bluuebunny/crossref_metadata_2025 huggingface dataset:
An open-label study to assess the safety and efficacy of naporafenib (ERAS-254) administered with trametinib in previously treated patients with locally advanced unresectable or metastatic solid tumor malignancies with RAS Q61X mutations (SEACRAFT-1).
Authors: Spira Alexander I. , McKean Meredith , Daud Adil , Thein Kyaw Zin , Van Tine Brian Andrew , Wang Judy S. , Antal Joyce , Sutton Rebecca , Cui Yue , Hong David S.
Published: June 2024

TPS3178

Background: The rat sarcoma viral oncogene (RAS)/mitogen-activated protein kinase (MAPK) pathway is a key signaling cascade that drives cell proliferation, differentiation, and survival. Inappropriate activation of this pathway drives tumorigenesis in a subset of solid tumors. There are 3 isoforms of RAS (KRAS, NRAS, and HRAS) with the most commonly mutated codons being 12, 13, and 61. While these codon mutations map to the active site of RAS, they appear to have differential impacts on pathway activation. Mutations at codon 61 (RAS Q61X) are generally thought to be the most MAPK pathway-activating relative to mutations at codons 12 and 13 and are therefore thought to be the most oncogenic. Naporafenib is a pan-RAF inhibitor that is being evaluated in combination with trametinib, which inhibits MEK, a downstream node of the RAS/MAPK pathway. Clinical proof of concept (PoC) in patients with NRASm melanoma (of which 80 to 90% have Q61X mutations) and preliminary PoC for patients with RAS Q61X NSCLC have been established for the combination. Preclinical data across tumor types suggest that RAS Q61X is a potential predictive biomarker for the combination of naporafenib with trametinib, a hypothesis being tested in this trial. Methods: SEACRAFT-1 (NCT05907304) is a Phase 1b, open-label study evaluating the clinical activity and safety of the combination of naporafenib and trametinib in pts with locally advanced, unresectable, or metastatic solid tumor malignancies that are not responsive to standard therapies or for which there are no standard therapies. Eligible pts must be ≥18 years (or ≥12 and <18 years in an adolescent substudy) with documented RAS Q61X mutation by an analytically validated assay. Pts must also have ≥1 measurable lesion per RECIST (Response Evaluation Criteria in Solid Tumors, v1.1) and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 (or Karnofsky/Lansky Performance Status ≥70 for adolescent pts). Exclusion criteria include prior therapy with an ERK, MEK, RAF, or RAS inhibitor, QTcF >450 ms at baseline, and left ventricular ejection fraction (LVEF) <50% at baseline. A total of up to 115 pts will be enrolled to receive naporafenib 200 mg BID and trametinib 1 mg QD continuous in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is ORR; secondary endpoints include assessment of PFS, DOR, safety, and tolerability. Clinical trial information: NCT05907304 .
Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study.
Authors: Lin Zhenyu , Zhang Peng , Tao Kaixiong , Zhang Tao
Published: June 2024

TPS3643

Background: For LARC patients (pts), long-course concurrent chemoradiotherapy or SCRT followed by chemotherapy is recommended by the NCCN guidelines (Version 1.2024) as neoadjuvant therapy. Compared with chemoradiotherapy, the addition of immune checkpoint inhibitors (ICIs) or anti-angiogenic drugs could further improve complete response (CR) rate in the neoadjuvant treatment of LARC. Fruquintinib, a highly selective small-molecule inhibitor of VEGFR-1, -2, and -3, has gained FDA approval for pts with metastatic colorectal cancer previously treated. For pts with LARC at high risk of recurrence, the CR rate of SCRT followed by chemotherapy was 29%. There is an urgent need for new therapeutical options to improve the CR rate in these pts. This study introduces an innovative approach, combining SCRT, chemotherapy, Fruquintinib, and ICIs as a total neoadjuvant therapy for high-risk LARC pts. Methods: This is a multicenter, single-arm, open-label, phase II study (NCT06234007) investigating the efficacy and safety of SCRT sequential fruquintinib, combined with adebrelimab (an anti-PD-L1 monoclonal antibody) and CAPOX in pts with LARC. Eligible participants were 18 years or older, with an ECOG PS of 0–1, and a biopsy-proven, newly diagnosed, primary, LARC, classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for surgery. Total neoadjuvant therapy included SCRT (5 × 5 Gy over 5 days, 1-week rest) followed by six cycles of fruquintinib (4mg, qd, po, q3w. For the initial 6 pts in the safety run-in period, dosage was adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Subsequently, pts who did not reach clinical CR underwent total mesorectal excision, others received the “Watch and Wait” policy or surgery. Primary endpoint was CR rate (including clinical CR & pathologic CR). Secondary endpoints included 3-year event free survival rate, overall survival, R0 resection rate and adverse events (AEs). Exploratory endpoints aimed to evaluate the correlation between potential biomarkers and efficacy. Using PASS 15 software (version 15.0.5.0), in the Tests for One Proportion analysis, with a two-sided α of 5% and to guarantee the power over 80%. The null hypothesis of CR rate was 29%, and the alternative hypothesis was 51%, accounting for a 10% drop-out rate, resulting in a sample size of 39 pts. With the 6 pts in the safety run-in period, a total of 45 pts would be enrolled in the study. Until Feb 1, 2024, 7 of planned 45 pts have been enrolled. Clinical trial information: NCT06234007 .
Adjuvant chemotherapy in clinical local advanced CRC following preoperational therapies and pT0-3N0M0 diagnosis (CANWATCH).
Authors: Huang Jun , Liu Ping , Liu Zheng , Li Yong , Pei Fengyun , Yao Qijun , Liu Zhimin , He Fang , Zhao Yandong , Huang Meijin , Wang Jianping
Published: June 2024

