bluuebunny/crossref_metadata_2025 huggingface dataset:
Pan-cancer illumination of TRIM gene family reveals immunology regulation and potential therapeutic implications
Authors: Gao Yueying , Pan Tao , Xu Gang , Li Si , Guo Jing , Zhang Ya , Xu Qi , Pan Jiwei , Ma Yanlin , Xu Juan , Li Yongsheng
Published: December 2022

Background

The tripartite motif (TRIM) proteins function as important regulators in innate immunity, tumorigenesis, cell differentiation and ontogenetic development. However, we still lack knowledge about the genetic and transcriptome alterations landscape of TRIM proteins across cancer types.

Methods

We comprehensively reviewed and characterized the perturbations of TRIM genes across > 10,000 samples across 33 cancer types. Genetic mutations and transcriptome of TRIM genes were analyzed by diverse computational methods. A TRIMs score index was calculated based on the expression of TRIM genes. The correlation between TRIMs scores and clinical associations, immune cell infiltrations and immunotherapy response were analyzed by correlation coefficients and gene set enrichment analysis.

Results

Alterations in TRIM genes and protein levels frequently emerge in a wide range of tumors and affect expression of TRIM genes. In particular, mutations located in domains are likely to be deleterious mutations. Perturbations of TRIM genes are correlated with expressions of immune checkpoints and immune cell infiltrations, which further regulated the cancer- and immune-related pathways. Moreover, we proposed a TRIMs score index, which can accurately predict the clinical outcome of cancer patients. TRIMs scores of patients are correlated with clinical survival and immune therapy response across cancer types. Identifying the TRIM genes with genetic and transcriptome alterations will directly contribute to cancer therapy in the context of predictive, preventive, and personalized medicine.

Conclusions

Our study provided a comprehensive analysis and resource for guiding both mechanistic and therapeutic analyses of the roles of TRIM genes in cancer.
Interpersonal Behaviors Questionnaire (IBQ) applied to parenting of emerging adults: dimensional structure and criterion validity
Authors: Vosylis Rimantas , Erentaitė Rasa
Published: December 2022

Background

The prolonged transitions to adulthood strengthen interest in parenting characteristics that can shape emerging adults’ development and progression to full-fledged adulthood. It also strengthens interest in instruments suitable for measuring such parenting characteristics. The current study contributes to this area of research by applying the Interpersonal Behavior Questionnaire (IBQ), to assess parenting behaviors that are pertinent for emerging adults’ development and wellbeing, and seeks evidence of its dimensional structure and criterion validity.

Method

The sample of the study consisted of 600 emerging adults (Mage = 24.94, SDage = 3.03, range 19–29 years; 52.3% women). The dimensionality of IBQ was assessed by testing a sequence of theoretically plausible models representing alternative factor score structures. Criterion validity was investigated by exploring the associations between the IBQ dimensions and basic psychological need satisfaction and frustration, negative affectivity, and thriving.

Results

The findings provide evidence of a hypothesized six-factor structure, but advocate for the use of exploratory structural equation as it may more accurately reflect associations between the six dimensions. Findings also provide evidence of criterion validity.

Conclusions

The findings indicate that IBQ applied to parenting targets dimensions highly relevant for EAs’ flourishing or impoverished functioning. Findings also offer evidence of structure and criterion validity for the IBQ applied to emerging adults’ parent behaviors. As such, researchers may find IBQ attractive, as it is relatively concise yet also a holistic measure that captures the behaviors that both support and thwart an emerging adult’s need for autonomy, competence, and relatedness. Findings also shed light on the process of becoming an adult, the shift in parent–child relationships during this process, and emerging adults’ wellbeing.
Potential antiviral peptides targeting the SARS-CoV-2 spike protein
Authors: Khater Ibrahim , Nassar Aaya
Published: December 2022

Background

The coronavirus disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an international pandemic and created a public health crisis. The binding of the viral Spike glycoprotein to the human cell receptor angiotensin-converting enzyme 2 (ACE2) initiates viral infection. The development of efficient treatments to combat coronavirus disease is considered essential.

Methods

An in silico approach was employed to design amino acid peptide inhibitor against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The designed inhibitor (SARS-CoV-2 PEP 49) consists of amino acids with the α1 helix and the β4 - β5 sheets of ACE2. The PEP-FOLD3 web tool was used to create the 3D structures of the peptide amino acids. Analyzing the interaction between ACE2 and the RBD of the Spike protein for three protein data bank entries (6M0J, 7C8D, and 7A95) indicated that the interacting amino acids were contained inside two regions of ACE2: the α1 helical protease domain (PD) and the β4 - β5 sheets.

Results

Molecular docking analysis of the designed inhibitor demonstrated that SARS-CoV-2 PEP 49 attaches directly to the ACE2 binding site of the Spike protein with a binding affinity greater than the ACE2, implying that the SARS-CoV-2 PEP 49 model may be useful as a potential RBD binding blocker.
Tricolored bats at a southern range edge exhibit partial migration northward in autumn
Authors: Smith Lisa M. , Gore Jeffery A. , Doonan Terry J. , Campbell Caitlin J.
Published: December 2022

Background

Animal migration is a widespread global adaptation by which individuals move in response to environmental conditions to reach more favorable conditions. For bats in temperate climates, migration and hibernation are often associated with each other when these bats must migrate to reach suitable overwintering sites. However, differences in movement across the geographical range of a species and the degree to which hibernation drives migratory behavior of bats in subtropical climates, where conditions may remain warm with available prey year-round, remains incomplete. Understanding the migratory strategies of subtropical bats during winter is of increasing importance as they are threatened by stressors such as disease and environmental change.

