bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy toxicity prediction in patients with melanoma using machine learning algorithms.
Authors: Sharma Lakshya , Mohan Esha , Balaji Vaishnavi , Wong Jonathan , Joshi Adwait , Mporas Iosif , Shi Jiaqi , Zhao Yi , Stoll-D'Astice Amy C. , Tailor Vipula , Powell Georgie , Alrifai Doraid , Shah Riyaz N.H. , Waters Justin S. , Adeleke Sola Michael
Published: July 2024

e21567

Background: Immune checkpoint inhibitor (ICI) related toxicity is common in melanoma patients, but identifying who will experience toxicity can be challenging. Precision medicine tools that accurately predict ICI toxicity could improve patient outcomes. This study aimed to use Machine Learning (ML) to predict ICI toxicity in patients with melanoma. Methods: 384 datasets were available for patients started on immunotherapy between 2014-2023 in a single, large regional cancer center in Kent, U.K. Raw data was preprocessed using a standard scaling function and one hot encoding, followed by SMOTE to balance the imbalanced classes. Six ML algorithms were developed using 80% of the training data, tested on 20% of validation data and used the Grid Search Cross-Validation technique for hyperparameter optimization. Shapley Additive Explanations (SHAP) explainable artificial intelligence was used to interpret the toxicity prediction model to improve the interpretation and transparency of the decision boundary. Results: Of the 384 patients, 112 patients (29%) had completely resected disease and then had adjuvant treatment while 272 (71%) were unresectable or had metastatic disease and had palliative treatment intent. In the metastatic setting, the commonest immunotherapy regimen was Pembrolizumab (155, 57%), followed by Ipilimumab/Nivolumab (85, 31%). The commonest regimen in the adjuvant setting was Pembrolizumab (86, 77%). 95 patients (25%) experienced ICI-related toxicity. The number of patients with Grades 1-4 toxicity was 2 ,4, 18 and 4 respectively, the remaining had unspecified toxicity grades. The commonest class of toxicity (CTCAE v5) was gastrointestinal (36, 38%), followed by endocrine (20, 21%) and skin (19, 20%). Linear Regression and Gaussian Naïve Bayes predicted toxicity with the most accuracy, 92% (Table 1). The model showed that increasing age, female gender and not receiving Nivolumab predicted toxicity. Regardless of the regimen or treatment intent, our ML model could also predict immunotherapy response with 90% accuracy. Conclusions: These ML algorithms used clinically available data to predict ICI toxicity accurately. Key predictors of toxicity included increasing age, female gender and not receiving Nivolumab in the setting of both adjuvant and palliative intent. Future work will aim to externally validate these models in other centers. We will also explore if models could be trained for use in patients treated with nivolumab in combination with new anti-LAG-3(relatlimab). [Table: see text]
A randomized, open-label phase II/III efficacy and safety study of atezolizumab in combination with FLOT versus FLOT alone in patients with gastric cancer and adenocarcinoma of the oesophagogastric junction and high immune responsiveness: The IKF633/DANTE trial, a trial of AIO in collaboration with SAKK.
Authors: Al-Batran Salah-Eddin , Lorenzen Sylvie , Heuer Vera , Angermeier Stefan , Ettrich Thomas Jens , Homann Nils , Haag Georg Martin , Kurreck Annika , Stein Alexander , Heinemann Volker , Ronellenfitsch Ulrich , Zander Thomas , Kubicka Stefan , Siebenhuener Alexander Rheinhard , Kopp Christina , Pauligk Claudia , Goetze Thorsten
Published: July 2024

TPS4184

Background: Despite recent advances, long-term survival of patients with locally advanced, operable esophagogastric adenocarcinoma (EGA) is below 50%. Immune checkpoint inhibitors in the neoadjuvant setting of this tumor type have lately been shown to increase pathological responses in all comers (IKF633/DANTE pII, KEYNOTE-585, Matterhorn), but the effect on survival is still unknown. The IKF633/DANTE pIII trial evaluates the efficacy and clinical activity of atezolizumab (ATZ) with perioperative FLOT in patients (pts) with locally advanced, resectable EGA considered having an immune-responsive profile. Methods: IKF633/DANTE is conducted as a randomized, multinational, multicenter, prospective, investigator-initiated, open label phase II/III trial. For the phase III portion, pts with histologically confirmed EGA of a clinical stage ≥cT2 and/or cN+ without evidence of distant metastases and with at least one immune response criterium (MSI, PD-L1 CPS≥1, TMB ≥10/MB or EBV+) are eligible. Pts are stratified acc. to nodal stage (cN- vs. cN+), tumor site (GEJ type I vs. GEJ type II/III vs. gastric) and PD-L1 expression levels (CPS≥5 vs. CPS<5). Pts are randomized 1:1 to receive 4 pre- and post-operative cycles FLOT/ATZ, followed by 8 cycles ATZ maintenance (Arm A) or 2x4 perioperative cycles FLOT alone (Arm B). In total, 556 pts will be enrolled, thereof 379 pts in phase III. This estimates to a recruitment time of 30 months plus 18 months follow-up for 80% statistical power and a significance level of p<0.05 (two-sided log rank test). The primary endpoint is event-free survival (EFS) with a target hazard ratio of 0.72, reflecting a clinically relevant improvement to 41.65 months in arm A. Main secondary endpoints are pCR, overall survival (OS) also in high immune-responsive subgroups (CPS ≥5/ CPS≥ 10/ MSI), R0 resection rate and safety/tolerability. In addition, a prospective biomarker study with serial circulating tumor DNA (ctDNA) analysis accompanying therapy is performed to explore the prognostic impact of ctDNA on efficacy and survival parameters, as well as on relapse incidence. Recruitment of phase III started in Aug 2023 and is still ongoing. Clinical trial information: NCT03421288 .
A phase 3, randomized study of adjuvant rilvegostomig plus chemotherapy in resected biliary tract cancer: ARTEMIDE-Biliary01.
Authors: Fan Jia , Bekaii-Saab Tanios S. , Aldrighetti Luca A. , Bridgewater John A , Ferrone Cristina R. , Harding James J. , Ikeda Masafumi , Knox Jennifer J. , Wang Julie , Kayhanian Hamzeh , Chen Xin , Bai Sally Yan , Drachsler Moritz Wolfgang , Oh Do-Youn
Published: July 2024

