bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term safety outcomes of
177
Lu-PSMA-617 in patients with prostate cancer.
Authors: Sartor Alton Oliver , Gupta Shilpa , Morgans Alicia K. , Nordquist Luke , Crosby Michael , Michalski Jeff M. , Saad Fred , Shore Neal D. , Kim Hyun , Carnahan Natalie , Alanee Shaheen , Jobst Arijana , Samantray Sanjay , Ospina Gonzalez Diego , Herrmann Ken
Published: February 2025

TPS294

Background:
Approval of [
177
Lu]Lu-PSMA-617 (
177
Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy, was based on the results of the Phase 3 VISION study (NCT03511664). It is important to further characterize long-term safety outcomes in
177
Lu-PSMA-617–treated patients, with particular regard to potential treatment-related risks. To this end, the long-term follow-up (LTFU) safety study (NCT05803941) has been established. Findings from the LTFU study will be crucial for assessing delayed toxicities for patients with PSMA-positive metastatic prostate cancer treated with
177
Lu-PSMA-617 globally.
Methods:
The LTFU study is a prospective, multi-center, non-EU post-authorization safety study. Patients who received ≥1 dose of
177
Lu-PSMA-617 within one of the prospective parent studies (Table 1) are eligible. Patients may enroll in the LTFU study after fulfilling the requirements of their corresponding parent study. The primary endpoint is the number and proportion of selected adverse events (AEs), including myelosuppression, xerostomia, renal failure, xerophthalmia, and second primary malignancies (eg, myelodysplastic syndrome or acute myeloid leukemia), other serious AEs, and changes in laboratory values. The secondary endpoint is the number and proportion of deaths. Following enrollment, patients will undergo assessments at baseline, and then every 6–8 months for up to 10 years after their first dose of
177
Lu-PSMA-617 or until death. At each visit, a review of selected treatment-related AEs (xerostomia, xerophthalmia, myelosuppression), any-cause AEs (renal toxicity, new diagnoses of second primary malignancies), and treatment-related serious AEs will be conducted. Physical and laboratory assessments, as well as details on concomitant medications and interventions, including anti-cancer therapies, will be collected. Patients may receive treatment with any medical intervention. Interim analyses are planned at 2 and 5 years post-study activation. Enrollment is ongoing (n=13). Clinical trial information:
NCT05803941
.

Parent studies of the long-term follow-up safety study.

Trial
Indication
Phase
N (all groups)
ClinicalTrials.gov ID

VISION (+sub-study)
Post-taxane mCRPC
3
831 (+30)
NCT03511664

PSMAfore
Pre-taxane mCRPC
3
469
NCT04689828

PSMAddition
mHSPC
3
1144
NCT04720157

177
Lu-PSMA-617 in patients with moderately or severely impaired, or normal renal function

Post-taxane mCRPC
2

20
a

NCT06004661

a
Planned.

mCRPC, metastatic castration-resistant prostate cancer; mHSPC, metastatic hormone-sensitive prostate cancer.
CHAPTER-Platform-201: Phase 2 trial of pimitespib plus enzalutamide for patients with metastatic castration-resistant prostate cancer.
Authors: Matsubara Nobuaki , Shiota Masaki , Uemura Hiroji
Published: February 2025

TPS296

Background:
Metastatic castration-resistant prostate cancer (mCRPC) patients (pts), especially those who experience disease progression while on androgen receptor signaling inhibitor (ARSI) therapy, have a poor prognosis and limited treatment options. Although taxanes are an available options, a second ARSI is more frequently used in this setting because of the toxicity of taxanes, pts’ preference, and comorbidities. However, the efficacy of a second ARSI is limited because of cross-resistance. The main mechanisms of cross-resistance are androgen receptor (AR) genomic alterations (AR amplification and mutation), AR splice variants, and upregulation of the glucocorticoid receptor (GR) and components of the PI3K/AKT pathway. Therefore, new treatment options for mCRPC after ARSI therapy are urgently needed. Pimitespib (PIMI) is a novel heat shock protein 90 (HSP90) inhibitor approved for treating Gastrointestinal Stromal Tumor. HSP90 is a molecular chaperone and forms the structure of client proteins. Many of HSP90's client proteins, such as AR and GR, which represent components of the PI3K/AKT pathway, have been identified as prostate cancer-related proteins required for tumor development; their activation depends on HSP90. PIMI suppresses the expression of AR and GR, which are client proteins related to bypass pathways, such as the PI3K/AKT pathway, by inhibiting HSP90 expression; this may help overcome acquired resistance to ARSI. This phase 2 study investigated the efficacy of PIMI in combination with enzalutamide (ENZ) in pts with mCRPC refractory to ARSI.
Methods:
This phase 2 study was conducted in pts with mCRPC who showed disease progression on one ARSI. The study includes two parts: feasibility part (FP) and expansion part (ExP). The FP is evaluated with six pts to determine the maximum tolerated dose of PIMI (160 mg/day or 120 mg/day, orally; 5 days on/2 days off) in combination with a standard dose of ENZ (160 mg/day, orally; once daily). The ExP is an open-label, randomized trial evaluating the efficacy and safety of a determined dose of PIMI in combination with ENZ versus ENZ monotherapy. Forty pts are randomized 1:1 to each arm. The primary endpoint of FP is dose-limiting toxicity, and ExP is blinded independent central review of radiographic progression-free survival (rPFS). The secondary endpoints include investigator-assessed rPFS, overall survival, objective response rate, pharmacokinetics, and safety. Among pts for whom mCRPC was diagnosed, those with histologically or cytologically confirmed prostate adenocarcinoma and prior refractory status to one ARSI are eligible for enrollment. Pts who had received taxanes for mCRPC are excluded. Enrollment began in July 2023 and is currently ongoing. Clinical trial information:
2031230263
.
Tislelizumab in combination with abiraterone/enzalutamide for metastatic castration-resistant prostate cancer with intraductal adenocarcinoma of the prostate after progression on prior androgen receptor pathway inhibitor.
Authors: Zhu Qiyu , Zhao Jinge , Shen Pengfei , Zhang Ming , Wang Qian
Published: February 2025

