bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fate of the downstream aorta after total arch replacement
Authors: Ikeno Yuki , Yokawa Koki , Yamanaka Katsuhiro , Inoue Takeshi , Tanaka Hiroshi , Okada Kenji , Okita Yutaka 
Published: September 2022

Abstract

OBJECTIVES
The goal of this study was to evaluate the fate of the downstream aorta following total arch replacement.

METHODS
Between October 1999 and March 2018, a total of 740 patients underwent total arch replacement. After excluding connective tissue disease, previous descending or thoracoabdominal aortic surgery, patients without adequate preoperative images or operative mortality, late outcomes consisting of additional surgery for distal dilation and distal aortic events were evaluated in 623 survivors (240 aortic dissections, including 139 patients with acute dissection and 383 with a non-dissection aneurysm). The mean follow-up was 5.0 ± 4.0 years.

RESULTS
The mean preoperative maximum diameter of the descending aorta was 36.9 ± 8.0 mm. An elephant trunk was inserted in 232 patients, including 183 patients with aortic dissection. Freedom from additional surgery for distal dilation was 88.5% at 5 years and 80.2% at 10 years. Freedom from distal aortic events was 81.9% at 5 years and 70.5% at 10 years. Multivariable regression analysis demonstrated that the preoperative diameter of the descending aorta was a significant risk factor for unfavourable distal aortic events. Computed tomography evaluation demonstrated a significant increase in the descending aortic diameter over time (P &lt; 0.001). Positive aortic remodelling was observed in the proximal descending (P &lt; 0.001) to mid-descending (P &lt; 0.001) aorta exclusively in patients with acute aortic dissection.

CONCLUSIONS
The diameter of the descending aorta increased significantly after total arch replacement, particularly in the distal descending aorta. The preoperative descending aortic diameter portended a significant risk for unfavourable distal aortic events.
Nonidentical function of Upc2A binding sites in the Candida glabrata CDR1 promoter
Authors: Vu Bao Gia , Moye-Rowley William Scott 
Published: September 2022

Abstract
Increased expression of the Candida glabrata CDR1 gene, encoding an ATP-binding cassette membrane transporter, is routinely observed in fluconazole-resistant isolates of this pathogenic yeast. CDR1 transcription has been well-documented to be due to activity of the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. Gain-of-function mutations in the gene encoding this factor are the most commonly observed cause of fluconazole hyper-resistance in clinical isolates. We have recently found that the sterol-responsive transcription factor Upc2A also acts to control CDR1 transcription, providing a direct link between ergosterol biosynthesis and expression of Pdr1 target genes. While this earlier work implicated Upc2A as an activator of CDR1 transcription, our further analyses revealed the presence of a second Upc2A binding site that negatively regulated CDR1 expression. This Upc2A binding site designated a sterol-responsive element (SRE) was found to have significant lower affinity for Upc2A DNA-binding than the previously described SRE. This new SRE was designated SRE2 while the original, positively acting site was named SRE1. A mutant version of SRE2 prevented in vitro DNA-binding by recombinant Upc2A and, when introduced into the CDR1 promoter, caused decreased fluconazole susceptibility and increased CDR1 expression. This negative effect caused by loss of SRE2 was shown to be Pdr1 independent, consistent with the presence of at least one additional activator of CDR1 transcription. The ability of Upc2A to exert either positive or negative effects on gene expression resembles behavior of mammalian nuclear receptor proteins and reveals an unexpectedly complex nature for SRE effects on gene regulation.
Effects of dietary protein content and crystalline amino acid supplementation patterns on growth performance, intestinal histomorphology, and immune response in weaned pigs raised under different sanitary conditions
Authors: Lee Jinyoung , González-Vega Jolie Caroline , Htoo John Kyaw , Yang Chengbo , Nyachoti Charles Martin 
Published: September 2022

