bluuebunny/crossref_metadata_2025_split huggingface dataset:
P26.10.B OPTIMIZING DELIVERY OF CHEMOTHERAPEUTIC AGENTS BY INTRA-ARTERIAL INFUSION IN GLIOBLASTOMA
Authors: Latulippe J , Roy L , Gobeil F J , Fortin D 
Published: October 2024

Abstract

BACKGROUND
Being the most aggressive malignant primary brain tumor, glioblastoma (GBM) is a difficult disease to treat. The first line treatment consists in maximal resection followed by concomitant radiotherapy and temozolomide. However, most patients will relapse during the after treatment. The overall survival is only 14,6 months while the progression-free survival is 6,9 months. Even if the first-line treatment is well established, there is no consensus for the second line. At our institution, Dr. Fortin prioritize the intra-arterial (IA) administration of chemotherapeutic agents (CTA), which conveys a higher drug concentration to the tumor site. Carboplatin is the most used chemotherapeutic, but certain patients will not respond or will even develop chemoresistance to this treatment. Therefore, there is a strong need for bringing different CTAs into clinical care to offer more options. Topotecan, cytarabine and paclitaxel are molecules evaluated in this study since they are all already used intravenously (IV) in the treatment of GBMs.

MATERIAL AND METHODS
Since these agents have never been used for IA, we need to determine their maximal tolerable dose (MTD) to avoid any adverse effects. As such, healthy rats were given the CTA by retrograde infusion in the external carotid. They were euthanized five days following that surgery. After determining the right dosages, the survival study was initiated. Indeed, every CTAs were administered IA but also IV to compare both administrations. We used the Fischer-F98 glioma rat model. For the efficacy study, we implanted 10 000 F98 cells into the brain of the Fischer rats. At day 10, they received the treatment associated to their group. The animals were followed every day following the surgeries and were euthanized when their condition was too deteriorated. The IV doses used (found in the literature) were topotecan: 4 mg/kg, cytarabine: 40 mg/kg and paclitaxel: 10 mg/kg.

RESULTS
The doses found in the MTD study for topotecan and cytarabine were 4 mg/kg and 8,75 mg/kg respectively. However, paclitaxel was toxic when administered via IA, probably because of its lipidic vehicle. As for the efficacy study, the IA group of topotecan showed a promising outcome with a higher survival rate (29 days) compared to IV (23,5 days). As for cytarabine groups, IA was detrimental, with a 22 days median survival, compared to 26,5 days for the IV group.

CONCLUSION
While topotecan and cytarabine could be given intra-arterially, only topotecan showed conclusive results with a higher survival rate. More animals will be added to this group to validate this outcome. Cytarabine does not appear to be a good option since the MTD IA dose yielded a worse survival rate than the dose administered via IV. As for paclitaxel, considering it cannot be used intra-arterially, intra-tumoral infusion will be tested to see if we can get positive results.
P27.04.A CLINICAL EXPERIENCES AND LEARNING CURVES FROM ROBOT-ASSISTED NEUROSURGICAL BIOPSIES WITH STEALTH AUTOGUIDEΤΜ
Authors: Ljungqvist J , Barchéus H , Abbas F , Ozanne A , Nilsson D , Corell A 
Published: October 2024

Abstract

BACKGROUND
Biopsies of intracranial lesions is a cornerstone in the diagnosis of unresectable tumors to guide neurooncological treatment; however, the procedure is also associated with risks. The results from the cranial robot guidance system Stealth AutoguideΤΜ were studied after introduction at a neurosurgical department. Primary aims include the presentation of clinical and radiological data, accuracy of radiological diagnosis, learning curves of the new technology, diagnostic yield, and precision. The secondary aim was to study complications.

METHODS
Retrospective data inclusion was performed on patients ≥18 years undergoing biopsy with Stealth AutoguideΤΜ due to suspected brain tumor in the first three years after introduction of the technique. Data regarding clinical characteristics, intraoperative variables, pathological diagnosis, and complications were recorded. Analyses of learning curves were performed.

RESULTS
A total of 79 procedures were performed on 78 patients with a mean age of 62 years (SD 12.7, range 23-82), 30.8% were female. Tumors were often multifocal (63.3%) and supratentorial (89.9%). The diagnostic yield was 87.3%. The first-hand radiological diagnosis was correct in 62.0%. A slight decrease in operation time was observed, although not significant. The surgeon contributed to 12% of the variability.

