bluuebunny/crossref_metadata_2025 huggingface dataset:
Complement factor H attenuates TNF-α-induced inflammation by upregulating EIF3C in rheumatoid arthritis
Authors: Jia Yimeng , Feng Bin , Ji Xin , Tian Xinping , Zhao Lidan , Zhou Jiaxin , Zhang Wen , Li Mengtao , Fei Yunyun , Wu Xunyao
Published: November 2023

Objective

To explore the role and underlying mechanism of Complement Factor H (CFH) in the peripheral and joint inflammation of RA patients.

Methods

The levels of CFH in the serum and synovial fluid were determined by ELISA. The pyroptosis of monocytes was determined by western blotting and flow cytometry. The inflammation cytokine release was tested by ELISA. The cell migration and invasion ability of fibroblast-like synoviocytes (FLS) were tested by Wound healing Assay and transwell assay, respectively. The potential target of CFH was identified by RNA sequencing.

Results

CFH levels were significantly elevated in the serum and synovial fluid from RA and associated with high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and disease activity score 28 (DAS28). TNF-α could inhibit CFH expression, and CFH combined with TNF-α significantly decreased cell death, cleaved-caspase 3, gasdermin E N-terminal (GSDME-N), and inflammatory cytokines release (IL-1β and IL-6) of RA-derived monocytes. Stimulated with TNF-α increased CFH levels in RA FLS and CFH inhibits the migration, invasion, and TNF-α–induced production of inflammatory mediators, including proinflammatory cytokines (IL-6, IL-8) as well as matrix metalloproteinases (MMPs, MMP1 and MMP3) of RA FLSs. The RNA-seq results showed that CFH treatment induced upregulation of eukaryotic translation initiation factor 3 (EIF3C) in both RA monocytes and FLS. The migration of RA FLSs was promoted and the expressions of IL-6, IL-8, and MMP-3 were enhanced upon EIF3C knockdown under the stimulation of CFH combined with TNF-α.

Conclusion

In conclusion, we have unfolded the anti-inflammatory roles of CFH in the peripheral and joints of RA, which might provide a potential therapeutic target for RA patients.
Impact of anakinra use on clinical outcomes in children with moderate or severe multisystem inflammatory syndrome in children: a propensity score matched retrospective cohort study
Authors: Akkoyun Esra B. , Most Zachary , Katragadda Harita , Yu Andrew , Nassi Lorien , Oakman Nicole , Ginsburg Sarah , Maamari Mia
Published: November 2023

Background

The treatment of children with multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 infection involves immunomodulatory therapies such as IVIG and steroids. Anakinra, an interleukin-1 receptor inhibitor, has also been used, but its effectiveness is not established yet. As optimal regimens for MIS-C remain unknown, we aimed to assess the effect of anakinra in reducing hospital stay in patients with MIS-C.

Methods

We included children admitted from May 2020 to May 2021 diagnosed with MIS-C based on CDC criteria. The exposure of interest was anakinra use at any point during admission. The anakinra exposed group and the anakinra unexposed group were propensity score matched based on demographic and clinical severity indicators at initial presentation. Our primary outcome was length of hospital stay. Secondary outcomes were duration of vasoactive support, vasoactive inotropic score (VIS), level of respiratory support, time to fever resolution, reduction of CRP levels, and length of ICU stay. We used Wilcoxon rank sum, t-test, Chi square and Fisher’s exact tests.

Results

Of 138 children diagnosed with MIS-C, 79% had moderate or severe illness and 41% received anakinra. Of those, 31 patients who received anakinra were propensity score matched to 31 who did not. The length of stay in the hospital but not in the ICU was longer in the anakinra group. There were no differences in median duration of vasoactive support, fever resolution, CRP reduction, or VIS.

Conclusions

In patients with moderate to severe MIS-C, use of anakinra was associated with longer duration of hospital stay.
Is it possible to extend the dose interval of canakinumab treatment in children with familial Mediterranean fever? PeRA group experience
Authors: Kavrul Kayaalp Gülşah , Çağlayan Şengül , Demirkan Fatma Gül , Guliyeva Vafa , Otar Yener Gülçin , Öztürk Kübra , Demir Ferhat , Özdel Semanur , Çakan Mustafa , Sönmez Hafize Emine , Sözeri Betül , Aktay Ayaz Nuray
Published: November 2023

Background

There is no clear data on the optimal duration of treatment with anti-interleukin-1 drugs in colchicine-resistant familial Mediterranean fever patients, as well as on the dose interval. This study aimed to assess patients whose canakinumab dose interval was adjusted according to a specific protocol, with the objective of evaluating the effectiveness of implementing this protocol for the patient care.

Methods

The files of 45 patients whose canakinumab treatment interval was opened with a standard protocol previously determined by the Delphi method were retrospectively reviewed.

Results

Canakinumab treatment was initiated once a month for all patients. In the sixth month of canakinumab treatment, a dose interval extension was introduced; however, 7 patients (15.5%) experienced an attack, and consequently, no further interval extension was administered to them. For 29 patients, the dose interval was successfully extended to once every three months, as they remained attack-free for a year after the first interval extension. Nine patients continued receiving the drug every 2 months, as they had not yet completed one year since the first extension. The study found no significant correlation between experiencing an attack during the dose interval extension protocol and the number, duration of attacks, or autoinflammatory diseases activity index score.

