bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose finding study of CBM588 in combination with nivolumab and ipilimumab in patients with metastatic renal cell carcinoma: A phase I study.
Authors: Agarwal Ruchi , Ebrahimi Hedyeh , Zengin Zeynep Busra , Barragán Carrillo Regina , Dizman Nazli , Zugman Miguel , Jaime-Casas Salvador , Meza Luis A , Li Xiaochen , Hsu Joann , Castro Daniela V. , Mercier Benjamin , Lee Peter P. , Takahashi Motomichi , Tripathi Abhishek , Dorff Tanya B. , Caporaso Gregory , Lee Keehoon , Pal Sumanta Kumar , Chehrazi-Raffle Alex
Published: February 2025

TPS611

Background:
The combination of nivolumab and ipilimumab is currently one of the standard-of-care treatments for patients with metastatic renal cell carcinoma (mRCC). However, in the vast majority of patients, disease progression eventually occurs. Thus, novel methods to increase the efficacy of nivolumab/ipilimumab are being explored. Recent evidence suggests that the gut microbiome can remarkably influence the efficacy of immune checkpoint inhibitors (ICI) in patients with mRCC, particularly through the modulation of microbial diversity and the presence of key bacterial species (Routy
et al
.
Science
2018; Salgia
et al
.
Eur Urol
2020). The current study explores the use of CBM588,
Clostridium butyricum
MIYARI588, which has demonstrated the potential to enhance clinical outcomes when combined with ICI therapy (Dizman
et al
.
Nature Medicine
2022; Ebrahimi
et al
.
Nature Medicine
2024). This ongoing phase I study aims to determine the maximum tolerated dose (MTD) of CBM588 in combination with nivolumab/ipilimumab in previously untreated mRCC patients, and to evaluate the biological effects of CBM588.
Methods:
This investigator-initiated, phase I, open-label, single-arm, dose-escalation study is being conducted in patients with untreated, histologically confirmed mRCC. Eligible patients must be ≥18 years old, have an ECOG performance status ≤2, and be diagnosed with clear cell and/or sarcomatoid histology. The study is open to all IMDC risk groups. Patients must have measurable disease by RECIST 1.1 and no prior systemic therapy for metastatic disease. The study follows a 3+3 dose-escalation design with three planned dose levels for CBM588 (4 × 10
8
CFU, 1.2 × 10
9
CFU, and 4 × 10
9
CFU), administered twice daily orally. Nivolumab (3 mg/kg every 3 weeks for four cycles, followed by 480 mg every 4 weeks) and ipilimumab (1 mg/kg every 3 weeks for four cycles) are administered intravenously. The primary objective is to assess the safety and tolerability with escalating doses of CBM588 in combination with nivolumab and ipilimumab. Secondary objectives include evaluating changes in the gut microbiome, modulation of immune pathways, alterations to the systemic metabolome, and clinical outcomes such as overall response rate (ORR) and progression-free survival (PFS). Responses are assessed by CT every 12 weeks. Dose level one has been completed without dose-limiting toxicities. Enrollment at dose level two began in October 2024. Clinical trial information:
NCT06399419
.
A prospective, single-center, single-arm clinical study of adjuvant toripalimab combined with axitinib in non-clear renal cell carcinoma (nccRCC) patients with high-risk recurrence factors (IUNU-RC-102).
Authors: Liu Guangxiang , Zhang Shun , Qin Haixiang , Ji Changwei , Guo Hongqian
Published: February 2025

TPS613

Background:
Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25–30% of all renal cell carcinoma (RCC) cases and is associated with a poor prognosis. While early-stage treatment typically involves surgery, there is a significant risk of postoperative recurrence. Once recurrence or distant metastasis occurs, management becomes more challenging. Current clinical trial results for metastatic advanced nccRCC have shown variability, and no standard treatment protocol has been established. For advanced clear cell renal cell carcinoma (ccRCC), however, the combination of immunotherapy and targeted therapy has become the standard of care. The RENOTORCH study demonstrated the efficacy and safety of toripalimab combined with axitinib as a first-line treatment for advanced ccRCC[1]. This study aims to investigate the efficacy and safety of toripalimab combined with axitinib as adjuvant therapy in postoperative patients with high-risk nccRCC.
Methods:
IUNU-RC-102 (NCT05768464) is a single-center, prospective, single-arm clinical trial. The study plans to enroll 30 patients. Key inclusion criteria include: a clinical diagnosis of high-risk recurrent nccRCC following nephrectomy, age between 18 and 75 years, an ECOG performance status of 0–1, no prior systemic therapy for renal cancer, and confirmed pathological histology of nccRCC following partial or radical nephrectomy, with exclusions for clear cell carcinoma, chromophobe carcinoma, and eosinophilic renal cell carcinoma. All participants will receive axitinib (5 mg twice daily) for 4 weeks, along with toripalimab (240 mg intravenously on the first day of each 21-day cycle). The treatment duration will extend up to 52 cycles. The study follows Simon’s minimax two-stage design. In the first stage, three patients will be enrolled and will receive two treatment cycles to assess safety. If dose-limiting toxicity (DLT) occurs in one or more of the three patients, the study will be paused. Investigators will then determine whether to terminate or amend the study protocol after further deliberation. In the second stage, the primary endpoint will be 2-year disease-free survival (DFS). Secondary endpoints will include 3-year overall survival (OS), disease recurrence-specific survival (DRSS), and safety. The first participant was enrolled in IUNU-RC-102 in October 2023. We anticipate that the combination of toripalimab and axitinib will offer a promising new treatment option for these patients. Clinical trial information:
NCT05768464
.
Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).
Authors: Cole Suzanne , Kim Se Eun , Wentland Andrew , Lin Mu-Han , Kapur Payal , Wulff-Burchfield Elizabeth Marie , Shevrin Daniel , Gurley Tami , Lin John C , Wagner Lynne I. , McKay Rana R. , Brugarolas James , Qin Qian , Gunter Tyler , Kyriakopoulos Christos , Harichand-Herdt Seema , Sykes Glenn , Haas Naomi Balzer , Carducci Michael A , Hannan Raquibul
Published: February 2025