Methods

We evaluated migration patterns of tricolored bats (Perimyotis subflavus) in Florida, USA, through analysis of stable hydrogen isotope ratios of the fur. We inferred the summer geographic origins of the fur samples and estimated the minimum distance and likely direction traveled by hibernating individuals. We used linear models to examine whether hibernation region, colony size, and an individual’s sex affected the distance traveled.

Results

We sampled 111 bats hibernating at 40 sites and found that more than half (54.1%) of individuals were residents of the area in which they hibernated. We found that almost half of the sampled bats (43.2%) traveled from southern Florida to overwinter in North Florida. We also documented three individuals that traveled > 100 km from northerly origins, one of which had traveled an estimated minimum distance of 1382 km. We also found that tricolored bats moved farther to reach hibernacula in Northwest Florida and hibernacula with more populous colonies, with no difference in movement between sexes.

Conclusions

Our results indicate a pattern of northward autumnal movements of tricolored bats in the subtropical southeastern portion of their range. We suggest that bats are differentially constrained at the edge of their geographical range, resulting in movement contrary to what is expected. Even though we found that few (2.7%) bats moved into Florida from farther north, those migrants can potentially transfer the fungus that causes the deadly white-nose syndrome, which does not currently occur in the state. Our results support the characterization of tricolored bats as flexible partial migrators, with a rarely exercised capacity for long-distance movements.
Demystifying Iranian EFL teachers’ perceptions and practices of learning-oriented assessment (LOA): challenges and prospects in focus
Authors: Derakhshan Ali , Ghiasvand Farhad
Published: December 2022

As a growing approach to assessment, learning-oriented assessment (LOA) has recently flourished to position learning at the center of assessment practices. It aims to unify assessment, teaching, and learning. However, little is written and known about its benefits, challenges, and practices in English as a foreign language (EFL) contexts. To shed light on these aspects, the present study was a bid to unpack Iranian EFL teachers’ perceptions about the benefits, challenges, and professional activities that facilitate LOA understanding and practice. To this end, 40 EFL teachers including both genders were invited to a semi-structured interview held in person. The results of the thematic analysis obtained by MAXQDA revealed that Iranian EFL teachers had different perceptions regarding LOA. They argued that LOA is a process-based, feedback-oriented, formative, and alternative assessment technique that foregrounds feedback and progress rather than the final outcome. Furthermore, it was identified that LOA can be practiced by using alternative assessment, performance assessment, dynamic assessment, peer assessment, self-assessment, and portfolio assessment. Likewise, the results demonstrated that LOA is beneficial in enhancing classroom interaction, collaboration, and engagement, integrating assessment, teaching, and learning, and monitoring students’ progress. However, the time budget, large classes, and teachers’ lack of knowledge and training on LOA were perceived as challenges for applying LOA. Furthermore, it was found that Iranian EFL teachers supported the use of training courses, reading articles and books, and attending assessment-related workshops, webinars, seminars, and conferences to improve LOA knowledge and skills. The study provides implications for EFL teachers and trainers, who can use different assessment techniques/practices representative of LOA.
Impact of the COVID-19 pandemic on critical care utilization in Japan: a nationwide inpatient database study
Authors: Ohbe Hiroyuki , Sasabuchi Yusuke , Matsui Hiroki , Yasunaga Hideo
Published: December 2022

Background

The coronavirus disease 2019 (COVID-19) pandemic has disrupted critical care services worldwide. Examining how critical care systems responded to the COVID-19 pandemic on a national level will be useful in setting future critical care plans. The present study aimed to describe the utilization of critical care services before and during the COVID-19 pandemic using a nationwide Japanese inpatient administrative database.

Methods

All patients admitted to an intensive care unit (ICU) or a high-dependency care unit (HDU) from February 9, 2019, to February 8, 2021, in the Japanese Diagnosis Procedure Combination inpatient database were included. February 9, 2020, was used as the breakpoint separating the periods before and during COVID-19 pandemic. Hospital and patient characteristics were compared before and during the COVID-19 pandemic. Change in ICU and HDU bed occupancy before and during the COVID-19 pandemic was evaluated using interrupted time-series analysis.

Results

The number of ICU patients before and during the COVID-19 pandemic was 297,679 and 277,799, respectively, and the number of HDU patients was 408,005 and 384,647, respectively. In the participating hospitals (383 ICU-equipped hospitals and 460 HDU-equipped hospitals), the number of hospitals which increased the ICU and HDU beds capacity were 14 (3.7%) and 33 (7.2%), respectively. Patient characteristics and outcomes in ICU and HDU were similar before and during the COVID-19 pandemic except main etiology for admission of COVID-19. The mean ICU bed occupancy before and during the COVID-19 pandemic was 51.5% and 47.5%, respectively. The interrupted time-series analysis showed a downward level change in ICU bed occupancy during the COVID-19 pandemic (− 4.29%, 95% confidence intervals − 5.69 to − 2.88%), and HDU bed occupancy showed similar trends. Of 383 hospitals with ICUs, 232 (60.6%) treated COVID-19 patients in their ICUs. Their annual hospital case volume of COVID-19 ICU patients varied greatly, with a median of 10 (interquartile range 3–25, min 1, max 444).

Conclusions

The ICU and HDU bed capacity did not increase while their bed occupancy decreased during the COVID-19 pandemic in Japan. There was no change in clinicians’ decision-making to forego ICU/HDU care for selected patients, and there was no progress in the centralization of critically ill COVID-19 patients.
Comparable rates of secondary surgery between anterior cruciate ligament repair with suture tape augmentation and anterior cruciate ligament reconstruction
Authors: Hopper G. P. , Wilson W. T. , O’Donnell L. , Hamilton C. , Blyth M. J. G. , MacKay G. M.
Published: December 2022

Purpose

The aim of this study was to determine the frequency of secondary surgery following anterior cruciate ligament (ACL) repair with suture tape augmentation in comparison to conventional hamstring ACL reconstruction. We hypothesised that there would be no differences between the groups.