Conclusion

Extending treatment intervals with canakinumab in colchicine-resistant familial Mediterranean fever shows promise for favorable outcomes.
Mendelian randomization studies of depression: evidence, opportunities, and challenges
Authors: Ma Wang-ran , Zhang Lei-lei , Ma Jing-ying , Yu Fang , Hou Ya-qing , Feng Xiang-rui , Yang Lin
Published: November 2023

Background

Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches.

Methods

In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions.

Results

We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially.

Conclusions

While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.
Does structural form matter? A comparative analysis of pooled procurement mechanisms for health commodities
Authors: Parmaksiz Koray , van de Bovenkamp Hester , Bal Roland
Published: November 2023

Introduction

Pooled procurement can be seen as a collaboration initiative of buyers. Such mechanisms have received increased attention during the Covid-19 pandemic to improve access to affordable and quality-assured health commodities. The structural form of pooled procurement mechanisms ranges from a third-party organization that procures on behalf of its buyers to a buyer’s owned mechanism in which buyers operate more collaboratively. However, little is known about how these types of pooled procurement mechanisms differ in terms of characteristics, implementation and developmental process. To fill this gap, we compared four pooled procurement mechanisms. Two buyer’s owned mechanisms: the Organisation of the Eastern Caribbean States (OECS) and the Pacific Island Countries (PIC). And two third-party mechanisms: the Global Drug Facility (GDF) and the Asthma Drug Facility (ADF).

Methods

For this qualitative study, we used a multiple case-study design. The cases were purposefully selected, based on a most-similar case study design. We used the Pooled Procurement Guidance to collect data on individual cases and compared our findings between the case studies. For our analysis, we drew upon peer-reviewed academic articles, grey literature documents and 9 semi-structured interviews with procurement experts.

Results

Buyers within a buyer’s owned mechanisms differ in procurement systems, financing structures, product needs and regulatory and legal frameworks. Therefore, buyers within such mechanisms require relative alignment on motivations, goals and operations of the mechanism. Our study showed that buyers’ relative homogeneity of characteristics and their perceived urgency of the problems was particularly relevant for achieving that alignment.

Third-party organization mechanisms require less alignment and consensus-building between buyers. To participate, buyers need to align with the operations of the third-party organization, instead of other buyers. Elements that were essential for the successful implementation and operation of such mechanisms included the procurement secretariat’s ability to create local and global awareness around the problem, to induce political will to act upon the problem, to mobilize sufficient funding and to attract qualified staff.

Conclusion

To successfully sustain pooled procurement mechanisms over time, key actors should drive the mechanism through continuous and reflexive work on stakeholder engagement, mobilization of funding and alignment of interests and needs.
The relationship between creamatocrit and cumulative percentage of total milk volume: a cross-sectional study in mothers of very preterm infants in Bangkok, Thailand
Authors: Bowornkitiwong Walaiporn , Komoltri Chulaluk , Ngerncham Sopapan
Published: November 2023

Background

Human hindmilk contains higher concentrations of fat than foremilk and is more desirable for growth in preterm infants who can tolerate limited volumes of breastmilk. There is currently no clear demarcation between foremilk and hindmilk. This study characterized the change in breastmilk’s fat content from the start to end of milk flow and defined this demarcation.

Methods

Mothers of infants born at ≤ 32 weeks gestational age and ≥ 14 days after childbirth in a University hospital in Bangkok, Thailand between July, 2011, and April, 2012 were included in this cross-sectional study. Breastmilk samples were sequentially collected from the start to end of milk flow in 5-mL aliquots using breast pumps. The fat content of each aliquot from each breast was determined through creamatocrit. The average creamatocrit of foremilk and hindmilk were compared in predefined foremilk to hindmilk ratios of 20:80, 25:75, 33:67, and 50:50. Creamatocrit of the first and last aliquots were compared for mothers who expressed low- (≤ 25-mL per breast) and high-volumes (> 25-mL per breast) of breastmilk.

Results

Of the 25 mothers enrolled, one was excluded due to unsuccessful creamatocrit measurement. The last aliquot of breastmilk had a significantly higher creamatocrit than the first from the same breast (median [interquartile range] of 12.7% [8.9%, 15.3%] vs. 5.6% [4.3%, 7.7%]; test statistic 1128, p < 0.001). Mean creamatocrit in hindmilk portions (9.23%, 9.35%, 9.81%, and 10.62%, respectively) was significantly higher than foremilk portions (6.28%, 6.33%, 6.72%, and 7.17%, respectively) at all predefined ratios. Creamatocrit increased by 1% for every 10% incremental increase in expressed breastmilk volume until the breast was emptied. Low-volume mothers had a significantly higher creamatocrit in the first aliquot compared with high-volume mothers (U = 437, p = 0.002). No significant difference in breastmilk volume was observed between mothers with and without breastfeeding experience.

Conclusions

Fat content in breastmilk increased on an incremental basis. More fluid definitions of foremilk and hindmilk should be adopted. Mothers should prepare their breastmilk into aliquots based on the required feeding volume of their infant. Hindmilk aliquots can be prioritized over foremilk aliquots to ensure infants obtain optimal caloric intake.
Discrimination between the effects of pulsed electrical stimulation and electrochemically conditioned medium on human osteoblasts
Authors: Bielfeldt Meike , Budde-Sagert Kai , Weis Nikolai , Buenning Maren , Staehlke Susanne , Zimmermann Julius , Arbeiter Nils , Mobini Sahba , González María Ujué , Rebl Henrike , Uhrmacher Adelinde , van Rienen Ursula , Nebe Barbara
Published: November 2023

Background

Electrical stimulation is used for enhanced bone fracture healing. Electrochemical processes occur during the electrical stimulation at the electrodes and influence cellular reactions. Our approach aimed to distinguish between electrochemical and electric field effects on osteoblast-like MG-63 cells. We applied 20 Hz biphasic pulses via platinum electrodes for 2 h. The electrical stimulation of the cell culture medium and subsequent application to cells was compared to directly stimulated cells. The electric field distribution was predicted using a digital twin.