TPS3645

Background: Adjuvant chemotherapy is often deemed unnecessary in pathological stage II colorectal cancer (CRC) following initial surgery without high-risk factors for recurrence. However, the efficacy of adjuvant chemotherapy for pT1-3N0M0 CRC following preoperative chemotherapy or chemoradiotherapy remains uncertain. Some cases of clinical locally advanced CRC (cTxN1-2M0), which are down-staged to pT0-3N0M0 after preoperative chemotherapy or chemoradiotherapy, may not truly require adjuvant chemotherapy due to the down-staging effects of preoperative treatments or false-positive imaging diagnosis of lymph nodes. Methods: CANWATCH is a multicenter, open-label, randomized, phase III study with a parallel design conducted in China. Patients were randomly assigned (1:1) to the wait-and-watch group or the adjuvant chemotherapy group. Enrollment and random assignment were performed using a computerized randomization management system. Patients in the wait-and-watch group did not receive adjuvant chemotherapy but were followed up periodically, while patients in the adjuvant chemotherapy group continued to receive adjuvant chemotherapy based on 5-FU or 5-FU analogues (mFOLFOX6 or Capeox). This study is the first prospective randomized controlled study to assess the necessity of adjuvant chemotherapy for patients with locally advanced CRC who received neoadjuvant therapy and achieved a down-staging to pT0-3N0M0. The study aims to provide precise clinical evidence for individualized precision treatment in locally advanced CRC patients. Key inclusion criteria included preoperative clinical tumor stage III (cTxN1-2M0) CRC, pathologically confirmed CRC adenocarcinoma by endoscopic biopsy, postoperative pathological stage T0-3N0M0 without high-risk factors for recurrence, and patient ability to understand and sign written informed consent. Main exclusion criteria were a history of other malignant tumors, complications requiring emergency surgery (occlusion, sub-occlusion, massive hemorrhage, and abscesses), colorectal tumor extension toward the abdominal wall and/or adjacent organs preventing immediate R0 resection of liver metastases, non-resectable lymph node metastasis, American Society of Anesthesiologists (ASA) grading ≥ IV, and/or Eastern Cooperative Oncology Group (ECOG) score ≥ 2. A total of 650 patients are planned to be enrolled in this study, and 301 patients have been enrolled as of February 6, 2024. The study is registered with ClinicalTrials.gov (NCT03748485) and is ongoing. Clinical trial information: NCT03748485 .
Chemotherapy-Induced Peripheral Neuropathy and Falls in Cancer Survivors Relate to Digital Balance and Gait Impairments
Authors: Shah Vrutangkumar V. , Muzyka Daniel , Guidarelli Carolyn , Sowalsky Kristen , Horak Fay B. , Winters-Stone Kerri M.
Published: June 2024

PURPOSE

Chemotherapy-induced peripheral neuropathy (CIPN) and falls can be persistent side effects of cancer treatment. Standing postural sway and gait tests with body-worn, inertial sensors provide objective digital balance and gait measures that represent several different domains controlling mobility. Specific domains of balance and gait that related to neuropathy and falls are unknown. The aim of this study was to determine which domains of balance and gait differed between cancer survivors who report (1) CIPN symptoms versus no symptoms, (2) a history of falls in the past 6 months versus no falls, and (3) prospective falls over 12 months versus no falls.

METHODS

Postural sway during 30 seconds of quiet standing and gait characteristics from a 7-m timed up and go test were recorded with six synchronized inertial sensors (Opals by APDM Wearable Technologies, a Clario Company) in 425 older, female cancer survivors (age: 62 ± 6 years). A principal component analysis (PCA) approach was used to identify independent domains of mobility from 15 balance and gait measures.

RESULTS

PCA analysis revealed five independent domains (PC1 = sway amplitude, PC2 = gait pace, PC3 = sway frequency, PC4 = gait spatial-temporal, and PC5 = turning) that accounted for 81% of the variance of performance. Cancer survivors who reported CIPN symptoms had significantly higher sway frequency (PC3) than asymptomatic survivors. Past fallers had significantly larger sway area (PC1) and slower gait pace (PC2) than nonfallers. Prospective fallers showed a significantly smaller stride length (PC4) than nonfallers.

CONCLUSION

Digital balance and gait measures using wearable sensors during brief standing and walking tests provide objective metrics of CIPN-related mobility impairment and fall risk that could be useful for oncology clinical trials.
ALK Inhibition With Alectinib for Refractory Metastatic Renal Cell Carcinoma With ALK Rearrangement: A Rare Case Report and Literature Review
Authors: Kathuria-Prakash Nikhita , Lopez Lidia P. , Raman Steven , Ye Huihui , Anaokar Jordan , Sisk Anthony , Pantuck Allan J. , Drakaki Alexandra
Published: June 2024

ALK-rearranged RCC refractory to several lines of treatment has a durable response when treated with alectinib.
Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens
Authors: Charoensri Suranut , Rege Juilee , Lee Chaelin , Marko Xhorlina , Sherk William , Sholinyan Julieta , Rainey William E , Turcu Adina F
Published: June 2024

Context

Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme 11β-hydroxylase (CYP11B1) executes the final step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyandrostenedione and 11-hydroxytestosterone, respectively. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated androgens (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T.

Objective

To assess the gonadal contribution to the circulating pool of 11-oxyandrogens.

Methods

We used liquid chromatography–tandem mass spectrometry to measure 13 steroids, including traditional and 11-oxyandrogens in: (i) paired gonadal and peripheral vein blood samples obtained during gonadal venograms from 11 patients (7 women), median age 37 (range, 31-51 years); and (ii) 17 women, median age 57 (range, 41-81 years) before and after bilateral salpingo-oophorectomy (BSO). We also compared CYP11B1, 17α-hydroxylase/17,20-lyase (CYP17A1), and 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) mRNA expression in adrenal, ovarian, and testicular tissue.

Results

A4, T, estradiol, estrone, progesterone, 17α- and 16α-hydroxyprogesterone were all higher in gonadal veins vs periphery (P < .05 for all), while four 11-oxyandrogens were similar between matched gonadal and peripheral vein samples. Equally, in women who underwent BSO, A4 (median [interquartile range]: 59.7 [47.7-67.6] ng/dL vs 32.7 [27.4-47.8] ng/dL, P < .001) and T (24.1 [16.4-32.3] vs 15.5 [13.7-19.0] ng/dL, P < .001) declined, while 11-oxyandrogens remained stable. Gonadal tissue displayed negligible CYP11B1 mRNA.