AbstractThe aim of this experiment was to investigate the effects of dietary crude protein (CP) contents and crystalline amino acids (CAA) supplementation patterns on growth performance, intestinal histomorphology, and immune response in weaned pigs under clean (CSC) or unclean sanitary conditions (USC). A total of 144 weaned pigs (6.35 ± 0.63 kg body weight) were assigned to 6 treatments in a 3 × 2 factorial arrangement based on CP content and sanitary conditions using a randomized complete block design, giving 8 replicates per treatment with 3 pigs per pen. Pigs were fed one of three diets for 21 d: one high CP (HCP; 22%) and two low CP (LCP; 19%) diets supplemented with 9 indispensable AA or only 6 AA (Lys, Met, Thr, Trp, Val, and Ile) as CAA. The CSC room was washed weekly, whereas the USC room had sow manure spread in the pens and was not washed throughout the experiment. Body weight and feed disappearance were recorded weekly. Blood was sampled from 1 pig per pen weekly, and the same pig was euthanized for jejunal tissues sampling on day 21. Pigs raised under USC had reduced (P &lt; 0.05) average daily gain (ADG) and gain to feed ratio (G:F) in week 2, but contrary results that greater (P &lt; 0.05) ADG and G:F were found in pigs under USC in week 3. Overall, there was an interaction where G:F did not differ between HCP and LCP under CSC, however, LCP decreased (P &lt; 0.05) G:F compared to HCP under USC. Pigs fed the HCP diet had higher (P &lt; 0.05) fecal scores than those fed the LCP diets throughout the experiment. Pigs fed the LCP had higher (P &lt; 0.05) villus height to crypt depth ratio than those fed the HCP. An interaction was observed where goblet cell density in the jejunum was higher (P &lt; 0.05) in pigs fed LCP than HCP under CSC, but no difference was found between HCP and LCP under USC. Different CAA supplementation patterns did not influence both growth performance and histomorphology. Pigs raised under USC had greater (P &lt; 0.05) plasma interleukin (IL)-10 and IL-6 concentrations and reduced (P &lt; 0.05) plasma tumor necrosis factor-alpha concentration. Also, the LCP diets resulted in a greater (P &lt; 0.05) plasma IL-10 concentration. In conclusion, overall growth performance did not differ between HCP and LCP under CSC, but LCP diets reduced G:F under USC. Feeding LCP diets to weaned pigs improved gut morphology under USC and ameliorated systemic inflammation induced by USC, whereas CAA supplementation patterns did not affect growth performance and gut morphology.
How advances in animal efficiency and management have affected beef cattle’s water intensity in the United States: 1991 compared to 2019
Authors: Klopatek Sarah C , Oltjen James W 
Published: September 2022

Abstract
Updating the static model by Beckett and Oltjen (1993), we determined that from 1991 to 2019, U.S. beef cattle blue water consumption per kg of beef decreased by 37.6%. Total water use for the U.S. cattle herd decreased by 29%. As with the 1993 model, blue water use included direct water intake by animals, water applied for irrigation of crops that were consumed by beef cattle, water applied to irrigated pasture, and water used to process animals at marketing. Numbers of cattle, crop production, and irrigation data were used from USDA census and survey data. On 1 January 2019, a total of 31.7-million beef cows and 5.8-million replacement heifers were in U.S. breeding herds, and 26-million animals were fed annually. In total, the U.S. beef cattle herd (feedlot and cull cows) produced 7.7-billion kg of boneless beef, an increase of 10% since 1991. Beef cattle directly consumed 599-billion L of water per year. Feedlot cattle were fed various grain and roughage sources corresponding to the regions in which they were fed. Feeds produced in a state were preferentially used by cattle in that state with that state’s efficiency; any additional feedstuffs required used water at the national efficiency. Irrigation of crop feedstuffs for feedlot cattle required 5,920-billion L of water. Irrigated pasture for beef cattle production required an additional 4,121-billion L of water. Carcass processing required 91-billion L of water. The model estimated that in the U.S. 2,275 L of blue water was needed to produce 1 kg of boneless meat. As with the previous model, the current model was most sensitive to changes in the dressing percentage and the percentage of boneless yield in carcasses of feedlot cattle (62.8 and 65, respectively). In conclusion, with more beef, fewer cows, and lower rates of irrigation, beef cattle’s water intensity has decreased at an annual rate of 1.34% over a 28-yr period.
Invasive type B2 thymoma associated with myasthenia gravis, resection with superior vena cava reconstruction
Authors: Wilde Sawley A , Carroway William P , Hsu Diana S , Banks Kian C , Velotta Jeffrey B 
Published: September 2022

