bluuebunny/crossref_metadata_2025 huggingface dataset:
The focus clinical research in intrahepatic cholangiocarcinoma
Authors: Song Yinghui , Cai Mengting , Li Yuhang , Liu Sulai
Published: July 2022

Intrahepatic cholangiocarcinoma (ICC), highly invasive and highly heterogeneous, has a poor prognosis. It has been confirmed that many risk factors are associated with ICC including intrahepatic lithiasis, primary sclerosing cholangitis (PSC), congenital abnormalities of the bile ducts, parasite infection, toxic exposures chronic liver disease (viral infection and cirrhosis) and metabolic abnormalities. In recent years, significant progress has been made in the clinical diagnosis and treatment of ICC. Advances in functional and molecular imaging techniques offer the possibility for more accurate preoperative assessment and detection of recurrence. Moreover, the combination of molecular typing and traditional clinical pathological typing provides accurate guarantee for clinical decision-making. Surgical resection is still the only radical treatment for ICC, while R0 resection, lymph node dissection, postoperative adjuvant therapy and recurrence resectomy have been confirmed to be beneficial for patients. New therapies including local therapy, molecular targeted therapy and immunotherapy are developing rapidly, which brings hopeful future for advanced ICC. The combination of traditional therapy and new therapy is the future development direction.
Effects of furosemide and tadalafil in both conventional and nanoforms against adenine-induced chronic renal failure in rats
Authors: Hamdy Moustafa Mahmoud , Abdel-Rahman Mahran S. , Badary Dalia M. , Sabra Mahmoud S.
Published: July 2022

Background

Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. The aim of this study was to study the efficacy of furosemide and tadalafil nanoforms compared to conventional forms against adenine-induced CRF rat-model.

Methods

Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1 beta (IL-1β) in renal tissues were performed.

Results

Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations had better renoprotective effect than individual drugs. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL).

Immunohistochemical studies showed that the deteriorated renal cellular changes indicated by increased expression of caspase-3 and IL-1β were greatly improved by the combined treatment particularly with the nanoforms.

Conclusions

The nanoforms of both furosemide and tadalafil had greater renopreventive effects compared with conventional forms against adenine-induced CRF in rats.
Association between sensitivity to thyroid hormone indices and the risk of osteoarthritis: an NHANES study
Authors: Chen Shuai , Sun Xiaohe , Zhou Guowei , Jin Jie , Li Zhiwei
Published: July 2022

Objectives

Thyroid hormones play an instrumental role in chondrogenic differentiation and matrix maturation. However, studies investigating the relationship between thyroid function and the risk of osteoarthritis (OA) remain scarce. This study was designed to investigate the correlation between thyroid status and OA from a novel perspective of sensitivity to thyroid hormones.

Methods

The study included 8478 people from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. The sensitivity to thyroid hormone indices included Thyrotroph Thyroxine Resistance Index (TT4RI), Thyroid-stimulating hormone (TSHI), Thyroid Feedback Quantile-based Index (TFQI), and Free Triiodothyronine /Free thyroxine (FT3/FT4), which were calculated based on serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH). Considering the complex survey design and sample weights, we employed multivariate linear regression models and stratified analysis to evaluate the correlation between sensitivity to thyroid hormone indices and OA.

Results

Study results indicated that participants with OA had elevated TT4RI, TSHI, and TFQI levels, and lower FT3/FT4 levels compared to those with non-arthritis. After adjusting for other covariates, FT3/FT4 was negatively associated with the risk of OA (OR = 1.162, 95%CI 1.048–1.478, P = 0.021); (OR = 1.261, 95%CI 1.078–1.623, P = 0.042). In subgroup analyses stratified by gender and BMI, participants with OA had higher TFQI levels compared to those without OA in both genders. (OR = 1.491, 95%CI 1.070–2.077, P = 0.018); (OR = 2.548, 95%CI 1.929–3.365, P < 0.001). The higher TFQI levels were consistently associated with the increased prevalence of OA in the BMI (< 18.5 kg/m2) group after adjusting for different covariates, but not in other BMI groups. In, addition, TFQI performed better than FT3/FT4, TSHI, and TT4RI on ROC analyses for OA prediction.

Conclusions

The levels of FT3/FT4, TSHI, TT4RI, and TFQI are strongly associated with the prevalence of OA, which illustrates the complex correlation between the thyroid system and chondrogenic differentiation. TFQI may be used as a helpful indicator to predict OA and provide novel ideas for the evaluation and treatment of OA.
Predictors of COVID-19-related health anxiety among health care workers: a cross-sectional study
Authors: Saeedi Maryam , Yazdi Sahar , Bahador Rasoul Corani
Published: July 2022

Background

One of the psychological issues that may affect health care workers (HCWs) during the outbreak of COVID-19 is health anxiety. Health anxiety disorder goes beyond normal health concerns and can seriously affect occupational and interpersonal performance. The present study was designed to determine the level of COVID-19-related health anxiety and its predictors in Iranian HCWs.

Methods

This is a cross-sectional study. Data were collected online through a demographic information questionnaire and the short version of the Health Anxiety Questionnaire. The online questionnaires were created via Google Form and the URL link was sent to HCWs via email or social networking applications. In total, questionnaires were sent to more than 1,500 HCWs throughout Iran. Data were analyzed with SPSS software version 23.