Conclusion

Despite producing substantial amounts of A4 and T, human gonads are not relevant sources of 11-oxyandrogens.
First British and Irish Press Reports of Surgical Etherization
Authors: Haridas Rajesh P. , Mather Laurence E.
Published: June 2024

In mid-December 1846, British and Irish newspapers reported the news of surgical etherization far more extensively than previously described. Reports about etherization had appeared at least 20 British and Irish newspapers in the days before Robert Liston’s first operations under etherization on December 21, 1846. These reports were based on four separate accounts, 2 of which could be traced to New York, and 1 account had been published in a Parisian newspaper Galignani’s Messenger on December 9, 1846.
Introducing Ordinariness
Authors: Barry Annabel
Published: June 2024

This introduction begins with Hortense J. Spillers’s return to the ordinary in her essay “Interstices: A Small Drama of Words,” first delivered as an address at the 1982 Barnard Center Conference on Sexuality. For Spillers, recovering the vernacular language and everyday experiences of Black women unsettles the exclusions of mainstream feminist theory, yet attending to ordinary grammar means not relinquishing theoretical critique but recognizing the ordinary as itself a domain of injustice and obfuscation. By starting with Spillers, rather than Ludwig Wittgenstein, this introduction questions who counts as a theorist of “ordinary language.” It then shows how Wittgenstein’s own return to the ordinary displays an ambivalence similar to that of Spillers. For Wittgenstein, many seemingly philosophical problems are undone by noticing language as it is ordinarily used, yet the ordinary poses new problems as much as it dissolves old ones. Summarizing the disciplinarily diverse contributions to this special issue and surveying a surge of recent scholarship on the ordinary, this introduction proposes the orthogonal term ordinariness to capture the plural and diffuse way that language, people, or social, economic, and political conditions might be ordinary.
Ordinary Expectation
Authors: Muller Sean Michael
Published: June 2024

Rural America is shaped by a conflicted sense of the ordinary: a place where a pastoral imagination of the countryside overlaps with, obscures, and, at times, is obscured by images of addiction and economic abandonment. This essay explores how these two senses of the ordinary are interdependent: how the possibility of a postindustrial future depends on the abjection of a deindustrial present. The essay approaches this problem through the analytic lenses of three scenes along a road known as “heroin highway” in rural New York. Tracing the ambivalence of these ordinary scenes makes it possible to see people and places excluded from the American dream as essential products of its logic.
The Pathos of Finitude
Authors: Sutherland Thomas
Published: June 2024

Although it is sometimes construed as a mere negation of philosophical discourse, François Laruelle maintains that there is a positive side to his project of “nonphilosophy.” Often this takes the form of a defense of the “ordinary man,” a faceless individual, without qualities, defined by absolute finitude. Laruelle claims to articulate a rigorous science of man, capable of thinking human individuals in their essence, outside the philosophical interpellation to which they are usually submitted. This science intends to finally break apart the post-Kantian empirico-transcendental doublet, which is, for Laruelle, emblematic of the divided, fragmented, and alienated figure with which philosophy has always (mis)represented man. It does this by relinquishing all empirical and figural content in the name of an uncompromising formalism—a purely transcendental method. Yet, despite this intention, a preoccupation with subjective finitude, and the pathos derived from it, is both retained and amplified, describing an invariably fraught relationship between the ordinary man and the extraordinary world furnished by philosophy. Ultimately, nonphilosophy offers less a science of ordinary individuals and more an ethos for academic philosophers, guiding its readers toward a specific subject position, achieved through an ongoing labor of abstraction.
An optimized method for mulberry silkworm, Bombyx mori (Bombycidae:Lepidoptera) sex classification using TLBPSGA-RFEXGBoost
Authors: Thomas Sania , Thomas Jyothi
Published: June 2024

Silkworm seed production is vital for silk farming, requiring precise breeding techniques to optimize yields. In silkworm seed production, precise sex classification is crucial for optimizing breeding and boosting silk yields. A non-destructive approach for sex classification addresses these challenges, offering an efficient alternative that enhances both yield and environmental responsibility. Southern India is a hub for mulberry silk and cocoon farming, with the high-yielding double-hybrid varieties FC1 (foundation cross 1) and FC2 (foundation cross 2) being popular. Traditional methods of silkworm pupae sex classification involve manual sorting by experts, necessitating the cutting of cocoons – a practice with a high risk of damaging the cocoon and affecting yield. To address this issue, this study introduces an accelerated histogram of oriented gradients (HOG) feature extraction technique that is enhanced by block-level dimensionality reduction. This non-destructive method allows for efficient and accurate silkworm pupae classification. The modified HOG features are then fused with weight features and processed through a machine learning classification model that incorporates recursive feature elimination (RFE). Performance evaluation shows that an RFE-hybridized XGBoost model attained the highest classification accuracy, achieving 97.2% for FC1 and 97.1% for FC2. The model further optimized with a novel teaching learning-based population selection genetic algorithm (TLBPSGA) achieved a remarkable accuracy of 98.5% for FC1 and 98.2% for FC2. These findings have far-reaching implications for improving both the ecological sustainability and economic efficiency of silkworm seed production.
HemK2 functions for sufficient protein synthesis and RNA stability through eRF1 methylation during Drosophila oogenesis
Authors: Xu Fengmei , Suyama Ritsuko , Inada Toshifumi , Kawaguchi Shinichi , Kai Toshie
Published: June 2024

HemK2 is a highly conserved methyltransferase, but the identification of its genuine substrates has been controversial, and its biological importance in higher organisms remains unclear. We elucidate the role of HemK2 in the methylation of eukaryotic Release Factor 1 (eRF1), a process that is essential for female germline development in Drosophila melanogaster. Knockdown of hemK2 in the germline cells (hemK2-GLKD) induces apoptosis, accompanied by a pronounced decrease in both eRF1 methylation and protein synthesis. Overexpression of a methylation-deficient eRF1 variant recapitulates the defects observed in hemK2-GLKD, suggesting that eRF1 is a primary methylation target of HemK2. Furthermore, hemK2-GLKD leads to a significant reduction in mRNA levels in germline cell. These defects in oogenesis and protein synthesis can be partially restored by inhibiting the No-Go Decay pathway. In addition, hemK2 knockdown is associated with increased disome formation, suggesting that disruptions in eRF1 methylation may provoke ribosomal stalling, which subsequently activates translation-coupled mRNA surveillance mechanisms that degrade actively translated mRNAs. We propose that HemK2-mediated methylation of eRF1 is crucial for ensuring efficient protein production and mRNA stability, which are vital for the generation of high-quality eggs.
BET activity plays an essential role in control of stem cell attributes in Xenopus
Authors: Huber Paul B. , Rao Anjali , LaBonne Carole
Published: June 2024

