bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic drug screening for trophoblast syncytialization reveals a novel role for MLL1 in regulating fetoplacental growth
Authors: Wu Jiayi , Qin Chuanmei , Tian Fuju , Liu Xueqing , Hu Jianing , Wu Fan , Chen Cailian , Lin Yi
Published: February 2024

Background

Abnormal placental development is a significant factor contributing to perinatal morbidity and mortality, affecting approximately 5–7% of pregnant women. Trophoblast syncytialization plays a pivotal role in the establishment and maturation of the placenta, and its dysregulation is closely associated with several pregnancy-related disorders, including preeclampsia and intrauterine growth restriction. However, the underlying mechanisms and genetic determinants of syncytialization are largely unknown.

Methods

We conducted a systematic drug screen using an epigenetic compound library to systematically investigate the epigenetic mechanism essential for syncytialization, and identified mixed lineage leukemia 1 (MLL1), a histone 3 lysine 4 methyltransferase, as a crucial regulator of trophoblast syncytialization. BeWo cells were utilized to investigate the role of MLL1 during trophoblast syncytialization. RNA sequencing and CUT&Tag were further performed to search for potential target genes and the molecular pathways involved. Human placenta tissue was used to investigate the role of MLL1 in TEA domain transcription factor 4 (TEAD4) expression and the upstream signaling during syncytialization. A mouse model was used to examine whether inhibition of MLL1-mediated H3K4me3 regulated placental TEAD4 expression and fetoplacental growth.

Results

Genetic knockdown of MLL1 or pharmacological inhibition of the MLL1 methyltransferase complex (by MI-3454) markedly enhanced syncytialization, while overexpression of MLL1 inhibited forskolin (FSK)-induced syncytiotrophoblast formation. In human placental villous tissue, MLL1 was predominantly localized in the nuclei of cytotrophoblasts. Moreover, a notable upregulation in MLL1 expression was observed in the villus tissue of patients with preeclampsia compared with that in the control group. Based on RNA sequencing and CUT&Tag analyses, depletion of MLL1 inhibited the Hippo signaling pathway by suppressing TEAD4 expression by modulating H3K4me3 levels on the TEAD4 promoter region. TEAD4 overexpression significantly reversed the FSK-induced or MLL1 silencing-mediated trophoblast syncytialization. Additionally, decreased hypoxia-inducible factor 1A (HIF1A) enrichment at the MLL1 promoter was observed during syncytialization. Under hypoxic conditions, HIF1A could bind to and upregulate MLL1, leading to the activation of the MLL1/TEAD4 axis. In vivo studies demonstrated that the administration of MI-3454 significantly enhanced fetal vessel development and increased the thickness of the syncytial layer, thereby supporting fetoplacental growth.

Conclusions

These results revealed a novel epigenetic mechanism underlying the progression of syncytialization with MLL1, and suggest potential avenues for identifying new therapeutic targets for pregnancy-related disorders.
Comparison of Sysmex XN-V body fluid mode and deep-learning-based quantification with manual techniques for total nucleated cell count and differential count for equine bronchoalveolar lavage samples
Authors: Lapsina Sandra , Riond Barbara , Hofmann-Lehmann Regina , Stirn Martina
Published: February 2024

Background

Bronchoalveolar lavage (BAL) is a diagnostic method for the assessment of the lower respiratory airway health status in horses. Differential cell count and sometimes also total nucleated cell count (TNCC) are routinely measured by time-consuming manual methods, while faster automated methods exist. The aims of this study were to compare: 1) the Sysmex XN-V body fluid (BF) mode with the manual techniques for TNCC and two-part differential into mononuclear and polymorphonuclear cells; 2) the Olympus VS200 slide scanner and software generated deep-learning-based algorithm with manual techniques for four-part differential cell count into alveolar macrophages, lymphocytes, neutrophils, and mast cells. The methods were compared in 69 clinical BAL samples.

Results

Incorrect gating by the Sysmex BF mode was observed on many scattergrams, therefore all samples were reanalyzed with manually set gates. For the TNCC, a proportional and systematic bias with a correlation of r = 0.79 was seen when comparing the Sysmex BF mode with manual methods. For the two-part differential count, a mild constant and proportional bias and a very small mean difference with moderate limits of agreement with a correlation of r = 0.84 and 0.83 were seen when comparing the Sysmex BF mode with manual methods. The Sysmex BF mode classified significantly more samples as abnormal based on the TNCC and the two-part differential compared to the manual method. When comparing the Olympus VS200 deep-learning-based algorithm with manual methods for the four-part differential cell count, a very small bias in the regression analysis and a very small mean difference in the difference plot, as well as a correlation of r = 0.85 to 0.92 were observed for all four cell categories. The Olympus VS200 deep-learning-based algorithm also showed better precision than manual methods for the four-part differential cell count, especially with an increasing number of analyzed cells.