Results

Five hundred and fifty-two HCWs completed and sent the questionnaires. The mean scores of health anxiety of HCWs were higher than the cutoff point of health anxiety (17.28 ± 8.84) and 58.1% of HCWs had health anxiety. There was a significant inverse relationship between health anxiety score and age (r = − 0.13;P = 0.002), work experience (r = − 0.16;P < 0.001) and income level (r = − 0.097;P = 0.03). The rate of health anxiety was significantly higher in females (P = 0.03). Based on regression results, age and hospital category were significant risk factors for health anxiety.

Conclusion

Based on the results of this study, employees working in health centers in Iran had high health anxiety. Due to the high level of health anxiety in HCWs, it is important to consider strategies to reduce their health anxiety in the current situation.
A novel nitidine chloride nanoparticle overcomes the stemness of CD133+EPCAM+ Huh7 hepatocellular carcinoma cells for liver cancer therapy
Authors: Li Danni , Zhang Qiying , Zhou Yuzhu , Zhu Hua , Li Tong , Du Fangkai
Published: July 2022

Background

Stemness of CD133+EPCAM+ hepatocellular carcinoma cells ensures cancer resistance to apoptosis,which is a challenge to current liver cancer treatments. In this study, we evaluated the tumorcidal activity of a novel nanoparticle of nitidine chloride (TPGS-FA/NC, TPGS-FA: folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate, NC: nitidine chloride), against human hepatocellular carcinoma (HCC) cell line Huh7 growth in vitro and in vivo.

Methods

Huh7 cells were treated with TPGS-FA/NC. Cell proliferation was assessed using MTT and colony assays. The expression of cell markers and signaling proteins was detected using western blot analyses. A sphere culture technique was used to enrich cancer stem cells (CSC) in Huh7 cells. TPGS-FA/NC (7.5, 15, 30, 60, 120 μg/mL) dose-dependently inhibited the proliferation of HCC cells, which associated with a reduction in AQP3 and STAT3 expression. Importantly,TPGS-FA/NC (10, 20, and 40 μg/mL) significantly reduced the EpCAM+/CD133+cell numbers, suppressed the sphere formation. The in vivo antitumor efficacy of TPGS-FA/NC was proved in Huh7 cell xenograft model in BALB/c nude mice, which were administered TPGS-FA/NC(4 mg· kg − 1· d − 1, ig) for 2 weeks.

Results

TPGS-FA/NC dose-dependently suppressed the AQP3/STAT3/CD133 axis in Huh7 cells. In Huh7 xenograft bearing nude mice, TPGS-FA/NC administration markedly inhibited Huh7 xenograft tumor growth .

Conclusions

TPGS-FA/NC inhibit HCC tumor growth through multiple mechanisms, and it may be a promising candidate drug for the clinical therapy of hepatocellular carcinoma.
Porosity estimation of a geothermal carbonate reservoir in the German Molasse Basin based on seismic amplitude inversion
Authors: Wadas Sonja Halina , von Hartmann Hartwig
Published: July 2022

The Molasse Basin is one of the most promising areas for deep geothermal exploitation in Germany and the target horizon is the aquifer in the Upper Jurassic carbonates. Carbonate deposits can be very heterogeneous even over a small area due to diagenetic processes and varying depositional environments. The preferential targets for geothermal exploitation in carbonate deposits are fault zones, reef facies and karstified areas, since they are expected to act as hydraulically permeable zones due to high porosity and high permeability. Therefore, identifying these structures and characterizing, e.g., their internal porosity distribution are of high importance. This can be accomplished using 3D reflection seismic data. Besides structural information, 3D seismic surveys provide important reservoir properties, such as acoustic impedance, from which a porosity model can be derived. In our study area in Munich we carried out a seismic amplitude inversion to get an acoustic impedance model of the Upper Jurassic carbonate reservoir using a 3D seismic data set, a corresponding structural geological model, and logging data from six wells at the ‘Schäftlarnstraße’ geothermal site. The impedance model and porosity logs were than used to calculate a porosity model. The model shows a wide porosity range from 0 to 20% for the entire reservoir zone and the lithology along the wells reveals that dolomitic limestone has the highest porosities and calcareous dolomite has the lowest porosities. The study area is cut by a large W–E striking fault, the Munich Fault, and the footwall north of it shows higher porosities and more intense karstification than the hanging wall to the south. Considering the entire study area, an increase in porosity from east to west is observed. Furthermore, we identified a complex porosity distribution in reef buildups and pinnacle reefs. The reef cores have mostly low porosities of, e.g., < 3% and the highest porosities of up to 7 to 14% are observed at the reef caps and on the reef slopes. The reef slopes show a characteristic interfingering of the reef facies with the surrounding bedded facies, which indicates a syn-sedimentary reef development with slightly varying build up growth rates. We also assessed the reservoir quality with regard to porosity distribution and determined areas with moderate to good quality for geothermal exploitation by defining porosity evaluation levels. The porosity evaluation maps show that the carbonate rocks of Berriasian to Malm$$\zeta$$ζ1 are preferential targets for exploitation, especially in the footwall of the Munich Fault and to the west of the hanging wall, because these areas are characterized by high porosities due to intense karstification of bedded and massive facies, although the latter is mainly restricted to reef caps and reef slopes.
Estimating the health burden of road traffic injuries in Malawi using an individual-based model
Authors: Manning Smith Robert , Cambiano Valentina , Colbourn Tim , Collins Joseph H. , Graham Matthew , Jewell Britta , Li Lin Ines , Mangal Tara D. , Manthalu Gerald , Mfutso-Bengo Joseph , Mnjowe Emmanuel , Mohan Sakshi , Ng’ambi Wingston , Phillips Andrew N. , Revill Paul , She Bingling , Sundet Mads , Tamuri Asif , Twea Pakwanja D. , Hallet Timothy B.
Published: July 2022

Background

Road traffic injuries are a significant cause of death and disability globally. However, in some countries the exact health burden caused by road traffic injuries is unknown. In Malawi, there is no central reporting mechanism for road traffic injuries and so the exact extent of the health burden caused by road traffic injuries is hard to determine. A limited number of models predict the incidence of mortality due to road traffic injury in Malawi. These estimates vary greatly, owing to differences in assumptions, and so the health burden caused on the population by road traffic injuries remains unclear.