Neural crest cells are a stem cell population unique to vertebrate embryos that retains broad multi-germ layer developmental potential through neurulation. Much remains to be learned about the genetic and epigenetic mechanisms that control the potency of neural crest cells. Here, we examine the role that epigenetic readers of the BET (bromodomain and extra terminal) family play in controlling the potential of pluripotent blastula and neural crest cells. We find that inhibiting BET activity leads to loss of pluripotency at blastula stages and a loss of neural crest at neurula stages. We compare the effects of HDAC (an eraser of acetylation marks) and BET (a reader of acetylation) inhibition and find that they lead to similar cellular outcomes through distinct effects on the transcriptome. Interestingly, loss of BET activity in cells undergoing lineage restriction is coupled to increased expression of genes linked to pluripotency and prolongs the competence of initially pluripotent cells to transit to a neural progenitor state. Together these findings advance our understanding of the epigenetic control of pluripotency and the formation of the vertebrate neural crest.
Οι επί πατριάρχου Φωτίου Σύνοδοι Πρωτοδευτέρα και 879
Authors: Τζουμαλάκη Βασιλική
Published: June 2024

Αντικείμενο και σκοπός της μελέτης μας ήταν η σύγκληση των συνόδων επί πατριαρχίας Φωτίου, της Πρωτοδευτέρας το 861 και της Αγίας Σοφίας το 879/880. Η παρουσίαση των συνόδων και των κανόνων τους γίνεται με βάση τα ιστορικά γεγονότα της εποχής. Πιο συγκεκριμένα, μετά το τέλος της δεύτερης εικονομαχικής περιόδου, το 843 ο μοναχισμός εξαργυρώνει τη συμβολή του στη νίκη του δογματικού αγώνα ενάντια στις χριστολογικές έριδες. Η ακμή που γνωρίζει ο μοναχισμός λειτουργεί σφετεριστικά από μερίδα ανθρώπων που αποζητούν τη μετοχή τους στα προνόμια που έχει και του σεβασμού που έχει αποκτήσει. Έτσι, καταγράφονται οι πνευματικές τάσεις στο Βυζάντιο, οι σχέσεις ανάμεσα στον μοναχισμό και την «κοσμική» Εκκλησία και τις φυγόκεντρες δυνάμεις, στην Κωνσταντινούπολη στην μετά εικονομαχική περίοδο, που έθεταν σε κίνδυνο την ενότητα της Εκκλησίας. Στην παρούσα μελέτη εξετάστηκε επίσης η νομοθετική σκέψη του ιερού Φωτίου και της εποχής του καθώς και τα κανονικά ζητήματα που ανακύπτουν από το νομοθετικό έργο των δυο συνόδων, τα οποία αξιολογήθηκαν σε σχέση με την προγενέστερη και μεταγενέστερη κανονική παράδοση της Εκκλησίας. Στη συνέχεια, καταγράφονται οι σύνοδοι που συγκλήθηκαν τα έτη 863, 867 και 869/870 που τάραξαν τόσο τις σχέσεις των δυο Εκκλησιών και οδήγησαν σε σχίσμα. Επίσης, παρουσιάζονται όλα τα αίτια που οδήγησαν στη σύγκληση της συνόδου στο ναό της Αγίας Σοφίας το 879/880. Γι’ αυτό, αργότερα η σύνοδος αυτή θεωρήθηκε ενωτική, επειδή αποκατέστησε τις σχέσεις Ανατολής και Δύσης και αναγνωρίστηκε ο Φώτιος νόμιμος πατριάρχης Κωνσταντινουπόλεως. Τέλος, η μελέτη των πρακτικών της συνόδου και η καταγραφή βασικών αλλά σημαντικών στοιχείων (τόπος και χρόνος σύγκλησης, μέλη, έκδοση και ερμηνεία κανόνων), συνέβαλαν στην εξέταση του ζητήματος της οικουμενικότητας της συνόδου του 879/880.
Η εκπαιδευτική ηγεσία στην Ήπειρο από το 1870 έως το 1913 και η επίδρασή της στα πολιτικά δρώμενα της περιοχής
Authors: Μαγειρίας Μιχαήλ
Published: June 2024

Η συμβολή της εκπαιδευτικής ηγεσίας στο κοινωνικο-πολιτικό γίγνεσθαι έχει επισημανθεί και διαπιστωθεί στην ερευνητική βιβλιογραφία. Ιδιαίτερα, σε παλαιότερες ιστορικές περιόδους, όπου η αποκέντρωση του εκπαιδευτικού συστήματος ήταν δεδομένη, οι ηγέτες των σχολικών μονάδων έπαιζαν σημαντικό ρόλο στην προώθηση κοινωνικών και εν συνεχεία πολιτικών αλλαγών. Χαρακτηριστικό παράδειγμα στην ελληνική πραγματικότητα αποτελεί ο ρόλος των διευθυντών ελληνικών σχολείων της οθωμανικής αυτοκρατορίας που συνέβαλλαν αποφασιστικά και δυναμικά στη διαμόρφωση της εθνικής συνείδησης και στην αφύπνιση του ελληνικού κράτους. Ωστόσο, η ερευνητική βιβλιογραφία στρέφεται κυρίως στο τμήμα της Ελλάδας που απελευθερώθηκε, κατά την πρώτη φάση της Ελληνικής Επανάστασης. Δεν έχει δοθεί ιδιαίτερη έμφαση σε περιοχές που απελευθερώθηκαν αργότερα. Μία τέτοια περίπτωση αποτελεί και η Ήπειρος, η οποία ενσωματώθηκε στην ελληνική επικράτεια το 1913, σχεδόν έναν αιώνα αργότερα. Συνεπώς, η παρούσα ερευνητική μελέτη σκοπεύει να προάγει τη γνώση αναφορικά με τη συμβολή των ηγετών εκπαίδευσης στη διαμόρφωση των πολιτικών πεπραγμένων στην περιοχή της Ηπείρου, κατά το κρίσιμο χρονικό διάστημα πριν από την απελευθέρωσή της 1870-1913.
Αμοιβαίες ελληνογερμανικές προσλήψεις, 1919-1933
Authors: Κώρης Πέτρος
Published: June 2024