Conclusions

The Sysmex XN-V BF mode can be used for TNCC and two-part differential count measurements after reanalyzing the samples with manually set gates. The Olympus VS200 deep-learning-based algorithm correlates well with the manual methods, while showing better precision and can be used for a four-part differential cell count.
Targeting of H19/cell adhesion molecules circuitry by GSK-J4 epidrug inhibits metastatic progression in prostate cancer
Authors: Pecci Valeria , Troisi Fabiola , Aiello Aurora , De Martino Sara , Carlino Angela , Fiorentino Vincenzo , Ripoli Cristian , Rotili Dante , Pierconti Francesco , Martini Maurizio , Porru Manuela , Pinto Francesco , Mai Antonello , Bassi Pier Francesco , Grassi Claudio , Gaetano Carlo , Pontecorvi Alfredo , Strigari Lidia , Farsetti Antonella , Nanni Simona
Published: February 2024

Background

About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer. Previously, we showed a transcriptional down-regulation of H19 under combined pro-tumoral estrogen and hypoxia treatment in PCa cells that, in turn, induced both E-cadherin and β4 integrin expression. H19, indeed, acts as transcriptional repressor of cell adhesion molecules affecting the PCa metastatic properties. Here, we investigated the role of H19/cell adhesion molecules circuitry on in vivo PCa experimental tumor growth and metastatic dissemination models.

Methods

H19 was silenced in luciferase-positive PC-3 and 22Rv1 cells and in vitro effect was evaluated by gene expression, proliferation and invasion assays before and after treatment with the histone lysine demethylase inhibitor, GSK-J4. In vivo tumor growth and metastasis dissemination, in the presence or absence of GSK-J4, were analyzed in two models of human tumor in immunodeficient mice by in vivo bioluminescent imaging and immunohistochemistry (IHC) on explanted tissues. Organotypic Slice Cultures (OSCs) from fresh PCa-explant were used as ex vivo model to test GSK-J4 effects.

Results

H19 silencing in both PC-3 and 22Rv1 cells increased: i) E-cadherin and β4 integrin expression as well as proliferation and invasion, ii) in vivo tumor growth, and iii) metastasis formation at bone, lung, and liver. Of note, treatment with GSK-J4 reduced lesions. In parallel, GSK-J4 efficiently induced cell death in PCa-derived OSCs.

Conclusions

Our findings underscore the potential of the H19/cell adhesion molecules circuitry as a targeted approach in PCa treatment. Modulating this interaction has proven effective in inhibiting tumor growth and metastasis, presenting a logical foundation for targeted therapy.
The interplay between obesity, immunosenescence, and insulin resistance
Authors: Shimi Ghazaleh , Sohouli Mohammad Hassan , Ghorbani Arman , Shakery Azam , Zand Hamid
Published: February 2024

Obesity, which is the accumulation of fat in adipose tissue, has adverse impacts on human health. Obesity-related metabolic dysregulation has similarities to the metabolic alterations observed in aging. It has been shown that the adipocytes of obese individuals undergo cellular aging, known as senescence. Senescence can be transmitted to other normal cells through a series of chemical factors referred to as the senescence-associated secretory phenotype (SASP). Most of these factors are pro-inflammatory compounds. The immune system removes these senescent T-cells, but immunosenescence, which is the senescence of immune cells, disrupts the clearance of senescent T-cells. Immunosenescence occurs as a result of aging or indirectly through transmission from senescent tissues. The significant occurrence of senescence in obesity is expected to cause immunosenescence and impairs the immune response to resolve inflammation. The sustained and chronic inflammation disrupts insulin's metabolic actions in metabolic tissues. Therefore, this review focuses on the role of senescent adipocyte cells in obesity-associated immunosenescence and subsequent metabolic dysregulation. Moreover, the article suggests novel therapeutic approaches to improve metabolic syndrome by targeting senescent T-cells or using senotherapeutics.

Graphical Abstract
The impact of goal-directed fluid therapy on postoperative pulmonary complications in patients undergoing thoracic surgery: a systematic review and meta-analysis
Authors: Han Shuang , Wu Xiaoqian , Li Pan , He Kun , Li Jianli
Published: February 2024

Background

Pulmonary complications after thoracic surgery are common and associated with significant morbidity and high cost of care. Goal-directed fluid therapy (GDFT) could reduce the incidence of postoperative pulmonary complications (PPCs) and facilitate recovery in patients undergoing major abdominal surgery. However, whether GDFT could reduce the incidence of PPCs in patients undergoing thoracic surgery was unclear. The present meta-analysis was designed to assess the impact of Goal-directed Fluid Therapy on PPCs in patients undergoing thoracic surgery.

Methods

Randomized controlled trials (RCTs) comparing GDFT with other conventional fluid management strategies in adult patients undergoing thoracic surgery were identified. Databases searched included PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 (The Cochrane Collaboration, Oxford, UK) software was used for statistical analysis. Heterogeneity was analyzed using I2 statistics, and a standardized mean difference with 95% CI and P value was used to calculate the treatment effect for outcome variables. The primary study outcomes were the incidence of PPCs. Secondary outcomes were the total volume infused, the length of hospitalization, the incidence of cardiac complications, and the incidence of renal dysfunction. Subgroup analysis was planned to verify the definite role of GDFT.