TPS4199

Background: Biliary tract cancer (BTC) is a rare but aggressive heterogenous group of gastrointestinal cancers that arise from the intra- or extrahepatic bile ducts (cholangiocarcinoma [CCA]) or the gallbladder (GBC). In early-stage disease following curative resection, adjuvant chemotherapy with a fluoropyrimidine- or gemcitabine-based regimen is usually recommended, however, recurrence rates remain high (e.g. in the BILCAP study, 5-year recurrence-free survival with adjuvant capecitabine was 34%). Immunotherapy is efficacious as adjuvant therapy in other cancer types. Results from the TOPAZ-1 and KEYNOTE-966 studies support combining immunotherapy and chemotherapy in advanced BTC, including in locally advanced non-metastatic disease. Furthermore, dual inhibition of programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and the novel immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), has shown promising results across multiple tumor types without major increases in high-grade toxicity compared with PD-1 or PD-L1 inhibition alone. Rilvegostomig is an anti-PD-1/-TIGIT bi-specific monoclonal antibody that appears active and well tolerated in non-small-cell lung cancer. ARTEMIDE-Biliary01 will investigate the efficacy of rilvegostomig plus standard of care adjuvant chemotherapy in patients with BTC after curative intent resection. Methods: ARTEMIDE-Biliary01 (NCT06109779) is a Phase 3, randomized, double-blind, placebo-controlled, multicenter, global study to assess the efficacy and tolerability of rilvegostomig IV every three weeks versus placebo in combination with investigator's choice of chemotherapy (capecitabine, S-1 [tegafur/gimeracil/oteracil] or gemcitabine/cisplatin) as adjuvant treatment in patients with BTC after curative intent resection. This study will enroll approximately 750 adults with histologically confirmed adenocarcinoma of the biliary tract (intrahepatic or extrahepatic CCA or muscle-invasive GBC) after macroscopically complete resection (R0 or R1) and an ECOG PS of 0–1. Key exclusion criteria include locally advanced, unresectable, or metastatic disease at initial diagnosis and any anti-cancer therapy for BTC prior to surgery. The primary endpoint is recurrence-free survival, and the key secondary endpoint is overall survival. Additional endpoints include progression-free survival following recurrence, patient-reported tolerability, and safety. Enrollment has begun, and approximately 200 sites will be recruiting globally across Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT06109779 .
Xevinapant with radiation and concurrent carboplatin and paclitaxel in patients ineligible for cisplatin with locoregionally advanced squamous cell carcinoma of the head and neck (EXtRaCT study).
Authors: Mir Nabiel Ali , Juloori Aditya , Swiecicki Paul , Katipally Rohan Reddy , Agrawal Nishant , Blair Elizabeth A. , Haraf Daniel J. , Pearson Alexander T. , Vokes Everett E. , Rosenberg Ari Joseph
Published: July 2024

TPS6126

Background: Locoregionally advanced (LA) head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT) who are ineligible for cisplatin have comparatively poor outcomes, with only ~40% alive at 5 years. There is an urgent unmet need to improve survival in these vulnerable patients with no standard therapeutic approach. Xevinapant, an oral inhibitor of XIAP and cIAP1/2, sensitizes cancer cells to apoptosis. Randomized phase II results in patients eligible for cisplatin combining xevinapant with CRT showed improved locoregional control, manageable toxicity, and promising survival outcomes. (Sun et al. Lancet Oncol. 2020) The current trial aims to extend these benefits to patients ineligible for cisplatin using xevinapant with carboplatin-paclitaxel-based CRT, hypothesizing safety and tolerability in this high-risk group. Methods: This phase I dose escalation/expansion study investigates xevinapant combined with carboplatin and paclitaxel to treat LA HNC in patients ineligible for cisplatin. Key eligibility includes previously untreated LA HNC and specific cisplatin ineligibility criteria, including >=70yo with moderate to severe comorbidity or vulnerability (Geriatric-8 score ≤ 14 and/or CARG score ≥ 30%) or <70yo with severe comorbidity and/or vulnerability, or >=18yo with an absolute contraindication to cisplatin. The treatment regimen comprises escalating doses of oral xevinapant (50-200 mg daily) on days 1-14 of a 21-day cycle for 3 cycles concurrent with CRT and 3 cycles adjuvant, weekly carboplatin AUC 1.5 IV, and paclitaxel 30 mg/m2 IV for 7 doses, and radiotherapy to 70 Gy in standard 2Gy fractions over 7 weeks with primary endpoint of tolerability and recommended phase 2 dose. A Bayesian-modified toxicity probability interval design will identify the maximum tolerated dose (MTD), targeting a 25% dose-limiting toxicity rate, with a sample size of 24 patients in dose-finding. 18 additional patients will be enrolled in the dose-expansion cohort at the MTD, totaling 42 patients. Secondary objectives include safety, response, progression-free, overall survival, and locoregional and distant control. Exploratory aims: in-clinic geriatric evaluations (Katz ADL, Lawton iADL, MMSE), QoL surveys, symptom tracking via smartphone, and wearable-derived steps and sarcopenia assessment. Recruitment began 02/2024. Clinicaltrials.gov ID: NCT06110195. Clinical trial information: NCT06110195 .
Fetal/Maternal-Determined Birth Weight and Adulthood Type 2 Diabetes and Its Subtypes: A Mendelian Randomization Study
Authors: Wang Wenxiu , Xiao Wendi , Song Zimin , Zhuang Zhenhuang , Huang Ninghao , Zhao Yimin , Huang Tao
Published: July 2024

Background

Lower birth weight (BW) might increase the risk of adulthood type 2 diabetes, but its associations with the highly heterogeneous type 2 diabetes subtypes remain to be studied. In addition, whether the associations between lower BW and adulthood type 2 diabetes risks depend on fetal or maternal effect is largely unknown.