Methods

We use an individual-based model and combine an epidemiological model of road traffic injuries with a health seeking behaviour and health system model. We provide a detailed representation of road traffic injuries in Malawi, from the onset of the injury through to the final health outcome. We also investigate the effects of an assumption made by other models that multiple injuries do not contribute to health burden caused by road accidents.

Results

Our model estimates an overall average incidence of mortality between 23.5 and 29.8 per 100,000 person years due to road traffic injuries and an average of 180,000 to 225,000 disability-adjusted life years (DALYs) per year between 2010 and 2020 in an estimated average population size of 1,364,000 over the 10-year period. Our estimated incidence of mortality falls within the range of other estimates currently available for Malawi, whereas our estimated number of DALYs is greater than the only other estimate available for Malawi, the GBD estimate predicting and average of 126,200 DALYs per year over the same time period. Our estimates, which account for multiple injuries, predict a 22–58% increase in overall health burden compared to the model ran as a single injury model.

Conclusions

Road traffic injuries are difficult to model with conventional modelling methods, owing to the numerous types of injuries that occur. Using an individual-based model framework, we can provide a detailed representation of road traffic injuries. Our results indicate a higher health burden caused by road traffic injuries than previously estimated.
mRNA vaccine development for cholangiocarcinoma: a precise pipeline
Authors: Tang Tian-Yu , Huang Xing , Zhang Gang , Lu Ming-Hao , Liang Ting-Bo
Published: July 2022

Cholangiocarcinoma (CHOL) is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments, including immune checkpoint blockade therapy. The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases, however, its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection. A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines. In spite of a promising prospect, further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
Effect of preoperative nutritional support in malnourished patients with pancreatobiliary cancer: a quasi-experimental study
Authors: Park Hyeong Min , Kang Young Hwa , Lee Dong Eun , Kang Mee Joo , Han Sung-Sik , Park Sang-Jae
Published: July 2022

Background

In malnourished patients, postoperative morbidity, hospitalization period, and medical expenses are reportedly to be high. We evaluated the clinical impact of a preoperative nutritional support program (PNSP) among malnourished cancer patients.

Methods

For this quasi-experimental study, we enrolled 90 patients who underwent major pancreatobiliary cancer surgery. Malnutrition was defined as at least one of the following: (1) Patient-Generated Subjective Global Assessment (PG-SGA) grade B or C; (2) > 10% weight loss within 6 months; (3) body mass index <18.5 kg/m2; and (4) serum albumin level < 3.0 g/dL. Forty-five malnourished patients allocated to the PNSP group received in-hospital PNSP for a median of 6 (4–35) days. In the PNSP group, the nutrition support team calculated the patients’ daily nutritional requirements based on their nutritional status and previous day’s intake. The supplementation targets were as follows: total calorie intake, 30–35 kcal/kg/day; protein intake, 1.2–1.5 g/kg/day; and lipid intake, 1–1.5 g/kg/day. Patients who did not meet the diagnostic criteria for malnutrition were allocated to the well-nourished group and underwent surgery without receiving the PNSP (n = 45). We compared the perioperative nutritional indices (as measured using PG-SGA), postoperative outcome, and quality of life (QOL) according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0.

Results

In the PNSP group, the proportion of patients with serum prealbumin <16 mg/dL decreased significantly after PNSP (29.5% vs. 8.9%, p = 0.013). Moreover, patients with PG-SGA grade A had a statistically significant increase (2.2% vs. 50%, p < 0.001). The overall and major complication rates were higher in the PNSP group than in the well-nourished group without significance (51.1%, 33.3%; 42.2%, 26.7%, respectively). However, the overall and major complication rates were similar between the subgroup with PG-SGA improvement after PNSP and the well-nourished group (40.9% vs. 42.2%, p = 0.958; 27.3% vs. 26.7%, p = 0.525, respectively). QOL indicators in the PNSP group were comparable with those in the well-nourished group after PNSP.

Conclusion

PNSP may improve perioperative nutritional status and clinical outcomes among malnourished patients with pancreatobiliary cancer.
Choosing the right model for unified flexibility modeling
Authors: Brandt Jonathan , Frost Emilie , Ferenz Stephan , Tiemann Paul Hendrik , Bensmann Astrid , Hanke-Rauschenbach Richard , Nieße Astrid
Published: July 2022

