was assessed. The results suggest that from the Leaf Water Index, other spectral indices can be recovered with a root mean square error up to 0.02, a bias of 1.12%, and a coefficient of determination of 0.77. The latter encourages using a sensor with discrete wavelengths instead of a continuum spectrum to estimate the forestry’s essential parameters.
Affinity Sensors for the Diagnosis of COVID-19

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was proclaimed a global pandemic in March 2020. Reducing the dissemination rate, in particular by tracking the infected people and their contacts, is the main instrument against infection spreading. Therefore, the creation and implementation of fast, reliable and responsive methods suitable for the diagnosis of COVID-19 are required. These needs can be fulfilled using affinity sensors, which differ in applied detection methods and markers that are generating analytical signals. Recently, nucleic acid hybridization, antigen-antibody interaction, and change of reactive oxygen species (ROS) level are mostly used for the generation of analytical signals, which can be accurately measured by electrochemical, optical, surface plasmon resonance, field-effect transistors, and some other methods and transducers. Electrochemical biosensors are the most consistent with the general trend towards, acceleration, and simplification of the bioanalytical process. These biosensors mostly are based on the determination of antigen-antibody interaction and are robust, sensitive, accurate, and sometimes enable label-free detection of an analyte. Along with the specification of biosensors, we also provide a brief overview of generally used testing techniques, and the description of the structure, life cycle and immune host response to SARS-CoV-2, and some deeper details of analytical signal detection principles.
Diversifying the Utilization of Maize at Household Level in Zambia: Quality and Consumer Preferences of Maize-Based Snacks

This study evaluated the nutritional, antinutritional properties, and consumer preferences of five maize-based snacks at the household level. The physical, nutritional, and antinutritional properties were analyzed with standard laboratory methods, while a structured questionnaire was used for the data collection on consumer preferences of the maize products. There were significant (p < 0.05) differences in the proximate parameters of the maize snack samples. Antinutritional properties among maize snacks all fell within the permissible range. Respondents from all districts showed no significant (p > 0.05) differences in maize chin-chin variants’ and maize finger variants’ except for Serenje and Mkushi districts where maize chin-chin and maize finger showed significant (p < 0.05) differences in their sensory ratings. However, across districts, the most rated maize finger variant was the spiced 100% maize finger. In conclusion, maize-based snacks enriched with soybean flour have proven nutritious with a reasonable acceptability level.
Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by Tacrolimus: A Case Report

Immune checkpoint inhibitors (ICIs) increase T-cell activity and antitumor immune response. However, they also have immune-related adverse effects that can affect the gastrointestinal (GI) tract. A 62-year-old male patient who had undergone right lung upper lobectomy for adenocarcinoma of the lung received chemotherapy with pemetrexed sodium hydrate, carboplatin, and pembrolizumab to prevent postoperative recurrence of liver metastasis. However, the patient experienced severe diarrhea four months after the start of chemotherapy. Although a corticosteroid and two biological preparations were administered to alleviate the diarrhea, no improvement was observed. Eventually, remission was achieved when tacrolimus was administered. Treatment with corticosteroids is recommended for patients with GI adverse effects of ICIs. Rapid introduction of infliximab is necessary for refractory patients. Nevertheless, for refractory cases such as that of our patient, for whom even this regimen is inefficacious, tacrolimus might be recommended to induce remission as with cases of ulcerative colitis.
The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication

Myeloperoxidase is a signature enzyme of polymorphonuclear neutrophils in mice and humans. Being a component of circulating white blood cells, myeloperoxidase plays multiple roles in various organs and tissues and facilitates their crosstalk. Here, we describe the current knowledge on the tissue- and lineage-specific expression of myeloperoxidase, its well-studied enzymatic activity and incoherently understood non-enzymatic role in various cell types and tissues. Further, we elaborate on Myeloperoxidase (MPO) in the complex context of cardiovascular disease, innate and autoimmune response, development and progression of cancer and neurodegenerative diseases.
Sphingomyelinase D Activity in Sicarius tropicus Venom: Toxic Potential and Clues to the Evolution of SMases D in the Sicariidae Family

The spider family Sicariidae includes three genera, Hexophthalma, Sicarius and Loxosceles. The three genera share a common characteristic in their venoms: the presence of Sphingomyelinases D (SMase D). SMases D are considered the toxins that cause the main pathological effects of the Loxosceles venom, that is, those responsible for the development of loxoscelism. Some studies have shown that Sicarius spiders have less or undetectable SMase D activity in their venoms, when compared to Hexophthalma. In contrast, our group has shown that Sicarius ornatus, a Brazilian species, has active SMase D and toxic potential to envenomation. However, few species of Sicarius have been characterized for their toxic potential. In order to contribute to a better understanding about the toxicity of Sicarius venoms, the aim of this study was to characterize the toxic properties of male and female venoms from Sicarius tropicus and compare them with that from Loxosceles laeta, one of the most toxic Loxosceles venoms. We show here that S. tropicus venom presents active SMases D. However, regarding hemolysis development, it seems that these toxins in this species present different molecular mechanisms of action than that described for Loxosceles venoms, whereas it is similar to those present in bacteria containing SMase D. Besides, our results also suggest that, in addition to the interspecific differences, intraspecific variations in the venoms’ composition may play a role in the toxic potential of venoms from Sicarius species.
Digital Assessment of Gingival Dimensions of Healthy Periodontium