Methods

This was a retrospective comparison study of patients undergoing ACL surgery between September 2011 and April 2018. Two hundred and 73 patients underwent ACL reconstruction using hamstring autograft. During the same timeframe, 137 patients with an acute proximal ACL rupture underwent ACL repair with suture tape augmentation. One patient was lost to follow-up in the ACL reconstruction group leaving 272 patients (99.6%) for the final analysis. In the ACL repair group, three patients were lost to follow-up leaving 134 patents (97.8%) for the final analysis. Secondary surgery was identified by contacting the patients by email/telephone and reviewing patient notes at the time of this analysis.

Results

Re-rupture occurred in 32 patients (11.8%) in the ACL reconstruction group compared to 22 patients (16.4%) in the ACL repair group (p = 0.194). Contralateral ACL rupture occurred in four patients (1.5%) in the ACL reconstruction group compared to three patients (2.2%) in the ACL repair group (p = 0.224). In the ACL reconstruction group, nine patients (3.3%) required secondary meniscal surgery whilst five patients (3.7%) required meniscal surgery in the ACL repair group (p = 0.830). Seven other operations were performed in the ACL reconstruction group (2.6%) compared to three other operations in the ACL repair group (2.2%) (p = 0.374). The overall number of patients undergoing secondary surgery in the ACL reconstruction group was 52 (19.1%) in comparison to 30 (22.4%) in the ACL repair group (p = 0.114).

Conclusion

ACL repair with suture tape augmentation for acute proximal ruptures demonstrated comparable rates of secondary surgery with hamstring ACL reconstruction.
Data analysis guidelines for single-cell RNA-seq in biomedical studies and clinical applications
Authors: Su Min , Pan Tao , Chen Qiu-Zhen , Zhou Wei-Wei , Gong Yi , Xu Gang , Yan Huan-Yu , Li Si , Shi Qiao-Zhen , Zhang Ya , He Xiao , Jiang Chun-Jie , Fan Shi-Cai , Li Xia , Cairns Murray J. , Wang Xi , Li Yong-Sheng
Published: December 2022

The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.
Modularized bioceramic scaffold/hydrogel membrane hierarchical architecture beneficial for periodontal tissue regeneration in dogs
Authors: Wei Yingming , Wang Zhongxiu , Han Jiayin , Jiang Xiaojian , Lei Lihong , Yang Xianyan , Sun Weilian , Gou Zhongru , Chen Lili
Published: December 2022

Background

Destruction of alveolar bone and periodontal ligament due to periodontal disease often requires surgical treatment to reconstruct the biological construction and functions of periodontium. Despite significant advances in dental implants in the past two decades, it remains a major challenge to adapt bone grafts and barrier membrane in surgery due to the complicated anatomy of tooth and defect contours. Herein, we developed a novel biphasic hierarchical architecture with modularized functions and shape based on alveolar bone anatomy to achieve the ideal outcomes.

Methods

The integrated hierarchical architecture comprising of nonstoichiometric wollastonite (nCSi) scaffolds and gelatin methacrylate/silanized hydroxypropyl methylcellulose (GelMA/Si-HPMC) hydrogel membrane was fabricated by digital light processing (DLP) and photo-crosslinked hydrogel injection technique respectively. The rheological parameters, mechanical properties and degradation rates of composite hydrogels were investigated. L-929 cells were cultured on the hydrogel samples to evaluate biocompatibility and cell barrier effect. Cell scratch assay, alkaline phosphatase (ALP) staining, and alizarin red (AR) staining were used to reveal the migration and osteogenic ability of hydrogel membrane based on mouse mandible-derived osteoblasts (MOBs). Subsequently, a critical-size one-wall periodontal defect model in dogs was prepared to evaluate the periodontal tissue reconstruction potential of the biphasic hierarchical architecture.

Results

The personalized hydrogel membrane integrating tightly with the nCSi scaffolds exhibited favorable cell viability and osteogenic ability in vitro, while the scratch assay showed that osteoblast migration was drastically correlated with Si-HPMC content in the composite hydrogel. The equivalent composite hydrogel has proven good physiochemical properties, and its membrane exhibited potent occlusive effect in vivo; meanwhile, the hierarchical architectures exerted a strong periodontal regeneration capability in the periodontal intrabony defect models of dogs. Histological examination showed effective bone and periodontal ligament regeneration in the biomimetic architecture system; however, soft tissue invasion was observed in the control group.

Conclusions

Our results suggested that such modularized hierarchical architectures have excellent potential as a next-generation oral implants, and this precisely tuned guided tissue regeneration route offer an opportunity for improving periodontal damage reconstruction and reducing operation sensitivity.

Graphical Abstract
Equiosmolar doses of hypertonic saline versus mannitol for brain relaxation in patients undergoing elective craniotomies: an updated systematic review and meta-analysis
Authors: Johansyah Theodorus Kevin Putra , Jonathan Jeremy , Yusari I. G. A. A. Andra , Nolan John , Alamsyah Alif Hakim , Ramadhana Geizar Arsika
Published: December 2022

Background

Hypertonic saline and mannitol are hyperosmolar agents frequently used to lower ICP and relax the brain during surgeries. Several methods have been used to achieve a good and relaxed brain, such as hyperventilation, cerebrospinal fluid drainage, head position correction, and administration of hyperosmolar agents. Comparing equiosmolar doses between hypertonic saline and mannitol in patients undergoing elective craniotomies is important to further notice the differences in several outcomes. This study aims to compare the outcome of hypertonic saline versus mannitol on brain relaxation in patients undergoing elective craniotomy.