Παρά τη διαρκή παραγωγή συγγραμμάτων ελληνογερμανικών διασταυρώσεων, η ελληνική και η γερμανική ταυτότητα δεν έχουν αντιπαρατεθεί ακόμα στο πλαίσιο της Πολιτισμικής Ιστορίας και του δημόσιου λόγου την περίοδο του Μεσοπολέμου και συγκεκριμένα τα δεκαπέντε χρόνια ζωής της Δημοκρατίας της Βαϊμάρης (1919-1933). Η παρούσα διατριβή επιχειρεί να συμβάλει στην κάλυψη αυτού του κενού και, κυρίως, να αναδείξει τους κυρίαρχους ετεροπροσδιοριστικούς δημόσιους Λόγους που συνέβαλαν στην ετεροπρόσληψη και την ετεροκατασκευή της ελληνικότητας και της γερμανικότητας. Παράλληλα, επιδιώκει να απαντήσει στα κάτωθι ερωτήματα: κατά πόσο το βάρος της αρχαιοελληνικής κληρονομιάς (παρελθόν), ο Εθνικός Διχασμός (παρόν) και ο μεσοπολεμικός μοντερνισμός (μέλλον), τρεις καθοριστικές διαστάσεις της εποχής, επικαθόρισαν τη γερμανική και την ελληνική εικόνα; Ποια ήταν η διαδικασία μεταστροφής των πολιτικών και ιστορικών αποφάσεων σε ζητήματα αξεπέραστων (φαινομενικά) πολιτισμικών διαφορών; Τι ρόλο έπαιξαν, για παράδειγμα, η ήττα της Γερμανίας και ο Εθνικός Διχασμός στην πρόσληψη της ελληνικής και της γερμανικής εθνικής ταυτότητας; Πώς μεταφραζόταν πολιτισμικά η υποστήριξη στον βασιλιά Κωνσταντίνο, αλλά και η εναντίωση στον Βενιζέλο; Ή γιατί ο ελληνικός και ο γερμανικός Τύπος επιβεβαίωναν με τις περιγραφές τους αυτές τις αξεπέραστες πολιτισμικές διαφορές, εμπλέκοντας στη διαμάχη τον αρχαίο ελληνικό πολιτισμό και τον περιβαλλοντικό ντετερμινισμό; Πώς ο ελληνικός και ο γερμανικός δημόσιος λόγος καθρέπτιζαν την οριενταλιστική και τη δυτικιστική (Occidentalism) σημειολογία άλλων ευρωπαϊκών αφηγημάτων, απομονώνοντας τη γερμανικότητα από την ελληνικότητα και το αντίθετο; Τι σήμαινε αυτή η αντανάκλαση για το μέλλον και τον εκμοντερνισμό της Ελλάδας, αλλά και την αξιακή συνέχεια της Γερμανίας; Ποια παρατηρηθέντα κατά τη διάρκεια του Μεσοπολέμου ελληνικά και γερμανικά στερεοτυπικά σχήματα διακρίνονται για τη διαχρονία τους, αντανακλώντας, ειρωνικά, τη διαχρονία της ελληνικής και της γερμανικής εθνικής ταυτότητας; Τέλος, για ποιο λόγο η ελληνικότητα και η γερμανικότητα βρέθηκαν σε τέτοια πολιτισμική αντιπαράθεση, πριν ακόμα τα εγκλήματα του Δευτέρου Παγκοσμίου Πολέμου;
Πολιτική και τραγούδι στην Αθήνα του Εθνικού Διχασμού, 1920
Authors: Κόκορης Αργύριος
Published: June 2024

Η παρούσα διδακτορική έρευνα εκπονήθηκε στο Αριστοτέλειο Πανεπιστήμιο Θεσσαλονίκης, στο Τμήμα Μουσικών Σπουδών της Σχολής Καλών Τεχνών, με υποτροφία του Ελληνικού Ιδρύματος Έρευνας και Καινοτομίας τυπικά από το Μάρτιο του 2022 έως τον Φεβρουάριο 2025. Εντάσσεται στην Ιστορική Εθνομουσικολογία, και αφορά στην ελληνική ιστορική «ταραγμένη» περίοδο του Εθνικού Διχασμού, στην εθνογραφική αναπαράσταση της οποίας αποσκοπεί μέσα από το εγγενές λαϊκό μουσικό παρελθόν όπως παρουσιάζεται στον αθηναϊκό Τύπο και τα ημερολόγια προσωπικοτήτων της εποχής: το ελληνικό τραγούδι και η αυτοσχέδια στιχουργική δημιουργία, τους θούριους και τα εμβατήρια που αποτέλεσαν σύμβολα της παραταξιακής συνείδησης, καθώς και τα λαϊκά συνθήματα που εκφράστηκαν κατά την υπό εξέταση εποχή. Παρουσιάζεται υλικό της λαϊκής μουσικής εκφραστικής κουλτούρας της σύγκρουσης μέσα από την περιπτωσιολογική μελέτη ενός ικανού ιστορικού χρονολογικού διαστήματος, το οποίο περιλαμβάνει και τις δύο πλευρές του Διχασμού στην κυβερνητική εξουσία, κατά το έτος 1920. Ως διεπιστημονικού ενδιαφέροντος θεματική, για την ερμηνεία και ανάλυση του πραγματολογικού υλικού αξιοποιείται αρχικά το θεωρητικό μοντέλο ερμηνείας και ανάλυσης του Εθνικού Διχασμού από τον Γιώργο Θ. Μαυρογορδάτο 1915: Ο εθνικός διχασμός (2015), το οποίο προσαρμόζεται ειδικά στην παρούσα έρευνα προκειμένου να εξυπηρετήσει την ανάγνωση των ευρεθεισών αναφορών. Σκιαγραφείται το συγκρουσιακό προεκλογικό, εκλογικό και «νικητήριο» μετεκλογικό μουσικό, θορυβώδες και ευρύτερο αστικό ηχοτοπίο των ημερών· αναδεικνύονται παραλλαγές σε αρκετά λαϊκά και δημοτικά τραγούδια τόσο από τη βενιζελική παράταξη, όσο και από την αντιβενιζελική· επισημαίνεται η κυκλοφορία νέων παραταξιακών θουρίων και τραγουδιών, και η συλλογική διαδικασία της δημιουργίας τους· αποκρυσταλλώνεται ο τρόπος μουσικού εορτασμού στα κέντρα των Αθηνών, τα λαϊκά μουσικά όργανα, και τέλος η συλλογική παραταξιακή τραγουδιστική επιτέλεση στην εμφύλια σύγκρουση Βενιζελικών – Αντιβενιζελικών στους δημόσιους χώρους. Τέλος, σε μια αντιστροφή της οπτικής και σε μια αμφίδρομη ανάγνωση του υλικού, αξιοποιείται το θεωρητικό υπόδειγμα του βρετανού πολιτικού επιστήμονα John Street, ο οποίος συνδέει μουσική και πολιτική μέσα από την προπαγάνδα, τη λογοκρισία, την αντίσταση και τα κοινωνικά κινήματα.
First language attrition
Authors: Κλάιν Τζιάκομο
Published: June 2024