Results

Cyclic voltammetry and electrochemical impedance spectroscopy revealed partial electrolysis at the electrodes, which was confirmed by increased concentrations of hydrogen peroxide in the medium. While both direct stimulation and AC-conditioned medium decreased cell adhesion and spreading, only the direct stimulation enhanced the intracellular calcium ions and reactive oxygen species.

Conclusion

The electrochemical by-product hydrogen peroxide is not the main contributor to the cellular effects of electrical stimulation. However, undesired effects like decreased adhesion are mediated through electrochemical products in stimulated medium. Detailed characterisation and monitoring of the stimulation set up and electrochemical reactions are necessary to find safe electrical stimulation protocols.
Evaluation of a novel surface-coating formulation with time-extended antimicrobial activity for healthcare environment disinfection
Authors: Marano Roberto Bruno Maria , Merezhko Diana , Resnick Keren Anat , Moran-Gilad Jacob , Oster Yonatan
Published: November 2023

Background

The importance of environmental contamination in the transmission of pathogens among hospitalized patients is universally recognized, and disinfection of surfaces is a widely accepted modality for reducing healthcare-associated infections. Nevertheless, hospital disinfection is still suboptimal. In this study, we evaluated the sustained effects of the novel formulation OxiLast™ which extends the antimicrobial effects of chlorine-based disinfectants.

Methods

In an experimental lab phase, PVC surfaces were coated with OxiLast™ and then inoculated with representative Gram-positive and Gram-negative pathogenic bacteria. Cells were recovered at different contact times (5, 15, 30 min) to assess the reduction in bacterial counts compared to uncoated surfaces and also subject to various challenges to assess robustness. A similar methodology was then applied in an unoccupied hospital room to evaluate the sustained effect of OxiLast™ on high-touch surfaces.

Results

OxiLast™ demonstrated notable activity against the range of bacterial strains tested with ≥ 4 log10 reduction in bacterial counts observed for up to seven days following one surface application, for various strains and contact times. Similar results were observed following challenges such as simulated abrasion of coated surfaces, organic contamination or successive inoculations. The results were confirmed in a simulated patient care environment.

Conclusions

The addition of OxiLast™ to common chlorine-based disinfectants has shown a substantial and sustained reduction in bacterial pathogen counts for up to 7 days following one application. The consistent results in the laboratory and hospital are promising and should be tested in a real-life clinical scenario.
Volatile organic compounds produced by some synthetic essential oils as biological fumigants against Botrytis cinerea on apples
Authors: Karakus Sinem , Atıcı Okkes , Turan Metin , Azizi Sahar , Hajizadeh Hanifeh Seyed , Kaya Ozkan
Published: November 2023

Background

Gray mold, attributed to Botrytis cinerea, poses a substantial threat to food security in fruit-growing regions impacted by global climate change. Addressing this disease requires the utilization of either resilient plant varieties or advanced technological interventions. In this study, the research focused on examining the volatile organic compounds (VOCs) emitted by synthetic essential oils, namely thymol, eugenol, 1,8-cineol, and their combination, as potential biological fumigants against B. cinerea on Golden Delicious apples.

Results

In this study, a total of 53 compounds were identified and categorized into six distinct classes, which included (1) terpenes, (2) esters, (3) C6 compounds, (4) alcohols, (5) acids, and (6) aldehydes. The results we obtained revealed significant variations in the volatile compounds present in apples after harvest when treated with different essential oils to combat B. cinerea. Among the VOCs found in the fruits, the most abundant ones were pentanal, nerol, and ethyl octanoate. The essential oil combination of thymol, eugenol, and 1,8-cineol (Thy + Eug + Fun) had the most significant impact on the volatile compound content in the fruits. Conversely, both B. cinerea and the essential oils were observed to increase the volatile organic compound content in the fruits after harvest.

Conclusion

The findings from this study underscore the significance of essential oils as effective biological fumigants for countering Botrytis cinerea on apples. Furthermore, the study suggests that these essential oils have the potential to influence the composition of volatile organic compounds in postharvest apples. This research offers valuable insights into the intricate interplay between volatile organic compounds and essential oils in apples, emphasizing the critical role of essential oils in preserving fruit quality during the post-harvest period.

Graphical abstract
Reconciling opposite trends in the observed and simulated equatorial Pacific zonal sea surface temperature gradient
Authors: Bai Wenrong , Liu Hailong , Lin Pengfei , Li Xichen , Wang Fan
Published: November 2023

The reasons for large discrepancies between observations and simulations, as well as for uncertainties in projections of the equatorial Pacific zonal sea surface temperature (SST) gradient, are controversial. We used CMIP6 models and large ensemble simulations to show that model bias and internal variabilities affected, i.e., strengthened, the SST gradient between 1981 and 2010. The underestimation of strengthened trends in the southeast trade wind belt, the insufficient cooling effect of eastern Pacific upwelling, and the excessive westward extension of the climatological cold tongue in models jointly caused a weaker SST gradient than the recent observations. The phase transformation of the Interdecadal Pacific Oscillation (IPO) could explain ~ 51% of the observed SST gradient strengthening. After adjusting the random IPO phase to the observed IPO change, the adjusted SST gradient trends were closer to observations. We further constrained the projection of SST gradient change by using climate models’ ability to reproduce the historical SST gradient intensification or the phase of the IPO. These models suggest a weakened SST gradient in the middle of the twenty-first century.
The association between empirical dietary inflammatory pattern and colorectal cancer risk: a case-control study
Authors: Shateri Zainab , Makhtoomi Maede , Mansouri Fatemeh , Rajabzadeh-dehkordi Milad , Nouri Mehran , Rashidkhani Bahram
Published: November 2023

Background

Colorectal cancer (CRC) is the third most common cancer in Iran. Inflammation plays an essential role in developing CRC. A dietary pattern called the empirical dietary inflammatory pattern (EDIP) has recently been designed based on the inflammatory potential of the diet. Therefore, the present study aimed to investigate the impact of EDIP on the risk of CRC.