TPS615

Background:
The optimal frontline management strategy for oligometastatic renal cell carcinoma (omRCC) is uncertain. Systemic therapy (ST) is the standard, but Stereotactic Ablative Radiation (SAbR) offers an alternative, and may potentially reduce ST-associated toxicity. However, concerns remain about occult micro-metastases progression with SAbR. Retrospective studies suggest focal therapies may improve outcomes in select patients, but prospective data is limited. This ECOG-ACRIN phase 3 randomized trial compares SAbR with ST in omRCC, assessing whether SAbR followed by delayed ST can offer non-inferior OS with lower toxicity compared to upfront ST. The co-primary endpoints are OS and grade ≥3 toxicity. Hypothesis: For omRCC patients with 2-5 measurable metastases, SAbR followed by delayed ST will result in non-inferior OS compared to immediate while reducing grade ≥3 toxicity.
Methods:
This phase 3 trial will enroll patients with oligometastatic RCC with 2-5 extracranial metastases amenable to SAbR and an ECOG performance status of 0-2, categorized as favorable or intermediate risk according to modified IMDC criteria. Patients must have their primary tumor treated by surgery or radiation before enrollment. Exclusions include brain metastases, sarcomatoid histology, prior systemic therapy for metastatic disease (adjuvant therapy is allowed), and poor-risk IMDC classification. Participants will be stratified by number of metastases, histology, IMDC risk, prior adjuvant therapy, and time since primary site treatment. Patients will be randomized to either upfront ST or SAbR with delayed ST. Statistical Design: The trial has 85% power to establish non-inferiority of SAbR with respect to OS, assuming a null hazard ratio of 1.24 and an alternative of 0.85. If non-inferior OS is shown, the study will test whether SAbR reduces grade ≥3 toxicity. Secondary endpoints include progression-free survival (PFS) and quality of life, measured by NFKSI-19 and EQ-5D-5L scales. Exploratory endpoints will assess cost-effectiveness and circulating tumor DNA (ctDNA) as a biomarker. The study opened in September 2023. Research sponsor: U.S. National Institutes of Health. Clinical trial information:
NCT05863351
.
A phase 1, first-in-human, dose escalation and expansion study to evaluate the safety and tolerability of XmAb541 (claudin-6 x CD3) T-cell engaging bispecific antibody in subjects with germ cell tumors and other advanced solid tumors.
Authors: Levitz David , Gutierrez Martin , Winer Ira Seth , Reilley Matthew , Duska Linda R. , Subbiah Vivek , Richardson Debra L. , Bohac Chet , CHIARELLA MICHAEL , Naranjo Carlos , Kanodia Jitendra , Woo Jacky , Nevadunsky Nicole
Published: February 2025

TPS652

Background:
Claudin-6 (CLDN6) is overexpressed in solid tumors including germ cell tumors (GCTs) with minimal expression in healthy tissue. This differential expression profile makes CLDN6 a suitable tumor-associated antigen for a T-cell engaging bispecific antibody (bsAb). XmAb541 is a first-in-class humanized, anti-CLDN6 x anti-CD3 bsAb that directs T-cell cytotoxicity. The XmAb 2+1 format provides avid tumor targeting and selectivity. Importantly, XmAb541 selectively binds CLDN6, with reduced binding to other claudin family proteins (e.g., CLDN9) and non-CLDN6-expressing healthy tissue [1]. This study focuses on subjects with GCT and other CLDN6+ solid tumors who have failed standard therapy and have a high unmet medical need. The primary objective of the trial is to determine an optimal and tolerated dose(s) for further evaluation.
Methods:
This is a first-in-human, Phase 1, open-label study to evaluate the safety and tolerability of XmAb541 in advanced solid tumors. The study will be conducted in 2 Parts. Part 1, Dose Escalation, will establish a dosing regimen inclusive of a priming dose, step-up dose(s), and the target dose. Part 2 Dose Expansion will further evaluate safety and tolerability and provide an initial evaluation of preliminary antitumor activity for the dose regimen(s) established in Part 1. XmAb541 will be administered intravenously. Key inclusion criteria are age ≥ 18 years (for subjects with GCTs, age ≥15 years). Have histological evidence of locally advanced, recurrent, or metastatic GCT, ovarian, fallopian tube, peritoneal cancer, or adenocarcinoma of the endometrium. Have documented progressive disease on standard-of-care therapies; exhausted therapies with a survival benefit, or the standard therapy has no survival benefit or proven to be ineffective, intolerable, or subject is not a candidate for such available therapy. Subjects must have an Eastern Cooperative Oncology Group performance status of 0-2 and a life expectancy ≥ 3 months with adequate liver, kidney, and bone marrow function. Key exclusion criteria include the following: known active central nervous system metastases and/or carcinomatous meningitis. Subjects with treated brain metastases may participate, provided they are radiologically stable. Ethics approval: This study was approved by WCG IRB. References: 1. Faber, M. Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells. (AACR 2021, Abstract No. 1860). Clinical trial information:
NCT06276491
.
Outcomes with multi parametric MRI (mpMRI) compared to diagnostic transurethral resection of bladder tumor (TURBT) in patients (pts) with suspected muscle-invasive bladder cancer (MIBC): A pilot study.
Authors: Mar Nataliya , Macaraeg Amanda , Raad Ali , Kaakour Dalia , Rezazadeh Arash , Daneshvar Michael A
Published: February 2025

