bluuebunny/crossref_metadata_2025_split huggingface dataset:
P18.02.B Influence of preoperative embolization on intraoperative parameters, hospital stay and neurocognitive outcome compared to surgery alone
Authors: Pedersen M , Eibl T , Nania A , Voit-Höhne H , Schrey M , Steiner H , Holtmannspötter M 
Published: September 2022

Abstract

Background
Preoperative embolization of meningiomas is used to reduce intraoperative blood loss and facilitate resection. So far, a risk-benefit stratification of this additional intervention on the neurocognitive outcome is missing. This study investigates the influence of preoperative embolization with liquid Embolisate on intraoperative parameters, length of hospital stays and functional outcome.

Material and Methods
Patients treated for intracranial meningiomas at a single center between January 2019 and June 2021 were reviewed in a retrospective matched-pair analysis. Patients were matched to group A (tumor resected) and group B (preoperatively embolized and tumor resected after 2,27 ± 3,05 days). Matching criteria were tumor diameter and location (convexity, falx cerebri or skull base, frontal, parietal, occipital, temporal). Data collection included MRI (location, tumor- and necrosis volume, edema, complications), DSA (tumor blush, arterial supply), medical history, histological, surgical, clinical course, complications, and haematological parameters, as well as neurocognitive symptoms on admission and discharge from hospital.

Results
44 patients with intracranial Meningiomas were included, divides into 2 groups, each encompassing 22 patients (mean age 62,41 years, 40,5% female). The matching criteria tumor diameter (64.21 vs. 63.55 mm, p=0.725) and tumor localisation (p=0.381) showed no significant differences. There were no significant differences in postoperative hospital stay (14.41 ± 9.5 vs. 14.25 ± 16.88 days, p=0.814) and in preoperative perifocal oedema (82% vs. 82%, p=0.397). Preoperative embolization was associated with decreased intraoperative tumor bleeding (67% vs. 14%, p=0.001, PHI= 0.534), longer duration of surgery (4:58 ± 2:44 vs. 06:07 ± 03:00 hours, p=0.037), trend for decrease in perifocal oedema (p=0.052, PHI=0,498), neurocognitive improvement on discharge from hospital (23% vs. 86%, p=0.045, PHI=0.339) and decreased of epileptic seizures (preoperative 18% vs. 18% and postoperative 23% vs. 5%). There was no increase in cumulative complication rate (p=1.0) and no long-term neurocognitive impairments associated with embolization.

Conclusion
This study suggests that preoperative embolization of intracranial meningiomas significantly decreased intraoperative tumor blood loss but is also associated to an improvement on neurocognitive abilities compared to surgery alone. Importantly, complication rate is not increased. In the future, larger studies and perhaps a randomised control trial might be of value in corroborating these findings. Furthermore, the neurocognitive symptoms should be assessed in a standardised examination form, qualitative parameters such as bleeding tendency should be supplemented by quantifiable parameters, e.g., blood loss in ml.
P18.04.A Cay10603, HDAC6 inhibitor, enhances radiosensitivity in meningioma via supressing the nuclear beta-catenin accumulation
Authors: Na J , Laney R , Hanemann C 
Published: September 2022

Abstract

Background
Meningioma is the most frequent primary central nervous system tumour (PCNST) which account ca 36% of all PCNST. Due to the lack of efficient chemotherapy for meningioma, radiotherapy often become a first-line treatment especially when the tumour is not operable. Radiotherapy plays a crucial role in local control but its efficacy is restricted by radioresistance and by normal tissue radiation tolerance. Therefore, developing and evaluating potential radiosensitisers to enhance therapeutic efficacy are needed.Histone deacetylase (HDACs) expression is generally increased in many cancer types and regulate the expression of numerous proteins involved in tumorigenesis. Targeting HDAC using HDAC inhibitor (HDACi) represent promising radiosensitisers that affect various biological processes, such as cell survival, apoptosis, and DNA repair.