Methods

The current case-control study was conducted on 142 controls and 71 CRC cases in three general hospitals and Hospital Cancer Organization in Tehran, Iran. We calculated EDIP by a semi-quantitative food frequency questionnaire. The association between EDIP and CRC were evaluated by logistic regression. The level of significance was p < 0.05.

Results

The results revealed that people who were in the highest tertile of the EDIP had higher odds of CRC (in the adjusted model: odds ratio (OR) = 3.74; 95% confidence interval (CI): 1.38–10.14; P = 0.011).

Conclusion

The present study demonstrated the potential role of dietary-induced inflammation in developing CRC. In the current study, an increase in the intake of red meat, processed meats, and refined grains was observed in the higher EDIP tertiles compared to the lower tertiles. Consequently, to decrease the risk of CRC, it is recommended to reduce the consumption of these foods.
Vegetarian diets and risk of all-cause mortality in a population-based prospective study in the United States
Authors: Blackie Keeley , Bobe Gerd , Takata Yumie
Published: November 2023

The popularity of vegetarian diets has increased the need for studies on long-term health outcomes. A limited number of studies, including only one study from a non-vegetarian population, investigated the risk of mortality with self-identified vegetarianism and reported inconsistent results. This study evaluated prospective associations between vegetarian diets and all-cause mortality among 117,673 participants from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort study. Vegetarian diet status was self-identified on the questionnaire. Deaths were ascertained from follow-up questionnaires and the National Death Index database. Multivariable Cox regression models were used to estimate the risk of all-cause mortality in hazard ratio (HR) and 95% confidence intervals (CI). By diet group, there were 116,894 omnivores (whose diet does not exclude animal products), 329 lacto- and/or ovo-vegetarians (whose diet excludes meat, but includes dairy and/or eggs), 310 pesco-vegetarians (whose diet excludes meat except for fish and seafood) and 140 vegans (whose diet excludes all animal products). After an average follow-up of 18 years, 39,763 participants were deceased. The risk of all-cause mortality did not statistically significantly differ among the four diet groups. Comparing with the omnivore group, the HR (95% CI) were 0.81 (0.64–1.03) for pesco-vegetarian group, 0.99 (0.80–1.22) for lacto- and/or ovo-vegetarian group and 1.27 (0.99–1.63) for vegan group, respectively. Similarly, mortality risk did not differ when comparing lacto- and/or ovo-vegetarians plus vegans with meat/fish eaters (omnivores and pesco-vegetarians) (HR [95% CI] = 1.09 [0.93–1.28]). As this study is one of the two studies of vegetarianism and mortality in non-vegetarian populations, further investigation is warranted.
Dividend policy framework and bank risk-taking in Africa: do women inclusion in governance system offer new insight?
Authors: Ofori-Sasu Daniel , Dzeha Gloria Clarissa , Fiador Vera Ogeh , Abor Joshua Yindenaba
Published: November 2023

This study examines the role of women included in governance system in explaining the impact of dividend policy framework on the risk-taking of banks, using a panel dataset of 52 African countries over the period, 2006–2020. The empirical outcome confirms that independent women on the board has a lower probability of paying dividend, reduce dividend yield and induce less risk-taking of banks while women in country-level governance position seek to protect the interest of shareholders and subsequently increase the likelihood of dividend payments and risk-taking of banks. The study found that banks that pay dividends face stricter market discipline, which in turn reduces banks' risk-taking. The study found that dividend policy framework generally acts as a complement for risk-taking when independent women are included in corporate boards while it acts as a substitute control device for banks’ risk-taking when women are included in country-level governance positions. Based on the net effects, the study found robust and strong evidence to support that the dividend policy framework reduces the risk-taking at higher level of women included in governance system.
Coupled propagation dynamics on complex networks: A brief review
Authors: Wang Zhishuang , Li Haoxian , Chen Jiaxing , Hong Zhiyong , Yin Qian , Xia Chengyi
Published: November 2023

Coupled propagation dynamics based on complex networks have received widespread attention in recent years. This work reviews the research work related to coupling propagation dynamics on single-layer complex networks, multi-layer complex networks and high-order complex networks. We sort out relevant research results from three aspects: competitive propagation, cooperative propagation and asymmetric coupled propagation, finding that different coupling mechanisms focus on different dynamic properties. The dynamic characteristics such as coexistence threshold in competitive propagation, discontinuous phase transition in cooperative propagation, outbreak threshold and propagation prevalence in asymmetric coupling propagation have been extensively discussed. We conclude by giving some valuable future research topics in coupled propagation dynamics.
Method development for the determination of compounds of biological interest with modern analytical techniques in biological samples applied to health sciences
Authors: Μεϊκόπουλος Θωμάς
Published: November 2023