Results

10 articles from 2007 to 2021 were included. Hypertonic saline is associated with better brain relaxation (OR  = 1.84, 95% CI 1.31–2.59; P = 0.001) but significantly increase blood natrium level, both serum and arterial (MD = 3.03, 95% CI 1.70–4.36; P =  < 0.001 and MD = 7.14, 95% CI 0.04–14.24; P =  < 0.001, respectively). Mannitol was associated with increased fluid input and urine output (SMD = − 0.56, 95% CI − 0.98 to − 0.15; P =  < 0.001 and SMD = − 0.96, 95% CI − 1.42 to − 0.50; P =  < 0.001, respectively). Serum osmolality and hemodynamic parameters difference was insignificant.

Conclusions

Hypertonic saline is associated with significantly better brain relaxation score and increased blood sodium level without increase in urine. This may prove to be clinically significant in patients with electrolyte imbalance.
Impact of direct-acting antivirals on neuropsychiatric and neurocognitive dysfunction in chronic hepatitis C patients
Authors: Shehata Ghaydaa A. , Ahmed Gellan K. , Hassan Elham Ahmed , Rehim Abeer Sharaf El-Din Abdel , Mahmoud Saad Zaky , Masoud Noha Ali , Seifeldein Gehan S. , Hassan Waleed Attia , Aboshaera Khaled O.
Published: December 2022

Background

Hepatitis C virus (HCV) infection is associated with psychiatric and cognitive dysfunctions. We aimed to investigate depression, anxiety, and cognitive function of chronic hepatitis C (CHC) patients before and after treatment with direct-acting antivirals (DAAs). Forty CHC patients (20 non-cirrhotic and 20 cirrhotic) who had undergone DAA treatment in our outpatient clinic and ten controls. We administered the Hospital Anxiety and Depression questionnaires to measure the anxiety and depression symptoms and the Cognitive Abilities Screening Instruments (CASI) to measure the cognitive function at the beginning and 3 months after the end of the treatment.

Results

Sustained virological response (SVR) was achieved in all patients. Post-treatment anxiety and depression scores showed a significant improvement than pre-treatment ones in CHC patients. Regarding CASI, before and after the treatment, a statistical significance was found in short-term memory (P = 0.001), concentration (P = 0.033), abstract thinking and judgment (P = 0.024), total (P = 0.001) in non-cirrhotic, Also, an improvement was seen in long-term memory (P = 0.015), short-term memory (P < 0.001), concentration (P = 0.024) and total (P = 0.01) in cirrhotic. However, these changes were still impaired in post-treated cirrhotic compared to controls.

Conclusions

CHC patients' anxiety, depression, and cognitive function partially improved after DAA therapy. Besides, improving the status of CHC, reversibility of cognitive dysfunction in non-cirrhotic patients may indicate the importance of treatment in early stages of liver disease.
Resistance exercise training-induced skeletal muscle strength provides protective effects on high-fat-diet-induced metabolic stress in mice
Authors: Kim Hye Jin , Kim Youn Ju , Kim Il Yong , Seong Je Kyung
Published: December 2022

Background

Resistance exercise training is known to improve metabolic disorders, such as obesity and type2 diabetes. In this study, we investigated whether the beneficial effects of resistance exercise training persisted even after the discontinuation of training with high-fat diet (HFD)-induced metabolic stress. We further evaluated whether the improvement in skeletal muscle strength and endurance by training were correlated with improved metabolism. Eight-week-old male C57BL/6N mice were divided into groups that remained sedentary or had access to daily resistance exercise via ladder climbing for 8 weeks. Trained and untrained mice were fed an HFD for 1 week after the exercise training intervention (n = 5–8 per group).

Results

Resistance exercise-trained mice had a lean phenotype and counteracted diet-induced obesity and glucose tolerance, even after exercise cessation. Grip strength was significantly inversely correlated with the body weight, fat mass, and glucose tolerance. However, hanging time was significantly inversely correlated with body weight only.

Conclusions

These results have strong implications for the preventive effect of resistance exercise-induced metabolic improvement by enhancing skeletal muscle strength rather than endurance.
Σχεδιασμός και σύνθεση αναστολέων των κινασών MARK
Authors: Βούρα Μαρία
Published: December 2022