Abstract
After being diagnosed with myasthenia gravis, a 55-year-old male was referred for treatment of an invasive thymoma. Preoperative imaging revealed a thymoma adjacent to the superior vena cava (SVC) with possible invasion of the left innominate vein. After multidisciplinary discussion, he underwent upfront en bloc resection of the tumor with SVC resection and reconstruction. He was discharged after an uncomplicated postoperative course with improvement of his symptoms.
Evolutionary History and Strength of Selection Determine the Rate of Antibiotic Resistance Adaptation
Authors: Cisneros-Mayoral Sandra , Graña-Miraglia Lucía , Pérez-Morales Deyanira , Peña-Miller Rafael , Fuentes-Hernández Ayari 
Published: September 2022

Abstract
Bacterial adaptation to stressful environments often produces evolutionary constraints whereby increases in resistance are associated with reduced fitness in a different environment. The exploitation of this resistance-cost trade-off has been proposed as the basis of rational antimicrobial treatment strategies designed to limit the evolution of drug resistance in bacterial pathogens. Recent theoretical, laboratory, and clinical studies have shown that fluctuating selection can maintain drug efficacy and even restore drug susceptibility, but can also increase the rate of adaptation and promote cross-resistance to other antibiotics. In this paper, we combine mathematical modeling, experimental evolution, and whole-genome sequencing to follow evolutionary trajectories towards β-lactam resistance under fluctuating selective conditions. Our experimental model system consists of eight populations of Escherichia coli K12 evolving in parallel to a serial dilution protocol designed to dynamically control the strength of selection for resistance. We implemented adaptive ramps with mild and strong selection, resulting in evolved populations with similar levels of resistance, but with different evolutionary dynamics and diverging genotypic profiles. We found that mutations that emerged under strong selection are unstable in the absence of selection, in contrast to resistance mutations previously selected in the mild selection regime that were stably maintained in drug-free environments and positively selected for when antibiotics were reintroduced. Altogether, our population dynamics model and the phenotypic and genomic analysis of the evolved populations show that the rate of resistance adaptation is contingent upon the strength of selection, but also on evolutionary constraints imposed by prior drug exposures.
PL01.4.A The relationship between neuronal activity and functional network properties in glioma patients
Authors: Zimmermann M L M , Breedt L C , Centeno E G Z , Kulik S D , Santos F A N , Stam C J , van Lingen M R , Hillebrand A , Douw L 
Published: September 2022

Abstract

Background
Glioma is associated with pathologically high neuronal activity around the tumor, which associates with faster tumor progression in patients. Concurrently, patients with glioma have local and widespread disturbances of the functional brain network as measured with magnetoencephalography (MEG) such as higher network clustering (the extent to which regions connected to a particular area are also connected to each other) and locally altered integrative connectivity (for instance assessed with a centrality measure). How local neuronal activity and nodal network properties relate to each other has yet to be investigated.

Material and Methods
We obtained eyes-closed resting-state MEG in 95 glioma patients before tumor resection and 57 matched healthy controls (HC). Broadband power (BBP, 0.5-48Hz) was used as a proxy for neuronal activity. The local clustering coefficient (CC) and eigenvector centrality (EC) were calculated for the functional network in the lower frequency bands (delta, theta, alpha). We compared averaged nodal network properties and local BBP between peritumoral (regions partially overlapping with the tumor) and contralateral homologue regions in patients and compared these to averaged values in HC. Linear mixed models were used to relate nodal CC and EC to local BBP. Results were corrected for multiple comparisons and deemed significant at alpha 0.05.