Methods

In this study, we performed a two-sample Mendelian randomization analysis to study the associations between overall, fetal-determined, and maternal-determined BW and the risks of type 2 diabetes and its subtypes, namely mild age-related diabetes (MARD), mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), and severe insulin-resistant diabetes (SIRD).

Results

Lower BW was genetically associated with increased risks of type 2 diabetes (odds ratio [OR]: 1.86; 95% CI: 1.53, 2.26), MARD (OR: 2.15; 95% CI: 1.43, 3.23), MOD (OR: 1.75; 95% CI: 1.10, 2.77), SIDD (OR: 1.86; 95% CI: 1.11, 3.10), and SIRD (OR: 1.66; 95% CI: 1.06, 2.60). When examining the fetal-determined genetic effects independently, lower BW remained associated with type 2 diabetes and its subtypes, except for MOD. Using maternal-determined BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it raised offspring risks of type 2 diabetes.

Conclusion

Fetal-determined but not maternal-determined lower BW were associated with increased risks of adulthood type 2 diabetes and its subtypes. Our results underscored the importance of early targeted management among people with a low BW in the prevention of type 2 diabetes.
Mechanisms underlying the direct programming of mouse embryonic fibroblasts to thymic epithelial cells by FOXN1
Authors: Ma Zhongyao , Kang Seung Woo , Condie Brian G. , Manley Nancy R.
Published: July 2024

Thymic epithelial cells (TECs) are crucial to the ability of the thymus to generate T cells for the adaptive immune system in vertebrates. However, no in vitro system for studying TEC function exists. Overexpressing the transcription factor FOXN1 initiates transdifferentiation of fibroblasts into TEC-like cells (iTECs) that support T-cell differentiation in culture or after transplant. In this study, we have characterized iTEC programming at the cellular and molecular level in mouse to determine how it proceeds, and have identified mechanisms that can be targeted for improving this process. These data show that iTEC programming consists of discrete gene expression changes that differ early and late in the process, and that iTECs upregulate markers of both cortical and medullary TEC (cTEC and mTEC) lineages. We demonstrate that promoting proliferation enhances iTEC generation, and that Notch inhibition allows the induction of mTEC differentiation. Finally, we show that MHCII expression is the major difference between iTECs and fetal TECs. MHCII expression was improved by co-culturing iTECs with fetal double-positive T-cells. This study supports future efforts to improve iTEC generation for both research and translational uses.
Social Exclusion of People Who Abstain from Mandatory COVID-19 Vaccination for Medical Reasons: A Contemporary Ethical Conflict
Authors: Grigoriadou Virginia , Alifieri Sofianna , Tsagdi Sofia , Balatsou Maria , Theologou Kostas
Published: July 2024

The measures of obligatory vaccination against COVID-19 disease in Greece, have failed to cater to people, who for serious medical reasons, were prohibited by their private doctors to be vaccinated. This fact, however, leads to their unwilling social seclusion, since they cannot obtain the vaccination certificate that ensures access to all social activities. They are, therefore, faced with the dilemma of consenting to vaccination, disregarding possible health or even fatal consequences, or social exclusion and isolation. This research study aims to discuss this ethical conflict, between what is considered ethical for society in contrast to restriction of personal will and health. It wishes to rediscover the very essence of the commitment to protecting human rights-health and social well-being. This dilemma will be viewed and examined under the scope of core ethical values and principles met in Hippocrates’ oath and the fundamental ethical theory of Utilitarianism. The study will try, drawing from these ethical theories and definitions, to test these questions and conclude on what the indicative ethical choice is. The study wishes to propose suggestions of measures that can be taken to ensure equal operations for all citizens, based on medical ethics and self-disposition principles. It will also propose actions that should be put in the equation, sensitive groups. We feel that a balanced ethical approach that does not accentuate disparities within and among different groups, could ensure health equality, better social resilience, and commitment to effective prospective preparedness.
Professor Nikolaos Louros, a concerned scientist in twentieth-century Athens
Authors: Gardikas Katerina
Published: July 2024

The personal papers of Nikolaos Louros present an invaluable source of information on Louros’s place in the medical, social, cultural and political history of twentieth-century Greece. A royalist, liberal and keen observer of scientific and social developments, he participated actively in the shaping of the country’s post-war progress in medical education, institutions and ideas.
On some ancient Greek and Latin medical recipes in verse. Their position in the world. Part A
Authors: Diamandopoulos Athanasios
Published: July 2024

In Part A of our article, we examine medical recipes in verse within Greek literature, spanning from the Hellenistic period to the Roman Imperial era. We also briefly touch upon analogous recipes in Classical and Late Latin, as these two literary forms were intertwined for centuries. A comprehensive analysis of Latin literature in this domain remains a necessity. We explore the motivations behind these didactic poems and the metrical patterns employed in their composition. The article presents fragments of these recipes, all translated into English and several retained in their original language as well, arranged chronologically alongside succinct biographical details of their authors. These include Homer, considered their distant forebear, followed by Ovid, Aglaias of Byzantium, Andromachus the Elder, Philo of Tarsus, Damocrates, Nicander, Rufus of Ephesus, Eudemus of Pergamum, Galen, Serenus Sammonicus, The Carmen graecum de herbis, and Marcellus Empiricus. In Part B, we will continue to explore similar recipes from the Middle and Late Byzantine periods. This section will also feature examples from Medieval Latin and Islamic medical literature, illustrating the intercultural context in which these Greek verses stood. A General Discussion and Conclusions will be provided at the end of Part B.
Η συμβολή του νομικού ελέγχου στην αξιολόγηση ευθυνών χειρουργού - αναισθησιολόγου για ασθενείς που υποβάλλονται σε αναισθησία στην ιατρική πρακτική
Authors: Τζούμας Λάμπρος
Published: July 2024