Η παρούσα διατριβή διερεύνησε την ανάπτυξη και εφαρμογή αναλυτικών μεθόδων LC-MS για τον προσδιορισμό μικρών ενδογενών και εξωγενών μορίων (<1000 Da) σε βιολογικά δείγματα. Σε όλη τη διάρκεια της διατριβής περιγράφονται καινοτόμες αναλυτικές μέθοδοι και οι εφαρμογές τους στη διερεύνηση σύγχρονων ζητημάτων που σχετίζονται με την ανθρώπινη υγεία. Πιο συγκεκριμένα, επιτεύχθηκε η ανάπτυξη και επικύρωση μεθόδων για τον ποσοτικό προσδιορισμό 13 ακυλοκαρνιτινών σε ανθρώπινο ορό, 4 κεραμιδίων σε δείγματα qDBS (ξηρές κηλίδες αίματος) και 14 αμινοξέων σε δείγματα DUS (ξηρές κηλίδες ούρων). Επιπλέον, αναπτύχθηκε αξιόπιστο πρωτόκολλο για τον προσδιορισμό 26 παράνομων ναρκωτικών σε δείγματα qDBS. Εκτός από τις στοχευμένες μεθόδους, εφαρμόστηκαν μη στοχευμένη μέθοδος λιπιδομικής ανάλυσης για μια ολιστική προσέγγιση βιολογικών ερωτημάτων, όπως η επίδραση της άσκησης στην ανθρώπινη ευεξία.
Μελέτες δομής και δυναμικής πρωτεϊνών που συνδέονται με ασθένειες μέσω προσομοιώσεων μοριακής δυναμικής
Authors: Λεσγίδου Ναστάζια-Λεμονιά
Published: November 2023

Οι πρωτεϊνικές κινάσες αποτελούν ένα πολυσύνθετο σύστημα με περίτεχνες και εξειδικευμένες αλληλεπιδράσεις, με βασικό τους ρόλο την ρύθμιση της καταλυτικής δραστηριότητας και την μετάδοση ενδοκυτταρικών μηνυμάτων ανάμεσα σε πρωτεΐνες. Αποτελούν εξαιρετικά δυναμικά μόρια, που λαμβάνουν μια χαρακτηριστική δίλοβη διαμόρφωση και έχουν δομικά συντηρημένες λειτουργικές περιοχές. Κατά την μετάβασή τους στα διάφορα στάδια του καταλυτικού τους κύκλου, εκτελούν μια δομική αναδιοργάνωση, ενώ ο μηχανισμός λειτουργίας τους έγκειται σε μια σειρά αλληλοεξαρτώμενων γεγονότων που έχει ως αποτέλεσμα την εναλλαγή ενεργών και ανενεργών καταστάσεων (διακόπτης ΟΝ/OFF). Η ΤΥΚ2 είναι µια κυτταροπλασµατική κινάση τυροσίνης, μέλος της ευρείας οικογένειας των πρωτεϊνικών κινασών JAK (Just Another Kinase), η οποία λαμβάνει μέρος σε διάφορα σηματοδοτικά μονοπάτια που συνδέονται με κρίσιμες ανοσορυθμιστικές λειτουργίες του οργανισμού. Ως εκ τούτου, η αλλαγή της λειτουργίας της είναι συνδεδεμένη με διάφορα νοσήματα και καρκίνους. Ιδιαίτερο ενδιαφέρον παρουσιάζει ένας συγκεκριμένος πολυμορφισμός του γονιδίου της ΤΥΚ2 (rs34536443) που οδηγεί σε αλλαγή της προλίνης 1104 σε αλανίνη και έχει αποδειχτεί ότι παρέχει προστασία σε διάφορα αυτοάνοσα νοσήματα όπως ψωριασική αρθρίτιδα, ερυθηµατώδης λύκος, ϱευµατοειδής αρθρίτιδα, σκλήρυνση κατά πλάκας, ϕλεγµονώδης νόσος του εντέρου και ενδοµητρίωση, ενώ ταυτόχρονα συνδέεται με διάφορους καρκίνους όπως καρκίνος στομάχου, καρκίνος μαστού, καρκίνος εντέρου, καρκίνος του πνεύμονα, λέμφωμα non-Hοdgkin και μελάνωμα. Σκοπός της παρούσας διατριβής είναι η διαλεύκανση του μηχανισμού λειτουργίας της ΤΥΚ2 καθώς μεταβαίνει στα διαφορετικά στάδια του καταλυτικού της κύκλου, η διερεύνηση του συσχετισμού της με μεταλλάξεις που προκαλούν καρκίνο και η κατανόηση του μηχανισμού λειτουργίας του μεταλλάγματος Ρ1104Α που παρέχει προστασία σε αυτοάνοσα νοσήματα. Η προσέγγιση που ακολουθείται περιλαμβάνει μεγάλου μήκους προσομοιώσεις μοριακής δυναμικής (ΜΔ) και ποικίλες μεθόδους ανάλυσης τους.
Archiwa jako pamięć czynna w ramach polityki historycznej. Zarys problematyki
Authors: Jaskółka-Leśniak Katarzyna
Published: November 2023