Material and Methods
We investigated whether pre-treatment with the hydroxamate-based HDAC6 inhibitor, Cay10603, impacts radiation-induced DNA double-strand break (DSB) induction, cell survival, cell cycle arrest, and cell death using immunocytochemistry, clonogenic assay, and flow cytometry in meningioma cell lines. Low concentration (100 nM) of Cay10603 was treated 24 hr prior to high energy x-ray irradiation (2 Gy) by a medical linear accelerator (LINAC). To investigate the nuclear localisation of beta-catenin, subcellular fractionation and Western Blotting were conducted.

Results
We found that tumour cells survival was synergistically decreased after combination treatment of Cay10603 and radiation. Combination therapy induced DNA damage with activation of histone gH2AX and increased G2/M arrest compared to drug or radiation alone. Both apoptotic and necrotic cell death were increased after combination therapy. To focus on the mechanisms of action of HDAC6 inhibition followed by radiation, we further investigated nuclear localisation of beta-catenin levels. The results showed the both beta-catenin and c-myc expression in the nucleus was suppressed after combination therapy.

Conclusion
In meningioma cells, radiotherapy in combination with HDAC6 inhibitor reduces the nuclear localisation of beta-catenin and synergistically decreases cell survival. Our findings demonstrate a potential therapeutic strategy of Cay10603 to improve the radiosensitisation for meningioma cells.
P18.05.A Bevacizumab in atypical and anaplastic meningiomas: the BEMEN study
Authors: Cerretti G , Bosio A , Maccari M , Padovan M , Caccese M , Zagonel V , Lombardi G 
Published: September 2022

Abstract

Background
meningiomas are the most frequent primary brain tumours. The current standard treatment for atypical and anaplastic meningioma can include surgical resection and radiotherapy. Despite the high rate of relapse no systemic treatment is indicated. Few data are available regarding the effectiveness of bevacizumab (BEV) in this setting. We performed a retrospective analysis investigating the efficacy and safety of BEV in meningioma patients relapsed after receiving surgery and radiotherapy. Gene mutations were also collected

Material and Methods
we retrospectively analyzed patients treated with off-label BEV at the Veneto Institute of Oncology from July 2019 to February 2022. Major inclusion criteria were histologically-confirmed diagnosis of grade 2-3 meningioma (according to WHO 2016 classification), previous treatment with surgery and radiotherapy, no indication to further surgical reintervention or reirradiation, absence of major contraindications to the use of BEV. Data were estrapolated from local clinical records. Bevacizumab was administered at 10 or 5mg/Kg every 2 weeks (at physician’s discretion) until progressive disease/death or unacceptable toxicity. Kaplan-Meier curves were used to estimate the survival rate; CTCAE v 5.0 was used to estimate treatment-related toxicities; RANO criteria were used for radiological assessment; NGS Foundation One panel was used to examine molecular data

Results
the median follow up was 13 months (3-30 range). 26 patients were enrolled. Median age was 68 ys (29-84); male pts were 16 (61%); 61% (16 pts) with atypical meningioma, 38.5% (10 pts) with anaplastic meningioma; 27% (7 pts) had underwent 2 or more surgeries; 58% had had 2 or more RT treatments; 96.1% (25 pts) received &lt;2 previous lines of systemic treatment. 77% (20 pts) and 23% (6) received BEV 10 and 5mg/Kg every 2 weeks, respectively. For 61% of patients (16 pts), NGS analyses were available; 62% (10 pts) harboured NF2 mutations (1 patient had a confirmed diagnosis of neurofibromatosis type 2), 23% (6 pts) CDKN2A/2B deletion, 11% (3 pts) PTEN mutation, 8% (2 pts) FGFR mutation, 8% (2 pts) JAK alteration. Overall survival (OS) rate was 82% and 62% at 6 and 12 months respectively; 6 months PFS rate was 83%. 4 patients showed PR, 11 SD, 6 PD, no patient had CR; 5 patients were not evaluable for response. Among evaluable patients the disease control rate (stability+response) was 71% and the objective response rate was 19%. Median PFS and OS were not reached19% (5 pts) experienced CTCAE grade 1 or 2 toxicity, mainly hypertension (4 pts); 1 patient experienced grade 3 hypertension.