Εισαγωγή: Η ανάλυση δικαστικών αποφάσεων κακής ιατρικής πρακτικής κατά τη διάρκεια της αναισθησίας ή μίας χειρουργικής επέμβασης, μπορεί να παρέχει μια λεπτομερή εικόνα της θνησιμότητας και της νοσηρότητας των ασθενών και των αιτιών που οδήγησαν σε κακή ιατρική πρακτική. Σκοπός: Σκοπός της έρευνας αυτής είναι να αναλυθούν μέσα από δημοσιευμένες κυρίως δικαστικές αποφάσεις περιστατικά φερόμενων ιατρικών σφαλμάτων από Αναισθησιολόγους και ιατρούς χειρουργικών ειδικοτήτων στην Ελλάδα. Υλικό και μέθοδος: Αναζητήθηκαν δικαστικές αποφάσεις για κακή ιατρική πρακτική που αφορούσαν Αναισθησιολόγους και ιατρούς χειρουργικών ειδικοτήτων κυρίως από ελληνικές νομικές τράπεζες και περιοδικά. Καταγράφηκαν οι αιτίες ανθρωποκτονιών και σωματικών βλαβών από αμέλεια και ερευνήθηκε το κριτήριο απόδοσης της ευθύνης. Αποτελέσματα: Βρέθηκαν 596 αποφάσεις που αντιστοιχούν σε 290 υποθέσεις, από τις οποίες οι 147 ήταν ποινικές καταδικαστικές, 91 αστικές - επιδικαστικές αποζημίωσης αφορώσες 118 ανθρωποκτονίες και 120 σωματικές βλάβες από αμέλεια λόγω κακής ιατρικής πρακτικής, ενώ 52 ήταν ποινικές αθωωτικές – αστικές απορριπτικές αγωγών αποζημίωσης. Οι Μαιευτήρες / Γυναικολόγοι είναι η ειδικότητα με την πιο συχνή εμπλοκή σε υποθέσεις ιατρικής αμέλειας. Ακολουθεί η γενική χειρουργική και η αναισθησιολογία. Η μη συνεχής και επιτεταμένη παρακολούθηση, η εσφαλμένη / καθυστερημένη διάγνωση και η εσφαλμένη χειρουργική / αναισθησιολογική πρακτική εμφανίζονται ως οι κύριες αιτίες ανθρωποκτονιών και σωματικών βλαβών από αμέλεια. Στο 80% των περιπτώσεων η κακή έκβαση θα μπορούσε να αποφευχθεί, εάν υπήρχε συνεχής παρακολούθηση και εάν τηρούνταν οι κατευθυντήριες οδηγίες για την αντιμετώπιση του προβλήματος. Συμπέρασμα: Για την αποφυγή κακής ιατρικής πρακτικής και τη βελτίωση των αποτελεσμάτων απαιτείται λήψη ιστορικού, ενημερωμένη συναίνεση, συνεχής παρακολούθηση και τήρηση των κατευθυντήριων οδηγιών για την αντιμετώπιση του προβλήματος.
Ανάπτυξη νέων καινοτόμων χημειοθεραπευτικών από την σύζευξη μιτοχονδριοτροπικών παραγόντων με οξαδιαζολικά παράγωγα
Authors: Βαγενάς Γεώργιος
Published: July 2024

Στην παρούσα διδακτορική διατριβή συντέθηκαν, χαρακτηρίστηκαν και μελετήθηκαν πέντε νέες σύμπλοκες ενώσεις από την αντίδραση των υποκατεστημένων θειονο-οξαδιαζολίων-1,3,4 (X-PODT) με το άλας του AgNO3 και την μιτοχονδριοτροπική τριφαίνυλοφωσφίνη. Επίσης μελετήθηκε η κρυσταλλική δομή των υποκατεστημένων θειονο-οξαδιαζολίων-1,3,4. Τα νέα σύμπλοκα 1-5 χαρακτηρίστηκαν σε στερεή κατάσταση με μελέτη της περίθλασης ακτίνων Χ (XRD), φασματοσκοπία υπερύθρου (FT-IR), μελέτη του σημείου τήξεως και σε υγρή κατάσταση με φασματοσκοπία υπεριώδους-ορατού (UV-Vis) και φασματοσκοπία πυρηνικού μαγνητικού συντονισμού πρωτονίου (1H-NMR). Οι μοριακοί τύποι τους είναι οι: Ag(PPh3)3H-PODT (1), Ag(PPh3)3o-Cl-PODT (2), Ag(PPh3)3m-Cl-PODT (3), Ag(PPh3)3o-F-PODT (4), Ag(PPh3)3p-F-PODT (5). Επίσης ελέγχθηκε η σταθερότητα τους σε διάλυμα DMSO-d6 με φασματοσκοπία UV-Vis και 1H-NMR για χρονικό διάστημα 48 ωρών. Το X-PODT συναρμόζεται στον άργυρο μέσω του ατόμου του θείου του διπλού δεσμού άνθρακα-θείου και με τα τρία άτομα φωσφόρου των μορίων τριφαινυλοφωσφίνης, σχηματίζοντας μια παραμορφωμένη τετραεδρική δομή. Στη συνέχεια ελέγχθηκε η αντιπολλαπλασιαστική δράση των νέων συμπλόκων έναντι δύο καρκινικών κυτταρικών σειρών του μαστού: την MCF-7, η οποία εκφράζει υποδοχείς ορμονών και την MDA-MB-231, όπου απουσιάζουν οι υποδοχείς ορμονών. Όλα τα σύμπλοκα έδειξαν αντικαρκινική δράση. Επιπλέον τα νέα σύμπλοκα έδειξαν εκλεκτική δράση έναντι της κυτταρικής σειράς MCF-7 σε σχέση με τη κυτταρική σειρά MDA-MB-231. Όλα τα σύμπλοκα είναι 1.8-10.6 φορές πιο δραστικά από το cisplatin έναντι των δύο καρκινικών σειρών. Εξ’ αυτών τα σύμπλοκα Ag(PPh3)3m-Cl-PODT καιAg(PPh3)3p-F-PODT εμφάνισαν την ισχυρότερη αντικαρκινική δράση. Η τοξικότητα τους ελέγχθηκε in vitro στους φυσιολογικούς ινοβλάστες MRC-5, ενώ η πιθανή γονοτοξικότητα ελέγχθηκε in vitro με μελέτη μικροπυρηνίσκων, όπου τα νέα σύμπλοκα έδειξαν χαμηλή γονοτοξικότητα. Οι μελέτες της μορφολογίας των κυττάρων, του κατακερματισμού του πυρηνικού DNA, της χρώσης με τις χρωστικές AO/EB καθώς και της διαπερατότητας της μιτοχονδριακής μεμβράνης οδηγούν στο συμπέρασμα ότι τα νέα σύμπλοκα Ag(PPh3)3Χ-PODT προκαλούν απόπτωση μέσω του κατακερματισμού του DNA, είτε δρώντας απευθείας σε αυτό, είτε με ενεργοποίηση των μονοπατιών που οδηγούν σε κατακερματισμό του κυτταρικού DNA. Τέλος ελέγχθηκε ο μηχανισμός δράσης ex vivo των συμπλόκων στο CT-DNA και αποκαλύφθηκε ότι αυτά έχουν την ικανότητα να αλληλεπιδρούν με τα μόρια DNA μέσω συναρμογής στη μικρή αύλακα της διπλής έλικας, ενώ το σύμπλοκο Ag(PPh3)3p-F-PODT εμφανίζει την μεγαλύτερη συγγένεια (μεγαλύτερη σταθερά δέσμευσης,kb) με το CT-DNA.
Biskup Bogusław Korwin Gosiewski (1669–1744): zarys biografii
Authors: Gosiewski Jan Paweł
Published: July 2024