Using aggregated flexibility from distributed small-scale power devices is an extensively discussed approach to meet the challenges in modern and increasingly stochastic energy systems. It is crucial to be able to model and map the flexibility of the respective power devices in a unified form to increase the value of the cumulative flexibility from different small-scale power devices by aggregation. In order to identify the most suitable approach for unified flexibility modeling we present a framework to evaluate and compare the advantages and disadvantages of already existing modeling approaches in different levels of detail. As an introduction to flexibility modeling and as a basis for the evaluation process we initially provide a comprehensive overview of the broad range of flexibility models described in scientific literature. Subsequently, five selected modeling approaches allowing the generation of a unified flexibility representation for different power devices are presented in detail. By using an evaluation metric we assess the suitability of the selected approaches for unified flexibility modeling and their applicability. To allow a more detailed performance analysis, the best evaluated models are implemented and simulations with different small-scale devices are performed. The results shown in this paper highlight the heterogeneity of modeling concepts deriving from the various interpretations of flexibility in scientific literature. Due to the varying complexity of the modeling approaches, different flexibility potentials are identified, necessitating a combination of approaches to capture the entire spectrum of the flexibility of different small-scale power devices. Furthermore, it is demonstrated that a complex model does not necessarily lead to the discovery of higher flexibility potentials, and recommendations are given on how to choose an appropriate model.
PLCL1 regulates fibroblast-like synoviocytes inflammation via NLRP3 inflammasomes in rheumatoid arthritis
Authors: Luo Shuai , Li Xiao-Feng , Yang Ying-Li , Song Biao , Wu Sha , Niu Xue-Ni , Wu Yuan-Yuan , Shi Wen , Huang Cheng , Li Jun
Published: July 2022

Background

Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA).

Methods

In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB.

Result

When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1.

Conclusion

Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.
Improved non-uniform subdivision scheme with modified Eigen-polyhedron
Authors: Zhang Jingjing , Tian Yufeng , Li Xin
Published: July 2022

In this study, a systematic refinement method was developed for non-uniform Catmull-Clark subdivision surfaces to improve the quality of the surface at extraordinary points (EPs). The developed method modifies the eigenpolyhedron by designing the angles between two adjacent edges that contain an EP. Refinement rules are then formulated with the help of the modified eigenpolyhedron. Numerical experiments show that the method significantly improves the performance of the subdivision surface for non-uniform parameterization.
How evolutionary science can help us understand vaccine refusal in the COVID-19 pandemic
Authors: Swanepoel Annie , Abed Riadh , Kaser Muzaffer , St John Smith Paul
Published: July 2022

Unvaccinated people have a mortality rate from COVID-19 that is 32-fold that of fully vaccinated people. Yet, in the UK, more than 4% of adults have not accepted a vaccine to protect them against COVID-19 and at the time of writing only 73% of people were fully vaccinated. Psychological and societal factors underlying vaccine hesitation or refusal are complex. In this paper, we use evolutionary science to help explain how vaccine refusal can be the result of an historic adaptation to protect against the repetition of past trauma, including, for many, that of systemic racism and/or deprivation, and misguided attempt to preserve fertility. We discuss some resulting cognitive biases and conclude with recommendations for practice.
Reactive Oxygen Species Contributes to Type 2 Diabetic Neuropathic Pain via the Thioredoxin-Interacting Protein-NOD–Like Receptor Protein 3-N-Methyl-D-Aspartic Acid Receptor 2B Pathway
Authors: Wang Jun-Wu , Ye Xiu-Ying , Wei Ning , Wu Shi-Shu , Zhang Zhe-Hao , Luo Guang-Hui , Li Xu , Li Jun , Cao Hong
Published: July 2022

BACKGROUND:

The number of patients with diabetic neuropathic pain (DNP) continues to increase, but available treatments are limited. This study aimed to examine the influence of reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NOD–like receptor protein 3 (NLRP3)-N-methyl-D-aspartic acid receptor 2B (NR2B) pathway on type 2 DNP.

METHODS:

Male Sprague-Dawley rats were fed with a high-fat and high-sugar diet for 8 weeks. Then, rats were intraperitoneally injected with streptozotocin (STZ, 35 mg/kg) to induce type 2 diabetes mellitus in rats. Diabetic rats with <85% of their basic levels in mechanical withdrawal threshold and thermal withdrawal latency were classified as DNP rats on day 14 after STZ injection. DNP rats were treated with ROS scavenger N-tert-Butyl-α-phenylnitrone (PBN, 100 mg·kg–1·d–1) or TXNIP small interfering ribonucleic acid (10 μg/d) once daily for 14 days. The level of ROS, protein levels of NLRP3, TXNIP, cysteinyl aspartate-specific proteinase-1 (caspase-1), interleukin-1β (IL-1β), NR2B phosphorylation at Tyr1472 (p-NR2B), total NR2B (t-NR2B), and distribution of NLRP3 in the spinal cord were examined. In vitro experiments, BV2 cells and PC12 cells were individually cultured and cocultured in a high-glucose environment (35 mmol/L D-glucose). The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, and IL-1β in BV2 cells, and p-NR2B, t-NR2B in PC12 cells were detected. The level of ROS was detected by the flow cytometry approach. The protein levels were detected by the Western blot technique. The location of NLRP3 was observed by immunofluorescent staining. The interaction between TXNIP and NLRP3 was detected by coimmunoprecipitation assay.

RESULTS:

The level of spinal ROS increased in DNP rats. The mechanical allodynia and thermal hyperalgesia of DNP rats were alleviated after systemic administration of PBN. This administration decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B and the coupling of TXNIP to NLRP3 in spinal cords of DNP rats. Furthermore, knockdown of spinal TXNIP alleviated nociceptive hypersensitivity and decreased protein levels of NLRP3, TXNIP, caspase-1, IL-1β, and p-NR2B in DNP rats. The level of ROS and protein levels of NLRP3, TXNIP, caspase-1, IL-1β, the coupling of TXNIP to NLRP3, and the IL-1β secretion increased in BV2 cells, and the protein expression of p-NR2B increased in cocultured PC12 cells in a high-glucose environment. All of these in vitro effects were significantly blocked after treatment of PBN.