TPS881

Background:
TURBT is a standard diagnostic procedure to determine the depth of bladder tumor invasion into the bladder wall, particularly whether the muscularis propria layer is involved by tumor. This is crucial in order to distinguish between non-MIBC and MIBC, providing accurate tumor staging and determining appropriate therapy. However, TURBT may be associated with multiple complications such as pain, infection, need for Foley catheters, blood loss requiring transfusions, hospitalization, and a small mortality risk. A proportion of pts end up with a superficial resection out of concern for bladder perforation, where the muscularis propria layer is absent from the surgical specimen, and require a repeat TURBT that is typically performed 4-6 weeks following the initial procedure. Further, TURBT scheduling requires coordination with urology and operating room availability. These factors may cause delays in initiation of cancer-directed therapy. Recent data suggests that mpMRI may accurately predict the degree of invasiveness of bladder tumors by generating a Vesical Imaging-Reporting and Data System (VI-RADS) score. mpMRI is not commonly associated with complications and can be performed quickly by radiology.
Methods:
This is an IRB-approved, single-institution, prospective, single-arm, phase 2 pilot study, which aims to compare two diagnostic modalities for bladder cancer - TURBT versus mpMRI. Pts are identified based on tumor appearance during initial routine cystoscopy, if MIBC is suspected. If eligible for the study, pts then proceed with an mpMRI and a diagnostic TURBT. Primary study endpoint is incidence of concordance between VI-RADS score 4 and 5 bladder tumors on mpMRI, which represent “likely” and "very likely" muscularis propria invasion, and pathologic muscularis propria invasion on TURBT. Secondary study endpoints include time from initial cystoscopy to performing each diagnostic test, time from performing each diagnostic test to initiation of cancer-directed therapy, incidence of repeat TURBT, patient-assessed quality of life with each diagnostic test, incidence of adverse events related to each diagnostic test, progression free survival, and financial toxicity of each diagnostic test. Based on prior literature, the rate of detecting muscularis propria invasion with TURBT is about 90%. We hypothesized that diagnostic accuracy of mpMRI would be non-inferior to TURBT, within a 10% difference. Power calculations for this study were based on a one-sided, one-proportion exact test, with a power of 80% at a significance level of 0.05 using a non-inferiority design. Out of 30 anticipated pts, 11 have been enrolled to date. Clinical trial information:
NCT06335667
.
ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non–muscle-invasive bladder cancer.
Authors: Shore Neal D. , Dickstein Rian J. , Tyson Mark , Narayan Vikram M. , Agarwal Gautum , Goldfischer Evan R. , Williams Michael Brandon , Baayen Corine , Juul Kristian , Sandstrom Per , Bivalacqua Trinity
Published: February 2025

TPS888

Background:
There is currently no Food and Drug Administration (FDA)-approved treatment for intermediate-risk non–muscle-invasive bladder cancer (IR NMIBC), defined by the AUA as recurrence of low-grade (LG) Ta within 1 year, solitary LG Ta >3 cm, multifocal LG Ta, high-grade (HG) Ta (≤3 cm), and/or LG T1. Nadofaragene firadenovec-vncg is the first FDA-approved intravesical nonreplicating gene therapy for the treatment of adult patients with high-risk Bacillus Calmette Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. In a nonrandomized, multicenter, open-label, repeat-dose, phase 3 study, 53.4% of participants (55/103) with CIS ± HG Ta/T1 achieved complete response 3 months after the first instillation. Nadofaragene firadenovec was well tolerated, with no grade 4/5 study drug-related AEs. Because maintenance treatment with nadofaragene firadenovec following tumor resection may improve clinical outcomes in patients with IR NMIBC, the ABLE-32 open-label randomized study is being conducted to evaluate the efficacy of nadofaragene firadenovec administered every 3 months versus observation in participants with IR NMIBC.
Methods:
This phase 3 study includes approximately 100 global sites with 454 anticipated participants. Adults diagnosed with new or recurrent IR NMIBC and having undergone transurethral resection of bladder tumor within 60 days prior to randomization are eligible. Participants will be randomly assigned 1:1 to receive nadofaragene firadenovec or continue observation. The nadofaragene firadenovec group will receive quarterly doses unless disease recurs or progresses. The observation group will be followed quarterly and may receive nadofaragene firadenovec if IR NMIBC recurs within 24 months. All participants will be evaluated for recurrence and progression using cytology, cystoscopy, and for-cause biopsy for up to 5 years. The primary endpoint is recurrence-free survival (RFS), from randomization to first documented recurrence, progression, or death. Secondary endpoints include RFS at 12 and 24 months and safety. Exploratory endpoints include effect on potential biomarkers and health-related quality of life. Final results are expected in 2031. Clinical trial information:
NCT06510374
.
NEO-BLAST: Neoadjuvant therapy for bladder cancer followed by active surveillance vs treatment.
Authors: St-Laurent Marie-Pier , Eigl Bernhard J. , Yuan Ren , Chang Silvia , Black Peter Colin
Published: February 2025

TPS890

Background:
Neoadjuvant therapy (NAT) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). Approximately 35-40% of patients have no residual cancer at the time of surgery, suggesting that these patients could potentially avoid definitive bladder treatments (DBT), including RC or trimodal therapy (TMT). However, the current clinical tools used to detect residual disease prior to cystectomy are inadequate. The question remains whether patients with complete response (CR) require DBT or if active surveillance (AS) could be a safe alternative. The NEO-BLAST trial investigates whether a combination of bladder MRI, circulating tumor DNA (ctDNA), urinary tumor DNA (utDNA) and transurethral bladder tumor resection (TURBT) can accurately identify MIBC patients with a clinical CR (cCR) following NAT, and whether AS is non-inferior to standard of care (SOC) in those who achieved cCR.
Methods:
This is a multicenter, phase II/III, non-inferiority open-label clinical trial that will randomize patients with MIBC who achieve cCR after NAT to AS versus SOC DBT, including either RC or trimodal therapy (TMT) (NCT06537154). The primary endpoint is feasibility of randomization for the phase II pilot-RCT, and metastasis-free survival (MFS) at two years for the phase III. Eligible patients will be adults with non-metastatic MIBC (≥T2, N0M0) who are candidates to SOC NAT followed by DBT as per the current practice. After enrolment, ctDNA and utDNA will be collected. Only participants who complete SOC NAT will then undergo a comprehensive clinical restaging process, including repeat ctDNA and utDNA, bladder mpMRI, urine cytology, and TURBT with template biopsies. Participants meeting criteria for cCR, defined as negative ctDNA, utDNA, MRI, and TURBT, will be randomized to either AS-arm or DBT-arm, while those without cCR will receive SOC. Participants will be monitored with cystoscopy and urine cytology (if bladder in situ) every three months for 2 years, along with ctDNA and imaging at 3, 6, 12, 18, and 24 months. The pilot-RCT will plan to enrol 72 patients, and if 25% is found to have cCR and accept to be randomized, the trial will be considered feasible. Assuming a 5% event rate at 2 years (MFS) in both groups and a type I error of 5% (1-sided), 78 per group will provide 80% power to reject the hypothesis of inferiority. We anticipate enrolling 688 patients for the phase 3 to have a total of 172 patients with cCR randomized, assuming 10% lost to follow-up. An independent Data Monitoring Committee will oversee safety and efficacy throughout the trial. Clinical trial information:
NCT06537154
.
RAD-SG: Adaptive radiation therapy with concurrent sacituzumab govitecan (SG) for bladder preservation in patients (pts) with muscle invasive bladder cancer (MIBC).
Authors: Gupta Shilpa , Almassi Nima , Bukavina Laura , Wee Christopher Eing , Stephans Kevin L. , Diaz-Montero C. Marcela , Tendulkar Rahul D. , Mian Omar Y. , Chan Timothy An-thy
Published: February 2025