CONCLUSION
Robot-assisted biopsies with Stealth AutoguideΤΜ seem to be comparable, with regards to complications, to frame-based and other frame-less neurosurgical biopsies. Learning curves demonstrated no statistical differences in time of surgery and only 12% surgeon related variation (i.e. variation caused by change of performing surgeon), suggesting a successful implementation of this technical adjunct.
P27.10.B FACTORS INFLUENCING TIMELY DIAGNOSIS IN NEUROLYMPHOMATOSIS
Authors: Doubrovinskaia S , Egert A , Karschnia P , Scheffler G , Huttner A , Fulbright R , Baehring J M , Kaulen L D 
Published: October 2024

Abstract

BACKGROUND
Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in NL and factors facilitating or delaying diagnosis have not been thoroughly evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort from a tertiary referral center.

MATERIAL AND METHODS
The quality control database at Yale Cancer Center, Section of Neuro-Oncology, was searched for neurolymphomatosis cases diagnosed between 2001-2021. Univariate analyses were performed to identify parameters influencing diagnostic intervals.

RESULTS
We identified 22 neurolymphomatosis cases including 7 without previous NHL (primary NL) and 15 with PNS relapse of NHL (secondary NL), which occurred after a median of 16 months (range: 4-144). Patients typically presented with painful polyneuropathy (73%), that was asymmetrical and rapidly progressive. Diagnosis was based on PNS biopsy (50%) or integration of neuroimaging findings (50%) with NHL history and diagnostic cerebrospinal fluid examinations. NL was diagnosed a median of 3 months (range: 1-12) after symptom onset. Secondary NL (median 2 vs 6 months; p =0.02), presentation with rapidly-progressive asymmetrical neuropathy (median 2 vs 6 months; p &lt; 0.001), upfront evaluation with either MRI or FDG-PET (median 2 vs 5 months; p = 0.04), and absence of nerve root lesions (median 1.5 vs 4 months; p = 0.04) were associated with earlier diagnosis after symptom onset.

CONCLUSION
Diagnostic delays in NL are common, particularly in patients with primary disease, atypical clinical presentation, upfront assessment with conventional CT, and nerve root lesions. Findings may guide prompt initiation of appropriate diagnostic work-up in NL.
P27.16.A PREDICTIVE ROLE OF INTRACRANIAL PD-L1 EXPRESSION IN A REAL-WORLD COHORT OF NSCLC PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITION FOLLOWING BRAIN METASTASIS RESECTION
Authors: Murad S , Wasilewski D , Onken J , Höricke P , Bukatz J , Früh A , Shaked Z , Misch M , Kühl A , Klein O , Ehret F , Kaul D , Radbruch H , Capper D , Vajkoczy P , Horst D , Frost N , Bischoff P 
Published: October 2024

Abstract

BACKGROUND
Emerging evidence suggests that treatment of NSCLC brain metastases with immune checkpoint inhibitors (ICIs) is associated with response rates similar to those of extracranial disease. Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) serves as a predictive biomarker for ICI response. However, the predictive value of brain metastasis specific (intracranial) PD-L1 TPS is not established. We investigated the role of intra- and extracranial PD-L1 TPS in NSCLC patients treated with ICI following brain metastasis resection.

MATERIAL AND METHODS
Clinical data from NSCLC patients treated with ICI following brain metastasis resection (n = 64) were analyzed. PD-L1 TPS of brain metastases (n = 64) and available matched extracranial tumor tissue (n = 44) were assessed via immunohistochemistry. Statistical analyses included cut point estimation via maximally selected rank statistics, Kaplan-Meier estimates, and multivariable Cox regression analysis for intracranial progression-free survival (icPFS), extracranial progression-free survival (ecPFS), and overall survival (OS).

RESULTS
PD-L1 expression was found in 54.7% of brain metastases and 68.2% of extracranial tumor tissues, with a median intra- and extracranial PD-L1 TPS of 7.5% (0 - 50%, IQR) and 15.0% (0 - 80%, IQR), respectively. In matched tissue samples, extracranial PD-L1 TPS was significantly higher than intracranial PD-L1 TPS (p = 0.013). Optimal cut points for intracranial and extracranial PD-L1 TPS varied according to outcome parameter assessed. Notably, patients with a high intracranial PD-L1 TPS (&gt; 40%) exhibited significantly longer icPFS as compared to patients with a low intracranial PD-L1 TPS (≤ 40%). The cut point of 40% for intracranial PD-L1 TPS was independently associated with OS, icPFS and ecPFS in multivariable analyses.