CONCLUSIONS:

Our findings suggest that spinal ROS can contribute to type 2 DNP through TXNIP-NLRP3-NR2B pathway.
Μελέτη της ανοσολογικής ρύθμισης της αλλεργικής φλεγμονής των αεραγωγών
Authors: Ταγκαρέλη Σοφία
Published: July 2022

Παρόλο που τα FoxP3+ ρυθμιστικά Τ κύτταρα (Treg) αποτελούν έναν εξαιρετικά ετερογενή πληθυσμό, με ποικίλες ρυθμιστικές δυνατότητες που διαφέρουν ανάλογα με το πλαίσιο της νόσου, τα διακριτά υποσύνολα ή οι φαινότυποι δεν έχουν πλήρως χαρακτηρισθεί και μελετηθεί. Έτσι, εμποδίζεται η ανάπτυξη ανοσοθεραπευτικών μοντέλων για αλλεργικές και αυτοάνοσες διαταραχές. Η παρούσα μελέτη στοχεύει στον χαρακτηρισμό διακριτών FoxP3+ Treg υποπληθυσμών που συμμετέχουν στην καταστολή της από Th2 αλλεργικής φλεγμονής στον πνεύμονα.Για τη διεξαγωγή των πειραμάτων χρησιμοποιήσαμε ένα καθιερωμένο μοντέλο αλλεργικής νόσου των αεραγωγών σε μύες που περιλαμβάνει την ευαισθητοποίηση και την πρόκληση με οβαλβουμίνη (OVA). Τα FoxP3+ Treg κύτταρα αναλύθηκαν κατά την δημιουργία και την λύση της φλεγμονής ώστε να εντοπιστούν δείκτες που διακρίνουν και χαρακτηρίζουν τους πιο κατασταλτικούς φαινοτύπους. Αναπτύξαμε επίσης ένα νέο μοντέλο knock-in μυός (Foxp3creCd103dtr) που επιτρέπει συγκεκριμένη απαλοιφή του CD103+FoxP3+ Treg κυτάρων για τη μελέτη των λειτουργιών τους.Τα αποτελέσματα έδειξαν ότι κατά τη λύση της αλλεργικής φλεγμονής των αεραγωγών σε μύες, το >50% των FoxP3+ Treg κυττάρων εξέφρασαν την ιντεγκρίνη CD103 που χαρακτηρίζει FoxP3+ Treg κύτταρα με υψηλή παραγωγή της IL-10, αυξημένη έκφραση ανοσορυθμιστικών μορίων όπως KLRG1, ICOS και CD127 και ενισχυμένη κατασταλτική ικανότητα σε Th2 φλεγμονώδεις αποκρίσεις. Τα CD103+FoxP3+ Treg κύτταρα αποδείχθηκαν απαραίτητα για τη ρύθμιση της αλλεργικής φλεγμονής καθώς η ειδική απαλοιφή τους στους Foxp3creCd103dtr μύες οδήγησε σε σοβαρή βλάβη των κυψελιδικών τριχοειδών, ηωσινοφιλική πνευμονία και σημαντικά μειωμένη διάρκεια ζωής των πειραματοζώων. Από την άλλη πλευρά, η μεταφορά των CD103+FoxP3+ Treg κυττάρων αντιμετώπισε αποτελεσματικά τη νόσο, μετριάζοντας τις Th2 αποκρίσεις και την αλλεργική φλεγμονή μέσω της IL-10.Η μελέτη μας προσδιορίζει έναν νέο ρυθμιστικό πληθυσμό Τ-κυττάρων, που ορίζεται από την έκφραση του CD103, έχει προγραμματιστεί να αποτρέπει την τύπου 2 φλεγμονή. Τέλος, έχει την ικανότητα να ελέγχει την ομοιόσταση της αναπνευστικής οδού με σημαντικές θεραπευτικές επιπτώσεις.Η παρούσα μελέτη δημοσιεύτηκε στο διεθνές επιστημονικό περιοδικό Allergy με τίτλο: «CD103 integrin identifies a high IL-10-producing FoxP3+ regulatory T-cell population suppressing allergic airway inflammation».
Signals for invisible matter from solar - terrestrial observations
Authors: Μαρούδας Μάριος
Published: July 2022