Results
The peritumoral area was significantly more active than the non-peritumoral homologue in patients, and showed pathologically higher activity in comparison to HCs. Pathologically high neuronal activity was restricted to the peritumoral areas and not found in the contralateral homologue. However, patients’ functional network was disturbed throughout the brain in terms of pathologically high clustering, but not with regards to centrality. Whereas high activity related to high centrality in HCs and patients alike, high activity seemed to relate to low clustering in homologue regions in patients but not HCs, potentially indicating that lower neuronal activity relates to pathologically high clustering in these patients.

Conclusion
Glioma patients show pathologically high brain activity around the tumor and whole-brain disturbances in local network clustering, while integrative connectivity is preserved. We also find that the relationship between neuronal activity and functional network properties is complex in these patients, further underlining the importance of investigating how local activity may impact global network topology in order to understand how neuron-glioma interactions shape brain functioning.
PL01.6.A Radiomics outperforms semantic features for prediction of response to stereotactic radiosurgery in brain metastases
Authors: Gutsche R , Lohmann P , Hoevels M , Ruess D , Galldiks N , Visser-Vandewalle V , Treuer H , Ruge M I , Kocher M 
Published: September 2022

Abstract

Background
Brain metastases show different patterns of contrast enhancement, potentially reflecting hypoxic and necrotic tumor regions with reduced radiosensitivity. An objective evaluation of these patterns might allow a prediction of response to radiotherapy. We therefore investigated the potential of MRI radiomics in comparison with the visual assessment of semantic features to predict early response to stereotactic radiosurgery in patients with brain metastases.

Material and Methods
In this retrospective study, 150 patients with 308 brain metastases from solid tumors (NSCLC in 53% of patients) treated by stereotactic radiosurgery (single dose of 17-20 Gy) were evaluated. The response of each metastasis (partial or complete remission vs. stabilization or progression) was assessed within 180 days after radiosurgery. Patterns of contrast enhancement in the pre-treatment T1-weighted MR images were either visually classified (homogenous, heterogeneous, necrotic ring-like) or subjected to a radiomics analysis. Random forest models were optimized by cross-validation and evaluated in a hold-out test data set (30% of metastases).

Results
In total, 221/308 metastases (72%) responded to radiosurgery. The optimal radiomics model comprised 10 features and outperformed the model solely based on semantic features in the test data set (AUC, 0.71 vs. 0.56; accuracy, 69% vs. 54%). The diagnostic performance could be further improved by combining semantic and radiomics features resulting in an AUC of 0.74 and an accuracy of 75% in the test data set.

Conclusion
The developed radiomics model allowed prediction of early response to radiosurgery in patients with brain metastases and outperformed the visual assessment of patterns of contrast enhancement.
PL02.3.A Survival and T-cell tumor reactivity in patients treated with nivolumab and bevacizumab for recurrent glioblastoma in the clinical trial CA209-9UP
Authors: Maarup S , Skadborg S , Draghi A , Borch A , Hasselbalch B , Yde C , Svane I , Hadrup S , Christensen I , Law I , Skjoeth-Rasmussen J , Scheie D , Skovgaard Poulsen H , Lassen U 
Published: September 2022

Abstract

Background
Glioblastoma (GBM) is an aggressive brain tumor with a median survival of 14.6 months. We have no standard treatment for relapse and current treatment options have limited effect. Novel treatments are necessary to improve survival and quality of life.

Material and Methods
We present data from; a phase II open label, two-armed clinical trial studying nivolumab and bevacizumab in treatment of recurrent GBM, with progression after Stupp’s regime. Patients were included in two arms depending on the possibility of salvage neurosurgical resection. All patients had biopsies for genome sequencing at primary tumor and recurrence. Both arms received nivolumab and bevacizumab administrated every second week and the surgical arm also received neoadjuvant nivolumab 7 days prior to surgery. Fresh tissue samples were collected for tumor digest, TILs (tumor infiltrating lymphocytes) for phenotype exploration and intracellular staining to test reactivity. Patients were treated until progression, death, or intolerable side effects. Toxicity screens were reported, and follow-up ended in Marts 2022.