CONCLUSION
Our study highlights the potential role of intracranial PD-L1 TPS in NSCLC, which could be used to predict ICI response in cases where extracranial tissue is not available for PD-L1 assessment as well as to specifically predict intracranial response.
P27.31.B VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA POPULATION. INCIDENCE, RISK FACTORS AND SURVIVAL ANALYSIS
Authors: Meca Santamaria G , Comas Antón S , Hernandez Gonzalez A , Domenech Viñolas M , Izquierdo Gracia C , Muriel Sanchez R , Hostalot Panisello C , Teixidor Rodriguez P , Gutierrez Garcia B , Molero Savall J , Villà Freixa S 
Published: October 2024

Abstract

BACKGROUND
Patients diagnosed with Glioblastoma (GB) are at an increased risk of developing venous thromboembolism (VTE) compared to other cancers. This is a relevant clinical concern due to its associated comorbidity and risk of mortality. We analyzed the incidence and characteristics of symptomatic VTE in a cohort patient diagnosed with GB.

MATERIAL AND METHODS
A cohort of patients diagnosed and treated for GB between 2009 and 2023 were retrospectively analyzed. Patient-, tumor- and treatment-related variables were evaluated in order to determine risk factors for VTE development as well as the impact on survival.

RESULTS
Forty-seven (16.84 %) out of 279 patients developed symptomatic VTE. In 38.3% of patients, it was presented as deep vein thrombosis (DVT), in 14.9% as pulmonary thromboembolism, and 46.8% presented both events synchronously. DVT were located in the lower extremity in 94.8% of cases. The periods at greatest risk of VTE were the course of adjuvant Temozolomide (29.8% of events) during rescue treatment after relapse (25.5%) and the 4-week window between the end of radiotherapy and the start of adjuvant temozolomide (19,2%). No statistical impact on VTE development was found according to sex, age, pMGMT methylation status; Karnofsky performance status (≤70% versus &gt;70%), presence of paresis and type of surgery. Neither the presence of one, two or more than three cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, heart disease, tobacco) were related to a higher risk of VTE. Median overall survival (OS) and relapse free survival (RFS) were 13,8 (95% CI 12,5-16,4) and 7,3 (95% CI 6,6-8,2) months respectively for all patients. The development of VTE did not show an impact in OS nor RFS. Among patients who developed EVT, the need for dexamethasone coverage at the time of the event resulted in a decreased median OS (21,8 vs 12,9 months; p&lt;00.5) and RFS (15,7 vs 7,2 months; p&lt;00.5).

CONCLUSION
In our sample, clinical features related to the patient, treatment or tumor were not associated to an increased risk of VTE and the occurrence of VTE did not impact survival. Despite these results, the development of VTE is associated with potential increased comorbidity and mortality, so it must be considered as relevant from the clinical and health management point of view. The increased risk of thromboembolic events in patients with GB compared to other neoplasms requires further study of biomarkers to identify those patients at higher risk in order to consider the need of VTE prophylaxis.
Low magnesium levels and prognosis in newly diagnosed diffuse large B-cell lymphoma
Authors: Gile Jennifer J , Maurer Matthew , Ruan Gordon J , Abeykoon Jithma P , Heimgartner Joy R , Baumann Nikola A , McMahon Molly , Lin Yi , Witzig Thomas E 
Published: October 2024

Abstract
Magnesium (Mg) is an essential element involved in cellular metabolism. We demonstrated that in patients with diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant (SCT), those with a serum Mg &lt; 2.0 mg/dL at the time of transplant had worse outcomes. In this study, we aimed to learn the prognostic value of low serum Mg in patients with untreated DLBCL. We analyzed serum from 408 patients and tested 2 Mg cutpoints—low (&lt;1.7 mg/dL) and low normal (&lt;2.0 mg/dL), a range we found associated with lower survival in the SCT group. We found 3% of patients with low levels and 23% with low normal levels. Low normal serum Mg levels were associated with a higher stage at diagnosis, more extranodal involvement, higher international prognostic index score, lower overall survival (OS), and event-free survival. These data warrant testing Mg replacement to a target of &gt;2.0 mg/dL to learn if survival can be improved.
Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma
Authors: Tang Bixia , Xiao Jun , Chi Zhihong , Duan Rong , Cui Chuanliang , Si Lu , Liu Yixun , Hu Xuechun , Liu Zhi , Xiang Ping , Li Siming , Yan Xieqiao , Zhou Li , Li Juan , Li Yujie , Yu Xiaohui , Dai Xiangrong , Li Xiaoyi , Guo Jun , Sheng Xinan 
Published: October 2024