TPS896

Background:
Concurrent chemoradiotherapy (CRT) is a recommended treatment option for pts with MIBC interested in bladder-preservation and/or not candidates for radical cystectomy (RC). Systemic radio-sensitizing chemotherapy may have off target side effects and exploring novel agents with radiation is an unmet need. SG is an antibody drug conjugate (ADC) and has shown efficacy in metastatic urothelial cancer (UC). RAD-SG is a single-arm phase 1 trial investigating the concurrent administration of SG with adaptive radiotherapy (RT) in pts with MIBC.
Methods:
Eligibility criteria include pts with localized MIBC (T2-T4aN0M0), ECOG PS Score of 0-2, normal organ and marrow function including creatinine clearance ≥ 30 mL/min, must undergo a TURBT within ≤ 60 days prior to treatment. Variant subtypes are allowed. Pts must not have had UC or any histological variant at any site outside of bladder within 24 months except Ta/T1/Carcinoma in situ (CIS) of the upper urinary tract including renal, pelvis, and ureter if underwent complete nephroureterectomy. Other exclusion criteria include bilateral hydronephrosis and prior pelvic / local RT for MIBC or any other cancer type. SG targets TROP-2, a surface protein expressed in UC, it will be given IV at 7.5 mg/kg every 21days starting prior to RT and 2 subsequent cycles with concurrent adaptive RT over a period of 6 weeks (64 Gy). The primary endpoint is safety, tolerability, and feasibility of trimodality therapy with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. The secondary endpoints are bladder intact event-free survival (BI-EFS) with concurrent SG and RT for MIBC and compare historical controls with other concurrent CRT regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, RC, or death from any cause. Correlative objectives include 1) elucidation of the genetic and microenvironmental mechanisms that drive efficacy and resistance to combined ADC plus RT and 2) characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following treatment with SG plus RT. The study will accrue 20 pts at Cleveland Clinic Foundation and enrollment is ongoing. (NCT05833867). Clinical trial information:
NCT05833867
.
Close Encounters of the Anxious Kind
Authors: Venturi Tristan
Published: February 2025

This essay considers the shared ideological foundation underlying transfeminine exclusion from sports and transfeminine exclusion from dating. While biological advantage and sexual preference are often cited as indisputable, legitimate, and scientifically supported criteria for prohibiting transgender participation in these two domains, the author argues that both sports and dating operate according to fallacious cisheteronormative assumptions that work to ostracize sex/gender-transgressive bodies through three main practices: the exercise of suspicion, the legitimization of inspection, and the criminalization of nondisclosure.
Expanding the Repertoire of Trans Masculinities
Authors: Vipond Evan
Published: February 2025

Original Plumbing (OP) is a trans male quarterly zine cocreated and coedited by Amos Mac and Rocco Kayiatos. OP holds historical and cultural importance as a t4t publication made for trans men by trans men and serves as an entry point for theorizing trans masculine embodiments and subjectivities. Inspired by the format of OP, this piece brings together personal narrative, critical analysis, cover images, and an interview with OP's cocreator and coeditor, Amos Mac.
Destabilisation of bam transcripts terminates the mitotic phase of Drosophila female germline differentiation
Authors: Samuels Tamsin J. , Torley Elizabeth J. , Nadmitova Valeriia , Naden Emily L. , Blair Phoebe E. , Hernandez Frometa Frankjel A. , Karam Teixeira Felipe
Published: February 2025

The tight control of the mitotic phase of differentiation is crucial to prevent tumourigenesis while securing tissue homeostasis. In the Drosophila female germline, differentiation involves precisely four mitotic divisions, and accumulating evidence suggests that bag-of-marbles (bam), the initiator of differentiation, is also involved in controlling the number of divisions. To test this hypothesis, we depleted Bam from differentiating cells and found a reduced number of mitotic divisions. We examined the regulation of Bam using RNA imaging methods and found that the bam 3’ UTR conveys instability to the transcript in the 8-cell cyst and early 16-cell cyst. We show that the RNA binding protein, Rbp9, is responsible for timing bam mRNA decay. Rbp9 itself is part of a sequential cascade of RNA binding proteins activated downstream of Bam, and we show that it is regulated through a change in transcription start site, driven by Rbfox1. Altogether, we propose a model in which Bam expression at the dawn of differentiation initiates a series of events that eventually terminates the Bam expression domain.
Plasticity in voltage-gated ion channels following overwintering in respiratory motoneurons of American bullfrogs
Authors: Filogonio Renato , Saunders Sandy E. , Gray Michael , Viteri Jose A. , Santin Joseph M.
Published: February 2025