Współczesne dyskusje o polityce historycznej pojawiają się w kręgach historyków, a także zwykłych obywateli. Jaką rolę odgrywają archiwa w pamięci zbiorowej i polityce historycznej? Czy są one tylko biernymi repozytoriami pamięci kulturowej, jak twierdzi Aleida Assmann? Czy są raczej instytucjami pamiętania aktywnego? Tekst jest próbą zarysowania tej tematyki i udzielenia odpowiedzi na te pytania, analizując współczesne przykłady działalności różnego typu archiwów, zarówno instytucji państwowych jak i społecznych. Przedstawione działania archiwów sytuują je, podobnie jak muzea, w kręgu instytucji czynnej pamięci kulturowej. Archiwa działające w służbie historii krytycznej nie sposób w konsekwencji oderwać od polityki historycznej istniejącej niezależnie od czasów i systemów, prowadzonej jako polityka państwa albo jej przeciwstawna „kontrpolityka”.
Proces aktotwórczy w Biurze Komisarza Obwodu Kujawskiego (Naczelnika Powiatu Kujawskiego, Naczelnika Powiatu Włocławskiego) w latach 1816–1866
Authors: Guzman Daniel
Published: November 2023

System polskiej kancelarii akt spraw XIX w. wprowadzony do administracji Księstwa Warszawskiego znalazł kontynuacje w Królestwie Polskim. Celem artykułu jest przedstawienie procesu aktotwórczego, który dokonywał się w Biurze Komisarza Obwodu Kujawskiego, a następnie w Biurze Naczelnika Powiatu Włocławskiego. Charakterystykę procesu poprzedza omówienie struktury organizacyjnej urzędu. Przedstawienie obiegu dokumentacji zostało uzupełnione o szczegółowe informacje dotyczące ekspedycji pism, nieznane wcześniej w literaturze przedmiotu. Procesy aktotwórcze towarzyszyły również sprawom szczególnym, załatwianym przez samego zwierzchnika urzędu. Wspomagały je ściśle określone procedury, przewidziane prawem formularze dokumentów oraz ksiąg.
Porządek i budżet szwedzkiej kancelarii królewskiej z 1713 roku
Authors: Krawczuk Wojciech
Published: November 2023

Regulamin szwedzkiej kancelarii królewskiej z 1713 r., ustanowiony przez Karola XII, precyzyjnie definiował i określał zadania poszczególnych działów urzędu. Źródło służyć może jako punkt odniesienia dla porównań z innymi kancelariami królewskimi. Tłumaczenie ma ułatwić dostęp do tego ważnego aktu.
Drugie życie pieczęci urzędowej. Na przykładzie kolekcji typariuszy pieczęci urzędów PRL z lat 1945–1975 w zbiorze sfragistycznym Działu Numizmatycznego Muzeum książąt Lubomirskich w Ossolineum
Authors: Forysiak-Wójciński Robert
Published: November 2023

Zgodnie z przepisem prawnym dotyczącym wytwarzania i niszczenia pieczęci urzędowych, obowiązującym w PRL od 1955 r., wycofane z użytku tłoki pieczętne (typariusze) były zwracane przez urzędowych dysponentów do Mennicy Państwowej w celu ich kasacji. W 1975 r. Zakład Narodowy im. Ossolińskich jako instytucja, w której gromadzono także historyczne pieczęcie, zwrócił się z petycją do rządu, aby ten zatrzymał wykonanie ustawowego nakazu zniszczenia tłoków pieczęci urzędów powiatowych – zlikwidowanych na skutek bieżącej reformy administracyjnej – i przekazał je na własność do zbiorów instytucji. W następstwie pozytywnej odpowiedzi władz PRL do Działu Numizmatycznego Ossolineum trafiło blisko 3 tys. pieczęci używanych przez urzędy powiatowe i  inne terenowe władze w okresie 1945–1975 (z wyjątkami do 1977 r.). Artykuł przybliża ten mało znany epizod z historii sfragistyki urzędowej PRL, przedstawiając jego genezę, przebieg i rezultat, omawiając przy tym prawne uwarunkowania wytwarzania i niszczenia pieczęci urzędowych w okresie II RP i PRL. W drugiej części tekstu w oparciu o literaturę przedmiotu, nielicznie zachowane źródła archiwalne oraz na podstawie samego materiału sfragistycznego, tak licznie zgromadzonego w jednym zbiorze, a przez to stanowiącego reprezentatywną wartość dla niniejszych badań, odniesiono się do różnych kwestii istotnych dla sfragistyki w kontekście Mennicy Państwowej jako wytwórcy: formy i treści pieczęci, techniki wyrobu, materiału, wymiarów poszczególnych elementów tłoków, znaków i cech identyfikacyjnych, kwestii heraldycznych.
23. Ogólnopolski Zjazd Studentów Archiwistyki. Toruń, 1–3 czerwca 2022 r.
Authors: Aksamitowska Maja
Published: November 2023

Sprawozdanie sprawozdanie z 23. Ogólnopolskiego Zjazdu Stundetów Archiwistyki w Toruniu w dniach 1–3 czerwca 2022.
Archives as a Cultural Phenomenon.”4th Congress of Foreign Researchers of Polish History. Kraków, October 19.–22., 2022.
Authors: Janiarczyk Sylwia , Bubak Oliwia
Published: November 2023

Sprawozdanie z panelu "Archives as a Cultural Phenomenon". IV Kongres Zagranicznych Badaczy Dziejów Polski. Kraków, 19–22 października 2022 r.
Żeglińska, Anna. Finckensteinowie wschodniopruscy i ich archiwa. Gdańsk: Wydawnictwo Uniwersytetu Gdańskiego, 2021.
Authors: Syta Krzysztof
Published: November 2023

Recenzja: Żeglińska, Anna. Finckensteinowie wschodniopruscy i ich archiwa. Gdańsk: Wydawnictwo Uniwersytetu Gdańskiego, 2021.
Overconservativeness of Variance-Based Efficiency Criteria and Probabilistic Efficiency in Rare-Event Simulation
Authors: Bai Yuanlu , Huang Zhiyuan , Lam Henry , Zhao Ding
Published: November 2023