The aim of the present study was to re-visit the gingival dimension using digital scanning in a healthy Korean population. Forty-eight periodontally healthy volunteers (38 males and 10 females, mean age: 24.3 ± 2.2 years) were included. The mucogingival junction was highlighted using 2.5% diluted iodine solution. Then, the facial gingiva and mucosa of both jaws were digitally scanned using an intraoral digital scanner. Using computer software and periodontal probing, the heights and areas of keratinized gingiva (KG) and attached gingiva (AG) were measured. Similar distribution patterns in the gingival heights were noted in the maxilla and mandible. The maxilla showed substantially greater gingival values than the mandible. The heights of the KG and AG were notably smaller on the mandibular first premolar (2.37 mm and 1.07 mm, median value) and second molar (3.28 mm and 1.78 mm) than on the other teeth. The area of the KG was the largest in the canine (63.74 mm2 and 46.85 mm2) and first molar (64.14 mm2 and 58.82 mm2) in each jaw. Mandibular first and second molars, mandibular canine, and maxillary canine showed the highest value of the area under the receiver operation characteristics curve (>0.7) for differentiating between males and females. The gingival dimensions recorded using intraoral scanner demonstrated similar distribution patterns as in previous studies.
Synthesis of Poly(Ethylene Brassylate-Co-squaric Acid) as Potential Essential Oil Carrier

Bio-based compounds are a leading direction in the context of the increased demand for these materials due to the numerous advantages associated with their use over conventional materials, which hardly degrade in the environment. At the same time, the use of essential oils and their components is generated mainly by finding alternative solutions to antibiotics and synthetic preservatives due to their bioactive characteristics, but also to their synergistic capacity during the manifestation of different biological properties. The present study is devoted to poly(ethylene brassylate-co-squaric acid) (PEBSA), synthesis and its use for thymol encapsulation and antibacterial system formation. The synthesized copolymer, performed through ethylene brassylate macrolactone ring-opening and copolymerization with squaric acid, was physicochemical characterized. Its amphiphilic character allowed the entrapment of thymol (Ty), a natural monoterpenoid phenol found in oil of thyme, a compound with strong antiseptic properties. The copolymer chemical structure was confirmed by spectroscopic analyses. Thermal analysis evidenced a good thermal stability for the copolymer. Additionally, the antimicrobial activity of PEBSA_Ty complex was investigated against eight different reference strains namely: bacterial strains—Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Enterococcus faecalis ATCC 29212, Klebsiella pneumonie ATCC 10031 and Salmonella typhimurium ATCC 14028, yeast strains represented by Candida albicans ATCC10231 and Candida glabrata ATCC 2001, and the fungal strain Aspergillus brasiliensis ATCC9642.
Environmental Detection and Potential Transmission of Equine Herpesviruses

Equine herpesviruses (EHV) are a major health concern for domestic and wild equids and represent one of the most economically important disease agents of horses. Most known EHVs are transmitted directly between individuals as a result of direct exposure to exudates and aerosols. However, accumulating evidence suggests that environmental transmission may play a role including air, water, and fomites. Here, we reviewed studies on environmental stability and transmission of EHVs, which may influence viral dynamics and the use of environmental samples for monitoring EHV shedding.
Mild Head Trauma: Is Antiplatelet Therapy a Risk Factor for Hemorrhagic Complications?

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.
COVID-19 Vaccine Hesitancy among Young Adults in Saudi Arabia: A Cross-Sectional Web-Based Study

Ending the COVID-19 pandemic requires achieving herd immunity, either by previous infection or by vaccination. However, concerns about the COVID-19 vaccine are growing around the globe. The current study was conducted to investigate young the adult population’s hesitancy towards the vaccine. The study used a prospective cross-sectional design. Data was collected using an online self-administered questionnaire. A total of 862 Saudi adults participated. Information was gathered on the participants’ perspectives towards the severity and susceptibility of the COVID-19 infection, reasons for their hesitancy to receive the vaccine, perceived benefits, and reasons for action. Just under a quarter (19.6%) of respondents had previously tested positive for COVID-19. A small minority of the participants had already received the vaccine (2.1%), while 20.3% had registered in the Sehaty app (application) to receive the vaccine. Just under half of them (48%) will take the vaccine when mass vaccination is achieved and approximately the same number (46.7%) will only take it if it is made mandatory. Vaccine reluctance is highly prevalent among the general public in Saudi Arabia during the COVID-19 pandemic. While many are aware of a high likelihood of getting the infection, the efficacy and safety of the COVID-19 vaccine were reported as barriers to vaccination.