Η σύσταση του σκοτεινού σύμπαντος, παρόλες τις υποθέσεις παραμένει ένα από τα μεγαλύτερα μυστήρια της μοντέρνας φυσικής. Σε μικρότερες κλίμακες, υπάρχουν διάφορα ηλιακά φαινόμενα τα οποία η γνωστή φυσική δεν μπορεί να εξηγήσει, όπως το πρόβλημα της θέρμανσης του ηλιακού στέμματος, η προέλευση των ηλιακών κηλίδων, ο μηχανισμός πυροδότησης των ηλιακών εκλάμψεων, αλλά και το ανοιχτό ζήτημα από τη δεκαετία του 1850 σχετικά με τις πλανητικές επιπτώσεις του ενεργού Ήλιου. Σημειωτέον, ο 11-ετής ηλιακός κύκλος παραμένει ένα από τα παλαιότερα ανοικτά ερωτήματα της ηλιακής φυσικής. Ταυτόχρονα, αρκετές επίγειες παρατηρήσεις σχετικά με τη δυναμική γήινη ατμόσφαιρα, όπως ο ιονοσφαιρικός ιονισμός τον Δεκέμβριο, είναι απροσδόκητες στο πλαίσιο της συμβατικής φυσικής. Με βάση την συγκεκριμένη εργασία, η προτεινόμενη κοινή λύση για όλα αυτά τα συμβατικώς ανεξήγητα φαινόμενα βασίζεται σε μια εξωτερική πυροδότηση που προκαλείται από χαμηλής ταχύτητας συστατικά του σκοτεινού τομέα, τα οποία εστιάζονται ή εκτρέπονται βαρυτικά από τον Ήλιο και τους πλανήτες. Για να συμβεί αυτό, πρέπει να υπάρχουν ρεύματα αόρατης ύλης τα οποία θα πρέπει να αλληλεπιδρούν ισχυρά με την βαρυονική ύλη. Μερικοί ταιριαστοί υποψήφιοι από τον σκοτεινό τομέα περιλαμβάνουν τα Antiquark Nuggets, τα μαγνητικά μονόπολα και τα σκοτεινά φωτόνια. Για την υποστήριξη αυτής της υπόθεσης καθώς και για την ύπαρξη ενός ή περισσότερων ρευμάτων παρέχονται αποδείξεις βασισμένες στην ανάλυση συμπτώσεων μακροχρόνιων αστροφυσικών και πλανητικών βάσεων δεδομένων. Σημειώνεται πως η πλανητική συσχέτιση αποτελεί την βασική υπογραφή. Προβάλλοντας τον χρόνο εμφάνισης των παρατηρησιακών δεδομένων στην τροχιακή θέση των διαφόρων πλανητών, συμπεριλαμβανομένης της Σελήνης, εμφανίζεται μια εντυπωσιακή ομαδοποίηση. Αυτή η στατιστικώς σημαντική έντονη δραστηριότητα σε ορισμένα πλανητικά ηλιοκεντρικά μήκη υποδεικνύει προτιμώμενες κατευθύνσεις στη ροή των υποτιθέμενων ρευμάτων, όπως πιθανώς από το Γαλαξιακό μας κέντρο. Αξίζει να σημειωθεί ότι ακόμη ισχυρότερες πλανητικές συσχετίσεις εμφανίζονται όταν συνδυάζεται η βαρυτική επίδραση δύο ή περισσότερων πλανητών. Μερικά από τα αποτελέσματα υποστηρίζονται επίσης από αναλύσεις Fourier. Επιπροσθέτως, η προκύπτουσα στατιστικώς σημαντική περιοδικότητα 27.32 ημερών στις περισσότερες βάσεις δεδομένων, η οποία ταυτίζεται με τον αστρικό μήνα της Σελήνης, ενισχύει τον ισχυρισμό μιας σημαντικής εξω-ηλιακής επιρροής. Τέλος, προτείνεται μια νέα στρατηγική για άμεσες αναζητήσεις Σκοτεινής Ύλης που εστιάζουν σε σκοτεινές ροές. Αυτή η νέα διαδικασία εφαρμόστηκε με επιτυχία στον ανιχνευτή CAST-CAPP στο CERN ο οποίος ψάχνει για αξιόνια Σκοτεινής Ύλης.
Acetylation mediates taurocholate uptake in hepatocytes possibly through modulation of NTCP1 activity
Authors: López-Ramirez Sayra Y. , López-Barradas Adriana M. , Noriega Lilia G.
Published: July 2022

Hepatic Sodium Taurocholate cotransporter polypeptide (NTCP1) captures approximately 80% of the conjugated bile acids that come from the enterohepatic circulation. Transcriptionally, NTCP1 expression is activated by an RAR/RXR heterodimer, which is repressed by SHP when intracellular bile acids are high. In addition, NTCP1 activity is post-translational modulated by phosphorylation. However, whether NTCP1 could be regulated by acetylation is unknown. A bioinformatic analysis for the mouse NTCP1 protein sequence showed potential lysine acetylation sites. Thus, we evaluated taurocholate uptake in hepatocytes incubated with NAM, which induced a two-fold increase in the content of acetylated proteins. Interestingly, taurocholate uptake was reduced by 50% in hepatocytes incubated with NAM. These results demonstrate that acetylation mediates taurocholate uptake in hepatocytes possibly through modulation of NTCP1 activity.
Storytelling and its influence on the promotion of tourism for the national sanctuary of Huayllay, Pasco Region, Peru in 2021
Authors: Jara Miranda Robert Alexander , Obregon Trujillo Ghinnett Yoyssy , Obregon Trujillo Huberta Violeta , Calvanapón Alva Flor Alicia , Reaño Portal Winston Rolando
Published: July 2022

Background: The objective of the study was to determine the influence of storytelling in the tourism promotion of the Huayllay National Sanctuary.

Methods: A quantitative approach study was used, a pre-experimental design with a single control group, and the study population consisted of 19 visitors to whom a pre-test and post-test were performed to evaluate the results obtained. The information collected was processed through the SPSS 26 statistical program and subsequently the event tree analysis (ETA) was performed to determine the degree of influence between the study variables.

Results: Results of 0.677 and 0.795 indicate that storytelling does have an influence on the promotion of tourism for the study area.