In rare-event simulation, an importance sampling (IS) estimator is regarded as efficient if its relative error, namely, the ratio between its standard deviation and mean, is sufficiently controlled. It is widely known that when a rare-event set contains multiple “important regions” encoded by the so-called dominating points, the IS needs to account for all of them via mixing to achieve efficiency. We argue that in typical experiments, missing less significant dominating points may not necessarily cause inefficiency, and the traditional analysis recipe could suffer from intrinsic looseness by using relative error or, in turn, estimation variance as an efficiency criterion. We propose a new efficiency notion, which we call probabilistic efficiency, to tighten this gap. In particular, we show that under the standard Gartner-Ellis large deviations regime, an IS that uses only the most significant dominating points is sufficient to attain this efficiency notion. Our finding is especially relevant in high-dimensional settings where the computational effort to locate all dominating points is enormous.

This paper was accepted by Baris Ata, stochastic models and simulation.

Funding: This work was supported by the National Science Foundation Division of Information and Intelligent Systems [Grants IIS-1849280 and IIS-1849304], Division of Civil, Mechanical and Manufacturing Innovation [Grant CAREER CMMI-1834710], and Division of Computer and Network Systems [Grant CNS-2047454].

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.4973 .
Representation of Women in Ngeri-Ngeri Sedap Film (2022)
Authors: Nofriandi Mochammad Dhafa , Nur Fitrinanda An
Published: November 2023

This research is entitled Representation of Women in Ngeri-Ngeri Sedap Film (2022). This research aims to find out how the representation of women in film Ngeri-Ngeri Sedap (2022). Film is a form of electronic communication in the form of audiovisual media capable of displaying words, sounds, images, and their combinations. Film is also one of the second modern forms of communication to emerge in the world. This research uses a qualitative method that refers to Roland Barthes' Semiotic Theory, researchers will carefully select from each scene or piece of film that depicts women's gender in it, then will be described and analyzed for denotation, connotation, and mythical meanings. With observation and documentation techniques in the form of screenshots of each scene of the film Ngeri-Ngeri Sedap (2022) which indicates the representation of women. Researchers used six scenes to analyze with the results obtained by researchers, namely the character Ms. Domu represents a woman who must obey all decisions from her husband. Ms. Domu even follows choices that are not in accordance with Ms. Domu's heart. Sarma represents a woman who is considered less important than her brother by her family. Sarma is considered not to have the right to speak out as a daughter in her own family. In fact, Sarma's character has big dreams of becoming a chef, but she has to follow the will of a family that is different from her dreams.
Analysis of self-healing reception to the song Beautiful by NCT
Authors: Nadiya Tita Putri , Hariyanti Nunik
Published: November 2023

Social media is an online forum for interaction, collaboration, and self-expression. Social institutions, systems, values, behavior, and attitudes change as social relations change. All levels of society feel this change, especially teens in transition. This transition makes teens want to find and try something new to discover themselves. Indonesian sociologists estimate that 4.2% of students have considered suicide. Academics, bullying, family, and economic issues also cause teen depression and suicidal thoughts. Recently, many people have discussed mental health. The self-healing method heals wounds. Music is an easy self-healing method. This therapy achieves relief from anxiety and stress. This research uses qualitative analysis with Stuart Hall's reception analysis method, which divides the encoding-decoding process into three positions to determine listeners' reception of Beautiful—hegemonic readers who accept the song's content without resistance. Negotiated Position or negotiation audience may accept the dominant ideology but sometimes resist. Listeners who reject the message are called opposition readers.
Representation of family warmness in Sasa advertisement Aku Pulang
Authors: Nisa Nur Ainun , Wibowo Arif Ardy
Published: November 2023

This research aims to analyze the representation of the Sasa coconut milk advertisement entitled "warmth of family and wealth of Omega 3 Coconut Milk" and then attempts to identify certain codes through semiotic analysis as proposed by Ferdinand De Saussure, where semiotic analysis differentiates between signifier and signified. This research uses qualitative methods to describe research findings. Based on the results of Ferdinand de Saussure's semiotic analysis regarding the signifiers and signifieds in the Sasa Santan Omega 3 advertisement, it can be seen that the use of music, one family and the character of the cow convey the meaning intended in the advertisement. product excellence, emphasizing that Sasa coconut milk is an advertisement that depicts family harmony at the dinner table and the richness of Omega 3 in coconut milk
Representation of Javanese social values and culture in Sukun special baru advertisement - Beda Masa Satu Rasa
Authors: Gunawan Putro Satrio Dirgantoro , Wibowo Arif Ardy
Published: November 2023

This research aims to analyze the representation of Javanese social values and culture in the Sukun Spesial Baru advertisement - Beda Masa Satu Rasa. The method that will be used is a qualitative approach with Ferdinand de Saussure's semiotic method. The results of this research reveal that Javanese social values and cultural in Sukun Spesial Baru advertisements - Beda Masa Satu Rasa are represented through obedient behavior to parents, mutual help behavior, Javanese marriage culture, and gathering culture. The representation of Javanese social values and culture in this advertisement is expected to raise awareness among the audience regarding the importance of preserving social values and Javanese cultural in social life, ensuring they are not simply influenced by globalization and modernization.
@Promodazzle marketing communication strategy in increasing consumer buying interest
Authors: Naufal Fasya Miftakhul , Farihanto Muhammad Najih
Published: November 2023