Results

A total of 6 RCTs consisting of 680 patients were included in this meta-analysis, which revealed that GDFT did not reduce the incidence of PPCs in patients undergoing thoracic surgery (RR, 0.57; 95% CI 0.29–1.14). However, GDFT decreased the total intra-operative fluid input (MD, − 244.40 ml; 95% CI − 397.06 to − 91.74). There was no statistical difference in the duration of hospitalization (MD; − 1.31, 95% CI − 3.00 to 0.38), incidence of renal dysfunction (RR, 0.62; 95% CI 0.29–1.35), and incidence of cardiac complications (RR, 0.62; 95% CI 0.27–1.40).

Conclusions

The results of this meta-analysis indicate that GDFT did not reduce the postoperative incidence of pulmonary complications in individuals undergoing thoracic surgery. However, considering the small number of contributing studies, these results should be interpreted with caution.
Procedures to combine estimators of greenhouse gases emission factors
Authors: Marujo Ernesto C. , Rodrigues Gleice G. , Covatti Arthur A.
Published: February 2024

Background

This article describes a new procedure to estimate the mean and variance of greenhouse gases (GHG) emission factors based on different, possibly conflicting, estimates for these emission factors. The procedure uses common information such as mean and standard deviation usually reported in IPCC (Intergovernmental Panel on Climate Change) database and other references in the literature that estimate emission factors. Essentially, it is a procedure in the class of meta-analysis, based on the computation of $${S}_{a}^{2}$$

S

a

2

, a new estimator for the variance of the emission factor.

Results

We discuss the quality of this estimator in terms of its probability distribution and show that it is unbiased. The resulting confidence interval for the mean emission factor is tighter than those that would have resulted from using other estimators such as pooled variance and thus, the new procedure improves the accuracy in estimating GHG emissions.

The application of the procedure is illustrated in a case study involving the estimation of methane emissions from rice cultivation.

Conclusions

The estimation of emission factors using $${S}_{a}^{2}$$

S

a

2

was demonstrated to be more accurate because it is not biased and more precise than alternative methods.
The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer
Authors: Hosseinzadeh Leila , Kikhtyak Zoya , Laven-Law Geraldine , Pederson Stephen M. , Puiu Caroline G. , D’Santos Clive S. , Lim Elgene , Carroll Jason S. , Tilley Wayne D. , Dwyer Amy R. , Hickey Theresa E.
Published: February 2024

Background

The androgen receptor (AR) is a tumor suppressor in estrogen receptor (ER) positive breast cancer, a role sustained in some ER negative breast cancers. Key factors dictating AR genomic activity in a breast context are largely unknown. Herein, we employ an unbiased chromatin immunoprecipitation-based proteomic technique to identify endogenous AR interacting co-regulatory proteins in ER positive and negative models of breast cancer to gain new insight into mechanisms of AR signaling in this disease.

Results

The DNA-binding factor GATA3 is identified and validated as a novel AR interacting protein in breast cancer cells irrespective of ER status. AR activation by the natural ligand 5α-dihydrotestosterone (DHT) increases nuclear AR-GATA3 interactions, resulting in AR-dependent enrichment of GATA3 chromatin binding at a sub-set of genomic loci. Silencing GATA3 reduces but does not prevent AR DNA binding and transactivation of genes associated with AR/GATA3 co-occupied loci, indicating a co-regulatory role for GATA3 in AR signaling. DHT-induced AR/GATA3 binding coincides with upregulation of luminal differentiation genes, includingEHFandKDM4B, established master regulators of a breast epithelial cell lineage. These findings are validated in a patient-derived xenograft model of breast cancer. Interaction between AR and GATA3 is also associated with AR-mediated growth inhibition in ER positive and ER negative breast cancer.

Conclusions

AR and GATA3 interact to transcriptionally regulate luminal epithelial cell differentiation in breast cancer regardless of ER status. This interaction facilitates the tumor suppressor function of AR and mechanistically explains why AR expression is associated with less proliferative, more differentiated breast tumors and better overall survival in breast cancer.
Broken-fat pad sign: a characteristic radiographic finding to distinguish between knee rheumatoid arthritis and osteoarthritis
Authors: Wang Qizheng , Zhao Weili , Ji Xiaoxi , Chen Yongye , Liu Ke , Zhu Yupeng , Yan Ruixin , Qin Siyuan , Xin Peijin , Lang Ning
Published: February 2024

Objectives

Diagnostic imaging plays an important role in the pre-treatment workup of knee osteoarthritis (OA) and rheumatoid arthritis (RA). Herein, we identified a useful MRI sign of infrapatellar fat pad (IPFP) to improve diagnosis.