Η γλωσσική φθορά παραμένει ένας τομέας που δεν έχει διερευνηθεί επαρκώς. Η παρούσα διατριβή είχε ως στόχο να διερευνήσει διεξοδικά τους παράγοντες πρόβλεψης και τις εκδηλώσεις της φθοράς της ελληνικής ως πρώτης γλώσσας (Γ1) σε Έλληνες/ίδες που ζουν στη Γερμανία. Αντλώντας στοιχεία από την υπάρχουσα βιβλιογραφία για τη γλωσσική φθορά, καθώς και από μελέτες για την κατάκτηση γλωσσών κληρονομιάς και δεύτερης γλώσσας, η παρούσα μελέτη εξετάζει τα βιογραφικά δεδομένα των συμμετεχόντων/ουσών, αξιολογεί τους προγνωστικούς παράγοντες της φθοράς της L1, αξιολογεί τα επίπεδα επάρκειας των συμμετεχόντων/ουσών τόσο στην Γ1 (ελληνικά) όσο και στη δεύτερη γλώσσα (γερμανικά) και δημιουργεί συσχετίσεις μεταξύ των προγνωστικών παραγόντων και της επάρκειας για τον εντοπισμό χαρακτηριστικών που σχετίζονται με τη φθορά. Η μεθοδολογία που χρησιμοποιείται περιλαμβάνει λεπτομερή ανάλυση του κοινωνικού υπόβαθρου, των στάσεων και των κινήτρων των συμμετεχόντων/ουσών, ακολουθούμενη από αξιολογήσεις της επάρκειας και τη συλλογή προφορικών αφηγήσεων. Οι συμμετέχοντες/ουσες στρατολογήθηκαν κυρίως από τις ελληνικές κοινότητες του Μονάχου, του Άουγκσμπουργκ και της Νυρεμβέργης, με πρόσθετες προσπάθειες προσέγγισης μέσω των μέσων κοινωνικής δικτύωσης και πολιτιστικών οργανώσεων. Η συλλογή δεδομένων, τόσο αυτοπροσώπως όσο και εξ αποστάσεως λόγω της πανδημίας COVID-19, απέδωσε ένα δείγμα 66 Ελλήνων/ίδων συμμετεχόντων/ουσών στη Γερμανία. Τα ευρήματα δείχνουν μια ισχυρή σύνδεση με την Ελλάδα μεταξύ των συμμετεχόντων/ουσών, με την ελληνική γλώσσα να κυριαρχεί σε οικογενειακά και θρησκευτικά πλαίσια, ενώ η γερμανική γλώσσα είναι πιο διαδεδομένη σε επαγγελματικά και κοινωνικά περιβάλλοντα. Οι αξιολογήσεις της επάρκειας αποκαλύπτουν υψηλότερες επιδόσεις στα ελληνικά σε σύγκριση με τα γερμανικά, γεγονός που υποδηλώνει την κυριαρχία της Γ1. Οι αναλύσεις συσχέτισης υποστηρίζουν περαιτέρω την επίδραση ορισμένων προγνωστικών παραγόντων, όπως η ηλικία μετανάστευσης και η διάρκεια διαμονής, στα επίπεδα γλωσσομάθειας. Η ανάλυση των σωμάτων προφορικού λόγου αποκαλύπτει σημαντικές διαφορές μεταξύ των Ελλήνων/ίδων της Γερμανίας και μιας ομάδας ελέγχου Ελλήνων/ίδων που διαμένουν στην Ελλάδα, ιδίως όσον αφορά τη λεξιλογική ποικιλία, τα λεξιλογικά δάνεια, τη χρήση του ρηματικού χρόνου και τη δομή των προτάσεων. Η ανάλυση των προφορικών σωμάτων αποκάλυψε επίσης διαφορές στη χρήση αναφορικών εκφράσεων μεταξύ των Ελλήνων/ίδων στη Γερμανία και της ομάδας ελέγχου. Συγκεκριμένα, υπήρχαν αξιοσημείωτες διαφορές στη χρήση αντωνυμιών υποκειμένου και στην επίλυση αντωνυμικών αναφορών. Εξ όσων γνωρίζουμε, η παρούσα έρευνα αποτελεί την πρώτη εκτεταμένη διερεύνηση της φθοράς της Γ1 ελληνικής γλώσσας.
Cloning and characterization of the LvCTL genes encoding C-type lectin from white-leg shrimp (Litopenaeus vannamei)
Authors: Phuong Tran Vinh , Nguyen Xuan Huy , Quang Lich Nguyen , Tran Ngoc Nguyen , Nguyen Phuoc Ngoc , Linh Nguyen Quang
Published: June 2024