TPS299

Background:
Intraductal adenocarcinoma of the prostate (IDC-P) serves as an aggressive pathological pattern of prostate cancer. Previous retrospective study suggested limited therapeutic response of chemotherapy and androgen depriving therapy for patients with IDC-P. No standard of care treatment options are established for this type of tumor. IDC-P was characterized by genomic instability, high homologous recombination repair (HRD) scores and mutational enrichment of mismatch repair (MMR) pathway, which are predictive for response to immune checkpoint inhibitor. Tislelizumab, an investigative anti-PD-1 antibody, has demonstrated disease stabilization capacity to multiple advanced tumors. Thus in this study, we aim to investigated the efficacy and safety of tislelizumab in combination with androgen receptor pathway inhibitor (ARPI) in metastatic castration-resistant prostate cancer patients (mCRPC) after failure of first-line novel hormone therapy regimens.
Methods:
This is a phase II, multisite, open label study with one cohort. Eligible patients must have pathologically confirmed IDC-P. Patients with any component of neuroendocrine tumor are ineligible. Patients must have received one prior type of novel hormone therapy (e.g., abiraterone, enzalutamide) in mCRPC stage . Patients receiving chemotherapy in the mCRPC stage are excluded. Participants will receive tislelizumab 200mg IV every 21 days in combination with ARPI change (abiraterone 1000 mg PO QD+ prednisone 5 mg PO BID/enzalutamide 160 mg PO QD) for four cycles. The primary endpoint is prostate specific antigen progression-free survival (PSA-PFS) and radiographic PFS (rPFS), with key secondary endpoints including PSA response and overall survival (OS). Exploratory objectives include analyzing DNA and RNA sequencing of tumors, and measurement of ctDNA and TMB. Clinical trial information:
ChiCTR2400085267
.
Phase 1/2 OMAHA-01A substudy of oral CYP11A1 inhibitor opevesostat alone or in combination with other therapies for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Hussain Arif , Garratt Chris , Li Nan , Liu Yingjie , Poehlein Christian Heinrich , Fong Peter C.C.
Published: February 2025

TPS300

Background:
Current treatments for mCRPC are associated with hormone dependence and the development of resistance. Therapeutic agents with novel mechanisms of action are needed for this patient population. Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. In the phase 1/2 CYPIDES study, opevesostat demonstrated antitumor activity in patients with heavily pretreated mCRPC (1). OMAHA-U01 is an adaptive, open-label, rolling-arm, multicenter, phase 1/2 umbrella study that will evaluate the safety and efficacy of opevesostat-based investigational therapies in prostate cancer. Substudy 01A (NCT06353386) will evaluate opevesostat alone or in combination with other therapies in patients with previously treated mCRPC.
Methods:
Eligible patients have mCRPC that progressed during ADT ≤6 months before screening, and on/after 1-2 NHAs for metastatic or nonmetastatic hormone-sensitive prostate cancer and nonmetastatic or mCRPC. Prior treatment with ≤1 taxane for mCRPC is allowed. A safety lead-in phase for all opevesostat-based experimental combinations (~10 patients in each arm) will establish the recommended phase 2 dose (RP2D), followed by an efficacy phase (opevesostat alone, ≤100 patients; opevesostat-based combinations, ~40 patients each). Patients will be randomly assigned 1:1:1:1 to opevesostat 5 mg PO BID, opevesostat 5 mg PO BID + olaparib (RP2D), opevesostat 5 mg PO BID + docetaxel (RP2D), and opevesostat 5 mg PO BID + cabazitaxel (RP2D). The primary endpoint for the safety lead-in phase is safety and tolerability. Primary endpoints for the efficacy phase are safety and prostate-specific antigen response rate per Prostate Cancer Working Group criteria. 1. Fizazi et al.
NEJM Evid.
2024. Clinical trial information:
NCT06353386
.
OCOG-RATIONAL: A phase II randomized trial of optimal recurrence-directed therapy (RDT) without or with androgen-deprivation therapy (ADT) in radio-recurrent oligo-metastatic castrate sensitive prostate cancer (romCSPC).
Authors: Tsakiridis Theodoros , Gouveia Andre , Mesci Aruz , Vavassis Peter , Berlin Alejandro , Morgan Scott C. , Perlis Nathan , Niazi Tamim , Thoms John , Hotte Sebastien J , Wright Jim
Published: February 2025