Η κινάση MARK4 θεωρείται ένας πολλά υποσχόμενος στόχος στον σχεδιασμό φαρμάκων για τη θεραπεία ενός ευρέος φάσματος ασθενειών, συμπεριλαμβανομένων του καρκίνου, του διαβήτη και των νευροεκφυλιστικών διαταραχών. Στόχο της παρούσας διδακτορικής διατριβής αποτέλεσε ο σχεδιασμός, η σύνθεση και ο χαρακτηρισμός ενώσεων που θα αναστέλλουν ισχυρά τη δράση κινάσης της MARK4. Οι ενώσεις που επιλέχθηκαν διακρίνονται σε τρεις κατηγορίες: α) τα δισινδολο πυρρόλια και τα ινδολοκαρβαζόλια, β) τα παράγωγα ακριδόνης και γ) τις πρωτεολυτικές χίμαιρες ακριδόνης. Στο πρώτο μέρος της παρούσας διατριβής σχεδιάστηκαν δισινδολο πυρρόλια και ινδολοκαρβαζόλια, ως πιθανοί αναστολείς της MARK4. Πηγή έμπνευσης, τόσο για τις δομές όσο και για τη σύνθεση, αποτέλεσε το βιοσυνθετικό μονοπάτι της σταυροσπορίνης. Αρχικά, πραγματοποιήθηκε η in silico μελέτη μοριακής πρόσδεσης και βρέθηκε ο πιθανός τρόπος δέσμευσης των δισινδολο παραγώγων και οι αλληλεπιδράσεις τους με την καταλυτική περιοχή της MARK4. Στη συνέχεια, σχεδιάστηκε η συνθετική πορεία και επιτεύχθηκε η σύνθεση 21 δισινδολο παραγώγων, εκ των οποίων έξι είναι φυσικά προϊόντα και δέκα από αυτά δεν έχουν ξανασυντεθεί. Η βιολογική τους αξιολόγηση έδειξε ότι είναι αναστολείς της MARK4 με τιμές IC50 στη χαμηλή μικρογραμμομοριακή περιοχή, με ισχυρότερη τη λυναμικίνη G. Στο δεύτερο μέρος της διατριβής παρουσιάζεται ο σχεδιασμός παραγώγων του Ν-οξικού οξέος της 2-μεθυλακριδόνης, ως πιθανών αναστολέων της δράσης κινάσης της MARK4. Τα αρχικά in silico πειράματα μοριακής πρόσδεσης αφορούσαν αμιδικά παράγωγα ακριδόνης, με σκοπό τη διερεύνηση του τρόπου δέσμευσής τους στην καταλυτική περιοχή της MARK4. Τα in vitro αποτελέσματά τους έναντι της δράσης κινάσης της MARK4 ήταν ικανοποιητικά, και οδήγησαν στον σχεδιασμό νέων ακριδονών. Στη συνέχεια, πραγματοποιήθηκαν περαιτέρω in silico μελέτες, με σκοπό την εύρεση ισχυρότερων και περισσότερο εκλεκτικών αναστολέων. Από τα παράγωγα που ελέγχθηκαν, τα καλύτερα in silico αποτελέσματα είχαν τα παράγωγα ακριδόνης-πιπεραζίνης και ακριδόνης-τρυπτοφάνης. Έπειτα, συντέθηκαν 18 νέες ακριδόνες, που φέρουν στον σκελετό τους την πιπεραζίνη και 14 νέα παράγωγα L-τρυπτοφάνης-ακριδόνης. Τέλος, κατά το τρίτο μέρος της διατριβής σχεδιάστηκαν και συντέθηκαν επτά πρωτεολυτικές χίμαιρες, οι οποίες φέρουν ως αναστολέα το Ν-οξικό οξύ της 2-μεθυλακριδόνης και θα στοχεύουν στην πρωτεόλυση της MARK4. Επιλέχθηκαν και συντέθηκαν, ως προσδέτες Ε3 λιγάσης, η πομαλιδομίδη - η οποία δεσμεύεται στη CRBN - και το VHL ligand 1 - το οποίο δεσμεύεται στη pVHL. Ως συνδέτες επιλέχθηκαν αλκυλο και αιθερικές αλυσίδες, καθώς και ετεροκυκλικοί δακτύλιοι, και μέσω υπολογιστικών μελετών μοριακής πρόσδεσης, επιβεβαιώθηκε ότι οι πρωτεολυτικές χίμαιρες, που σχεδιάστηκαν, δεν επηρεάζουν τις αλληλεπιδράσεις του αναστολέα με την κινάση. Επιλέχθηκαν να συντεθούν έξι πρωτεολυτικές χίμαιρες με προσδέτη την πομαλιδομίδη και επιτεύχθηκε η σύνθεση τεσσάρων εξ αυτών. Επιπλέον, συντέθηκαν τρεις πρωτεολυτικές χίμαιρες με προσδέτη το VHL ligand 1.
Basin-scale occurrence and distribution of mesophotic and upper bathyal red coral forests along the Italian coasts
Authors: TOMA MARGHERITA , BO MARZIA , CATTANEO-VIETTI RICCARDO , CANESE SIMONEPIETRO , CANESSA MARTINA , CANNAS RITA , CARDONE FRINE , CARUGATI LAURA , CAU ALESSANDRO , CORRIERO GIUSEPPE , FOLLESA MARIA CRISTINA , MERCURIO MARIA , GRECO SILVESTRO , ANDALORO FRANCO , BAVESTRELLO GIORGIO
Published: December 2022

The analysis of 879 ROV dives carried out along the Italian coasts on hard substrata at mesophotic and upper bathyal depths (40-775 m) allowed us to evaluate the current basin-scale presence, relative abundance, bathymetric limits, and habitat preferences of one of the most charismatic Mediterranean habitat-former anthozoan species, Corallium rubrum (Linnaeus, 1758). The species is widespread, and its occurrence ranged from 13% of the explored sites in Ionian Calabria to a hotspot of approximately 80% in Sardinia. Population relative densities were generally low (< 10 colonies m-2), except along the Sardinian coasts and in some areas along the Apulian coast. Almost no red coral colonies were observed between 60 m and 590 m in the nine explored offshore seamounts in the Ligurian and Tyrrhenian Seas. A distinctive coastal distribution discontinuity was found in the Ionian Sea. The optimum bathymetric distribution was between 75 m and 125 m, and no colonies were found below 247 m. Red coral colonies showed a preference for biogenic habitats dominated by crustose coralline algae (CCA) and vertical substrata. The species was absent on iron wrecks. Corallium rubrum disappeared from 14% of the historical fishing banks, while it was confirmed in 86% of them, some of which have been deeply harvested in the past. In particular, the still flourishing Sardinian populations could be supported by the high reproductive potential and favourable hydrodynamic conditions in the area.
Different patterns of population structure and genetic diversity of three mesopelagic fishes in the Greek Seas
Authors: SARROPOULOU XENIA , TSAPARIS DIMITRIS , TSAGARAKIS KONSTANTINOS , BADOUVAS NICHOLAS , TSIGENOPOULOS COSTAS S.
Published: December 2022