Many animals undergo prolonged dormancy periods to survive cold or dry environments. While humans and most laboratory-based mammals experience a loss of neuromuscular function during inactivity, hibernators possess physiological mechanisms to mitigate this loss. The American bullfrog provides an extreme model of this phenomenon, as brainstem circuits that generate breathing are completely inactive during underwater hibernation, during which motoneurons employ various types of synaptic plasticity to ensure adequate respiratory motor output in the spring. In addition to synapses, voltage-gated ion channels may undergo plasticity to boost neuronal output. Therefore, we hypothesized that motoneuron excitability would also be enhanced after hibernation via alterations in voltage-gated ion channels. We used whole-cell patch clamp electrophysiology to measure membrane excitability and activities of several voltage-gated channels (K+, Ca2+, Na+) from motoneurons that innervate muscles of the buccal pump (hypoglossal) and glottal dilator (vagal). Surprisingly, compared to controls, overwintered hypoglossal motoneurons displayed multiple indices of reduced excitability (hyperpolarized resting membrane potential, lower firing rates, greater lag to first spike). Mechanistically, this occurred via enhanced voltage-gated K+ and reduced Ca2+ channel activity. In contrast, vagal motoneurons excitability was unaltered, but exhibited altered ion channel profiles which seemed to stabilize neuronal output, involving either reduced Ca2+ or K+ currents. Therefore, different motoneurons of the same neuromuscular behavior respond differently to overwintering by altering the function of voltage-gated channels. We suggest divergent responses may reflect different energetic demands of these neurons and/or their specific contribution to breathing and other orofacial behaviors.
Patterns of Referral for Common Cancer Surgery in the United States
Authors: Montgomery Kelsey B. , Ross Elizabeth , Amu-Nnadi Chimaraije , Bhatia Smita , Broman Kristy K.
Published: February 2025

Background

Shifts in healthcare delivery have resulted in most U.S. hospitals participating in integrated health systems, many of which selectively refer complex cancer surgery to high-volume centers. However, this centralization may exacerbate barriers to access and may not be necessary for all cancer types. This study describes the prevalence and pattern of referral for surgery for common cancers and evaluate associated factors.

Methods

The National Cancer Database was used to identify adult patients who underwent curative-intent surgical resection between 2010 and 2020 for 12 common cancers (bladder, breast, colon, kidney, lung, melanoma, oral cavity, pancreas, prostate, rectum, thyroid, and uterus). The primary outcome was receipt of referred surgical cancer care.

Results

Overall, 5,406,813 patients underwent surgical resection for common cancers, with 33.7% referred for surgery after diagnosis elsewhere. Rates of referred surgery varied by disease site, ranging from 13.7% (bladder) to 58.2% (melanoma). On multivariable analysis, patients with melanoma, oral cavity, prostate, rectal, and uterine cancers (referent = breast), higher clinical stages, and increasing year of diagnosis had higher adjusted odds of referred surgical care. Nonacademic facility types, lower facility volume, higher comorbidity burden, and nonprivate insurance were associated with reduced odds of referred surgical care.

Conclusions

Likelihood of referred surgical cancer care increased over time for 11 of 12 common cancers, with the prevalence of referred care varying significantly based on disease site and sociodemographic factors. Future work evaluating associated clinical outcomes will aid in decisions regarding allocation of referral of surgical cancer care within health systems.
Zooming into the sponge microbiome in the omics era
Authors: Γαβριηλίδου Ασημένια
Published: February 2025

Οι θαλάσσιοι σπόγγοι (φύλο Porifera) είναι οι αρχαιότεροι ζώντες μεταζωικοί οργανισμοί και διαδραματίζουν κρίσιμο οικολογικό ρόλο στα βενθικά οικοσυστήματα λόγω της υψηλής ικανότητάς τους στη διήθηση νερού. Επιπλέον, φιλοξενούν πυκνές και ποικιλόμορφες μικροβιακές κοινότητες που ανήκουν και στους τρεις τομείς της ζωής, σχηματίζοντας πολύπλοκα holobionts. Ωστόσο, η πλειονότητα των σπόγγων-συμβιωτών παραμένει ακαλλιέργητη, περιορίζοντας την κατανόηση των λειτουργικών τους ρόλων. Η παρούσα διατριβή διερευνά τη σχέση μεταξύ σπόγγων και βακτηρίων μέσω της ενσωμάτωσης καλλιεργητικών και μη καλλιεργητικών μεθόδων. Η μελέτη αναδεικνύει τη μεταβολική ευελιξία των Flavobacteriaceae που σχετίζονται με τους σπόγγους, τα οποία εμφανίζουν γονιδιωμακή ικανότητα για κινητικότητα ολίσθησης, αποδόμηση υδατανθράκων και παραγωγή δευτερογενών μεταβολιτών, αν και τα φαινοτυπικά πειράματα υπέδειξαν σιωπηρή γονιδιακή έκφραση υπό in vitro συνθήκες. Επιπλέον, η ανάλυση γονιδιωμάτων και η βιοδραστική δοκιμή βακτηρίων προερχόμενων από σπόγγους (Proteobacteria και Actinobacteria) αποκάλυψαν την παρουσία αντιμικροβιακών και κυτταροτοξικών ενώσεων, συνδέοντας βιοσυνθετικά γονιδιακά συμπλέγματα με τις παρατηρούμενες βιοδραστικότητες. Εστιάζοντας σε σπόγγους-συμβιώτες που δεν έχουν καλλιεργηθεί στο εργαστήριο, η έρευνα περιγράφει ένα νέο υποψήφιο γένος, το Candidatus Thalassonella, εντός του φύλου Tectomicrobia, το οποίο μοιράζεται μεταβολικά χαρακτηριστικά με το Ca. Entotheonella, έναν γνωστό «υπερπαραγωγό» βιοδραστικών μεταβολιτών. Επιπλέον, η μελέτη αποσαφηνίζει τη φυλογένεση και τις μεταβολικές δυνατότητες των σπόγγων-συμβιωτών Ca. Dadabacteria (‘Desulfobacterota__D’), αποκαλύπτοντας μία ειδική για σπόγγους τάξη (Ca. Nemesobacterales) εμπλουτισμένη σε γονίδια που σχετίζονται με την προσαρμογή στον ξενιστή και τον δευτερογενή μεταβολισμό. Με τη χρήση φθορίζουσας in situ υβριδοποίησης, τα Ca. Nemesobacterales οπτικοποιήθηκαν εντός των βακτηριοκυττάρων των σπόγγων Geodia barretti, υποστηρίζοντας τον συμβιωτικό τους τρόπο ζωής. Συμπερασματικά, η παρούσα διατριβή γεφυρώνει το χάσμα μεταξύ των γνώσεων που προκύπτουν από τις ομικές επιστήμες και της λειτουργικής κατανόησης των αλληλεπιδράσεων σπόγγων-μικροβίων. Τα ευρήματα υποδεικνύουν ότι οι συμβιωτικοί μικροοργανισμοί των σπόγγων συμβάλλουν στην ετεροτροφία, την ανταλλαγή μεταβολιτών και την χημική άμυνα, ενισχύοντας τη στενή σχέση τους με τον ξενιστή. Η μελλοντική έρευνα θα πρέπει να ενσωματώσει τόσο καλλιεργησιακές όσο και γονιδιωματικές προσεγγίσεις για την περαιτέρω διερεύνηση του οικολογικού και βιοτεχνολογικού δυναμικού των μικροβιωμάτων των σπόγγων.
Η ζωολογία του Πλίνιου του Πρεσβύτερου και του Κλαύδιου Αιλιανού
Authors: Παπαδόπουλος Δημήτριος
Published: February 2025