Results
Forty-four patients were included from November 2018 to January 2022; 20 in each arm (four screen-failures). Treatment was overall well tolerated. Median (m) age at inclusion was 57,5 years (arm A) and 50,5 years (arm B), and the groups had an even distribution. The surgical and non-surgical arm had an mPFS of 5.95 and 3.83 months respectively, while the mOS was 13.96 months and 6.77 months, respectively. Multivariate analysis was performed by variables such us steroid, MGMT, gender, age at diagnosis, resection extent and arm. Steroid at inclusion was a significant negative predictor of outcome (p = 0.0378). Controls from our GBM registry (N=140), which were treated with neurosurgical resection and then bevazicumab and irinotecan in recurrent setting had an mOS of 8.64 months (log-rank p=0.0181).Furthermore, reactive tumor infiltrating lymphocytes (TIL) were detected in four of the patients who presented with a longer mOS and mPFS of 16.75 months and 9.18 months, while the 16 patients without TIL reactivity had mOS and mPFS of 12.63 months and 5.13 months, respectively (not significant).

Conclusion
We found an increased mOS in patients treated with nivolumab and bevacizumab at recurrence, compared to our controls: 13.96 months and 8.64 months, respectively. Four patients with T-cell reactivity towards tumor cells showed an even longer mPFS and mOS. Though not significant, these results warrant further research evaluation in larger patient cohorts. We are currently investigating proteomics and sequencing data to identify predictive biomarkers.
KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study
Authors: Ho V K Y , Anten M M , Garst A , Bos E M , Snijders T J , Eekers D B P , Seute T 
Published: September 2022

Abstract

Background
Meningiomas are the most common primary tumours of the central nervous system. As the majority of meningiomas are benign, initial management often consists of observation only. Consequently, estimates on meningioma incidence are generally considered too low, with many registries mainly depending on pathology notifications. With additional notification sources, this study provides more complete population-based estimates on the incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands.

Material and Methods
Data on patients diagnosed with meningioma during 2000-2019 were obtained from the Netherlands Cancer Registry (NCR), which was expanded to the Dutch Brain Tumour Registry (DBTR) for meningiomas as of 2016. In addition to histological confirmations, the NCR/DBTR receives case notifications from hospital administrative registrations on cost reimbursement and outpatient care. In addition, a data linkage was performed with a clinical database maintained by one of the Dutch neuro-oncology centres to evaluate local completeness of the NCR/DBTR. Time trends of the age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar-Perme estimator.

Results
From 2000 to 2019, a total of 22,605 cases of meningioma were registered; 11,423 (50.5%) were histologically confirmed, while 11,182 (49.5%) had a radiological diagnosis. Over time, incidence increased from 4.7 per 100,000 inhabitants (European Standardized Rate, ESR) to 10.7 (EAPC 4.6%, p&lt;0.01); the incidence of radiological diagnosis increased from 1.2 to 6.9 per 100,000 ESR (EAPC 9.6%, p&lt;0.01). Local data completeness was estimated at 98% for histologically confirmed meningiomas and 87% for radiological diagnoses. On the basis of these incidence estimates, the prevalence of meningioma is estimated at 105/100,000 on January 1st of 2020, with over 17,500 individuals having had a diagnosis of meningioma at that moment. Relative survival rate at 5 years for grade I meningiomas was 94.8% (95%-confidence interval: 94.0%-95.4%), 84.0% (95%CI: 81.0%-86.5%) for grade II meningiomas, and 47.3% (95%CI: 38.2%-55.8%) for grade III meningiomas.

Conclusion
As the incidence estimates in this study may be considered most complete, the results obtained should approximate the true incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands.