bluuebunny/crossref_metadata_2025_split huggingface dataset:
A category-selective semantic memory deficit for animate objects in semantic variant primary progressive aphasia
Authors: Henderson Shalom K , Dev Sheena I , Ezzo Rania , Quimby Megan , Wong Bonnie , Brickhouse Michael , Hochberg Daisy , Touroutoglou Alexandra , Dickerson Bradford C , Cordella Claire , Collins Jessica A 
Published: September 2021

Abstract
Data are mixed on whether patients with semantic variant primary progressive aphasia exhibit a category-selective semantic deficit for animate objects. Moreover, there is little consensus regarding the neural substrates of this category-selective semantic deficit, though prior literature has suggested that the perirhinal cortex and the lateral posterior fusiform gyrus may support semantic memory functions important for processing animate objects. In this study, we investigated whether patients with semantic variant primary progressive aphasia exhibited a category-selective semantic deficit for animate objects in a word-picture matching task, controlling for psycholinguistic features of the stimuli, including frequency, familiarity, typicality and age of acquisition. We investigated the neural bases of this category selectivity by examining its relationship with cortical atrophy in two primary regions of interest: bilateral perirhinal cortex and lateral posterior fusiform gyri. We analysed data from 20 patients with semantic variant primary progressive aphasia (mean age = 64 years, S.D. = 6.94). For each participant, we calculated an animacy index score to denote the magnitude of the category-selective semantic deficit for animate objects. Multivariate regression analysis revealed a main effect of animacy (β = 0.52, t = 4.03, P &lt; 0.001) even after including all psycholinguistic variables in the model, such that animate objects were less likely to be identified correctly relative to inanimate objects. Inspection of each individual patient’s data indicated the presence of a disproportionate impairment in animate objects in most patients. A linear regression analysis revealed a relationship between the right perirhinal cortex thickness and animacy index scores (β = −0.57, t = −2.74, P = 0.015) such that patients who were more disproportionally impaired for animate relative to inanimate objects exhibited thinner right perirhinal cortex. A vertex-wise general linear model analysis restricted to the temporal lobes revealed additional associations between positive animacy index scores (i.e. a disproportionately poorer performance on animate objects) and cortical atrophy in the right perirhinal and entorhinal cortex, superior, middle, and inferior temporal gyri, and the anterior fusiform gyrus, as well as the left anterior fusiform gyrus. Taken together, our results indicate that a category-selective semantic deficit for animate objects is a characteristic feature of semantic variant primary progressive aphasia that is detectable in most individuals. Our imaging findings provide further support for the role of the right perirhinal cortex and other temporal lobe regions in the semantic processing of animate objects.
The 3-Extra Connectivity of the Data Center Network BCube
Authors: Yi Yi , Fan Jianxi , Cheng Baolei , Wang Yan , Yu Jia 
Published: September 2021

Abstract
Connectivity is a significant metric to assess the fault tolerance of a network. For a faulty vertex set $H$, the $h$-extra connectivity is defined under the assumption that every component of the network removing $H$ has at least $h+1$ fault-free vertices. Compared to the traditional connectivity, which is defined under the assumption that the network removing $H$ is disconnected or trivial, the $h$-extra connectivity can better reflect the true fault tolerance of the network. The $BCube$ is an important server-centric data center network; it has good fault tolerance and scalability. In this paper, our research focuses on the logical structure of $BCube$, named $BC_{n,k}$, which is actually a specific type of generalized hypercubes. We prove that the 3-extra connectivity of $BC_{n,k}$ is $4(k+1)(n-1)-4n$ for $k\geq 4$ and $n\geq 4$.
Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model
Authors: Nyns Emile C A , Jin Tianyi , Fontes Magda S , van den Heuvel Titus , Portero Vincent , Ramsey Catilin , Bart Cindy I , Zeppenfeld Katja , Schalij Martin J , van Brakel Thomas J , Ramkisoensing Arti A , Zhang Guoqi , Poelma René H , Ördög Balazs , de Vries Antoine A F , Pijnappels Daniël A 
Published: September 2021

Abstract

Aims
Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination.

Methods and results
In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8–10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination.