TPS305

Background:
This is a Canadian, multi-center study that investigates whether addition of ADT to RDT improves oncological outcomes in early romCSPC. The primary outcome is a 36-month composite Progression-free survival (cPFS). Secondary outcomes include metastasis-free survival, time to salvage therapy, time to castrate-resistant PC, OS, Quality of Life and toxicity.
Methods:
Population: Patients with biochemical recurrence after definitive or adjuvant/salvage radiotherapy for localized prostate cancer (PC) with oligo-metastatic disease (≤5 sites) without or with local recurrence. All patients will be staged with conventional imaging (CT/BS), mpMRI, PSMA-PET and biopsy of the prostate if in situ. Randomization: Patients are randomized 1:1 to RDT versus RDT+ADT for 12 months and stratified for, i) presence of local recurrence (Y/N), ii) volume of metastatic disease [0 (local recurrence alone) versus 1-3 versus 4-5 metastases]. iii) treatment centre, and iv) metastasis detected on conventional imaging (Y/N). Interventions: RDT options include Stereotactic Body Radiotherapy (SBRT), hypo-fractionated radiotherapy (HFRT), brachytherapy and surgical resection. Concurrent and adjuvant ADT involves four 3-month leuprolide acetate injections. Statistics: A clinically meaningful improvement for the use of ADT is defined as an improvement in the 30-month cPFS of ≥20% (from 50% to 70%). With an expected accrual period of 3 years, an additional 1 year of follow-up, a 1-sided log-rank test with α=0.05 would have over 80% power to distinguish between the two group with 73 patients in each arm. This number is inflated by 10% for stratification factors and patients lost-to-follow-up, for a total of 162 patients. Coordination: The study is coordinated by the Ontario Clinical Oncology Group (OCOG) and is expected to open in 10-12 institutions across Canada. This trial will provide evidence on the impact of ADT in romCSPC managed with optimal recurrence directed therapy. Findings will support phase III trial design to help define the optimal management of romCSPC in the future. Clinical trial information:
NCT06654336
.
Circulating tumor DNA (ctDNA) monitoring in the assessment and prediction of the efficacy of PARP inhibitors (PARPi).
Authors: Zhao Diwei , Zhao Junliang , Li Yuanwei , Cai Xinyang , Yang Zhenyu , Zhou Fangjian , Li Yonghong , Wang Jun
Published: February 2025

TPS307

Background:
PARP inhibitors (PARPi) emerged as an promising treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutation. However, prediction of treatment response remains a challenge. Still, some patients with mutations other than BRCA1/2 responded to PARPi. Circulating tumor DNA (ctDNA) is a promising biomarker that can offer real-time insights into tumor dynamics, allowing for non-invasive monitoring of therapeutic efficacy. This study aims to assess ctDNA monitoring as a predictor of response and relapse for mCRPC patients receiving PARPi.
Methods:
This trial is an open-label, single-center, observational, prospective cohort study. This study intends to enroll 30 male mCRPC participants aged 18 to 75 years, who have progressed from second-line treatment at mCRPC stage and exhibit homologous recombination deficiency (HRD) or carrying DNA damage repair (DDR) gene mutations. The study involves whole blood and tumor tissue sampling for ctDNA detection, homologous recombination repair (HRR) gene testing, and whole exome sequencing. The primary outcomes include radiological progression-free survival (rPFS), objective response rate (ORR), and PSA response rate, with overall survival (OS) as a secondary outcome. The Institutional Review Board of Sun Yat-sen University Cancer Center approved this study. Recruitment is ongoing, with a target follow-up duration of 12 months and 26.7% (8/30) of the target sample size achieved. Data analysis is expected to commence in 2025 upon completion of recruitment. Clinical trial information:
NCT05116579
.
CORE-008: A phase 2, multi-arm, multi-cohort, open-label study to evaluate intravesical cretostimogene grenadenorepvec in participants with high-risk non-muscle invasive bladder cancer.
Authors: Bivalacqua Trinity , Daneshmand Siamak , Shore Neal D. , Joshi Shreyas , Dinney Colin P.N.
Published: February 2025

TPS901

Background:
Treatment for patients with High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) consists of Transurethral Resection of Bladder Tumor (TURBT) followed by intravesical Bacillus Calmette–Guérin (BCG). Despite high initial response rates, over 50% of patients will recur and 20-40% are at risk for progression. Treatment of HR NMIBC is challenged by the BCG shortage, thus there exists a need for clinically effective, well-tolerated, and readily available treatment options for patients with HR NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates and lyses bladder cancer cells with Retinoblastoma (Rb)-E2F pathway alterations. The subsequent release of virus- and tumor- specific antigens initiate antitumor immune activation amplified by the GM-CSF transgene, a potent cytokine. Cretostimogene received both Fast Track and Breakthrough Therapy Designations by the US FDA for the BCG-Unresponsive HR NMIBC with CIS indication. Given the strength of these data, the CORE-008 clinical trial (
NCT06567743
) was developed as a Phase 2, multi-arm, multi-cohort trial to further evaluate the safety and efficacy of cretostimogene in patients with HR NMIBC.
Methods:
Eligibility criteria include pathologic confirmation of HR NMIBC as defined by the American Urologic Association (AUA) Guidelines. Cohort A (BCG-naive) is comprised of CIS +/- HG Ta/T1 participants who have not received prior BCG. Cohort B (BCG-exposed) will consist of CIS +/- HG Ta/T1 or papillary-only patients who have received prior BCG, and recurred either immediately after induction therapy (BCG-resistant) or recurred at a delayed timepoint, after adequate or inadequate BCG. Intravesical cretostimogene will be instilled in combination with n-dodecyl-β-D-maltoside (DDM), an excipient, that enhances adenoviral delivery, for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through month 12, then every six months through month 36. Re-induction is permitted. The primary endpoint for the CIS population is Complete Response (CR) at any time. High-Grade Event-Free Survival is the primary endpoint for papillary-only participants. Secondary endpoints will include Duration of Response, all-cause Event-Free Survival, Bladder Cancer Specific Survival, Radical Cystectomy Free Survival, and safety. Exploratory outcome measures include Health-Related Quality of Life, Overall survival, and biomarker assessments. Additional HR NMIBC cohorts are under development. Multiple clinical sites have been identified and Cohort B has received collaborative support from the Society of Urologic Oncology-Clinical Trials Consortium. Clinical trial information:
NCT06567743
.
Expanded access program of cretostimogene grenadenorepvec in patients with non-muscle invasive bladder cancer unresponsive to bacillus Calmette-Guerin.
Authors: Psutka Sarah P. , Porten Sima P. , Scarpato Kristen R. , Westerman Mary E. , Merrill Suzanne B , Schuckman Anne K.
Published: February 2025