Abstract

Background
PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the post-platinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 50% of patients with aUC can tolerate platinum-containing treatment, treatments combining first-line ICIs with non-platinum drugs are urgently needed. Therefore, we assessed the safety and efficacy of the anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first-line therapy in aUC (NCT04603846).

Methods
This was a multi-center, single-arm, phase Ib study that enrolled patients with treatment-naive aUC. Patients received Socazolimab (5 mg/kg) and nab-paclitaxel (260 mg/m2) Q3w. The primary endpoint was safety and tolerability of the combination regimen. Second endpoints were the objective response rate (ORR) and progression-free survival.

Results
Between September, 2020 and September, 2021, 20 patients with urothelial carcinoma were enrolled, arising from renal pelvis (5), bladder (8), and ureter (7). After a median follow-up of 17 months, the median number of treatment cycles was 12. No patients had dose limiting toxicity. All patients had treatment-related adverse events (TRAEs), most of which were grade 1 or 2. The common TRAEs (≥20%) were peripheral neurotoxicity, alopecia, rash, increased ALT, weight loss, weakness, pruritus, increased AST, increased γGT, increased ALP, neutropenia, emesis, and anorexia. Nine patients (45%) developed grade 3 TRAEs including peripheral neurotoxicity (30.0%), increased ALT (10.0%), and increased γGT (5.0%). Two patients (10%) discontinued treatment because of grade 3 mouth ulcer (n = 1) and grade 2 lung fibrosis (n = 1). No grade 4-5 TRAEs were observed. Among the 17 patients who had received at least one tumor assessment, ORR was 58.8% (95% CI, 32.9%-81.6%) and the median progression-free survival was 8.3 months (95% CI, 5.2-19.5). The median duration of response was 13.3 months (95% CI, 2.0-20.1), and the overall survival was 19.5 months (95% CI, 11.2-not reached).

Conclusion
Socazolimab combined with nab-paclitaxel has shown good safety and promising antitumor activity as first-line therapy in patients with advanced urothelial carcinoma.
ASYMMETRIC LEAVES1 promotes leaf hyponasty in Arabidopsis by light-mediated auxin signaling
Authors: Lee Nayoung , Hwang Dae Yeon , Lee Hong Gil , Hwang Hyeona , Kang Hye Won , Lee Wonbok , Choi Min Gi , Ahn Ye Jin , Lim Chaemyeong , Kim Jeong-Il , Kwon Moonhyuk , Kim Sun Tae , Paek Nam-Chon , Cho Hyunwoo , Sohn Kee Hoon , Seo Pil Joon , Song Young Hun 
Published: October 2024

Abstract
In plants, balancing growth and environmental responses is crucial for maximizing fitness. Close proximity among plants and canopy shade, which negatively impacts reproduction, elicits morphological adjustments such as hypocotyl growth and leaf hyponasty, mainly through changes in light quality and auxin levels. However, how auxin, synthesized from a shaded leaf blade, distally induces elongation of hypocotyl and petiole cells remains to be elucidated. We demonstrated that ASYMMETRIC LEAVES1 (AS1) promotes leaf hyponasty through the regulation of auxin biosynthesis, polar auxin transport, and auxin signaling genes in Arabidopsis (Arabidopsis thaliana). AS1 overexpression leads to elongation of the abaxial petiole cells with auxin accumulation in the petiole, resulting in hyponastic growth, which is abolished by the application of an auxin transport inhibitor to the leaf blade. In addition, the as1 mutant exhibits reduced hypocotyl growth under shade conditions. We observed that AS1 protein accumulates in the nucleus in response to shade or far-red light. Chromatin immunoprecipitation analysis identified the association of AS1 with the promoters of YUCCA8 (YUC8) and INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19). In addition, AS1 forms complexes with PHYTOCHROME-INTERACTING FACTORs in the nucleus and synergistically induces YUC8 and IAA19 expression. Our findings suggest that AS1 plays a crucial role in facilitating phenotypic plasticity to the surroundings by connecting light and phytohormone action.
Recipient selection for lung transplantation: perspective in decision-making
Authors: Saribas Ertan , Citak Sevinc 
Published: October 2024

Abstract

Background
To determine the conditions that prevented transplant in patients referred to our center due to end-stage lung disease.