Conclusion
Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.
Heart transplantation in the era of COVID-19 pandemic: delirium, post-transplant depression, and visitor restrictions; the role of liaison and inpatient psychosomatic treatment—a case report
Authors: Sadlonova Monika , Gerecke Birgit , Herrmann-Lingen Christoph , Kutschka Ingo 
Published: September 2021

AbstractBackgroundHeart transplant recipients show a high risk of developing major depression with an increased risk of post-transplant morbidity and mortality. Heart transplant specialists and patients face unprecedented challenges during the COVID-19 pandemic, which have enormous clinical implications such as the increased risk of COVID-19 as well as visitor restrictions with social isolation during the post-transplant inpatient treatment.Case summaryWe present a case of a 64-year-old woman with end-stage heart failure caused by non-compaction cardiomyopathy who received an orthotopic heart transplant (OHT) without any intra-operative complications. Post-operatively, she showed acute psychotic symptoms in the intensive care unit (ICU) with improvement after switching intravenous tacrolimus treatment to an oral intake. Furthermore, the patient developed severe depressive symptoms with malnutrition and had a prolonged hospitalization. Standard medical care was complemented by intensive psychocardiological treatment to overcome the crisis.ConclusionHigh complexity of the post-transplant management after OHT underlines the importance of multidisciplinary teamwork, involving heart transplant specialists and allied mental health professionals. This collaboration led to an excellent long-term result. Facing the COVID-19 pandemic, the hospital visitor policies may be scrutinized, carefully looking at the role of social isolation, post-operative experience in the ICU, and medical complications after OHT.
DeePhage: distinguishing virulent and temperate phage-derived sequences in metavirome data with a deep learning approach
Authors: Wu Shufang , Fang Zhencheng , Tan Jie , Li Mo , Wang Chunhui , Guo Qian , Xu Congmin , Jiang Xiaoqing , Zhu Huaiqiu 
Published: September 2021

Abstract

Background
Prokaryotic viruses referred to as phages can be divided into virulent and temperate phages. Distinguishing virulent and temperate phage–derived sequences in metavirome data is important for elucidating their different roles in interactions with bacterial hosts and regulation of microbial communities. However, there is no experimental or computational approach to effectively classify their sequences in culture-independent metavirome. We present a new computational method, DeePhage, which can directly and rapidly judge each read or contig as a virulent or temperate phage–derived fragment.

Findings
DeePhage uses a “one-hot” encoding form to represent DNA sequences in detail. Sequence signatures are detected via a convolutional neural network to obtain valuable local features. The accuracy of DeePhage on 5-fold cross-validation reaches as high as 89%, nearly 10% and 30% higher than that of 2 similar tools, PhagePred and PHACTS. On real metavirome, DeePhage correctly predicts the highest proportion of contigs when using BLAST as annotation, without apparent preferences. Besides, DeePhage reduces running time vs PhagePred and PHACTS by 245 and 810 times, respectively, under the same computational configuration. By direct detection of the temperate viral fragments from metagenome and metavirome, we furthermore propose a new strategy to explore phage transformations in the microbial community. The ability to detect such transformations provides us a new insight into the potential treatment for human disease.

Conclusions
DeePhage is a novel tool developed to rapidly and efficiently identify 2 kinds of phage fragments especially for metagenomics analysis. DeePhage is freely available via http://cqb.pku.edu.cn/ZhuLab/DeePhage or https://github.com/shufangwu/DeePhage.
Radiological and clinical features of screening-detected pulmonary invasive mucinous adenocarcinoma
Authors: Kim Dae Hyeon , Bae So Young , Na Kwon Joong , Park Samina , Park In Kyu , Kang Chang Hyun , Kim Young Tae 
Published: September 2021

Abstract

OBJECTIVES
The current understanding of pulmonary invasive mucinous adenocarcinoma is largely based on studies of advanced stage patients and data about early-stage invasive mucinous adenocarcinoma are sparse. We evaluated the radiological and clinical features of screening-detected early-stage invasive mucinous adenocarcinoma (SD-IMA).

METHODS
Data from 91 patients who underwent surgical treatment for SD-IMA (≤3 cm) from 2013 to 2019 were reviewed retrospectively. Data on radiological characteristics, clinicopathological findings, recurrence and survival were obtained. Disease-free survival rate was analysed.