Background Lectins are carbohydrate-binding protein domains. The C-type lectin designates a requirement for calcium for binding. Proteins contain C-type lectin domains that have a diverse range of functions, including cell-cell adhesion, immune response to pathogens, and apoptosis. This study aimed to investigate the characters of LvCTL-encoding genes from white-leg shrimp (Litopenaeus vannamei) in Central Vietnam. Methods Two PCR products (LvCTL3 and LvCTL4) were cloned and sequenced. The structure and characterization of LvCTL proteins were predicted using bioinformatics tools. Results The results showed that the LvCTL3 gene was 444 nucleotides in length and 98.87% similar to the published LvCTL3 gene (accession number: KF156943). The polypeptide sequence had 147 amino acids, which were 97.28% identical to the reference sequence (AGV68681) and the LvCTL4 gene had a length of 417 nucleotides and homology of 99.52% compared to the published gene (KM387560). The deduced polypeptide sequence had 138 amino acids, and was 100% similar to the reference sequence (AKA64754). The LvCTL3 had a molecular weight of 16.91 kDa and an isoelectric point (pI) of 4.66, while LvCTL4 had 15.75 and 4.58 kDa, respectively. The structure prediction results showed that LvCTL3 and LvCTL4 had one domain (CTLD), LvCTL3 had two α helices and nine β sheets, and LvCTL4 had two α helices and eight β sheets. Conclusions Our results provide essential information for the heterologous expression and biosynthesis production of C-type lectins.
Protocol for assessment and correlation of Brandwein-Gensler criteria with P53 immunoexpression in oral squamous cell carcinoma: A retrospective study
Authors: Akolkar Sakshi , Hande Alka , Gawande Madhuri , Patil Swati , Sonone Archana , Pakhale Aayushi
Published: June 2024

Introduction The commonest type of malignancy in the head and neck region is oral squamous cell carcinoma (OSCC). Brandwein provided a risk model that includes scores for the following three factors: worst invasion pattern, lymphocytic host response and perineural invasion. This risk model accounts for overall survival and local recurrence. p53 is considered to be one of the most significant prognostic markers. Objectives To assess and correlate Brandwein-Gensler criteria with p53 immunoexpression in oral squamous cell carcinoma. Methods In this study, a total of 80 samples will be included from histopathologically diagnosed OSCC patients will be taken for the study. H&E-stained slides of all cases will be evaluated using Brandwein-Gensler criteria and then immunostaining will be done for p53 immunoexpression. A correlation between Brandwein-Gensler criteria and p53 immunoexpression will be determined. The present study will assess and correlate Brandwein-Gensler criteria with p53 immunoexpression. If the Brandwein-Gensler criteria score increases, the intensity of p53 immunoexpression will also increase. Conclusions We hypothesize that Brandwein-Gensler criteria may be significantly correlated with p53 immunoexpression in OSCC.
Case Report: Giant lung hamartoma : An usual cause of lobectomy in a five-year child
Authors: Louhaichi Sabrine , Hamdi Besma , Bouacida Imen , Haddar Yessmine , Trimech Sarra , Ammar Jamel , Ayadi Aida , Hamzaoui Agnès , Baccouche Ines , Marghli Adel
Published: June 2024

Pulmonary hamartomas are the most common benign tumors of the lung in adults. They are usually asymptomatic because of their small size and their slow-growing character. We report the case of a 5-year-old child presenting with a giant lung mass causing recurrent right pneumonia. Surgical resection with middle lobectomy was performed. Final histology revealed pulmonary hamartoma with predominant adenofibromatous and lipomatous differentiation.
Evaluation of centralised and decentralised models of care during the 2020 Ebola Virus Disease outbreak in Equateur Province, Democratic Republic of the Congo: A brief report
Authors: Lampaert Emmanuel , Nsio Mbeta Justus , Nair Divya , Mashako Maria , De Weggheleire Anja , Sprecher Armand , M. Coulborn Rebecca , Ahuka-Mundeke Steve
Published: June 2024

Background Traditionally in the Democratic Republic of the Congo (DRC), centralised Ebola treatment centres (ETCs) have been set exclusively for Ebola virus disease (EVD) case management during outbreaks. During the 2020 EVD outbreak in DRC’s Equateur Province, existing health centres were equipped as decentralised treatment centres (DTC) to improve access for patients with suspected EVD. Between ETCs and DTCs, we compared the time from symptom onset to admission and diagnosis among patients with suspected EVD. Methods This was a cohort study based on analysis of a line-list containing demographic and clinical information of patients with suspected EVD admitted to any EVD health facility during the outbreak. Results Of 2359 patients with suspected EVD, 363 (15%) were first admitted to a DTC. Of 1996 EVD-suspected patients initially admitted to an ETC, 72 (4%) were confirmed as EVD-positive. Of 363 EVD-suspected patients initially admitted to a DTC, 6 (2%) were confirmed and managed as EVD-positive in the DTC. Among all EVD-suspected patients, the median (interquartile range) duration between symptom onset and admission was 2 (1-4) days in a DTC compared to 4 (2-7) days in an ETC (p<0.001). Similarly, time from symptom onset to admission was significantly shorter among EVD-suspected patients ultimately diagnosed as EVD-negative. Conclusions Since <5% of the EVD-suspected patients admitted were eventually diagnosed with EVD, there is a need for better screening to optimise resource utilization and outbreak control. Only one in seven EVD-suspected patients were admitted to a DTC first, as the DTCs were piloted in a limited and phased manner. However, there is a case to be made for considering decentralized care especially in remote and hard-to-reach areas in places like the DRC to facilitate early access to care, contain viral shedding by patients with EVD and ensure no disrupted provision of non-EVD services.
RNA-sequencing Reveals Altered Gene Expression in the Ventromedial Hypothalamus Following Predator Odor Exposure
Authors: Shemery Ashely , Gibson Megan , Gorrell Erin , Daniel Diamond , Piontkivska Helen , Novak Colleen M
Published: June 2024