Methods

Eighty-one age- and sex-matched RA and OA patients each, with pathological diagnosis and pre-treatment MRI were retrospectively evaluated. All randomized MR images were blinded and independently reviewed by two radiologists. The assessment process included initial diagnosis, sign evaluation, and final diagnosis, with a 3-week interval between each assessment. Broken-fat pad (BFP) sign was assessed on sagittal T2-weighted-imaging in routine MRI. The area under the curve and Cohen’s kappa (κ) were used to assess the classification performance. Two shape features were extracted from IPFP for quantitative interpretation.

Results

The median age of the study population was 57.6 years (range: 31.0–78.0 years). The BFP sign was detected more frequently in patients with RA (72.8%) than those with OA (21.0%). Both radiologists achieved better performance by referring to the BFP sign, with accuracies increasing from 58.0 to 75.9% and 72.8 to 79.6%, respectively. The inter-reader correlation coefficient showed an increase from fair (κ = 0.30) to substantial (κ = 0.75) upon the consideration of the BFP sign. For quantitative analysis, the IPFP of RA had significantly lower sphericity (0.54 ± 0.04 vs. 0.59 ± 0.03, p < 0.01). Despite larger surface-volume-ratio of RA (0.38 ± 0.05 vs. 0.37 ± 0.04, p = 0.25) than that of OA, there was no statistical difference.

Conclusions

The BFP sign is a potentially important diagnostic clue for differentiating RA from OA with routine MRI and reducing misdiagnosis.

Critical relevance statement

With the simple and feasible broken-fat pad sign, clinicians can help more patients with early accurate diagnosis and proper treatment, which may be a valuable addition to the diagnostic workup of knee MRI assessment.

Key points

• Detailed identification of infrapatellar fat pad alterations of patients may be currently ignored in routine evaluation.

• Broken-fat pad sign is helpful for differentiating rheumatoid arthritis and osteoarthritis.

• The quantitative shape features of the infrapatellar fat pad may provide a possible explanation of the signs.

• This sign has good inter-reader agreements and is feasible for clinical application.

Graphical Abstract
Salivary gland secretory carcinoma presenting as a cervical soft tissue mass: a case report
Authors: Mokhles Parisa , Sadeghipour Alireza , Babaheidarian Pegah , Mohebbi Saleh , Keshtpour Amlashi Zahra , Gharib Mohammad Hadi , Ahmadi Mohammad Saeid , Khastkhodaei Zeinab
Published: February 2024

Background

Secretory carcinoma (SC) has been described as a distinct salivary gland tumor in the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. SC is generally considered as a slow-growing low-grade malignant tumor, while several cases have been reported with high-grade features, and even metastases in the literature up until now. In this article, a soft tissue SC case is discussed with high-grade microscopic features and neural invasion. A review of the salivary gland SC cases with aggressive behavior is also debated.

Case presentation

A 65-year-old Caucasian man presented with a left neck mass for the past six months. The imaging studies demonstrated a very large cystic cervical mass (46 × 23 mm) with papillary projections in the anterolateral aspect of the left neck zone Vb. He underwent left radical neck dissection (level I-V) and was followed up for 12 months with the diagnosis of Secretory carcinoma.

Conclusion

Although SC generally has a good outcome, multiple recurrences and unusual metastases may occur, which should be considered by either the pathologists or clinicians.
Effects of training flights of combat jet pilots on parameters of airway function, diffusing capacity and systemic oxidative stress, and their association with flight parameters
Authors: Bojahr Janina , Jörres Rudolf A. , Kronseder Angelika , Weber Frank , Ledderhos Carla , Roiu Immanuel , Karrasch Stefan , Nowak Dennis , Teupser Daniel , Königer Christian
Published: February 2024

Background

Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations.

Methods

Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2’-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used.

Results

DLNO, DLCO, KNO, KCO and VA were reduced (p < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DLNO (DLCO) were smaller (p < 0.001) than those of KNO (KCO). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising Gz-forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DLNO and DLCO.

Conclusions

The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet.
Role of HOXA1-4 in the development of genetic and malignant diseases
Authors: Wang Lumin , Sun Haifeng , Cao Li , Wang Jinhai
Published: February 2024

The HOXA genes, belonging to the HOX family, encompass 11 members (HOXA1-11) and exert critical functions in early embryonic development, as well as various adult processes. Furthermore, dysregulation of HOXA genes is implicated in genetic diseases, heart disease, and various cancers. In this comprehensive overview, we primarily focused on the HOXA1-4 genes and their associated functions and diseases. Emphasis was placed on elucidating the impact of abnormal expression of these genes and highlighting their significance in maintaining optimal health and their involvement in the development of genetic and malignant diseases. Furthermore, we delved into their regulatory mechanisms, functional roles, and underlying biology and explored the therapeutic potential of targeting HOXA1-4 genes for the treatment of malignancies. Additionally, we explored the utility of HOXA1-4 genes as biomarkers for monitoring cancer recurrence and metastasis.
Thermal tolerance in an extremophile fish from Mexico is not affected by environmental hypoxia
Authors: Pacher Korbinian , Hernández-Román Natalia , Juarez-Lopez Alejandro , Jiménez-Jiménez Jesús Emmanuel , Lukas Juliane , Sevinchan Yunus , Krause Jens , Arias-Rodríguez Lenin , Bierbach David
Published: February 2024