RESULTS
Radiologically, SD-IMAs presented as a pure ground-glass nodule (6.6%), part-solid nodule (38.5%) or solid (54.9%). Dominant locations were both lower lobes (74.7%) and peripheral area (93.4%). The sensitivity of percutaneous needle biopsy was 78.1% (25/32). Lobectomy was performed in 70 (76.9%) patients, and sublobar resection in 21 (23.1%) patients. Seventy-three (80.2%), 15 (16.5%) and 3 (3.3%) patients had pathological stage IA, IB and IIB or above, respectively. Seven patients developed recurrence, and 3 died due to disease progression. Pleural seeding developed exclusively in 2 patients who underwent needle biopsy. The 5-year disease-free survival rate was 89.4%. The disease-free survival rates at 5 years were 86.3% in the lobectomy group and 100% in the sublobar resection group.

CONCLUSIONS
SD-IMAs were mostly radiologically invasive nodules. SD-IMAs showed favourable prognosis after surgical treatment.
Global burden for dengue and the evolving pattern in the past 30 years
Authors: Yang Xiaorong , Quam Mikkel B M , Zhang Tongchao , Sang Shaowei 
Published: September 2021

Abstract

Background
Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease. We present the global, regional and national burden of dengue from 1990 to 2019 based on the findings from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019).

Methods
Based upon GBD 2019 dengue data on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR) and age-standardized disability-adjusted life years (DALYs) rate, this study estimates and presents annual percentage change (EAPC) to quantify trends over time to assess potential correlates of increased dengue activity, such as global travel and warming.

Results
Globally from 1990 to 2019, dengue incident cases, deaths and DALYs gradually increased. Those under 5 years of age, once accounting for the largest portion of deaths and DALYs in 1990, were eclipsed by those who were 15–49 years old in 2019. Age standardized incidence [ASIR: EAPC: 3.16, 95% confidence interval (CI): 2.90–3.43], death (ASDR: EAPC: 5.42, 95% CI: 2.64–8.28) and DALY rates (EAPC: 2.31, 95% CI: 2.00–2.62) accelerated most among high-middle and high sociodemographic index (SDI) regions. South-East Asia and South Asia had most of the dengue incident cases, deaths and DALYs, but East Asia had the fastest rise in ASIR (EAPC: 4.57, 95% CI: 4.31, 4.82), while Tropical Latin America led in ASDR (EAPC: 11.32, 95% CI: 9.11, 13.58) and age-standardized DALYs rate (EAPC: 4.13, 95% CI: 2.98, 5.29). SDI showed consistent bell-shaped relationship with ASIR, ASDR and age-standardized DALYs rate. Global land–ocean temperature index and air passenger travel metrics were found to be remarkably positively correlated with dengue burden.

Conclusions
The burden of dengue has become heavier from 1990 to 2019, amidst the three decades of urbanization, warming climates and increased human mobility in much of the world. South-East Asia and South Asia remain as regions of concern, especially in conjunction with the Americas’ swift rise in dengue burden.
Illuminated Caxtons and the Trade in Printed Books
Authors: James-Maddocks Holly 
Published: September 2021

Abstract
This article suggests that the illuminated initials and borderwork added to ten early printed books in England are attributable to a single illuminator, the ‘Incunables Limner’, an individual for whom there is circumstantial evidence that he specialized in the illumination of printed books. Five of these books are copies of William Caxton’s Golden Legend (Westminster, 1483–84), while the other five are Continental imprints (two from Strasbourg, and one from each of Basel, Verona, and Parma) printed between 1476 and 1484. In addition, a second illuminator can be identified in a sixth copy of Caxton’s Golden Legend, working to the same design as that employed within the five copies decorated by the Incunables Limner. The possibility is considered that books illuminated by the Incunables Limner were products of Caxton’s overseas trade, and that it was through acting in this capacity that the artist’s specialization was viable. The Continental books are explored for what they might imply about Caxton’s wider book-selling strategies, and three with evidence for early English ownership are selected for particular attention.
PL02.5.A The clinical significance of telomerase reverse transcriptase (TERT) promoter mutations, telomere length and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status in newly diagnosed and recurrent IDHwildtype glioblastoma (GBM) patients (PTS): A large mono-institutional study
Authors: Lombardi G , Giunco S , Cavallin F , Angelini C , Caccese M , Cerretti G , De Bonis P , De Rossi A , Zagonel V 
Published: September 2021