TPS902

Background:
The current American Urological Association (AUA) guideline recommendation for patients diagnosed with High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (HR BCG-UR NMIBC) is radical cystectomy. However, many patients are unwilling to undergo such a morbid intervention or are unfit due to competing medical risks. Therefore, a considerable unmet medical need exists for clinically effective, well-tolerated, and readily available bladder-sparing treatment options for patients with HR BCG-UR NMIBC. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with a dual mechanism of action. It selectively replicates and lyses bladder cancer cells with Retinoblastoma (Rb)-E2F pathway alterations. The subsequent release of virus- and tumor- specific antigens initiate antitumor immune activation amplified by the GM-CSF transgene, a potent cytokine. Based upon preliminary efficacy and safety results from the ongoing Phase 3 BOND-003 study, cretostimogene received both Fast Track and Breakthrough Therapy Designations by the US FDA for BCG-UR NMIBC with CIS indication. The cretostimogene Expanded Access Program (EAP) (
NCT06443944
) is an open-label, compassionate use clinical trial designed to provide cretostimogene to a diverse population of real-world patients with BCG-UR NMIBC with CIS who may not otherwise be eligible for currently enrolling clinical trials.
Methods:
Pragmatic real-world eligibility criteria include: age ≥18 years, ECOG performance status of 0-3, pathologically confirmed BCG-UR CIS +/- HG Ta/T1 disease after completion of adequate BCG treatment, as defined by the US FDA. Patients will receive intravesical cretostimogene in combination with n-dodecyl-β-D-maltoside (DDM), an excipient, that enhances adenoviral delivery for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 24. Re-induction is permitted. Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, and directed bladder biopsies as clinically indicated with local review of pathologic samples. The primary objective is to evaluate the safety of cretostimogene. The incidence of adverse events will be reported using Medical Dictionary for Regulatory Activities (MedDRA) and CTCAE v5.0. Secondary outcomes include Complete Response at any time and at 12 months, Duration of Response, high-grade Recurrence-Free Survival, Progression-Free Survival, and Radical Cystectomy-Free Survival. Exploratory outcome measures include Health-Related Quality of Life, Overall Survival, and biomarker assessments. A broad cross-section of geographically and socioeconomically diverse clinical sites have been identified. The study is open and actively recruiting. Clinical trial information:
NCT06443944
.
Ablation of Leptin Receptor Signaling Alters Somatotrope Transcriptome Maturation in Female Mice
Authors: Miles Tiffany K , Odle Angela K , Byrum Stephanie D , Lagasse Alex N , Haney Anessa C , Ortega Victoria G , Herdman Ashley K , MacNicol Melanie C , MacNicol Angus M , Childs Gwen V
Published: February 2025

Anterior pituitary somatotropes respond to metabolic signals from the adipokine leptin to optimize functional responses to the body’s nutritional state via growth hormone (GH) secretion. Molecular targets of leptin in pituitary somatotropes include GH, the GH-releasing hormone receptor (GHRHR), and, in females, the transcription factor POU1F1, all of which are dependent on leptin stimulation for expression. To identify the trophic mechanisms underlying leptin action upon somatotropes, we analyzed single-cell gene transcriptomes comparing pituitaries from a female mouse model bearing somatotropes lacking leptin receptors (LEPR-null mutants) and control pituitaries. Computational clustering of results identified all common pituitary cell types and differentially expressed genes. Mutant female somatotrope clusters showed decreased levels of Gh and Htatsf1 mRNA, which was also reduced in mutant pituitaries lacking Prop1 or POU1F1. Mutant Somatotropes also showed increased expression of markers for pituitary stem and progenitor cells (e.g., Sox9) and increased (1.73-6.7 fold) expression of non-somatotrope hormones, Pomc, Lhb, Tshb, Cga, and Prl. Conversely, the mutant female Sox2-positive stem cell cluster showed decreased expression of markers for stem cells and increased expression of pituitary hormone genes. The data support a model in which the female pituitary somatotrope cell population’s development and/or maintenance requires leptin trophic signals and also suggests that, in the absence of normal somatotrope maturation, pituitary stem cells are driven towards premature differentiation.
A New Mouse Model for Exploring Tranexamic Acid–Associated Seizures
Authors: Shen Jingjia , Liu Yue , Liao Xudong , Lv Hong , Li Ting , Shi Jia
Published: February 2025

BACKGROUND:

Tranexamic acid (TXA) plays a central role in antifibrinolytic strategies, raising intense concerns regarding TXA-associated seizures. The aim of the study was to develop an in vivo TXA-induced seizure (TIS) model and identify its features on behavior, electroencephalograph (EEG), histology, and metabolomics.