Conclusions: The study was able to determine that there is an influence between storytelling and tourism, and this can be used as a tourism promotion tool not only at the local level of the study site, but also at the national level.
Long-term health after Severe Acute Malnutrition in children and adults- the role of the Pancreas (SAMPA): Protocol
Authors: Ahmed Sana , PrayGod George , R. Lee Nanette , Kelly Paul , Trilok-Kumar Geeta , Chisenga Molly , Kweka Belinda , Faurholt-Jepsen Daniel , Krogh-Madsen Rikke , AM Shaw James , M. Paglinawan-Modoc Dixi , Solon Juan , Frahm Olsen Mette , Stefanovski Darko , Cox Sharon , Nitsch Dorothea , Keogh Ruth , Filteau Suzanne
Published: July 2022

Background: Prenatal growth retardation may increase the risk of later chronic non-communicable diseases (NCDs), including diabetes; however, long-term effects of wasting malnutrition in childhood or adulthood are less studied. Pancreatic exocrine and endocrine functions, both critical for nutrition and NCD aetiology, may not fully recover following malnutrition. However, the evidence and mechanistic information is piecemeal. We hypothesise that wasting malnutrition at any age has long-term detrimental effects on endocrine and exocrine pancreatic structure and function.

Methods: The SAMPA international research programme will assess pancreatic structure and function in 3700 participants from ongoing observational nutrition cohorts, two adolescent and four adult, in Zambia, Tanzania, Philippines, and India. Pancreas size, structure, and calcification will be assessed by ultrasound and computed tomography (CT) scan; exocrine function by faecal elastase and serum lipase; and endocrine function by haemoglobin A1c (HbA1c) and blood glucose, insulin and C-peptide concentrations during an oral glucose tolerance test (OGTT). In-depth hormonal analyses of incretins, glucagon, proinsulin and trypsinogen during OGTT and intravenous glucose tolerance tests will be done in subsets of adult participants. Pancreatic size and function outcomes will be compared between people with and without prior wasting malnutrition. Analyses will investigate effect modification by sex, current age, time since malnutrition, current body mass index and dietary patterns. Mathematical modelling of OGTT data will be used to estimate the relative contribution to glucose dysregulation of decreased insulin production, changes in insulin clearance and increased insulin resistance. Proinsulin/insulin ratio will be analysed in archived samples from the Tanzanian cohort using a nested case-control design to investigate whether abnormal values precede diabetes.

Conclusions: SAMPA, a large-scale multi-centre research programme using data from people with or without prior wasting malnutrition to assess several aspects of pancreatic phenotype, will provide coherent evidence for future policies and programmes for malnutrition and diabetes.
Hydrothermal carbonization (HTC) of dairy waste: effect of temperature and initial acidity on the composition and quality of solid and liquid products
Authors: Khalaf Nidal , Shi Wenxuan , Fenton Owen , Kwapinski Witold , Leahy J.J.
Published: July 2022

Background: Hydrothermal carbonization (HTC) of dairy processing waste was performed to investigate the effect of temperature and initial pH on the yield and composition of the solid (hydrochar) and liquor produced. All hydrochars met the EU requirements of organo-mineral solid fertilizers defined in the Fertilizing Products Regulation in terms of phosphorus (P) and mineral content.

Methods: Laboratory scale HTC was performed using pressurized reactors, and the products (solid and liquid) were collected, stored and analyzed for elemental composition and nutrient content using Inductively coupled plasma optical emission spectroscopy (ICP-OES), ultraviolet-visible spectrophotometry (UV-Vis) and other analytic techniques.

Results: Maximum hydrochar yield (60.67%) was observed at T=180℃ and pH=2.25, whereas the maximum P-recovery was 80.38% at T=220℃ and pH=4.6. The heavy metal content of the hydrochars was mostly compliant with EU limitations, except for Ni at T=220℃ and pH=8.32. Meanwhile, further study of Chromium (Cr) species is essential to assess the fertilizer quality of the hydrochars. For the liquid product, the increase in temperature beyond 200℃, coupled with an increase in initial acidity (pH=2.25) drove P into the liquor. Simultaneously, increasing HTC temperature and acidity increased the concentration of NO3- and NH4+ in the liquid products to a maximum of 278 and 148 mg/L, respectively, at T=180℃ and pH=4.6. Furthermore, no direct relation between final pH of liquor and NH4+ concentration was observed.

Conclusions: HTC improved the nutrient content of dairy waste, allowing for the production of potential solid organo-mineral fertilizers requiring additional treatment to ensure safe fertilizer application.
Strategic Directions of Development of Trade and Economic Relations of Russia in Global Value Chains
Authors: Morkovkin D. , Barinova V. , Nikonorova A. , Kolosova E.
Published: July 2022

The article analyzes the current trends in the formation of global value chains, identifies the main directions and factors for the creation and functioning of global value chains in the context of turbulent conditions of international trade in goods and services. The strategic directions of Russia's trade and economic relations in the context of the CDR are identified, taking into account the impact of the COVID-19 pandemic and sanctions restrictions.
Artificial Intelligence: Application and Development Prospects on the Example of Rocket and Space Instrumentation
Authors: Yadova N. , Osiko S.
Published: July 2022

The presented article deals with the implementation of artificial intelligence technologies in the instrument-making industry. The statistics of the use of systems with elements of artificial intelligence are analyzed. It presents the problems of legal regulation of artificial intelligence systems in the Russian Federation. In this regard, the purpose of the article is, on the one hand, to give the reader some information on state of intelligent systems in rocket and space instrumentation in the Russian Federation, and on the other hand, to identify the most promising areas of development in this area.
Modern ideas about the role of the hypothalamus in the implementation of adaptation programs under stressor loads (references)
Authors: Romanova K. , Hancheva O.
Published: July 2022