Abstract

BACKGROUND
the clinical significance of TERT promoter mutations, telomere length and their interactions with MGMT promoter methylation status in patients with IDH-wildtype GBM patients remain unclear. We performed a large monoinstitutional study to better investigate their impact and their interaction on clinical outcomes

MATERIAL AND METHODS
TERT promoter mutations (C228T and C250T), relative telomere length (RTL) and MGMT methylation status were assessed in 278 newly diagnosed and in 65 recurrent IDH-wildtype GBM PTS which were treated at Veneto Institute of Oncology (Padua, Italy) from Dec 2016 to Jan 2020. We have retrospectively explored association between gene characteristics and neuroradiological response (RANO criteria), progression-free survival (PFS), overall survival (OS). Telomere length was measured by monochrome multiplex PCR and RTL values were calculated as a telomere/single-copy gene ratio

RESULTS
characteristics of newly diagnosed GBM PTS were: median age 63 ys, ECOG PS 0–1 in 71% of PTS, radical surgery in 38%, 78% received radiation therapy plus TMZ, MGMT was methylated in 53%, TERT promoter was mutated in 80% (75% C228T, 25% C250T), median RTL was 1.57 (range 0.4–11.37). Objective response rate was reported in 15% of PTS, median OS was 15ms (95% CI 13-18ms), median PFS was 8ms (95% CI 7-9ms). At multivariable analysis, TERT promoter mutations and RTL were not associated with clinical outcomes; about OS, TERT promoter mutations and RTL reported a HR of 1.05 (95% CI 0.64–1.64) and 0.99 (95% CI 0.89–1.10), respectively; MGMT methylated tumors showed significant improved PFS and OS with a HR of 0.54 (95% CI 0.40–0.71) and 0.47 (95% CI 0.34–0.64), respectively. All interactions among MGMT status, TERT mutation status and RTL were not statistically significant. Characteristics of recurrent GBM PTS were: median age 55 ys, ECOG PS 0–1 in 60% of PTS, MGMTmet in 37%, TERT promoter mutations in 75% (75% C228T, 25% C250T), RTL was 1.67 (range 0.68–8.87). At multivariable analysis, only MGMT methylated tumors resulted significantly associated to prolonged OS (HR 0.16; 95% CI 0.07–0.40). No gene interaction was significant

CONCLUSION
for the first time worldwide, we analyzed the impact of TERT promoter mutations, RTL and MGMT methylation status in both newly diagnosed and recurrent IDH-wildtype GBM PTS. TERT promoter status and RTL were not associated with clinical outcomes at both diagnosis and relapse. MGMT promoter methylation status was the only prognostic factor in both cases. No significant interaction was demonstrated between TERT promoter mutations, RTL and MGMT methylation status
JS01.3.A Oncogenic chaperoning of Hsp90 in glioma with FGFR3-TACC3
Authors: Li T , Mehraein-Ghomi F , Forbes M , Namjoshi S , Ballard E , Song Q , Chou P , Wang X , Yang X , Zhang W 
Published: September 2021

Abstract

BACKGROUND
Fusion genes are chromosomal aberrations in malignancies that can be used as prognostic markers as well as therapeutic targets. The FGFR3-TACC3 (F3-T3) was initially discovered as an oncogenic molecule in glioblastoma and bladder cancer and subsequently found in many other cancer types. Based on clinical evidence, F3-T3 was found in glioblastoma patients before and after TMZ and radiotherapy treatment, suggesting that targeting F3-T3 is a valid strategy for glioblastoma treatment.