W artykule przedstawiono zarys biografii biskupa smoleńskiego Bogusława Korwina Gosiewskiego (1669–1744). Autor zwrócił szczególną uwagę na jego porywczy, wręcz awanturniczy charakter, złożone relacje rodzinne, stosunkowo wysokie ambicje polityczne, a także zaangażowanie religijne oraz mało znane zasługi dla dobroczynności. Podjął również próbę sprostowania występującej w wielu opracowaniach błędnej informacji, wskazującej, że był on synem hetmana Wincentego Korwina Gosiewskiego i Magdaleny z Konopackich.
Biogas: Strengthening Green Energy Infrastructure for a More Sustainable Future
Authors: Mulyono Yatin , Suranto Suranto , Yamtinah Sri , Sarwanto Sarwanto , Jamil Abdul
Published: July 2024

Biogas has been available as a renewable energy source to accelerate national economic development. This research aimed to analyze the potential of renewable energy production development in Indonesia and present the application of potential waste processing into biogas. This study fills the knowledge gap through a critical review of the potential for developing renewable energy from animal waste in Indonesia, including biogas, power generation, transportation, and value-added chemicals. This study was conducted using a critical review of research articles and is supported by other related literature. The result of the study showed that Indonesia has great potential to develop biogas production due to its substrate availability, particularly from farm animal waste or other organic waste, even though its utilization has not been maximized. The data showed that primary energy consumption, especially in the industrial and transportation sectors, was dominated by fossil fuels and coal. The production of biogas technology development comprehensively included the processes and techniques of waste handling from biogas production. Most of the biogas application approaches were still in the early stage. Identifying opportunities, obstacles, policies, research, and development is still needed, particularly in this relatively new sector.
Implementation of Information and Comuncation Technology (ICT) into UKI Learning During The Covid-19 Period
Authors: Sinaga Dameria
Published: July 2024

In 2020, around February, the spread of the corona virus disease occurred throughout the world, causing changes in the economic, educational and health sectors. Likewise, in our country, Indonesia, learning has been disrupted by the presence of the corona virus disease, where previously learning was carried out in classrooms, but to prevent the spread of this virus from becoming widespread, learning was not carried out in schools but in individual homes. In order for learning to take place effectively even if you do not meet face to face, learning is carried out online. The results of this research show that using ICT learning is useful in supporting the learning process. By using ICT, teachers can do homework, mid-semester exams, final semester exams and can give grades to students without disturbing them and not being late in the class promotion process. As a result of using ICT, the learning process runs smoothly and effectively, providing motivation and making the learning process easier in getting broader information about learning at UKI. The purpose of this study is to facilitate learning during the COVID-19 period. We know that during the COVID-19 period all learning was carried out at home using daring learning. The study was conducted at the Christian University of Indonesia with a sample of 58 students who were randomly selected. And using the experimental method with a 2 x 2 factorial design.The findings of this study are to make students more active in learning. The results showed that learning through E-Learning can improve learning and competency-based curriculum especially UKI during the COVID-19 period
O EFEITO DE VARIÁVEIS MACROECONÔMICAS NACIONAIS NAS RECEITAS PÚBLICAS: UM ESTUDO PARA A PREVISÃO DO ICMS DOS ESTADOS DO NORDESTE
Authors: Pedrosa Lucas , Moura Fábio Rodrigues de , Braatz Jacó , Marino Carlos Eduardo dos Santos
Published: July 2024

Este artigo tem por objetivo apresentar uma metodologia alternativa para a previsão de receitas tributárias dos estados do Nordeste. Para isto, utilizou-se um modelo de regressão linear para a projeção da receita do Imposto sobre Circulação de Mercadorias e Serviços (ICMS), com base nos efeitos parciais de curto prazo de variáveis macroeconômicas nacionais, como o PIB, inflação, taxa básica de juros e taxa de câmbio. Os resultados obtidos foram satisfatórios, de modo que se conseguiu prever as receitas anuais de ICMS dos estados do Nordeste com erros de previsão absolutos médios entre 1,48% e 6,83%.
Use of Magic Tricks as Analogies in the Science Classroom
Authors: Rudnick Danny , Boesdorfer Sarah B.
Published: July 2024