The thermal ecology of ectotherm animals has gained considerable attention in the face of human-induced climate change. Particularly in aquatic species, the experimental assessment of critical thermal limits (CTmin and CTmax) may help to predict possible effects of global warming on habitat suitability and ultimately species survival. Here we present data on the thermal limits of two endemic and endangered extremophile fish species, inhabiting a geothermally heated and sulfur-rich spring system in southern Mexico: The sulfur molly (Poecilia sulphuraria) and the widemouth gambusia (Gambusia eurystoma). Besides physiological challenges induced by toxic hydrogen sulfide and related severe hypoxia during the day, water temperatures have been previously reported to exceed those of nearby clearwater streams. We now present temperature data for various locations and years in the sulfur spring complex and conducted laboratory thermal tolerance tests (CTmin and CTmax) both under normoxic and severe hypoxic conditions in both species. Average CTmax limits did not differ between species when dissolved oxygen was present. However, critical temperature (CTmax=43.2°C) in P. sulphuraria did not change when tested under hypoxic conditions, while G. eurystoma on average had a lower CTmax when oxygen was absent. Based on this data we calculated both species' thermal safety margins and used a TDT (thermal death time) model framework to relate our experimental data to observed temperatures in the natural habitat. Our findings suggest that both species live near their thermal limits during the annual dry season and are locally already exposed to temperatures above their critical thermal limits. We discuss these findings in the light of possible physiological adaptions of the sulfur-adapted fish species and the anthropogenic threats for this unique system.
Exercise as Medicine for People with a Substance Use Disorder: An ACSM Call to Action Statement
Authors: Nock Nora L. , Stoutenberg Mark , Cook Dane B. , Whitworth James W. , Janke E. Amy , Gordon Adam J.
Published: February 2024

Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.
Η συμβολή της περιστροφικής θρομβοελαστομετρίας (ROTEM) στην πρόγνωση και θεραπεία της εγκαυματικής νόσου
Authors: Νικολαΐδου Ειρήνη
Published: February 2024

Σκοπός: Η εγκαυματική νόσος επιφέρει άμεσα σημαντικές τοπικές και συστηματικές μεταβολές, με αποτέλεσμα να εμφανίζει μεγάλη νοσηρότητα και θνητότητα. Απευθείας μετά τον θερμικό τραυματισμό, ο οργανισμός απαντά με φλεγμονώδη αντίδραση, ενώ ταυτόχρονα διαταράσσεται ο μηχανισμός πήξης – ινωδόλυσης. Οι παθοφυσιολογικές αυτές μεταβολές αυξάνουν τον κίνδυνο αιμορραγίας και συμβάλλουν στην εμφάνιση επιπλοκών. Σκοπός της μελέτης είναι η σύγκριση μιας δοκιμασία ιξωδοελαστικής πήξης (VCA - viscoelastic coagulation assay) - της Περιστροφικής Θρομβοελαστομετρίας (ROTEM- Rotational Thromboelastometry) με συμβατικές μεθόδους αξιολόγησης της πήξης (CCA - conventional coagulation assays), συμπεριλαμβανομένου του χρόνου προθρομβίνης (pt), ενεργοποιημένου χρόνου μερικής θρομβοπλαστίνης (ptt), international normalized ratio (INR), γενικής εξέτασης αίματος και παραγόντων πήξης κατά τις πέντε πρώτες μετεγκαυματικές ημέρες σε επιβιώσαντες και μη επιβιώσαντες, προκειμένου να συσχετιστούν τα αποτελέσματα με τις διαταραχές πήξης και την πρόγνωση στους σοβαρά εγκαυματίες. Υλικά και μέθοδοι: Στη μελέτη συμπεριλήφθηκαν δεκαεπτά επιβιώσαντες και δέκα μη επιβιώσαντες, με μέση συνολική επιφάνεια εγκαύματος 33,78%. Αποτελέσματα: Παρόλο που οι μετρήσεις CCA ήταν μη φυσιολογικές, δεν ήταν ικανές να ανιχνεύσουν τις διαταραχές πηκτικότητας. Όσον αφορά τις VCA, οι μετρήσεις FIBTEM MCF ήταν αυξημένες για τους μη επιβιώσαντες τη 2η μέρα (p=0,04) και παρέμειναν αυξημένες καθόλη τη μετεγκαυματική περίοδο. Επιπλέον, οι μετρήσεις FIBTEM A10, A20 τη 2η μέρα και EXTEM A10, A20, MCF και CFT την 5η μέρα έλαβαν παθολογικές τιμές για την ίδια ομάδα ασθενών (p<0,05). Οι διαταραχές αυτές επιβεβαιώθηκαν από τις μετρήσεις των παραγόντων πήξης. Συμπεράσματα: Ως αποτέλεσμα, οι CCA θεωρούνται φτωχοί δείκτες έκφρασης της κατάστασης πήξης, ενώ οι VCA αναγνωρίζουν ασθενείς με υψηλότερο κίνδυνο θνητότητας και διαταραχών του πηκτικού μηχανισμού.
TEACHER’S AND PUPIL’S IDENTITIES IN THE PROCESS OF WRITING
Authors: Gerdzhikova Nina
Published: February 2024