MATERIAL AND METHODS
We profiled the proteins that interacted with F3-T3 fusion protein in U-251 MG cells with F3-T3 through 2-D liquid chromatography-tandem mass spectrometry. To validate the result of proteomic analysis, we performed reverse immunoprecipitation by pulling down Hsp90 or Cdc37 in U-251 MG cells stably expressing F3-T3. To inhibit the association between F3-T3 and the Hsp90-Cdc37 complex, we treated U-251 MG and LN-229 cells stably expressing F3-T3 with Hsp90 inhibitors or siRNA of Cdc37. We applied the CCK8 assay to evaluate the sensitivity of glioblastoma cells stably expressing F3-T3, wild-type FGFR3, kinase-dead F3-T3 (K508R), and empty vectors to TMZ. Immunoblot and immunofluorescence staining were used to detect DNA damage marker pH2AX. The drug combination effect index was analyzed using software CalcuSyn. U-251 MG cells stably expressing F3-T3 infected with luciferase virus were intracranially injected in nude mice. The experimental group was administered with temozolomide (5mg/kg/day) by oral gavage, Hsp90 inhibitor Onalespib (30mg/kg/day) by tail vein injection or the combination of the two for indicated days.

RESULTS
We identified the proteins that showed increased binding ratios to F3-T3 over full-length FGFR3, the molecular chaperone proteins encoded by the genes HSP90AB1, HSP90AA1, and CDC37 emerged as 5th, 6th, and 7th on the top ten list, showing an approximately 4-fold increase in normalized spectral counts. Using Hsp90 inhibitors or Cdc37 siRNA disrupted the formation of the F3-T3/Hsp90/Cdc37 complex. Disruption of Hsp90-Cdc37 chaperoning caused a ubiquitination-mediated degradation of the glycosylated form of F3-T3 and abrogated the maturation of nascent F3-T3, resulting in suppression of F3-T3 signaling pathways. Additionally, our results provide evidence that the F3-T3 signaling pathway confers drug resistance to TMZ induced DNA damage. However, the resistance of TMZ was disrupted in glioblastoma cells harboring kinase-dead F3-T3 (K508R). We also demonstrated Hsp90 inhibitor significantly sensitized glioblastoma cells harboring the F3-T3 fusion gene to TMZ treatment and improved survival of xenograft model bearing F3-T3 tumor in vivo.

CONCLUSION
F3-T3 is a strong Hsp90 client that shows strong addiction to the Hsp90-Cdc37 chaperone system. Combination therapy with Hsp90 inhibitor overcomes the TMZ resistance conferred by F3-T3.
OS06.4A Identification of T cell receptors targeting ZFTA-RELA fusion-positive ependymoma
Authors: Kehl N , Friedrich M , Kilian M , Zheng T , Pajtler K , Bunse L , Platten M 
Published: September 2021

Abstract

BACKGROUND
The oncogenic gene fusion between ZFTA (formerly C11orf95) and RELA has in recent years been highlighted as oncogenic driver event ultimately leading to malignant transformation and progression of ependymoma. Representing a genetic hallmark in 17.6% of ependymomas, ZFTA-RELA fusion-positive tumors qualified as separate diagnostic entity in the 2016 revision of the WHO classification of CNS tumors. This tumor entity mainly occurs in pediatric patients and is characterized by poor prognosis and the lack of biology-driven therapy.

RESULTS
De novo prediction of putative gene fusion-derived neoepitopes in malignant CNS diseases yielded several potential candidates suitable for screening. Of these, vaccination of A2.DR1-transgenic major histocompatibility complex (MHC)-humanized mice with in silico compiled peptide vaccines encompassing the ZFTA-RELA fusion sequence elicited robust antigen-specific CD4+-restricted immune responses. We identified ZFTA-RELA-reactive T cell clones by multiplexed Interferon-γ / Interleukin-2 recall response. Single-cell VDJ-sequencing of reactive T cells demonstrated a highly clonal T cell receptor (TCR) repertoire and shared clonotypes among all vaccinated animals. Matching TCRα/β chains have been assembled from single-cell sequencing data and cloned for functional testing of neoepitope-reactive TCR-transgenic T cells in vitro as well as in vivo using a transposon system-based immunocompetent, MHC-humanized ZFTA-RELA fusion-positive ependymoma model.

CONCLUSION
Here we identify the oncogenic ZFTA-RELA gene fusion product as a novel tumor-specific neoepitope that is recognized by MHC class II-restricted TCRs. Therapeutic efficacy of TCR-transgenic cell therapy can be further investigated using an immunocompetent MHC-humanized mouse model of ZFTA-RELA fusion-positive ependymoma. Our findings provide initial evidence for neoepitope-specific immunotherapy in pediatric CNS tumors.