METHODS:

Adult healthy male C57BL/6J mice (n = 42) were randomized into 7 dosage groups to receive intracerebroventricular injection of TXA (vehicle, 1, 5, 7.5, 10, 25, 50 μg/μL, n = 6 each). The dose titration was based on behavioral observation according to the Racine scale. Further, continuous video-EEG was performed in another 8 TIS mice and 5 control mice with the stereotaxic implantation of electrodes and guide cannulas. Then hippocampus samples were obtained from an additional 10 TIS mice and 9 control mice for histological evaluation and metabolomic analysis.

RESULTS:

Behavioral observation revealed a dose-dependent relationship between the intensity of seizures and the intraventricular gradient of the agent. A dose of 2 μL 7.5 μg/μL TXA i.c.v. was confirmed as the target scheme to establish the model with intense behavioral seizures and typical spike epileptic EEG discharges. Histological exploration illustrated necrosis and loss of neurons as well as loss of Nissl granules in the CA3 area of the hippocampus. Additionally, metabolomic analysis revealed a variety of disturbed metabolic pathways related to seizures including amino acid, energy, antioxidant stress metabolism, and nerve signal regulation.

CONCLUSIONS:

The study provided an in vivo mouse TIS model with specific features on behavioral seizures, EEG discharges, histological findings, and metabolomic pathways.
Τεχνητή νοημοσύνη και το επιστημολογικό καθεστώς της συνείδησης
Authors: Μήτσας Γρηγόριος
Published: February 2025

Η έννοια της συνείδησης αποτελεί κεντρικής σημασίας θέμα για τη φιλοσοφική γραμματεία, καθώς ως νοητική κατάσταση αφορά στη διαχρονική προβληματική της σύνδεσης νου και σωματικής ύλης. Αυτά τα δύο μεγέθη βρίσκονται σε αμοιβαία σύνδεση. Η ψυχή και το σώμα απασχόλησαν το φιλοσοφικό στοχασμό με κομβικό σημείο τη σηματοδότηση της νεότερης φιλοσοφίας με τον καρτεσιανό δυϊσμό. Η τεχνητή νοημοσύνη διεκδικεί ακόμα ένα σεβαστό πεδίο στη θεωρητική προβληματική με την εφαρμογή της, βάσει συγκεκριμένων τεχνικών που αναπτύσσονται κυρίως στον ψηφιακό τομέα με την τεχνική της προσομοίωσης εγκεφαλικών λειτουργιών στο υπολογιστικό περιβάλλον. Η συγκεκριμένη απεικονιστική λειτουργία δημιουργεί ποικίλα ερωτήματα, διαφωνίες και κριτικές τοποθετήσεις από την πλευρά του φιλοσοφικού στοχασμού ως προς ζητήματα ετεροκαθορισμού ή ενδεχόμενης αυτοτέλειας των πραγματώσεων της τεχνητής νοημοσύνης.
A DIFFERENT SURGICAL TECHNIQUE FOR FINDING EMBEDDED LAD LOCALIZATION: "SEARCH TECHNIQUE WITH INCISIONS PERPENDICULAR TO THE LAD"
Authors: Unal Mustafa , Tashmamatov Md. Dr. Abdiashim , Nazarov Md. Dr Asan Nazarov , Osmonov Damirbek
Published: February 2025

Performing an anastomosis to the desired location of the left anterior descending artery (LAD) is not always easy for cardiac surgeons. The techniques described to solve this problem have advantages and disadvantages. Low likelihood of complications and easy to repair if they occur; We believe that it is a technique that has a rapid learning curve, does not cause coronary intimal damage, does not require additional equipment, and is suitable for the morphology and physiology of the heart; We wanted to define the “LAD search method with vertical incisions”.
Current structure and needs of congenital heart surgery in Europe – a narrative review
Authors: Kiraly Laszlo , Ong Zhi Xian
Published: February 2025