Mesopelagic fishes are among the most abundant groups of vertebrates on Earth. Despite their unique biological and ecological traits, research in this group has been particularly scarce. The present study investigates the intraspecific genetic diversity of three mesopelagic fishes (Hygophum benoiti, Maurolicus muelleri, and Benthosema glaciale) in the Greek Seas. Analyses of three mitochondrial DNA genes (COI, 12S, and 16S) from a total of 168 samples revealed a lack of genetic structure for M. muelleri and B. glaciale across the studied area. However, H. benoiti specimens from the Corinthian Gulf were differentiated from the rest of the populations, suggesting that the limited connection between the Corinthian and neighboring seas may act as a barrier to gene flow. Furthermore, the COI data of this study were co-analyzed with publicly available sequences, demonstrating lack of phylogeographic structure for all three species through their distribution range. Therefore, even though indications of genetic differentiation were observed, the three mesopelagic fishes are generally characterized by genetic homogeneity, which may be the result of their recent evolutionary history.
Sardine and anchovy as bioindicators of metal content in Greek coastal waters
Authors: SOFOULAKI KATERINA , KALANTZI IOANNA , ZERI CHRISTINA , MACHIAS ATHANASIOS , PERGANTIS SPIROS A. , TSAPAKIS MANOLIS
Published: December 2022

Metal and element concentrations (Li, Na, Mg, P, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Mo, Pd, Cd, Cs, Ba, Hg, Tl, Pb, U) were monitored in the tissues of sardine (Sardina pilchardus) and anchovy (Engraulis encrasicolus) from six Greek coastal areas subjected to different natural and anthropogenic forcings in order to be assessed as bioindicator species of marine metal pollution. Sardine and anchovy provided a thorough view of the metal pollution load of each site in accordance with local pollution sources. The wide range of pressures applied in Elefsina Gulf and Thermaikos Gulf are depicted in the large number and the kind of elements reaching maximum concentrations among the sites (e.g. Pb, Cu, Hg, As in Elefsina Gulf, and Cd, Ni, P in Thermaikos Gulf) while in the rest of the sites (Amvrakikos Gulf, Strymonian Sea, Thracian Sea, Artemisium Straits), few elements were found at maximum levels. Statistically significant site-specific differences in metal content were detected. The differentiation in metal content of the fish tissues among the sites could be attributed to anthropogenic pressures, different background levels and environmental conditions. Sardine and anchovy can be evaluated as appropriate, reliable and useful bioindicator species of marine metal pollution.
Entry of the antipsychotic drug, olanzapine, into the developing rat brain in mono- and combination therapies
Authors: Huang Yifan , Qiu Fiona , Habgood Mark , Nie Shuai , Dziegielewska Katarzyna , Saunders Norman
Published: December 2022

Background: Olanzapine is used to treat schizophrenia and bipolar disorder in women of childbearing age. Continuation of psychotropic medications throughout pregnancy and lactation is often required as cessation could be dangerous for both mother and child. However, there is a lack of information on the transfer of these drugs into the developing brain.

Methods: Sprague Dawley rats at three developmental ages: embryonic day E19, postnatal day P4 and non-pregnant adult females were administered unlabelled or radiolabelled (3H) olanzapine (0.15 mg/kg) either as monotherapy or in combination with each of seven other common medications. Similar injections were administered to pregnant E19 females to investigate placental transfer. Olanzapine in plasma, cerebrospinal fluid (CSF) and brain was measured by liquid scintillation counting after a single dose (acute) or following 5 days of treatment (prolonged).

Results: Olanzapine entry into brain and CSF was not age-dependent. Prolonged olanzapine treatment reduced placental transfer from 53% to 46% (p<0.05). Co-administration of digoxin or lamotrigine with olanzapine increased its entry into the fetal brain, whereas paracetamol decreased its entry into the CSF. Placental transfer of olanzapine was increased by co-treatment with cimetidine and digoxin, whereas co-treatment with lamotrigine, paracetamol or valproate led to a substantial decrease. Repeated co-treatment of digoxin and olanzapine increased olanzapine transfer into the brain and CSF, but not across the placenta. Overall entry of olanzapine from maternally administered drugs into the fetal brain was higher after combination therapy with cimetidine and digoxin.

Conclusions: Co-administration of olanzapine with some commonly used drugs affected its entry into the fetus and its developing brain to a greater extent than in adults. It appears that protection of the fetal brain for these drugs primarily comes from the placenta rather than from the fetal brain barriers. Results suggest that drug combinations should be used with caution particularly during pregnancy.
Wypadki intencji twórczych. Wokół autoryzowanych przez Tadeusza Konwickiego nowych kształtów utworów
Authors: Kaniecki Przemysław
Published: December 2022

Przedmiotem artykułu są różnego rodzaju zmiany edytorskie (od zmian pojedynczych słów, zdań, po dodane całe fragmenty tekstu), jak również inna forma układu tekstu – w autoryzowanej przez Tadeusza Konwickiego serii „Książek Wybranych” (Agora, 2010), także we wznowieniu tomu scenariuszy filmowych Ostatni dzień lata (Świat Książki, 2011). Wydania te zostały przygotowane na podstawie sczytywanych podstaw tekstów z rękopisami, zmiany omawiano z autorem, który je akceptował lub kwestionował, często jednak zawierzając opinii redaktora. Autor pokazuje kilka decyzji, które można uznać za kontrowersyjne, i zastanawia się, czy wprowadzone zmiany rzeczywiście można uznać za zgodne z „intencją twórczą” (termin Konrada Górskiego).
Książka kongenialna czy po prostu dobry projekt? Refleksje nad layoutami książek z różnych epok
Authors: Socha Klaudia
Published: December 2022