Science, magic, and education have always been linked, from science-based magic shows to teachers presenting demonstrations as magic tricks to capture their students’ interest and provide a mnemonic reference for the topics under discussion. Magic as an art form is also often used to convey information or act as an analogy for invisible phenomena. This study examined how the use of a magic effect designed as an analogy for active and passive transport in cells affected student scores and perception of the activity when compared to a standard story analogy in a high school integrated science course. To determine this, students participated in either a magic-based analogy activity (MBAA) or a concrete story-based analogy activity (SBAA), and then data was collected and analysed using a pre-test/post-test for the content and a Likert-scale anonymous survey for the student perception of the activity. The MBAA was shown to be similar to the SBAA in helping students learn but had the added benefit of increasing students’ reported engagement with the activity. This study shows how bringing magic into the science classroom can have a positive impact on student engagement and provides teachers with another option to support student learning.
Articulation Between a Technological Model and an Educational Model to Deepen the Reflection of Prospective Mathematics Teachers
Authors: Morales-López Yuri , Breda Adriana , Font Vicenç
Published: July 2024

This article is aimed at integrating the Technological Pedagogical Content Knowledge (TPACK) system with the Didactic Suitability Criteria (DSC) of the Didactic-Mathematical Knowledge and Competences (DMKC) system to improve the reflection of prospective mathematics teachers on online classes. Thirteen prospective teachers, divided into two subgroups, participated in a training cycle that addressed both models. Each participant used and created indicators of reflection of the assigned model to analyze an online class on functions, and subgroups exchanged reflections to examine the class from the other model’s perspective. It was noted that the DMKC model allows for a broad analysis of the class but has limitations in assessing technology and the teacher's technological knowledge, while TPACK’s emphasis is on technology and teacher knowledge but does not explicitly address mathematical interaction or affective aspects. It is concluded that combining the TPACK model and the DSC of the DMKC model can generate more complete tools to reflect on online math classes and consequently allow for a comprehensive evaluation that covers both the mathematical content and the technological and pedagogical skills of the teacher.
Improved Anti-nociceptive, Anti-pyretic and Anti-inflammatory Effects of Orally Administered Liposome-encapsulated Piroxicam
Authors: Chiong HS , Yong YK , Hijaz MS Mohd , Sulaiman MR , Yuen KH , Hakim MN
Published: July 2024

Piroxicam, a nonsteroidal anti-inflammatory drug, has been shown with low oral bioavailability and delayed onset of its therapeutic effects. In this work, a promising nano/liposomal drug delivery system was exploited to improve the in vivo therapeutic efficacies of piroxicam. The current liposome-encapsulated piroxicam formulation effectively boosted and prolonged peripherally mediated anti-nociceptive activities in tests for abdominal writhing induced by acetic acid (inhibition of pain 70.19% was in mice treated with 30 mg/kg liposome-encapsulated piroxicam), paw licking induced by formalin (81.36% inhibition when compared to free unencapsulated piroxicam), and hyperalgesia induced by carrageenan (55.8% inhibition when compared to free unencapsulated piroxicam). Even lower dose of liposomes-encapsulated piroxicam was also significantly inhibit Brewer’s yeast-induced hyperthermia. Carrageenan-induced paw-edema test and cotton pellet-induced granuloma test revealed that liposomes-encapsulated piroxicam had significantly more potent acute and chronic anti-inflammatory effects than piroxicam, even if lower drug dosages were used to treat animals. A better modulation in the generation of inflammatory mediators (nitric oxide, tumour necrosis factor-α, interleukin-1β, and interleukin-10) at 18.02% (TNFa), 23.97% (IL-1β) and 10.27% (IL-10) inhibition when compared to 30mg/kg free piroxicam group respectively. was ascribed to the higher in vivo therapeutic actions. Present nano-encapsulated piroxicam also significantly enhanced the inhibition of cyclooxgenase-2 (total percentage inhibition was increased by 18.25% and 19.22% at drug dosage of 3 and 30 mg/kg, respectively), but not cyclooxgenase-1 enzyme. In conclusion, present study showed that liposomal drug formulation was able to improve the in vivo therapeutic effects of orally administered piroxicam.
The Binding Capacity of the Lead Phytochemical Molecule to Cancer Cell Target Proteins and its Potential Anticancer Properties with Respect to Standard Drugs
Authors: P Kiranmayee
Published: July 2024

Molecular docking is an important tool for connecting molecular biological structure to computer-aided drug design. The purpose of this blind docking experiment is to compare the binding energies of these three drugs and to predict the most likely binding poses of a ligand with a known three dimensional structure of a protein. To substantiate our previous in vitro study findings, an in silico model was chosen to compare the binding properties of the three drugs. The work is entirely bioinformatics in nature. Blind docking was accomplished with the help of free software/(s). A comparison was made among the three drgus, used primarily in cancer treatment, namely, anastrazole, capecitabine and quercetin. In our in vitro study, these three drugs were extremely effective. CB dock-2 to blind dock, SwissTargetPrediction to choose the targets, PubChem and Protein Data Base to obtain 3D structures of ligand and target respectively were used. Absorption, Distribution, Metabolism, and Excretion (ADME) from SwissADME, drug likeness from MolSoft L.L.C. software, and Liponski’s rule was used to check the “Rule of five (RO5)”. The crystallographic structures have resolution values ranging from 1 Å to 3 Å. Lipinski’s rule of five, Swiss ADME and drug likeness were used to compare the three drugs. For all of the targets studied, quecetin appeared to have the highest AutoDock vina scores. To summarize the current findings and publicly available data, quercetin is chemoprotective and radioprotective to healthy/ normal cells and it can be used during cancer treatment.
Analysis of GC-MS from Acetone Extract of Canarium odontophyllum Miq Stem Bark (Dabai)
Authors: Ishak Siti Fairuz , Rajab Nor Fadilah , Basri Dayang Fredalina
Published: July 2024