Background/Objectives: Congenital heart surgery is a relatively small discipline dealing with a circumscript patient population. The statement contrasts with the discipline’s significant clinical impact for individual patients, and with the public health effect on the healthcare system. The aim of this narrative review is to survey the current landscape of congenital heart surgery in Europe, and especially to revisit the specific points of the recommendation document on the optimal center structure twenty years on.
Methods: European demographic patterns and prevalence/incidence of congenital heart disease were studied in national/international information resources. English-language literature of current congenital cardiac surgery practices, outcomes were reviewed. Recommendations on the optimal structure of a pediatric cardiac surgical department were specifically revisited.
Results: Europe is an ageing continent with stagnating birthrate. Promoters of congenital heart disease, e.g., consanguinity, segregated generative populations and lack of termination of pregnancy for fetal anomaly are absent. Congenital heart surgery has a long and successful history with world-renown centers of excellence. European professional organizations – joining forces with international counterparts – pioneer cooperation for establishing standards of quality-of-care, risk stratification and international databases. A review of the original recommendations for the optimal center and regional care structure show that statements on volume, quality are still valid; countries with higher socioeconomical index may have an abundance of centers that, in the pursuit of excellence to achieve the best possible outcomes, regionalization is advised. Owing to a much-improved survival, an increased adult population with operated congenital heart disease transits towards the adult services and requests specialized multidisciplinary teams to care for them.
Conclusions: Europe enjoys an advanced and accessible healthcare system for congenital heart disease. In fostering development, and focusing on quality-of-life rather than just a mere survival, a concentrated collaborative effort seems essential from the multidisciplinary team, researchers, and policymakers.
Ὅρος τῆς βασιλικῆς χώρας
Authors: Σαββοπούλου Θώμη , Χατζόπουλος Μιλτιάδης Β.
Published: February 2025

The discovery of a well-preserved boundary stone of royal land in a field near (ancient and modern) Europos, dating from the Hellenistic period, raises again the much-discussed question of royal land in Macedonia and, more generally, in the Hellenistic kingdoms. The authors of the present paper seize the opportunity of this unique discovery in order to review the use of boundary stones (ὅροι) in Macedonia and to discuss the meaning of 'royal' (βασιλικός) as opposed to 'civic' or 'sacred', and of the term 'land' (χώρα), which can apply to royal possessions as well as to land belonging to the Macedonian ethnos (normally subdivided in civic units). In fact, boundary stones of royal land are destined to preserve public property not for the sake of a king as an individual, but of the common weal which he represents.
On recognition of intangible assets in accounting
Authors: Vaganova Olga , Volkova Anna , Yazykova Svetlana
Published: February 2025

Taking into account the changes that took place in 2024 in the normative regulation of accounting for intangible assets, the article identifies problems and suggests ways to solve them through the systematization of accounting criteria
for the recognition of intangible assets. Th e authors summarize the factors influencing the recognition procedure for intangible objects in accounting and suggests methods for their presentation on accounts.
Low back pain – a review
Authors: Rusiński Kacper , Klimas Filip , Zatłoka-Mazur Dorota , Sienkiewicz Michał , Pawłowski Bartosz , Potoczek Adriana , Zięba Zuzanna , Pudełko Iwona , Gajda Zuzanna
Published: February 2025

Low back pain (LBP) is a common condition affecting many individuals worldwide. Furthermore, it represents a significant economic challenge for healthcare systems due to its substantial associated costs. The etiology of LBP is complex but, in most cases, is not caused by serious underlying diseases. Physical examination remains the cornerstone of diagnosis, while additional tests, including imaging, are determined based on the clinical context. Treatment involves a combination of non-pharmacological, pharmacological, and invasive interventions. Despite numerous attempts to prevent LBP, only a few methods have been scientifically proven to be effective.
The aim of this review was to provide a comprehensive summary of evidence-based information and approaches regarding the pathogenesis, treatment, and prevention of LBP. The literature reviewed was sourced from PubMed and Google Scholar Rusing the key words  "low back pain" combined  with terms such as "pathogenesis," "diagnostics," "imaging diagnostics," "treatment," and "prevention."
Entre el Trabajo Social y la Política Social
Authors: Zamanillo Peral Teresa , Rodríguez Rodríguez Alfonsa , Nogués Sáez Luis
Published: February 2025

A través del presente artículo, realizamos una reflexión acerca del papel de los/as trabaja-dores/as sociales en la actualidad, analizando su intervención de acuerdo a un término que está directamente relacionado con nuestra disciplina: la Política Social. Para ello, se realiza un recorrido por la actualidad del mundo en el que intervenimos y un análisis del Trabajo Social actual, concluyendo en la necesidad de adaptar nuestra intervención profesional de acuerdo a las necesidades existentes en nuestra población.
El rol del Trabajador Social: consideraciones psicosociales para la innovación de rol
Authors: Conde Vieitez Jorge A
Published: February 2025

El artículo aquí presentado, tiene como objetivo hacer una reflexión sobre ciertos elementos del rol del/de la trabajador/a social que son nece-sarios desarrollar y aplicar en la práctica pro-fesional, en correspondencia con las expectativas de la profesión y favorecido por los cambios sociales y tecnológicos de lo que se ha dado en llamar sociedad del conocimiento.
En una primera parte, se hace una aproximación al estado del debate en torno a tres problemas básicos de la identidad profesional del Trabajo Social, tales como el controvertido objeto de la profesión, su supuesto carácter científico o tecnológico y la polarización de la intervención entre el nivel individual y el nivel socio-estructural. En la segunda parte, se realiza un acercamiento empírico al desempeño del rol profe-sional sobre la base de distintos estudios y cuyos resultados revelan el escaso desarrollo de las actividades interdisciplinares, de coordinación y colaboración interprofesional e interinstitucional realizados por los/as trabajadores/as sociales. Por último, se proponen una serie de pautas innovadoras en la profesión, que pasan por la elaboración de estrategias de acción e interven-ción que enfatizan la cooperación y la coordina-ción como elementos sustantivos y centrales que refuercen la eficacia del rol del/de la trabajador/a social y contribuyan a su diferen-ciación identitaria frente a otras profesiones afines.
Ámbitos de intervención profesional, desarrollo humano y calidad en Trabajo Social
Authors: Barranco Expósito Carmen
Published: February 2025