Στόχος της παρούσας διατριβής είναι να εξετάσει τους τρόπους μετάδοσης και οργάνωσης της ζωολογικής γνώσης σε δύο εγκυκλοπαιδικού χαρακτήρα συγγράμματα της αυτοκρατορικής εποχής: την Historia Naturalis (στο εξής HN) του Ρωμαίου συγγραφέα του 1ου αι. μ.Χ. Πλίνιου του Πρεσβύτερου, και το Περὶ Ζῴων Ἰδιότητος του αυτοκρατορικού σοφιστή και διανοούμενου Κλαύδιου Αιλιανού, ο οποίος έζησε μεταξύ του ύστερου 2ου και τις αρχές του 3ου αι. μ.Χ. Στο πρώτο έργο η ζωολογία καταλαμβάνει 4 βιβλία (βιβλία 8-11), ενώ στα 17 βιβλία του δεύτερου έργου απαρτίζει εξ ολοκλήρου το περιεχόμενό τους. Τα δύο έργα δεν είναι γραμμένα από φιλοσόφους, αλλά από δύο πολυμαθείς Ρωμαίους συγγραφείς, οι οποίοι δεν παρουσιάζουν πρωτότυπη γνώση στους αναγνώστες τους, αλλά παραθέτουν με διαφορετικούς τρόπους όσες πληροφορίες έχουν συγκεντρώσει, μέσω της μελέτης πολυάριθμων όσο και ετερογενών γραπτών πηγών με προέλευση τη φιλοσοφία, την ποίηση και την ιστοριογραφία. Στη διατριβή μου μελετώ τις ζωολογικές πληροφορίες που εμπεριέχονται στα δύο έργα συγκριτικά ως προς τρία ζητήματα. Πρώτον, δίνω έμφαση στην αυτοπροβολή του Πλίνιου και του Αιλιανού και παρουσιάζω πώς κατασκευάζουν τη συγγραφική εικόνα τους ως φιλόσοφοι και Ρωμαίοι συγγραφείς. Υποστηρίζω ότι η σύγκρισή τους με επώνυμους και ανώνυμους φιλοσόφους παίζει καθοριστικό ρόλο στην καθιέρωση της θέσης και της συμβολής τους στην αρχαία ζωολογία. Επιπλέον, εξετάζω και το πώς προβάλλουν τη ρωμαϊκή τους ταυτότητα, εισάγοντας, μεταξύ άλλων, θέματα από τη ρωμαϊκή ζωή και ιστορία. Το δεύτερο ζήτημα που εξετάζω είναι οι πηγές της ζωολογικής γνώσης που ενσωματώνουν τα δύο έργα, με επικέντρωση στη χρήση προσωκρατικών, περιπατητικών και ποιητικών μαρτυριών. Υποστηρίζω ότι οι δύο συγγραφείς υιοθετούν μεθόδους παρουσίασης των πηγών τους που ενθαρρύνουν τους αναγνώστες τους να αναλάβουν ενεργό ρόλο στη μελέτη τους, έτσι ώστε να αντιληφθούν οι ίδιοι πώς οι φιλόσοφοι και οι ποιητές συνέβαλαν στη συγκέντρωση γνώσεων για τα ζώα. Η οργάνωση των ζωολογικών μαρτυριών στα δύο κείμενα αποτελεί το τρίτο θέμα της μελέτης μου. Εξετάζω από τη μία τα θεματικά κριτήρια οργάνωσης που υιοθετεί κυρίως ο Πλίνιος και, από την άλλη, την αισθητική αρχή της ποικιλίας, την οποία ακολουθεί ο Αιλιανός. Η συγκριτική μελέτη μου καταδεικνύει, τελικά, πως τα όρια μεταξύ των γραμματειακών ειδών που σήμερα ονομάζουμε ‘εγκυκλοπαίδεια’ και ‘ποικιλογραφία’ (miscellany) δεν ήταν αυστηρά στην αρχαιότητα. Καταδεικνύει επίσης ότι, αν και τα ζωολογικά βιβλία του Πλίνιου και του Αιλιανού δεν παρουσιάζουν καινοτόμα γνώση, ωστόσο δεν είναι άκριτα συμπιλήματα ζωολογικών πληροφοριών. Αντιθέτως, πρόθεση των δύο συγγραφέων είναι αφενός να διδάξουν τους αναγνώστες τους για τα ζώα με απώτερο σκοπό την ωφέλειά τους, και, αφετέρου, να τους επιτρέψουν να λάβουν ενεργό ρόλο, μέσω των κειμένων τους, σε αρχαίες ζωολογικές συζητήσεις και παραδόσεις.
Η συρροή αξιώσεων στον κανονισμό 1215/2012
Authors: Σαγρή Γεωργία
Published: February 2025