W artykule postawiono tezę, że współczesny termin „książka kongenialna” oznaczający harmonijne połączenie treści utworu (tekstu wraz z materiałem dodatkowym, w tym również graficznym) i jego funkcji w postaci odpowiedniej formy, czyli projektu typograficznego uwzględniającego wszelkie potrzeby czytelnika oraz jego realizację z użyciem odpowiednich materiałów (papieru, oprawy itp.), można rozszerzyć także na książki dawne.
Wśród współczesnych przykładów książek kongenialnych znalazły się prace Andrzeja Tomaszewskiego, który podkreśla, że projekt typograficzny musi wynikać z tekstu, oddawać jego charakter i spełniać konkretną funkcję, np. poznawczą, dydaktyczną lub estetyczną.
Te zasady nie są jednak wynalazkiem ostatniego półwiecza, lecz były stosowane przez projektantów książek od czasów najdawniejszych, o czym świadczą analizy publikacji z różnych epok. Zestawienie rękopisu biblijnego, podręcznika i atlasu anatomicznego, publikacji hagiograficznej, tomu poetyckiego i książki popularnonaukowej dowodzi, że każda z tych książek została starannie zaprojektowana, tak by uwydatnić treść i spełnić konkretną funkcję. Każda z nich ma również cechy typowe dla czasu swego powstania, co pozwala zauważyć, które elementy prac są uniwersalne, a które wynikają z tzw. gustu epoki.
Książkowe znaki proweniencyjne – komunikacja ponad granicami epok
Authors: Pawlak Przemysław
Published: December 2022

Książkowe znaki proweniencyjne i biblioteczne magazyny druków zbędnych, ich mikrobiom i oddziaływanie książek na innych aktantów układu, to znakomity materiał i przestrzeń dla badaczy reprezentujących metodologiczny zwrot ku materialności w analizie historycznej. Namysł nad pokonywaniem granic epok przez książki dopełniają studia dwóch przypadków. Pierwszym są Satyry Nicolasa Boileau-Despréaux w swobodnym przekładzie Jana Onufrego Gorczyczewskiego z 1818 roku, ozdobnie oprawiony wolumin z wszytym listem dedykacyjnym i wielością śladów pozostawionych przez kolejnych właścicieli, będący niegdyś narzędziem transcendentnej komunikacji wielu pokoleń rodziny Chrzanowskich herbu Suchekomnaty. Drugie studium dotyczy trzeciego tomu dzieła Euzebiusza Amorta, Theologia eclectica moralis et scholastica..., jednego z tak zwanych dubletów Miłkowskiego, oraz znalezionych w nim znaków własnościowych między innymi XVIII-wiecznych zakonników: Idziego Kłąbczyńskiego z Kalisza i Czesława Wróblewskiego z Sejn.
Forma edytorska tygodnika „Przyjaciółka” – inspiracje i przemiany. Część 1: lata 1948–1956
Authors: Wodniak Katarzyna
Published: December 2022

Prasowy przebój czytelniczy PRL-u, tygodnik „Przyjaciółka”, doczekał się wielu opracowań odnoszących się w głównie do jego zawartości, analizowanej w różnych kontekstach i perspektywach. Znacznie rzadziej podejmowano temat jego formy wydawniczej – kształtu edytorskiego, szaty graficznej, liternictwa czy typografii – ważnych narzędzi komunikacji wizualnej niosących określone przesłanie propagandowe politycznego dysponenta czasopisma. Te właśnie elementy zostały zarysowane w ujęciu chronologicznym, ze szczególnym wskazaniem na okres, kiedy wychodziło ono pod szyldem Instytutu Prasy Spółdzielni Wydawniczo-Oświatowej „Czytelnik” (III 1948–II 1951) oraz w pierwszych latach istnienia w Robotniczej Spółdzielni Wydawniczej „Prasa” (III 1951–1956). Punktem wyjścia analizy jest bezpośrednia poprzedniczka „Przyjaciółki”, przedwojenny ogólnopolski dwutygodnik „Moja Przyjaciółka” z wielkopolskiego Żnina ukazujący się w latach 1934–1939. Za jego oprawę graficzną odpowiadali młodzi absolwenci Państwowej Szkoły Sztuk Zdobniczych i Przemysłu Artystycznego w Poznaniu, tworzący dla tego pisma m.in. oryginalne ilustracje okładkowe. Choć tygodnik „Przyjaciółka”, wierny konwencjom realizmu, tego rodzaju rozwiązań na swoje okładki nie przenosił i posługiwał się fotografiami, na swojej tylnej okładce przez wiele lat zamieszczał jednak reprodukcje dzieł malarskich, a do jego rysowników w omawianym i późniejszym okresie należeli: Władysław Buśkiewicz, Jadwiga Lipowska, Antoni Uniechowski, Grażyna Staszko, Ada Święcicka, a także sporadycznie Maja Berezowska. Wysokie nakłady, sięgające nawet 2 mln egzemplarzy na numer, czyniły z niego, mimo wszystko, narzędzie kształtowania smaku estetycznego wielomilionowego audytorium.
Alegorie dzielenia się obrazami (na podstawie praktyki edukacyjnej)
Authors: Dąbrowska Danuta
Published: December 2022

Artykuł jest podsumowaniem dorobku Pracowni Projektowania Wydawnictw Multimedialnych i Książki Artystycznej prowadzonej w latach 2013–2021 w Akademii Sztuki w Szczecinie. Tytuł Alegorie dzielenia się historiami jest rozwinięciem tematu na podstawie praktyki edukacyjnej związanej z autorskim programem Pracowni.