Los/as trabajadores/as sociales en los diversos ámbitos de la acción profesional, vinculada a los Servicios Sociales, Salud, Educación, Vivienda, Urbanismo, Cooperación para el Desarrollo, Empleo y Justicia, han venido contribuyendo a satisfacer las necesidades globales de las personas, a mejorar los problemas, el Bienestar Social, la calidad de vida y el Desarrollo Humano de los pueblos. En dichos ámbitos, han ido creando y consolidando el espacio profesional y disciplinar, en un proceso abierto y dinámico, configurado desde la pluralidad de enfoques y en mestizaje científico con otras disciplinas sociales.
Este artículo versa sobre los ámbitos profesionales en Trabajo Social, el Desarrollo Humano y la Calidad, presentándose una introducción descriptiva y diacrónica sobre los mismos, situándolos en España. Así mismo, se realizan unas consideraciones generales sobre la intervención profesional y la calidad orientada a promover el Desarrollo Humano.
En el margen o marginado: el lugar epistemológico del Trabajo Social en Salud
Authors: Gil Martorell Daniel
Published: February 2025

Este artículo pretende ser un análisis del espacio profesional desarrollado por los trabajadores/as sociales en el ámbito de la salud, desde una reflexión epistemológica previa. Desde una reflexión sobre la relación del saber social con el modelo científico de conocimiento, relación que se plasma de manera clara en el contacto entre el saber social y el saber sanitario que se produce en los equipos multidisciplinares en los que interviene el/la trabajador/a social sanitario. Del trabajo de Foucault sobre el lugar epistemo-lógico del saber social y la filosofía de Gadamer con su filosofía práctica aristotélica, como modelo de saber social, llegamos la "práctica" de Smale y Tuson. Construyendo, en este triángulo, un espacio de reflexión sobre el Trabajo Social en el ámbito de la salud.
Desde esta reflexión nos situamos en los márgenes, nuestro espacio de intervención es ese, desde el margen construimos nuestro saber. El margen es nuestro espacio de intervención y nuestro espacio epistemológico constitutivo. En los equipos socio-sanitarios esta ubicación se hace patente de mane-ra más "cruda".
Trabajo Social: una profesión colegiada y comprometida con los derechos sociales
Authors: Gil Parejo Manuel
Published: February 2025

El artículo que a continuación se presenta es el texto que sirvió de base para el discurso, que, en representación de la Junta de Gobierno del Colegio Oficial de Diplomados en Trabajo Social y Asisten-tes Sociales de Madrid, pronunció su Decano con motivo del Acto de Clausura del 25 Aniversario del Colegio Oficial, celebrado el 10 de diciembre de 2008.
El Trabajo Social en Mary Richmond. La fundamentación de su teoría
Authors: García Fonseca Pilar , García Sedano Rosa , Esnaola Suquía Maite
Published: February 2025

Profundizar en el estudio del pensamiento de Mary Richmond mueve de inmediato a revisar nuestras prácticas y descubrir, al hacerlo, la vigencia de su teoría basada en el análisis sistemático de las experiencias del Trabajo Social de Casos.
Hicimos una lectura compartida, meditada y discutida en grupo y obtuvimos conclusiones que, en su aparente sencillez han supuesto un descubrimiento -o redescubrimiento en algunos casos-, de las raíces del Trabajo Social como disciplina. Hallazgos que contribuirán sin ninguna duda a mejorar la intervención profesional.
Clinical guidelines for the care of children aged under 5 with asthma: An overview of the recent national guidelines
Authors: Henry Heather
Published: February 2025

Heather Henry explains why it is critical that nurses in primary and community health services understand what has been described as a ‘sea change’ in the national guidelines for managing asthma

This is the first of 3 articles providing an in-depth overview of the recently updated British Thoracic Society (BTS), Scottish Intercollegiate Guidelines Network (SIGN), and National Institute for Health and Care Excellence (NICE) guidelines for the care of people with asthma, published on 27 November 2024. This article aims to equip nurses with the knowledge and tools needed to deliver evidence-based care and improve outcomes for children with asthma aged under 5 years.
CubEd: a 3D printable fluorescence cube microscope optimized for classroom and teaching use
Authors: Hammer Mathias , Tourtellotte Jocelyn , Hormann Colton , Flemming Selene , Tran Brian , Rong Hui , Grunwald David
Published: February 2025

“When all you have is a hammer, everything is a nail” diametrically opposes the “right tool for the job” mentality. After observing graduate students in the biological sciences often adopting the former approach towards fluorescence light microscopy – using religiously the closest available microscope rather than the most suitable on campus – we endeavored to shift mentality towards the latter through teaching how the tools work. We further observed that these students often lack an understanding of optics. To instill a practical knowledge of optics as applied in fluorescence microscopy, we set about to create an educational experience that linked theory and practice. As part of this effort, we provided students an opportunity to construct fluorescence microscopes in an open-ended, stepwise fashion with built-in features, such as the ability to track the beam along the beam path. As a result, we developed the CubEd, an easy-to-use, inexpensive, and extensible optics system that may lead students to a better understanding of how fluorescence microscopy works, and, as a result, will enable them to better design their own experiments in the future. This requires replacing expensive, closed system, boxed commercial microscopes with a modular, open frame system that allows direct access to the optics. Based on an early iteration of the UC2 microscope, the CubEd was conceived. It is an open-source microscope of modular design that balances cost, ease-of-use, flexibility of design, and extensibility.
Unsupervised neural network-based image stitching method for bladder endoscopy
Authors: Ye Zixing , Shao Chenyu , Zhu Kelei
Published: February 2025