Η προβληματική των συρρεουσών αξιώσεων στον Κανονισμό 1215/2012, όπως εξετάζεται στο παρόν πόνημα, ταξινομείται μεθοδολογικά στο πεδίο του Δικονομικού Διεθνούς Δικαίου. Ωστόσο η συνάφεια και διασύνδεση της με το ιδιωτικό διεθνές δίκαιο και το εκάστοτε ουσιαστικό δίκαιο το οποίο αυτό θα υποδείξει, είναι κάτι παραπάνω από προφανής ως προέκταση της συλλογιστικής πορείας του ερευνητή. Το ζήτημα αναδεικνύεται μέσα από την σταχυολόγηση και παρουσίαση θεωριών και απόψεων Ελλήνων και ξένων ακαδημαϊκών σχετικά με τη μέθοδο επίλυσης του ζητήματος σε συνδυασμό με τη νομολογία του ΔΕΕ η οποία αποτελεί τη βάση για τη διερεύνηση της προβληματικής από την οποία ο ερευνητής αντλεί δεδομένα και μεθοδολογικά εργαλεία για την εξαγωγή συμπερασμάτων σχετικά με την αντιμετώπιση της συρροής αξιώσεων από σύμβαση και αδικοπραξία, όταν και οι δύο αξιώσεις διαθέτουν το ίδιο αντικείμενο παροχής. Στόχευση της γράφουσας είναι , μέσω της ανάλυσης της θεωρίας , της νομολογίας και με γνώμονα τις αρχές που διατρέχουν τον Κανονισμό 1215/2012, πρώτον η ανάδειξη της προβληματικής της συρροής αξιώσεων η οποία άρχεται από τη διαδικασία χαρακτηρισμού των αξιώσεων που προβάλει ο ενάγων και δεύτερον η πρόταση πιθανών λύσεων προς αποφυγή του διαχωρισμού των αξιώσεων και εκδίκασής τους από διαφορετικά fora δυνάμει της αρχής της αμοιβαίας αποκλειστικότητας των ειδικών συντρεχουσών βάσεων των α. 7 παρ.1 και 2 του Κανονισμού. Για την εξαγωγή συμπερασμάτων περί επιτρεπτού ή μη της συνεκδίκασης των συρρεουσών αξιώσεων , ο ερευνητής καλείται να εξετάσει το περιεχόμενο του αντικειμένου της δίκης σύμφωνα με τον ΚανΒρΙα μέσα από αποφάσεις του ΔΕΕ καθώς και θεωρίες οι οποίες έχουν υποστηριχθεί για αυτό σε ευρωπαϊκό επίπεδο με αφορμή το θεσμό της ευρωπαϊκής εκκρεμοδικίας. Η ανωτέρω συνδυαστική έρευνα παρέχει επιπλέον τις απαιτούμενες απαντήσεις στο ερώτημα επί ταυτότητας ή μη του αντικειμένου της δίκης σε περιπτώσεις συρροής αξιώσεων οι οποίες στοχεύουν στην ίδια ακριβώς παροχή. Επιπλέον ερευνάται σε δεύτερο επίπεδο η αντιμετώπιση του ζητήματος της συρροής αξιώσεων στον ΚανΒρΙα σε συνδυασμό με το δεδικασμένο της παραγόμενης απόφασης όταν το εθνικό δικαστήριο έχει εκδώσει απόφαση για μία εκ των δύο αξιώσεων και ακολουθεί δικαστηριακή διαδικασία με άσκηση αγωγής σε άλλο κράτος-μέλος στηριζόμενη στην έτερη νομική βάση ήτοι συμβατική ή αδικοπρακτική. Εξετάζεται η πηγή καθορισμού των προϋποθέσεων του δεδικασμένου ( δίκαιο κράτους εκδόσεως της απόφασης- δίκαιο κράτους αναγνώρισης- αυτόνομη ευρωπαϊκή έννοια του δεδικασμένου) με αναφορά στις θέσεις της θεωρίας, της νομολογίας του ΔΕΕ αλλά και των πρόσφατων αποφάσεων κρατών μελών επί του θέματος.
National Innovation System (NIS) as a Means for Development: Policies, Opportunities, and Challenges in Ethiopia.
Authors: Sube Kassahun , Belay Tegegn , Hando Filimon , Bayinesagn Ashenafi
Published: February 2025

Background There is a need to go beyond mere measures of time used on social media. Existing tools inadequately capture the multidimensional nature of social media use, leaving a gap for concise yet comprehensive assessment tools. Aims This study aimed to develop a short questionnaire addressing three critical dimensions of social media use: self-presentation, negative experiences, and problematic use. The association between these dimensions and symptoms of anxiety and depression was also investigated. Methods This study uses two independent datasets of adolescents aged 16+ years in Norway. Using Ant Colony Optimization (ACO) analyses, a pool of 31 social media items was analyzed to investigate factor structure and associations with symptoms of anxiety and depression. For model development, the “LifeOnSoMe”-study was employed (>3,500 participants), and data from a pilot study (~500 participants) was used for external validation. Results Based on ACO-analyses, a 20-item six-factor model was identified, encompassing social comparison and self-presentation (five items), and three items for each of the following domains: negative experiences (Negative acts and Unwanted attention from others) and problematic use (Subjective overuse, Social obligations, and Source of concern). Confirmatory factor analyses demonstrated very good to excellent fit in both datasets, and consistent associations between the six different domains and symptoms of anxiety and depression. Discussion The suggested 20-item questionnaire provides a robust and succinct tool for evaluating social media’s impact on mental health, offering substantial explanatory power for variance in anxiety and depression symptoms. This can serve as meaningful tool for assessing the potential impact of social media use for mental health and related outcomes.
The Role of Radiotherapy in the Treatment of Lung Cancer: A Review of Therapeutic Methods and Effects
Authors: Komada Dawid , Doman Katarzyna , Najdek Agnieszka , Hermanowicz Kamil , Oleksy Daria , Kaczmarska Urszula , Mycyk Marcin , Cioch Michał Jakub , Woźniak Aleksandra , Nowak Julia
Published: February 2025