Książka jako obiekt sztuki stanowi chętnie wybierane medium, zwłaszcza przez najmłodsze pokolenia artystów. Jest uniwersalnym i wielowymiarowym językiem wypowiedzi. Doskonale wpisuje się w kontekst sztuki współczesnej z jej historiozoficznym zapleczem. Wszelkie formy i przejawy zjawiska, jakimi są artbooki, doczekały się wielu pogłębionych analiz, jednak z uwagi na duży progres tego nurtu cenny okazuje się każdy rodzaj refleksji i próby definiowania. Odważne i niejednokrotnie wnikliwe studenckie eksperymenty projektowe są asumptem do tej prezentacji.
Jak oceniać „Książkę po okładce”?
Authors: Makulec Daria
Published: December 2022

Rec.: Patryk Mogilnicki, Książka po okładce. O współczesnym polskim projektowaniu okładek książkowych, Karakter, Kraków 2021.
Wstęp
Authors: Bizior-Dombrowska Magdalena , Chłopek Patryk
Published: December 2022

Wstęp do numeru „Sztuki Edycji” zatytułowanego „Książka bez granic”.
Bots with Feelings: Should AI Agents Express Positive Emotion in Customer Service?
Authors: Han Elizabeth , Yin Dezhi , Zhang Han
Published: December 2022

The rise of emotional intelligence technology and the recent debate about the possibility of a “sentient” artificial intelligence (AI) urge the need to study the role of emotion during people’s interactions with AIs. In customer service, human employees are increasingly replaced by AI agents, such as chatbots, and often these AI agents are equipped with emotion-expressing capabilities to replicate the positive impact of human-expressed positive emotion. But is it indeed beneficial? This research explores how, when, and why an AI agent’s expression of positive emotion affects customers’ service evaluations. Through controlled experiments in which the subjects interacted with a service agent (AI or human) to resolve a hypothetical service issue, we provide answers to these questions. We show that AI-expressed positive emotion can influence customers affectively (by evoking customers’ positive emotions) and cognitively (by violating customers’ expectations) in opposite directions. Thus, positive emotion expressed by an AI agent (versus a human employee) is less effective in facilitating service evaluations. We further underscore that, depending on customers’ expectations toward their relationship with a service agent, AI-expressed positive emotion may enhance or hurt service evaluations. Overall, our work provides useful guidance on how and when companies can best deploy emotion-expressing AI agents.
Privacy Rights and Data Security: GDPR and Personal Data Markets
Authors: Ke T. Tony , Sudhir K.
Published: December 2022

General Data Protection Regulation (GDPR)—the European Union’s data protection regulation—has two key principles. It recognizes that individuals own and control their personal (but not contractual) data in perpetuity, leading to three critical privacy rights, namely, the rights to (i) explicit consent (data opt-in), (ii) to be forgotten (data erasure), and (iii) portability (data transfer). It also includes data security mandates against privacy breaches through unauthorized access. We study GDPR’s equilibrium impact by including these features in a dynamic two-period model of forward-looking firms and consumers. Firms collect consumer data for personalization and price discrimination. Consumers trade off gains from personalization relative to potential losses from privacy breaches and price discrimination in their purchase, data opt-in, erasure, and transfer decisions. Though data security mandates impose fines on firms for privacy breaches, firms can benefit from higher opt-in given lower breach risk. Surprisingly, data security mandates can hurt consumers. The effect of privacy rights is nuanced. Since the right to opt in separates goods exchange from the provision of personal data, it prevents market failure under high breach risk. But it also reduces consumer opt-in and personal data availability. Erasure and portability rights reduce consumers’ hold-up concerns by disciplining firms to provide ongoing value by limiting price discrimination and not slacking off on data security; but they also reduce the incentive to offer lower initial prices that encourages opt-in. Overall, privacy rights always benefit consumers in competitive markets, but they can surprisingly hurt consumers under monopoly, as monopolists have less incentives to subsidize consumer opt-in. They raise (reduce) firm profit and social welfare when breach risk is high (low). Finally, privacy rights increase firm profit most at moderate levels of data transferability.

This paper was accepted by Dmitri Kuksov, marketing.

Funding: T. T. Ke acknowledges financial support from the General Research Fund of the Hong Kong Research Grants Council [Grant 14500421].

Supplemental Material: The e-companion is available at https://doi.org/10.1287/mnsc.2022.4614 .
Laryngeal assessment in dogs: a clinical review
Authors: Ferrero Camilla , Borland Karla , Bradbrook Carl , Bennett Rachel
Published: December 2022

This article reviews the literature describing the anaesthetic and ancillary drugs used during the assessment of laryngeal function in dogs, and summarises the evidence for their use in clinical practice. A review of the literature was conducted using PubMed and Google Scholar, with the search terms ‘laryngeal assessment dogs’, ‘laryngeal collapse’, ‘laryngeal paralysis’, ‘premedication laryngeal assessment’, ‘induction agent laryngeal assessment’ and ‘dogs’. Further studies and reports were obtained from the reference lists of the retrieved papers. Related anaesthesia textbooks were also reviewed. Drugs used to induce anaesthesia affect laryngeal function by diminishing the laryngeal reflex. Based on the current literature, premedication using acepromazine and an opioid allows for the assessment of laryngeal examination without impairing laryngeal motion. Dexmedetomidine in combination with an opioid may offer an alternative, but there are no studies comparing these sedative drugs directly. Examination times were shorter with propofol compared to alfaxalone, while ketamine was not recommended as an anaesthetic induction agent for this purpose. The use of doxapram hydrochloride may be helpful, particularly when airway assessment remains equivocal. At low doses, doxapram causes minimal increases in arterial blood pressure and heart rate.