Conclusion
BEV showed very promising activity in recurrent grade 2-3 meningioma. The treatment was well tolerated. BEV should be considered an optimal therapeutic option in this setting of meningioma patients. The NGS results might be useful in identifying targetable mutations in case of further recurrence
PHYTOCHROME-INTERACTING FACTOR 4/HEMERA-mediated thermosensory growth requires the Mediator subunit MED14
Authors: Bajracharya Abhishesh , Xi Jing , Grace Karlie F , Bayer Eden E , Grant Chloe A , Clutton Caroline H , Baerson Scott R , Agarwal Ameeta K , Qiu Yongjian 
Published: September 2022

Abstract
While moderately elevated ambient temperatures do not trigger stress responses in plants, they do substantially stimulate the growth of specific organs through a process known as thermomorphogenesis. The basic helix–loop–helix transcription factor PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) plays a central role in regulating thermomorphogenetic hypocotyl elongation in various plant species, including Arabidopsis (Arabidopsis thaliana). Although it is well known that PIF4 and its co-activator HEMERA (HMR) promote plant thermosensory growth by activating genes involved in the biosynthesis and signaling of the phytohormone auxin, the detailed molecular mechanism of such transcriptional activation is not clear. In this report, we investigated the role of the Mediator complex in the PIF4/HMR-mediated thermoresponsive gene expression. Through the characterization of various mutants of the Mediator complex, a tail subunit named MED14 was identified as an essential factor for thermomorphogenetic hypocotyl growth. MED14 was required for the thermal induction of PIF4 target genes but had a marginal effect on the levels of PIF4 and HMR. Further transcriptomic analyses confirmed that the expression of numerous PIF4/HMR-dependent, auxin-related genes required MED14 at warm temperatures. Moreover, PIF4 and HMR physically interacted with MED14 and both were indispensable for the association of MED14 with the promoters of these thermoresponsive genes. While PIF4 did not regulate MED14 levels, HMR was required for the transcript abundance of MED14. Taken together, these results unveil an important thermomorphogenetic mechanism, in which PIF4 and HMR recruit the Mediator complex to activate auxin-related growth-promoting genes when plants sense moderate increases in ambient temperature.
Studies on Gamma Dose Rates in Outdoor Environment and Assessment of External Exposure to Public in Stepnogorsk Area, Northern Kazakhstan
Authors: Ibrayeva Danara , Ilbekova Kuralay , Aumalikova Moldir , Kazymbet Polat , Zhumadilov Kassym , Bakhtin Meirat , Hoshi Masaharu 
Published: September 2022

Abstract
The present study is based on a pilot study, which showed that the Stepnogorsk area of Northern Kazakhstan represents sources of potential contamination of the living environment. The aim of the study was measurement of outdoor gamma radiation levels, activity concentration in soil samples and assessment of external exposure to the public. According to our analysis, the highest ${\boldsymbol{H}}^{\ast}$(10) values ∼2870 nGy h−1 were detected in the Aqsu school territory, which were slightly higher than the control readings for this region. The average 226Ra, 232Th and 40K activities were 617.8 ± 3.2 Bq kg−1, 188.3 ± 2.9 Bq kg−1 and 731.5 ± 6.2 Bq kg−1, respectively. The annual effective dose received by the Aqsu population ranged from 0.08 to 3.5 mSv y−1, which was found higher by an order of magnitude than the upper annual dose limit. Changes in radiation background are an unfavourable factor for the population and may possibly become potential radiation risks for long-term effects.
Exosome from BMMSC Attenuates Cardiopulmonary Bypass-Induced Acute Lung Injury Via YAP/β-Catenin Pathway: Downregulation of Pyroptosis
Authors: Zhang Taoyuan , Lu Linhe , Li Man , Zhang Ding , Yu Peng , Zhang Xinhao , Zhang Zheng , Lei Chong 
Published: September 2022