This paper explores the identity notion in the context of the teacher-pupil relationship and its impact on professional development. The study draws on international comparative research focusing on Bulgarian teachers and an example of one lesson in the mother tongue (Bulgarian language). The concept of professional identity is examined, encompassing various components such as the profession's philosophy, skills, attitude toward work, and interactions with colleagues. It is argued that professional identity is tied to social dedication and cultural values closely. The relationship between teachers and pupils involves coordination, cooperation, and co-construction which are essential for creating an orderly learning environment. The teacher's identity, social interactions, and significant memories influence the pupil's identity formation. The connection between the body and identity is also explored, highlighting the nature of subjectivity and its cultural influences. The research emphasizes the need for a qualitative approach to understand how the body shapes the identities of both teachers and pupils and how environmental factors contribute to this process. Overall, this study contributes to our understanding of the complex nature of professional identity in the teaching profession.
GROUP REPLACEMENT AS MANAGEMENT ACTION IN MIRCE SCIENCE
Authors: Knezevic Jezdimir
Published: February 2024

The core principle of MIRCE Science revolves around the idea that the purpose of any working system is to perform work. The work is accomplished when a specific measurable function is carried out over time. All working systems require maintenance throughout their lifespan. It is generally understood that, during maintenance, the system is not actively performing any work. The duration and frequency of these tasks directly influence the amount of work lost due to maintenance. That work loss is known to have various consequences, such as monetary, reputational, or social implications. The main objective of this paper is to present how a proactive management approach, known as group replacement, can enhance work productivity compared to individual replacements. Under this strategy, the entire group must be replaced when any item within that group fails. This approach aims to minimize the number of maintenance tasks required and maximize the amount of work accomplished. The provided numerical example demonstrates the practical application of MIRCE Science in quantitatively evaluating the impact of group replacement on work productivity and resource allocation.
DEVELOPMENT OF THE TOURISM INDUSTRY IN THE SOUTH OF RUSSIA UNDER CONDITIONS OF RESTRICTIONS
Authors: Prigoda Lyudmila , Ashinova Marina , Eshugova Svetlana
Published: February 2024

The growth of investments in tourism and increase in production due to increased tourist demand has a positive synergistic effect on all sectors of the country's economy. That encourages investment activity, the creation of new jobs, the expansion of trade, and an increase in wages. A part of the income comes through taxes to the state budget. A synergistic effect occurs consequently. This research showed that the system of organization and development of the tourist services market represents a combination of financial and economic structures, models, and management methods. With the help of it, social, group coordination, and private interest arising from the growth of the tourist product market are achieved. The paper presents the methods and tools that enable the assessment of the region's competitiveness in the tourist and recreational services provisions and an overview of the main factors that influence the demand for these services. The consistency and objectivity of the considered problems in their mutual connection and interdependence are ensured by considering general economic principles and methods of analyzing the legality of economic development, logical analysis, decision theory methods, set theory, historical method, abstract-logical method, statistical methods (consideration of indicators in dynamics, grouping, method of detailing), methods of comparison, comparison, etc. The study is based on economic literature, works of contemporary scientists, the legislative framework of the Russian Federation, materials of state statistical authorities, materials of scientific conferences, and the information potential of the Internet.
SOME INFORMATION COMMUNICATION TECHNOLOGIES IN LOGISTICS AND SUPPLY CHAINS
Authors: Radovanovic Dragan
Published: February 2024

The digitization process, imposed by the rapid development of electronics, the Internet, the availability of IT, new software, devices, networks, and platforms, is gaining an almost unlimited reach. The concept of process visualization initially appeared as a comprehensive term for obtaining and using data and information with the application of new information and communication technologies (ICT) in the economy and beyond, intending to fully characterize the process with specific key performance indicators (KPI), which would enable its users to better insight into the state of their processes, vehicles, devices, people, at any time, from any place, according to the principle of each-and-everyone. The paper presents systematized communication technologies and services in the cloud that are in use or under development. The division into groups of technologies was made according to the functions significant in logistics and supply chains. Some of the technologies analyzed are described in brief. The work aims to present to businessmen and researchers some of the new technologies that are significant for their areas of business and interest so that they can direct their activities toward that area.
Vaccinations in Pregnancy. A Comprehensive Overview
Authors: Plewniok Ines , Maj-Dziedzic Monika , Sikora Marcelina , Zarzycka Marta , Brzozowska Anna , Dubiel Jeremiasz , Maj Adrian , Warno Martyna , Kozik Wiktor , Śmietana Greta
Published: February 2024