Canarium odontophyllum or dabai is a natural plant found along the river banks of the Sarikei, Kapit and Kanowit in Sarawak and it comes from the 'Burseraceae' family. C. odontophyllum also known as 'dabai' and this dabai fruit is eaten by the community in Sarawak. The fruit is a seasonal natural fruit that is less used because of its short lifespan. A few studies show that acetone extract of Canarium odontophyllum stem bark (dabai) exhibit antiproliferative and cytotoxicity effect on cancer colorectal cells. However, there is currently no analysis of bioactive compounds in acetone extract of Canarium odontophyllum stem bark (dabai). The various bioactive compounds detected in acetone extract were identified using gas chromatography-mass spectrometry (GC-MS). A total of 24 phytoconstituents were detected in this acetone extract. It was found that major peaks represented bicyclo [3.1.0] hex-2-ene,2-methyl-5-(1-methylethyl)-, bicyclo [3.1.0] hexane,4-methylene-1-(1-methylethyl)-, alpha cubebene, 1H cyclopenta [1,3] cyclopropa [1,2] benzene, octahydro-7-methyl-3-methylene-4-(1-methylethyl)-,[3aS-(3a.alpha., 3b.beta., 4.beta., 7.alpha., 7aS*)]-, phenol,2,4-bis(1,1-dimethylethyl)-, spathulenol, copaene, 9-Eicosene, (E)-, hexadecane, 5-Octadecene, (E)-, hexadecane, 2,6,10,14-tetramethyl-, nonadecane, n-Hexadecanoic acid, heptacosane, 1-chloro-, 9,12-Octadecadienoic acid (Z,Z)-, 9,12-Octadecadienoic acid, ethyl ester, octadecanoic acid, 10-Heneicosene (c,t), heptafluorobutyric acid, hexadecyl ester, dehydroabietic acid, phenol, 2,4-bis(1-phenylethyl)-, beta sitosterol, beta-amyrin and alpha-amyrin. The highest peak area (%) for this acetone extract is alpha-amyrin (16.6644%) followed by beta-amyrin (4.6159%), beta sitosterol (3.3369%) and 9,12-Octadecadienoic acid (Z,Z)- (3.2045%). In conclusion, various bioactive compounds detected in acetone extract of Canarium odontophyllum stem bark (dabai) were demonstrated various medicinal properties while alpha and beta-amyrin may be responsible for the cytotoxicity and apoptotic effect against HCT 116 cell.
Anti-inflammatory, Antioxidant, and Wound-healing Properties of the Methanolic Extracts from Hedera helix Fruits and Leaves
Authors: Al-jaafreh Ahmad M.
Published: July 2024

Common Ivy (Hedera helix L.) is an ornamental plant that is known for its aesthetic qualities and ability to provide natural greenery. It is also associated with potential health benefits. When evaluating the phytochemical constituents of H. helix methanolic extracts, the fruit extract had the highest levels of total phenolic compounds (TPC) at 100 GAE mg/g extract, compared to 89.47 GAE mg/g in the leaves extract. In contrast, total flavonoid compounds and total tannin were higher in leaves extracts, 37.14 TE mg/g extract and 24.79 GAE mg/g extract respectively. fruit extracts showed the greatest level of antioxidant properties in the FRAP test 75.5 and 62.35 AscE mg/g extract also in DPPH tests, the IC50 were 3.49 and 8.79 mg/ml for fruit and leaves respectively, demonstrating their potent capacity to neutralize free radicals and high reducing power. However, when evaluated by the ABTS method, the leaves extracts indicated the strongest antioxidant activity, suggesting their potent capacity to neutralize free radicals, the IC50 were 4.54 and 8.69 mg/ml for fruit and leaves respectively, the extracts' inhibitory effects on albumin denaturation were also assessed. The findings demonstrated the potential of the extracts as anti-inflammatory, with the leaf extract having the lowest IC50 values in these tests 75.26± 3.87 µg/ml and 115.62± 56.47 µg/ml, for ripe fruit extract. Furthermore, the lowest contraction value was 81.12% for pure ointment alone, followed by drug ointment and fruit ointment at 86.43 %and 90.21%, respectively, and the extract had the highest contraction rate at 95.82%, which demonstrated the strongest wound healing activity.
Probing the Memory-Enhancing Potential of Kiwi Fruit Against Scopolamine-Induced Memory Impairment in Experimental Rats
Authors: Kaur Awaneet , Alam Md. Aftab , Mahmood Tarique , Ahsan Farogh
Published: July 2024

It is good knowledge that the nutrient-dense kiwi fruit promotes better overall health. The antioxidant properties of kiwifruit have attracted attention as a possible reason for the fruit's health-enhancing effects. In comparison to chemical antioxidant assays, this study of the antioxidant capacity of kiwifruit discusses biologically relevant in vitro assays for predicting antioxidant activity in a biological location. These assays can be performed in a laboratory setting. The topic of discussion pertains to the potential of kiwifruit to serve as a cytoprotective agent against hydrogen peroxide-induced oxidative stress, hence mitigating cell death. In the final part of this article, we explore how the antioxidant and naturally occurring defence characteristics of kiwifruit may influence the health and welfare of humans. Compounds 1 and 2 have been subjected to additional research using scopolamine (SCOP)-induced memory impairment in a mice model of Alzheimer's disease (AD). The remarkable ability of these chemicals to enhance cognitive function has been shown to be highly impacted by their antioxidant and anticholinesterase capabilities.
Serum Total Bilirubin and Oxidative Stress Status in Diabetic Retinopathy – A Hospital-Based Observational Study
Authors: K Prabhavathi , Kunder Mamatha , K.N Shashidhar , K Kanthamani , A Raveesha
Published: July 2024