Introduction
Lung cancer is a leading cause of cancer-related deaths worldwide, with rising cases and mortality. In 2022, there were 2.48 million new cases and 1.8 million deaths globally. The primary risk factor is tobacco smoking, though genetic factors, pollution, and other exposures also contribute. Lung cancer is divided into Non-Small Cell Lung Cancer (NSCLC), which includes adenocarcinoma, squamous cell carcinoma, large-cell carcinoma; and Small Cell Lung Cancer (SCLC), characterized by rapid growth, early metastatic spread and greater chemosensitivity in comparison to NSCLC. Treatment depends on the cancer type and stage, with surgery and radiotherapy being treatment of choice for NSCLC and chemoradiotherapy for SCLC.
Materials and methods
This article is the result of the review of the scientific literature available in PubMed database using keywords: “Lung Cancer”, “Radiotherapy”, “Non-Small Cell Lung Cancer”; “Small Cell Lung Cancer”
Aim of study
The aim of the study is to summarize available knowledge about various methods of treatment of lung cancer by means of radiation therapy and its diverse techniques. The epidemiology, etiology, staging and methods of treatment were summarized and described. Modern radiotherapy techniques for treating lung cancer have also been included.
Conclusions
For NSCLC, modern techniques like stereotactic radiotherapy (SBRT/SABR) provide surgical-level effectiveness in early stages with reduced toxicity, while concurrent chemoradiotherapy is optimal for inoperable stage III disease. Palliative radiotherapy remains vital for symptom relief in advanced stages. For SCLC, concurrent chemoradiotherapy is the standard for limited-stage disease, while prophylactic cranial irradiation (PCI) and thoracic radiotherapy improve survival in extensive-stage cases responding to chemotherapy.
Code and Data Repository for Revisiting Semidefinite Programming Approaches to Options Pricing: Complexity and Computational Perspectives
Authors: Henrion Didier , Kirschner Felix , De Klerk Etienne , Korda Milan , Lasserre Jean-Bernard , Magron Victor
Published: February 2025

Given observable option prices and their respective strikes on various assets {1, ... , n}, we present methods to obtain inner and outer bounds on the feasible range of prices for a European basket call option with given strike relying on the assets {1, ... ,n}. The weights of the basket can be chosen freely. This problem can be stated as a Generalized Moment Problem (GMP); an optimization problem over the space of probability measures. The code we present ought to approximate the optimal solution, i.e., the optimal measure for the GMP, by a hierarchy of semidefinite programs, known as the Lasserre hierarchy.
Analysis of Market Structure, Behavior and Performance at the Manding Leather Industry Center of Bantul Yogyakarta
Authors: Suripto Suripto , Wulandari Isna Tri , Abasimi Ignatius
Published: February 2025

Bantul Regency has the largest and only leather product industry center in the DIY Province. Marketing at the center of the leather industry is competition between each leather producer. This is a crisis problem and must find a solution to overcome it. The analysis that can be used to determine the marketing system is SCP (Structure-Conduct-Performance) analysis. This research was conducted at the leather industry center in Manding, Sabdodadi, Bantul district, Bantul, Yogyakarta Special Region. This study aims to determine the structure, behavior and market performance of the leather industry center in Manding. The method used by the researchers in this study used primary data from leather craftsmen and secondary data (BPS) as well as interviews and filling out questionnaires. The results showed that the structure of the leather market in Manding was an oligopoly with a CR4 calculation of 70.14%. For the market behavior of the leather industry in Manding with the CLR calculation, it is included in the labor-intensive industry class with the calculation results below 20% and market performance seen from the PCM obtained an average of 0.53%. With the largest PCM is 0.95% but the largest PCM does not become the largest market share (MS) means the benefits seen from PCM do not affect the market share.
FORMAÇÃO DOCENTE E DESENVOLVIMENTO HUMANO:
Authors: Alves Cândida Beatriz
Published: February 2025

A partir de um relato de experiência na coordenação pedagógica (CP) de um campus do Instituto Federal de Brasília (IFB), objetiva-se analisar a importância da criação de espaços de diálogo e construção coletiva para o desenvolvimento humano na docência a partir da ação da CP. A experiência relatada é a de plantões pedagógicos conduzidos pela CP, ao longo da pandemia de covid-19. Diversos estudos já foram realizados acerca do papel do coordenador pedagógico no contexto da pandemia, com foco sobretudo na formação acadêmica de docentes. Entretanto, poucos enfatizaram a promoção da escuta e da circulação da palavra, com foco na construção de sentido e de desenvolvimento humano na docência e o papel da coordenação pedagógica nesse processo. Em um total de 11 plantões, diversos temas foram debatidos entre os docentes do campus, estabelecendo um espaço dialógico que permitiu ir além de questões estritamente pedagógicas em direção a percepções sobre as transformações que o momento exigia, levando a um repensar-se enquanto docente e o desenvolvimento de modos de ser e fazer docentes. Tendo em vista a pertinência do debate sobre formação docente em perspectiva dialógica, ressaltamos que tais discussões extrapolam as especificidades do período pandêmico.
ALÉM DA TUTORIA INTELIGENTE: EXPLORANDO O POTENCIAL DA INTELIGÊNCIA ARTIFICIAL PARA REVOLUCIONAR A EDUCAÇÃO BÁSICA E SUPERIOR
Authors: Gomes Silva Gutemberg , Amaral Santos Elisabete
Published: February 2025

O artigo em questão aborda a inteligência artificial (IA) na educação, com exemplificações de suas práticas e respectivas análises críticas. Ainda que seu começo tenha sido modesto, nos anos de 1980, suas aplicações são úteis na atualidade tanto na escola básica quanto na educação superior, impactando a esfera educacional indubitavelmente e justificando a elaboração deste artigo. O objetivo geral deste trabalho é refletir acerca das práticas que envolvem a inteligência artificial, ao passo que os objetivos específicos são delinear o conceito de inteligência artificial tanto na escola básica quanto na educação superior. A aplicação da IA pode começar dos três anos de idade em diante, prosseguindo em turmas de alfabetização e chegando até o ensino médio, introduzindo e aprimorando habilidades que alcançarão maior complexidade no futuro e aprimorando o universo discente através de cursos ampliadores de conhecimentos, bem como promovendo acessibilidade aos estudantes da rede pública e até mesmo integração ao desenvolvimento de atividades direcionadas para o empreendedorismo, dentre outras capacitações. O caminho da IA continua na educação superior, onde os discentes já experimentam a independência cotidiana, e segue seu percurso, m atividades nas quais os sistemas de tutoria orientam o aprendizado. Embora a aplicação da IA na educação não garanta melhorias por si só se não houver o engajamento dos diversos atores que compõem o panorama educacional, além de bom senso e reflexão, se bem utilizada pode ser um recurso relevante, hodiernamente, personalizando o aprendizado discente. A aplicação da IA na educação não se esgota nos exemplos disponibilizados neste artigo, pois existem muitas outras possibilidades em seu bojo que ultrapassariam o limite de páginas deste trabalho.