Introduction and purpose

Pregnancy is associated with many changes in the mother's body, allowing for the proper development of the fetus, but unfortunately it also predisposes many potentially harmless infections to become much more severe during pregnancy. Therefore, vaccinations during pregnancy play a very important protective role both for the mother, her unborn child and to the child immediately after birth. Immunization during pregnancy and in the preconception period protects against many infectious diseases and related complications. By receiving the vaccine, specific antibodies are synthesized and transported across the placenta to the fetus. They protect the baby during the first months of life, when the baby cannot receive vaccinations due to its age yet. Vaccinations during pregnancy can be divided into necessary, possible and recommended. Recommended vaccinations include against diphtheria, tetanus, pertussis, influenza, Covid19 and RSV. They are especially recommended for every pregnant woman who has no permanent or temporary contraindications. A special group of vaccinations are those necessary to perform, which play the main role as post-exposure prophylaxis and must be administered immediately after exposure to the agent causing the infection. These include mainly vaccination against tetanus and rabies. The vaccinations that can be performed include those targeted at a specific group of patients with various chronic diseases who are at risk or traveling to countries where there is an increased risk of illness. During a doctor's visit to a woman planning a pregnancy, it is important to collect a detailed interview regarding vaccination history, past infectious infections and chronic diseases. This allows us to prepare an individualized vaccination schedule recommended both before and during pregnancy.
Retail Buyer and Manufacturer Influence
Authors: Subramanian Upender , Zhang Z. John
Published: February 2024

Retailers often employ professionals known as retail buyers to determine the right quantities of products to order. However, in many economies and industries, a manufacturer may seek to unduly influence the buyer through various means. One such means is to offer the buyer kickbacks (incl. entertainment, travel, gifts) in return for a large order. Despite prominent examples of retailers taking initiatives against kickbacks, the practice persists in many economies and industries. To aid initiatives combating kickbacks, one needs to do the right diagnosis and identify the root cause. To this end, in this paper, we introduce the retail buyer as a distinct player in the retail channel and study the implications of the tug-of-war between the retailer and the manufacturer to influence the buyer. Interestingly, we find when kickbacks are feasible, the manufacturer need not always benefit, and the retailer need not always be the victim. We show a well-designed buyer compensation plan is key for the retailer to avoid kickbacks from distorting the buyer’s demand assessments. Moreover, when the reputational harm from kickbacks is not too high, the retailer may be the one tacitly facilitating kickbacks by undercompensating the buyer and influencing her demand assessments such that it can leverage kickbacks for shifting some of its buyer compensation cost to the manufacturer. This sharing of cost may allow for better channel coordination. Furthermore, this cost-shifting mechanism of kickbacks we have identified in this paper can explain their persistence. No retailer tolerates kickbacks when the reputational harm is high.

This paper was accepted by Eric Anderson, marketing.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/mnsc.2021.01646 .
Risk Hedging and Loan Covenants
Authors: Babenko Ilona , Bessembinder Hendrik , Tserlukevich Yuri
Published: February 2024

We study lending agreements and derivative positions of U.S. oil and gas producers, showing that loan covenants are important determinants of hedging policies. Hedging covenants appear in more than 85% of sample loan agreements, with explicit minimum hedging requirements in more than half. Covenants are more common when expected default costs are larger. The well-documented positive relation between borrowing and hedging is largely attributable in our sample to binding covenants, as the relation is much weaker in their absence. These results suggest that understanding firms’ hedging choices requires the consideration of lender interests along with those of owners and managers.

This paper was accepted by Lukas Schmid, finance.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01616 .
LIMA BARRETO: ESCRITOR NEGRO E EMPENHADO
Authors: Da Silva Roniê Rodrigues , Santos Alisson Matheus de Lima
Published: February 2024

Este trabalho objetiva cartografar o lugar que o escritor Lima Barreto e sua obra ocupam no processo de formação da literatura brasileira, destacando como, na condição de um intelectual negro, o autor se engaja na luta contra um conjunto de práticas que configuram um comportamento estruturalmente racista. Considerando a relação entre Nação e narração, observamos como a escrita barretiana representa a noção de literatura enquanto instrumento de conhecimento da identidade nacional (Bernd, 2003) e, a partir da leitura crítica do romance Recordações do Escrivão Isaías Caminha, discutimos a dramatização de um ethos do Brasil personificado na obra, problematizando, por último e nos termos do professor Antonio Candido (2000), a natureza da literatura empenhada de Lima Barreto.
O CORPO COMO TEXTO: A OBJETIFICAÇÃO COLONIZADORA NOS CONTOS “NEGRINHA” DE MONTEIRO LOBATO E “PAI CONTRA MÃE” DE MACHADO DE ASSIS
Authors: PENACHIO RENATA MOCELIN
Published: February 2024