The increasing growth of the internet in Indonesia can change the way companies market their products. Marketing activities that use the internet can be known as internet marketing. With easy internet access, many companies now use social media to carry out sales functions as promotional media. Dazzle is one of the companies that has used social media to introduce its products and continues to strive to attract people's buying interest through marketing communication strategies. The method used in this research is a descriptive method with a qualitative approach. The activities carried out in this research method are data collection through several stages such as observation, interviews and documentation. The results of this research are that the Dazzle company carries out a marketing communication strategy through first, advertising carried out by offline media using LED boards and demo units, while online media uses social media such as TikTok, Instagram, Whatsapp. Second, sales promotion in the form of discounts, bundling, giveaways and pwp via Instagram accounts and holding games in each area. Third, public relations by collaborating with youth organizations, UKM, campus organizations and the media. Fourth, personal selling is carried out via WhatsApp to ask for complaints and provide tips and tricks when using the product. Dazzle also implements a chat SOP using emojis to interact with consumers. Fifth, direct marketing in the form of services provided in accordance with the SOP for implementing 5S and the criticism and suggestion column available in the Instagram bio.
The relationship of the intensity of Instagram social media use with narcissic behavior (Case study of Ahmad Dahlan University communication science study program students)
Authors: Sari Mutiara Pupita , Sumarlan Iman
Published: November 2023

Humans as social creatures need communication to interact so they can fulfill their needs. One of the media used to communicate is social media. The most widely used social media currently is known as Instagram. Current use of Instagram can also cause narcissistic behavior. This research is included in quantitative research and data was taken through questionnaires. The analysis technique used is simple regression analysis. Based on the results of research that has been conducted, it shows that the intensity of social media use has a positive and significant effect on narcissistic behavior.
The image of the government of Yogyakarta Special Region on the privileged funds (Media online coverage on privileged funds issues in Tempo.co, Kompas.com and KrJogja.com 2012 – 2022)
Authors: Zulham Fachry Muhammad , Rochimah Tri Hastuti Nur
Published: November 2023

The Special Region of Yogyakarta (DIY) is a province that acquired a special status as a special region. The privilege of Yogyakarta has been running for 10 years and still raises pros and cons in its implementation. One of the controversies is the use of the privileged funds budget. National and local media have also reported many pros and cons about these issues. This study aims to determine the image of the Yogyakarta Special Region Regional Government through the management of privileged funds in online media coverage (Tempo.co, Kompas.com and KrJogja.com) in the period 2012 - 2022. This research uses a quantitative approach with content analysis method. The results of this study show that the image of the Yogyakarta Special Region Regional Government through the management of special privilege funds for 10 years, tends to be negative. Judging from the news topics that have emerged, it has not had an impact on the welfare of society and the privilege fund program has not been oriented towards the welfare of society. Online media Tempo.co and Krjogja.com tend to negative reporting, meanwhile, Kompas.com has a neutral reporting tendency.
Digital content marketing strategy on social media Instagram @billacreative.id to increase brand engagement with MSMEs in 2023
Authors: Arni Nimas Cindy Monica , Sari Sovia Sitta
Published: November 2023

Along with the development of technology, especially the internet and the large number of people using smartphones, the growth of the digital advertising industry in Indonesia continues to increase. The large number of existing advertising agency companies is a challenge for advertising agencies themselves because competition is increasingly fierce. Therefore, every agency must have a good and attractive marketing communications strategy to be able to compete with similar businesses. One way is to implement content marketing to increase brand engagement with customers. The implementation of content marketing must be accompanied by choosing the right strategy, otherwise, brand engagement will not be achieved. One creative agency in Yogyakarta that is trying to implement this strategy to increase brand engagement is Billa Creative Agency. Billa Creative Agency is part of PT Billa Corp Indonesia, which provides social media marketing, branding, and digital creative services. The main focus is to support Micro, Small and Medium Enterprises (MSMEs) and business owners. This research aims to determine the digital content marketing strategy on social media Instagram @billacreative.id in increasing brand engagement with MSMEs in 2023. The theoretical framework consists of digital content marketing strategy and brand engagement. This research approach is qualitative with descriptive methods. Obtain data from interviews as well as additional supporting data. The result of this research will show how the digital content marketing strategy carried out by @billacreative.id can increase brand engagement with MSMEs via instagram.Keywords: Brand engagement, Creative agency, Digital content marketing, Instagram, Strategy
Communication strategy by department of communication and informatics of Bantul Regency to increase the number of Bantulpedia application user in achieving Smart City in 2023
Authors: Pramesthi Yosi Diah , Sofyan Nur
Published: November 2023

Bantulpedia is a platform created by the Department of Communication and Informatics of Bantul Regency. Bantulpedia is an application that integrates several public service applications to facilitate community governance in simplifying the administrative system, which often becomes an obstacle in decision-making and public services. As a government institution, the Department of Communication and Informatics of Bantul Regency needs to be actively involved in efforts to communicate the Bantulpedia application to the public in realizing the smart city concept in Bantul Regency. This study will discuss how the Department of Communication and Informatics in Bantul Regency will increase the number of Bantulpedia application users to achieve a Smart City in 2023. This research adopts a qualitative case study approach with data collection techniques involving interviews and document analysis. The findings of this study indicate that the Department of Communication and Informatics implements communication strategies by identifying the target audience, determining communication objectives, designing communication, choosing communication channels, determining the budget amount, determining the promotion mix, managing integrated marketing communication, and measuring results through evaluation. To achieve this goal, they utilize various media, such as radio, television, print media, social media, and exhibitions.#