Abstract
Acute lung injury (ALI) accompanied with systemic inflammatory response is an important complication after cardiopulmonary bypass (CPB). Pyroptosis, which is induced by the secretion of inflammatory factors, has been implicated in ALI. However, recent studies have suggested that bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exo) can ameliorate ALI, but the mechanism is poorly understood. Therefore, we aim to examine the effects of BMMSC-Exo in CPB-induced ALI, and its underlying mechanism. CPB rat models (male Sprague-Dawley rats) were administered BMMSC-Exo intravenously before induction of ALI. Lung tissue, bronchoalveolar lavage fluid (BALF), and alveolar macrophage (AM) were collected after the treatments for further analysis, and rat AM NR8383 cells were used for in vitro study. HE staining was performed to detect macrophage infiltration. Western blot was used to detect related proteins expression. And ELISA assay was performed to investigate secretion of inflammatory factors. These results showed that BMMSC-Exo treatment ameliorated macrophage infiltration and oxidative stress, and downregulated expression of pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and GSDMD-N, in the lung tissue and AM, as well as decreased the secretion of IL-18 and IL-1β in BALF. Moreover, BMMSC-Exo activated YAP/β-catenin signaling pathway. Overall, these findings of this study indicated that BMMSC-Exo suppressed CPB-induced pyroptosis in ALI by activating YAP/β-catenin axis, which could be a novel strategy for lung protection during CPB.
Adalimumab versus ustekinumab as first-line biological in moderate-to-severe Crohn’s disease: real-life cohort from a tertiary referral center
Authors: Moens Annick , Alsoud Dahham , Verstockt Bram , Sabino João , Ferrante Marc , Vermeire Séverine 
Published: September 2022

Background
Therapeutic options for Crohn’s disease are growing, making the choice of first-line therapy relevant. Both adalimumab and ustekinumab are effective in moderate-to-severe Crohn’s disease. The Safety and Efficacy of Adalimumab Versus Ustekinumab for One Year trial suggested no difference in clinical or endoscopic remission at week 52 in biological-naive Crohn’s disease patients. We explored if results withstand in the real world.

Methods
We included bio-naive Crohn’s disease patients starting adalimumab or ustekinumab between 2017 and 2020. Patients had endoscopy-proven moderate-to-severe disease [Simple Endoscopic Score for Crohn’s disease (SES-CD) ≥3]. Clinical remission was defined as Harvey Bradshaw Index (HBI) <5 or physician global assessment. Endoscopic remission (SES-CD <3) and improvement (≥50% reduction in SES-CD from baseline) were assessed at W26-52. Propensity score matching was used.

Results
A total of 68 biological-naive Crohn’s disease patients were included (32 adalimumab and 32 ustekinumab) and followed for median of (IQR) 60 (33–104) weeks. Patients had significantly higher odds of achieving endoscopic remission with adalimumab than ustekinumab [adjusted odds ratio (aOR), 2.73; confidence interval (CI), 1.12–7.36; P = 0.03]. Also, more adalimumab-treated patients achieved endoscopic response, clinical remission at week 26 and 52 (aOR, 2.24; CI, 0.94–5.71; P = 0.07; aOR, 1.26; CI, 0.36–4.51; P = 0.72; aOR, 1.58; CI, 0.54–4.88; P = 0.41, respectively). Treatment persistence was not different between groups (P = 0.44). The number of adverse events was similar.

Conclusion
In a real-world cohort of biological-naive Crohn’s disease patients, adalimumab was superior to ustekinumab in achieving endoscopic remission. No differences in clinical remission at W26-52 or treatment persistence were observed. Both adalimumab and ustekinumab remain good options as first-line biologicals in moderate-to-severe Crohn’s disease.
Endoscopic submucosal dissection: a country dissemination experience and outcomes
Authors: Rodríguez-Carrasco Marta , Libânio Diogo , Pimentel-Nunes Pedro , Barreiro Pedro , Ferreira Anibal , Küttner-Magalhães Ricardo , Pinho Rolando , Boal Carvalho Pedro , Areia Miguel , Lage Jorge , Serrano Miguel , Silva João , Dias-Pereira António , Carvalho Laura , Cadime Ana Teresa , Cotter José , Carvalho João , Pedroto Isabel , Gonçalves Raquel , Chagas Cristina , Dinis-Ribeiro Mário 
Published: September 2022

Objective
An increasing use of endoscopic submucosal dissection (ESD) has been reported in Western countries, although some differences in training schemes and outcomes have been described. We aimed to report the training model, implementation, and outcomes of ESD in Portugal.

Methods
All endoscopists trained at our center from our country (n = 9) were invited to a survey regarding: (a) training period; (b) ESD outcomes and (c) implementation of ESD in each respective center.