Bladder endoscopy enables the observation of intravesical lesion characteristics, making it an essential tool in urology. Image stitching techniques are commonly employed to expand the field of view of bladder endoscopy. Traditional image stitching methods rely on feature matching. In recent years, deep-learning techniques have garnered significant attention in the field of computer vision. However, the commonly employed supervised learning approaches often require a substantial amount of labeled data, which can be challenging to acquire, especially in the context of medical data. To address this limitation, this study proposes an unsupervised neural network-based image stitching method for bladder endoscopy, which eliminates the need for labeled datasets. The method comprises two modules: an unsupervised alignment network and an unsupervised fusion network. In the unsupervised alignment network, we employed feature convolution, regression networks, and linear transformations to align images. In the unsupervised fusion network, we achieved image fusion from features to pixel by simultaneously eliminating artifacts and enhancing the resolution. Experiments demonstrated our method’s consistent stitching success rate of 98.11% and robust image stitching accuracy at various resolutions. Our method eliminates sutures and flocculent debris from cystoscopy images, presenting good image smoothness while preserving rich textural features. Moreover, our method could successfully stitch challenging scenes such as dim and blurry scenes. Our application of unsupervised deep learning methods in the field of cystoscopy image stitching was successfully validated, laying the foundation for real-time panoramic stitching of bladder endoscopic video images. This advancement provides opportunities for the future development of computer-vision-assisted diagnostic systems for bladder cavities.
Transcriptomic analysis of human primary T cells after short-term leucine-deprivation and evaluation of kinase GCN2’s role in regulating differential gene expression
Authors: Dougé Aurore , Cueff Gwendal , Keime Céline , Carraro Valérie , Jousse Céline , Rouzaire Paul , Bruhat Alain
Published: February 2025

Chimeric Antigen Receptor T (CAR-T) cells offer a promising strategy for cancer treatment. These CAR-T cells are either autologous or allogeneic T cells that are genetically modified to express a chimeric antigen receptor targeting a specific tumor antigen. Ongoing research aims to optimize the CAR-T cell efficacy, including strategies to modulate their metabolism. One such approach involves inducing transgene expression by activating the GCN2 kinase signaling pathway through dietary deprivation of an essential amino acid. In this study, we investigated the general impact of a 6-hour leucine deprivation on primary activated human T cells using RNA-seq technology. Our analysis identified 3,431 differentially expressed genes between T cells cultured in regular medium and those cultured in leucine-deprived medium. Gene Set Enrichment Analysis revealed that “TNFα signaling via NFκB”, “interferon-γ response”, and “unfolded protein response” gene sets were positively enriched, while “mTORC1 signaling”, “Myc targets”, and “oxidative phosphorylation” gene sets were negatively enriched. To further evaluate the involvement of GCN2 kinase in regulating the differential gene expression during the 6-hour leucine deprivation, T cells were cultured with or without a GCN2 inhibitor. We found that 59% of the differentially expressed genes in our dataset were dependent on the kinase GCN2 (n = 2028), with 1,140 up-regulated and 888 down-regulated genes. These findings suggest a promising strategy to enhance CAR-T cell efficacy by combining short amino acid starvation with transient overexpression of a target gene.
Transcriptome analyses reveal differences in the response to temperature in Florida and Northern largemouth bass (Micropterus spp.) during early life stages
Authors: Bernal Moisés A. , Aguilar Gavin L. , Sakmar Josh , Politis Sebastian N. , Oglesby Savannah L. , Nicholls Allen , Kelly Anita M. , Roy Luke A. , Butts Ian A. E.
Published: February 2025

Temperature is one of the most relevant factors influencing the development of aquatic species, making it a key parameter to consider for aquaculture. Largemouth bass (LMB; Micropterus spp.) are highly relevant for human consumption and sport fishing, representing one of North America’s most important freshwater fisheries. Yet, questions remain on how LMB raised in recirculating aquaculture systems (RAS) respond to different temperatures. The main objective of this study was to determine the impact of thermal rearing conditions (21°C, 24°C, and 27°C) on gene expression of Florida and Northern LMB larvae at 8- and 28-days post hatch (DPH). Using de novo transcriptomes as a reference, our results suggest that gene expression differences for Florida LMB were mostly associated with temperature, while differences for Northern LMB were controlled by temperature and developmental stage. In general, both lineages showed activation of molecular pathways associated growth, such as development of muscle, nervous system, and vascular system. There were molecular signatures of stress with warming as well, including immune function, apoptosis, regulation of inflammation, and heat shock proteins. Florida LMB showed large differences between temperatures at both stages, while differences were much larger for Northern LMB at 28 DPH, specifically for individuals reared at 27°C. The results from this study are in line with previous phenotypic studies that indicated faster growth at warmer temperatures and better performance of Northern LMB raised in RAS. Overall, this study exemplifies how controlling developmental temperatures during the critical early life stages can be essential to guarantee the success of commercial hatchery production techniques.