Neste artigo busco unir minhas aspirações, a antropologia e a literatura, para uma investigação cuidadosa que emerge a partir da complexa intersecção dos saberes que são as fronteiras da historiografia brasileira. O corpo como forma de elegibilidade do texto e o texto como forma de elegibilidade do corpo. Trazer para o corpo as discussões sobre as problemáticas étnicas do país é materializar as marcas da colonização, mesmo que essas marcas estejam representadas nas lacunas psicoexistênciais que transitam entre a verdade e a ficção. O exercício de alteridade que a literatura promove é o redimensionar das estruturas subjetivas que o pensamento colonial impõe e provoca antes, durante e e pós período escravocrata. Não é apenas do período histórico que advém a escravidão, mas do pensamento que perpetua na historicidade suas marcas de violência. Aqui, analiso os contos “Negrinha”, de Monteiro Lobato, e “Pai contra mãe”, de Machado de Assis, na intenção de encarar a importância e impacto da narrativa ficcional na reflexão e (re)constituição da história do país.
NÓS. HOMENS, GEÓGRAFOS…E FEMINISTAS?
Authors: Pequeno Victor Dantas Siqueira
Published: February 2024

Pretendo com o presente artigo mobilizar o pensamento geográfico que se quer feminista. Articulado a isso, meu objetivo consiste em verificar se há nas pesquisas desenvolvidas por homens geógrafos uma difusão do que estou chamado de éticas feministas. Trata-se, portanto, de uma pesquisa qualitativa-exploratória que utiliza da pesquisa bibliográfica para com a coleta de dados e a discussão dos resultados. Defendo que há um arco-íris de possibilidades teórico-metodológicas encaminhadas por corpos e mentes dissidentes, e que reivindicam à Geografia a saída do armário.
PODEMOS FALAR DE GEOGRAFIAS "PÓS-COLONIAIS" NA FRANÇA A PROPÓSITO DA GEOGRAFIA DOS CHAMADOS PAÍSES DO SUL?
Authors: Fournet-Guerin Catherine
Published: February 2024

Este texto é dedicado a uma análise do lugar das abordagens pós-coloniais na geografia francesa desde a década de 1990 até o período atual (final da década de 2010). Nele são identificados os pesquisadores em causa, em cujos trabalhoso lugar destas abordagens é limitado. No entanto, a abordagem pós-colonial, fundada na recusa de um olhar dominante e na denúncia de formas de injustiças nos países não ocidentais, é de fato muito difusa. A questão social está no centro de muitas obras. Além disso, a consideração de abordagens culturais e urbanas na geografia para esses espaços ditos do Sul enriquece muito os temas e abordagens de pesquisa.
Managing paradoxes of healthcare reform: the case of the General Healthcare System in Cyprus
Authors: Simpson Tamara , Simpson Ace Volkmann , Berti Marco
Published: February 2024

In 2019, Cyprus launched the General Healthcare System, aiming to make healthcare more accessible. This article discusses the implementation of this system using a paradox theory lens. Persistent and interdependent tensions in healthcare involve conflict between the aggregate needs of the collective on one ‘pole’ and needs of individual patients and medical practitioners on the other. This is represented by the performing and belonging paradox. The General Healthcare System aims to address this paradox using a public–private provider model that is funded by the public sector. However, this solution has given rise to other paradoxes. This article discusses how these paradoxes can be managed by oscillating between poles, through ongoing review, dialogue and policy updates to achieve greater individual and collective health and wellbeing.
A codesign approach to improving COVID-19 vaccine confidence and uptake in racial and ethnic minority communities
Authors: Li Jingquan
Published: February 2024

Jingquan Li explains how codesigning interventions with trusted community leaders can help to improve uptake among under-served populations, particularly those in racial and ethnic minority communities. Although this article focuses on the American context, these ideas may be applicable to public health efforts in the UK.
Unethical organ transplantation in China: preventing complicity in UK healthcare and related organisations
Authors: Stephenson Eleanor
Published: February 2024

International criminal lawyer Eleanor Stephenson discusses forced organ harvesting in China and the risk of complicity in UK healthcare organisations and related bodies. Readers are signposted to guidance to help them reduce these risks and protect staff from being unknowingly involved in unethical transplantation practices.
Angel in blue or registered mental health nurse? The impact of the angel and hero narrative on student mental health nurses
Authors: Judge Lucy , Fisher Jane
Published: February 2024

This article is a critical reflection on the media portrayal of nursing and its impact on student nurses and prospective students during the COVID-19 pandemic.
Ensuring continuity of care for young people transitioning to adult mental health services: issues faced and promising approaches
Authors: Appleton Rebecca
Published: February 2024

Rebecca Appleton discusses the issues that young people face when moving from child and adolescent mental health services to adult mental health services, and what approaches are being introduced to help with this transition.
The space in between
Authors: Cochrane Alice
Published: February 2024

In her first column, Alice Cochrane navigates the space in between university and practice