The starting point for the prevention of human disease is the study of the vital functions of a healthy organism, taking into account complex effects of external and internal factors. More often in clinical practice, doctors observe patients with advanced pathology, when the body has undergone significant changes, including at the level of systemic regulation (CNS, hypothalamus) and at the level of intercellular signaling and neuro-immune-endocrine interactions. Therefore, the basis of these changes, more often, are insignificant but permanent factors of the external or internal environment, which gradually accumulate and disrupt the functioning of central regulatory systems. The aim of our study was to analyze modern sources of information that highlight current issues of the role of the hypothalamus in the development of adaptation programs during the formation of stressors. Materials and methods: analysis of scientific publications taken from Google Scholar databases, Web of Science, Pub Med by keywords: rats, stress reactions, adaptation, neuroendocrine regulation, neurotransmitters, hypothalamus, supraoptic nucleus, paraventricular nucleus. Conclusions: Thus, the analysis of scientific sources demonstrated that the main stress studies were devoted to determining the state and role of dominant systems, but there were few facts that had explained the long-term changes of the hypothalamus in regulatory systems. These issues remain unresolved and need to be studied.

Introduction. Today, many facts and clinical observations about the complex effects of chronic stress of human body. The National Institutes of Health and the U.S. Veterans Health Administration conducted a large-scale cohort study that had provided evidence of an association between post-traumatic stress disorder and cardiovascular risk, had identified mechanisms that could cause this association, and had assessed prognostic risk, cardiovascular diseases [1]. Moreover, they form a post-stress syndrome, which by itself becomes a pathogenetic mechanism of disease formation.

Rebeca Robles-García together with other researchers in 2020 demonstrated that high urbanization could increase the risk of post-traumatic stress disorder due to the concentration of poverty, limited living space, substance use and crime. Women tend to be more disadvantaged socially and economically and are more likely to be victims of collective and domestic violence than men. Accordingly, urban women are more prone to traumatic events that increase the prevalence of post-traumatic stress disorder than rural women and men in both rural and urban areas, especially those without social and family protection and support [2]. That is, even minor and indistinct stressors that act constantly and can not be overcome by man become an important etiological factor in the formation of a number of diseases.
Oral collagen supplements intake on improving skin structure and function
Authors: Żyga Justyna
Published: July 2022

Introduction: Young and healthy skin is a beauty standard that generates the necessity of acceptance. Collagen supplements have recently grown in popularity and become a trendy product advertised as a remedy for various skin problems. As it turns out, numerous scientific studies have shown the benefits of hydrolyzed collagen supplementation in improving the signs of skin ageing. There are various animal sources of collagen, but marine fish collagen has the best safety profile, biocompatibility and bioavailability and remains the most frequent product used in scientific trials. Among newest randomised-control trials five were researched for this study to evaluate the efficacy of collagen supplementation and its influence of skin appearance with both objective and subjective assessment.

State of knowledge: hydrolysed collagen supplementation demonstrated a significant reduction in wrinkles, improvement in skin texture, firmness and appearance. Moreover, studies show significant enhancement of the water content in the stratum corneum and epidermis. Reduction of transepidermal water loss and increased level of natural moisturising factor was observed. 

Conclusions: hydrolysed collagen supplements can delay and improve the signs of skin ageing by decreasing facial wrinkles and improving skin hydration and elasticity. Supplement intake is effective and safe - analysed studies have not reported any major adverse effects. Since reviewed trials lasted for no longer than 12 weeks, further studies are needed to evaluate the long-term use of hydrolysed collagen peptides.
Przestrzeń i społeczeństwo Chrzanowa średniowiecznego i nowożytnego
Authors: Żurek Dorota
Published: July 2022

SPACE AND SOCIETY IN THE MEDIEVAL AND EARLY MODERN CHRZANÓW The thesis concentrates on the sociotopography of the city of Chrzanów. During the period under consideration it was a small city situated in the Kraków Land on the border of Lesser Poland and Silesia. The choice of this city was dictated mainly by the existence of a considerably rich source material. The main part of the source material used for the research consists of the municipal records preserved and stored in the National Archive in Kraków. The collection is comprised of twenty three municipal record books, thirteen of which were thoroughly analysed. One of the records is referred to as the counciltribunal record, two are labelled as the record of the municipal council, and the remaining ten are the records of the municipal tribunal. Apart from the municipal records other sources were used for the research, mainly fragments of the guild records and the guild privileges, records of the episcopal visitations, tax registers, and – essential for the sociotopographical research – city maps from the nineteenth century, including the cadastral map form 1848. The year 1655 marks the end point of the period under consideration, while the starting point is not precisely indicated. The analysis of the spatial and social structures covers a period from the first half of the fifteenth century, but it was also necessary to outline the earlier history of the town, especially the period prior to the location act, and settle the question of the date and circumstances of the location itself. Unfortunately it was impossible to decisively solve the last mentioned problem.
Many-Server Queues with Random Service Rates: A Unified Framework Based on Measure-Valued Processes
Authors: Büke Burak , Qin Wenyi
Published: July 2022

We consider many-server queueing systems with heterogeneous exponential servers, for which the service rate of each server is a random variable drawn from a given distribution. We develop a framework for analyzing the heavy-traffic diffusion limits of these queues using measure-valued stochastic processes. We introduce the measure-valued fairness process, which denotes the proportion of cumulative idleness experienced by servers whose rates fall in a Borel subset of the support of the service rates. It can be shown that these processes do not converge in the usual Skorokhod-J1 topology. Hence, we introduce a new notion of convergence based on shifted versions of these processes. We also introduce some useful martingales to identify limiting fairness processes under different routing policies. To demonstrate the power of our framework, we show how it can be used to prove diffusion limits for parallel server systems with within-pool heterogeneity.