Diabetic retinopathy (DR) is one of the common microvascular complications of Type 2 Diabetes Mellitus (T2DM). As an antioxidant, the serum total bilirubin is associated with vaso-occlusive disorders. Oxidative stress parameters such as Erythrocyte Glutathione (GSH) as an antioxidant and Malondialdehyde (MDA) as an oxidant are critical in the pathogenesis of diabetic complications. This study aimed to explore the possibilities of the endogenous protective role of serum total bilirubin on the retinal vasculature in DR patients by estimating and correlating the levels of serum total bilirubin, GSH, and MDA in DR cases. In this hospital-based case-control study, 288 participants were selected from R.L. Jalappa Hospital and Research Centre, Kolar, divided into three groups with 96 subjects per group. Group I: Controls, Group II: T2DM, and Group III: DR subjects. The fasting blood sugar, glycated hemoglobin, liver function test, and lipid profiles were estimated by standard methods. Oxidative stress parameters viz, GSH and MDA were assayed by chromogen 5,5'- di thiobis 2-nitrobenzoic acid (DTNB) and thiobarbituric acid reactive substances (TBARS) methods, respectively. The prevalence of DR was significantly lower among subjects with the highest bilirubin quartile than those with the lowest. There was a significant mean difference with p<0.001 between the groups for total bilirubin, FBS, HbA1c, GGT, TC, TG, LDL, GSH, and MDA. A Negative correlation of serum total bilirubin with FBS (r = - 0.375), HbA1c (r = -0.351), and MDA(r=-0.323), and a positive correlation with GSH (r = 0.335) was observed in DR group with a significant p-value. T2DM subjects with higher levels of bilirubin within biological reference intervals were less likely to develop retinopathy. The severity of DR was inversely proportional to the total bilirubin levels. Therefore, serum total bilirubin levels could be a biomarker to predict the risk of developing retinopathy in people with T2DM.
Unorthodox Pleas for Contract Schools: Mother Mary Joseph Lynch and the Boarding School for Native Students in Morris, Minnesota
Authors: Gross Stephen , Wright Elizabethada A.
Published: July 2024

ABSTRACT: To better understand how Catholic women religious could participate in the "cultural genocide" of Native Americans perpetrated by boarding schools, this article considers Mother Mary Joseph Lynch, a Sister of Mercy, who founded Minnesota's Morris Industrial School for Indians in 1887. Using lenses provided by Susan Neiman and Mary Fulbrook, the article delves into the beginnings of the boarding school in Morris and considers what prompted the Sisters of Mercy to begin such an endeavor before analyzing several texts created by Lynch. The article begins with the assumption that the Sisters of Mercy wanted to be true to the values articulated by their founder, Catherine McAuley, as it also trusts the countless Native peoples who have conveyed the generational harm done to them by a process that systematically attempted to destroy their identities and their cultures.
“How we go on”: Tradition’s Talent and the Individual Poet in Gary Snyder’s “Axe Handles”
Authors: Chandran K. Narayana
Published: July 2024

Abstract: This essay examines Gary Snyder’s poem from various aspects: T. S. Eliot’s “tradition,” Ezra Pound’s “ideas in action,” and Paulo Freire’s critical pedagogy, to name a few. The learning at issue here is open and unconstrained, if only because in the short “Axe Handles,” things heard, seen, learnt, and internalized a long while ago at first hand matter. Furthermore, students see the advantage of tradition’s talent guided along the “at-handed” ease of access. Indic traditions of learning through narratives, tales as gifts, make this business obligation-free— both for the masters and disciples. Snyder’s poem is that splendid common ground on which preceptors and pupils meet and come to terms with such concepts as work, art, and wisdom. They are framed in both western and eastern cultural terms in arguing why and how the poem shows, placed within the commercial concerns of the contemporary academic, the humanities matter deeply.
Golfines and Tabardíes in Exemplo 20 of El conde Lucanor : Don Juan Manuel's View of Thirteenth- and Fourteenth-Century Castilian Monetary Policy
Authors: Zuwiyya Z. David
Published: July 2024

Abstract: Juan Manuel's Exemplo 20 from El Conde Lucanor tells the story of a king whose foolhardiness allows a swindler to steal his money. The moral of the tale is not to risk one's wealth on a poor man. The swindler, called a golfín , although claiming to be poor, invests one hundred doubloons and dresses in fancy robes. The king is publically shamed for his poor judgement. This article examines possible connections between the tale and the historical context, including the possibility that the character of the king is modeled on Alfonso X, that the tabardíe refer to maravedíes , the principal monetary unit of fourteenth-century Castile, and that the golfín was a member of the Italian clan that defrauded Alfonso X of his imperial dream.
Humildad y humillación como formas de mediación femenina pacificadora en Carlos Maynes (MS Esc. h-I-13)
Authors: Zubillaga Carina
Published: July 2024

Abstract: The present article analyzes forms of female mediation in Carlos Maynes , the last work included in MS h-I-13 (Biblioteca de San Lorenzo de El Escorial). The latter is a mid-fourteenth-century collection that includes saints' lives as well as the stories of queens such as Sevilla, who are accused of adultery. This article shows how in Carlos Maynes the empress Sevilla is associated with hagiographic models, has important family ties, and her body serves to mediate female royal power and facilitates peace. Resumen: El presente artículo propone un análisis de las formas de mediación femenina en Carlos Maynes , la última de las historias que integra el MS h-I-13 de la Biblioteca de San Lorenzo de El Escorial, una antología literaria de mediados del siglo XIV que reúne relatos que progresan de las vidas de santas iniciales a las historias finales de reinas acusadas de adulterio, como Sevilla. La figura de esta emperatriz resulta relevante para el análisis por su asociación con modelos hagiográficos y la importancia de los lazos familiares y de su propio cuerpo como vehículos de la mediación femenina regia y su funcionalidad pacificadora.