Results
All endoscopists completed the survey. Learning ESD was centered on human ESD assistance in a high-volume center during a median time of 6 months and complemented mainly by hands-on courses (89%). During the surveyed period, a total of 1229 ESD were performed, mostly in gastric locations (74%). Median complete R0 and curative resection rate were 92% (IQR, 81–96.8) and 87% (IQR, 74–93.3), respectively, and median perforation rate was 0.89% (IQR, 0.25–6.22). The main limitations encountered during the implementation of ESD were related to the lack of initial mentoring or insufficient expertise to progress to more difficult lesions.

Conclusion
Learning ESD through participation in hands-on courses and visiting high-volume centers seems to be adequate to achieve a good competence at the initial stage of ESD, which in fact is in consonance with the European Society of Gastrointestinal Endoscopy recommendations. However, mentoring is essential for technical progression, and this represents the fundamental barrier during the adoption of ESD, which may be overcome by increasing hands-on training in animal or artificial simulators, but preferably with the implementation of a structured training program.
High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus
Authors: Yibirin Marcel , Hosry Jeff , Yepez Guevara Eduardo , Granwehr Bruno P. , Jiang Ying , Mustafayev Khalis , Angelidakis Georgios , Torres Harrys A. 
Published: September 2022

Objective
There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection.

Methods
Patients treated with DAAs at our center during 2014–2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed.

Results
We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86–99%) for the entire study cohort, 100% [17/17; 95% CI: 82–100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79–98%] for the patients treated with LDV/SOF. Fisher’s exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3–4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred.

Conclusion
Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.
Jack of all trades: genome assembly of Wild Jack and comparative genomics of Artocarpus
Authors: Patil Ajinkya Bharatraj , Vajja Sai Samhitha , Raghavendra S. , Satish B.N. , Kushalappa C.G. , Vijay Nagarjun 
Published: September 2022

AbstractKnown as breadfruits for their diverse nutritious fruits, the Artocarpus (Moraceae) genus is prized for its high-quality timber, medicinal value, and economic importance. Breadfruits are native to Southeast Asia but have been introduced to other continents. The most commonly cultivated species areArtocarpus heterophyllus(Jackfruit) andArtocarpus altilis(Breadfruit). With numerous smaller but nutritionally comparable fruits on a large tree,Artocarpus hirsutus, also called “Wild jack” or “Ayani” is an elusive forest species endemic to Indian Western Ghats. In this study, we sequenced and assembled the whole genome ofArtocarpus hirsutussampled from sacred groves of Coorg, India. We compared our Wild jack genome with previously published Jackfruit and Breadfruit genomes to decipher demography and evolution. Demographic history reconstruction indicates a stronger effect of habitat rather than phylogeny on the population histories of these plants. Repetitive genomic regions, especially LTR Copia, strongly affected the demographic trajectory ofA. heterophyllus. Upon further investigation, we found a recent lineage-specific accumulation of LTR Copia inA. heterophyllus, which results in its larger genome size. Gene family evolution and signatures of selection identified multiple genes from starch, sucrose metabolism, plant hormone signal transduction, etc., inArtocarpusspecies. Our comparative genomic framework provides important insights by incorporating endemic species such as the Wild jack.
Predictive neural representations of naturalistic dynamic input
Authors: de Vries Ingmar E.J. , Wurm Moritz F. 
Published: September 2022

AbstractAdaptive behavior such as social interaction requires our brain to predict unfolding external dynamics. While theories assume such dynamic prediction, empirical evidence is limited to static snapshots and indirect consequences of predictions. We present a dynamic extension to representational similarity analysis that uses temporally variable models to capture neural representations of unfolding events. We applied this approach to source-reconstructed magnetoencephalography (MEG) data of healthy human subjects and demonstrate both lagged and predictive neural representations of observed actions. Predictive representations exhibit a hierarchical pattern, such that high-level abstract stimulus features are predicted earlier in time, while low-level visual features are predicted closer in time to the actual sensory input. By quantifying the temporal forecast window of the brain, this approach allows investigating predictive processing of our dynamic world. It can be applied to other naturalistic stimuli (e.g., film, soundscapes, music, motor planning/execution, social interaction) and any biosignal with high temporal resolution.