Study design
Descriptive study.

Place and duration of the study
Department of lung transplant clinic, Koşuyolu High Specialization Education and Research Hospital, Istanbul, Turkey, from December 2017 to January 2022.

Methods
Patients with end-stage lung disease referred to our clinic were retrospectively evaluated with regard to reasons for exclusion, diagnosis, and demographic data. The Karnofsky Performance Status scoring scale was used to measure the functional status of the patients.

Results
A total of 311 patients were evaluated during the study period. The mean age was 44.2 (range 4–73) years. There were 207 (66.6%) male patients. The most common indications were idiopathic interstitial pneumonia in 104 (33.4%) patients, chronic obstructive pulmonary disease in 53 (17%) patients, bronchiectasis in 49 (15.7%) patients, and cystic fibrosis in 28 (9%) patients. Of the patients, 106 (34%) were not appropriate candidates for a lung transplant. The most common reasons for refusal were preventable situations such as activity limitation and poor performance in 53 (50%) patients, weight in 49 (46.2%) patients, and smoking in 10 (9.4%) patients.

Conclusion
Impaired performance status was the most common cause of lung transplant exclusion. Weight and smoking were preventable causes of exclusion. Implementing pulmonary rehabilitation in very few patients was the most important handicap. It is believed that providing optimal treatment with a multidisciplinary approach and timely referral to transplant centers will significantly reduce the reasons for exclusion.
Key message What is already known on this topic? Referring lung transplant candidates to clinics at the earliest stage is essential for assessing their condition and exploring treatment options. What this study adds? Factors like smoking, obesity, and muscle loss can hinder the transplantation process; thus, timely interventions are crucial. The primary reason for excluding candidates from lung transplantation is the decline in performance status. How this study might affect research, practice or policy? Programs focused on smoking cessation, weight management, and muscle strengthening can play a vital role in enhancing patients’ health before transplantation. It is imperative to expand and enhance the accessibility of pulmonary rehabilitation programs.
Democracy, Liberal Zionism, and Civil-Military Relations in Israel: A Review Article
Authors: Lustick Ian S 
Published: October 2024

Abstract
Two books on civil-military relations in Israel, published eighteen years apart, focus on Israel's future as a Jewish democracy. Peri's 2006 volume depicts the security establishment as a threat to civilian rule, whereas Ziv, in his 2024 book, portrays waning political influence of the Israeli military and security services as associated with democratic backsliding. The authors each favor the two-state solution to the Israeli-Palestinian conflict but differ on whether opportunities for it have been missed because the military and security establishment has had too much or too little influence over government policy. Consideration of the one-state reality suggests the extent to which both arguments have been overtaken by events.
Trust at Scale: The Economic Limits of Cryptocurrencies and Blockchains
Authors: Budish Eric 
Published: October 2024

Abstract
Satoshi Nakamoto (2008) invented a new kind of economic system that does not need the support of government or rule of law. Trust and security instead arise from a combination of cryptography and economic incentives, all in a completely anonymous and decentralized system. This article shows that Nakamoto’s novel form of trust, while undeniably ingenious, is deeply economically limited. The core argument is three equations. A zero-profit condition on the quantity of honest blockchain “trust support” (work, stake, etc.) and an incentive-compatibility condition on the system’s security against majority attack (the Achilles heel of all forms of permissionless consensus) together imply an equilibrium constraint, which says that the “flow” cost of blockchain trust has to be large at all times relative to the benefits of attacking the system. This is extremely expensive relative to traditional forms of trust and scales linearly with the value of attack. In scenarios that represent Nakamoto trust becoming a more significant part of the global financial system, the cost of trust would exceed global GDP. Nakamoto trust would become more attractive if an attacker lost the stock value of their capital in addition to paying the flow cost of attack, but this requires either collapse of the system (hardly reassuring) or external support from rule of law. The key difference between Nakamoto trust and traditional trust grounded in rule of law and complementary sources, such as reputations, relationships, and collateral, is economies of scale: society or a firm pays a fixed cost to enjoy trust over a large quantity of economic activity at low or zero marginal cost.