Background Physical activity is the second largest contributor to our total daily energy expenditure (EE). Uncovering ways to increase EE during activity could yield new approaches to treat obesity. The ventromedial hypothalamus (VMH) regulates body weight by modulating muscle metabolism and sympathetic nervous system (SNS) activity. The VMH also mediates behavioral responses to predator threat. While the VMH is a potential mediator of metabolic responses to predator threat, the mechanisms are unknown. Methods and Results Exposing rats to predator odor (PO) exposure causes a rapid increase in skeletal muscle thermogenesis that peaks between 20-30 min and dissipates to baseline by 4 hr. This thermogenic response is associated with weight loss and increased EE even when controlling for physical activity. To probe potential targets of PO-induced metabolic responses in the VMH, we first performed qPCR for genes known to be involved in brain regulation of muscle metabolism using VMH samples from rats exposed to PO or control odor for either 30 min or 4 hr. Next, to uncover novel, relevant genes, we performed RNA-sequencing on VMH samples of rats exposed to either PO or control odor for 20 min. qPCR results show that after 4 hr of PO exposure, Bdnf and Sirt1 expression were increased. RNA-sequencing analyses further identified 245 differentially expressed genes (DEGs) that showed at least 1.5-fold change in expression due to PO exposure. Functional and Gene Ontology annotation showed that pathways related to immune response, oxidative stress, and synaptic plasticity were overrepresented among these DEGs. Discussion Taken together, these findings suggest that acute PO exposure induces both rapid and delayed changes in VMH gene expression that likely have downstream metabolic consequences.
Building public trust and confidence in secondary use of health data for healthcare improvement and research: a qualitative study pre-protocol
Authors: Bedenik Tina , Cahir Caitriona , Bennett K.
Published: June 2024

Background  Secondary use of health data provides opportunities to drive improvements in healthcare provision, personalised medicine, comparative effectiveness research, health services innovation, and policy and practice. However, secondary data use requires compliance with relevant legislation, implementation of technical safeguards, ethical data management, and respect for data sharers. Existing evidence suggests widespread support for secondary use of health data among the public, which co-exists with concerns about privacy, confidentiality and misuse of data. Balancing the protection of individuals’ rights against the use of their health data for societal benefits is of vital importance, and trust underpins this process. The study protocol explores how to build public trust and confidence in the secondary use of health data through all key stakeholder groups in Ireland, towards developing a culture that promotes a safe and trustworthy use of data. Methods  This study will adopt a qualitative cross-sectional approach conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research COREQ guidelines. Participants in the study will include academics and researchers; healthcare professionals, data protection, ethics and privacy experts and data controllers; pharmaceutical industry and patients and public. Purposive and convenience sampling techniques will be utilised to recruit the participants, and data will be collected utilizing focus groups that may be supplemented with semi-structured interviews. Data will be coded by themes using reflexive thematic analysis (TA) and collective intelligence (CI) will be convened post-analysis to explore the preliminary findings with the participants. Ethics and Dissemination  Ethical approval was obtained from the Royal College of Surgeons in Ireland Research Ethics Committee (REC202208013). Final data analysis and dissemination is expected by Q1 2024. Findings will be disseminated through peer-reviewed journal publications, presentations at relevant conferences, and other academic, public and policy channels. Lay summaries will be designed for Public and Patient Involvement (PPI) contributors and general public.
Want doctors to use VR simulation? Make it mandatory, accessible, educationally valuable, and enjoyable!
Authors: Houlden Riki , Crichton Fiona
Published: June 2024

Background Virtual reality (VR) simulation training is mandatory for postgraduate year 1–2 doctors at the author’s hospital trust. Despite this, a preceding quantitative study demonstrated uptake below required levels. While the educational value of VR simulation has been highlighted, little attention has been paid to participant utilisation in postgraduate curricula. With the increasing development and incorporation of VR-based clinical education, it is essential to understand the factors influencing how frequently postgraduate doctors utilise it so that its potential can be maximised. Methods A qualitative study design was employed. All 108 postgraduate year 1–2 doctors from the 2020-21 training year were invited for a semi-structured interview. Interviews continued until data saturation was reached in the form of informational redundancy. Reflexive thematic analysis was conducted. Results A total of 17 interviews were conducted. Four main themes that influenced participation in VR simulation were identified: (1) the mandatory nature encouraged participation but led to negative perceptions as a tick-box exercise; (2) there were multiple challenges to accessing the resource; (3) the scenarios were felt to have limited educational value; and (4) there was untapped potential in drawing benefits from VR as an enjoyable leisure activity. Conclusions Recommendations from these findings include: (1) VR simulation should be mandatory but with a degree of learner autonomy; (2) sessions should be integrated into doctors’ rotas as protected time; (3) more challenging scenarios ought to be created aligned with postgraduate courses, examinations, and specialty training, and (4) presented as a difficulty level system akin to gaming experiences.
Jagoda kamczacka (Lonicera caerulea L. var. kamtschatica Sevast.) – nowe (?) źródło cennych substancji
Authors: Sokół-Łętowska Anna , Kucharska Alicja Z.
Published: June 2024

Zainteresowanie społeczeństwa zdrowym odżywianiem powoduje, że producenci owoców i przetworów owocowych poszukują nowych, bogatych w składniki bioaktywne surowców. Jedną z takich roślin jest jagoda kamczacka, która, chociaż znana jest od wielu lat, dopiero niedawno została dopuszczona do obrotu handlowego w Polsce. Dzięki wczesnemu terminowi dojrzewania jest ona pożądanym owocem, zdatnym do bezpośredniej konsumpcji, a dzięki wysokiej zawartości antocyjanów stanowi atrakcyjny surowiec dla przemysłu przetwórczego. Charakteryzuje się ona również wysoką zawartością związków fenolowych oraz rzadko występujących w owocach irydoidów, co przekłada się na jej szerokie działanie prozdrowotne.
El mito de la Administración Prusiana
Authors: Nieto García Alejandro
Published: June 2024

Los españoles nos quejamos de la leyenda negra, pero, si hay un país europeo con mala reputación, es Prusia, o ha sido, al grado de haberse visto condenada en 1947 a la extinción formal, con la acusación de que en su carácter militarista y autoritario estuvo la raíz de la actitud alemana en 1939 al provocar la Segunda Guerra Mundial. Como suele suceder, las cosas son más complejas. En los años diez y veinte del siglo XIX fue allí donde nació lo que puede llamarse la administración contemporánea, con una burocracia profesional y despolitizada al servicio de los intereses generales. Alejandro Nieto, con poco más de treinta años, tuvo el acierto de aprovechar su estancia en Göttingen para estudiar el asunto y de ahí este libro, que en la España actual presenta un renovado interés.