bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood-based liquid biopsies for prostate cancer: clinical opportunities and challenges
Authors: Trujillo Blanca , Wu Anjui , Wetterskog Daniel , Attard Gerhardt 
Published: June 2022

AbstractLiquid biopsy has been established as a powerful, minimally invasive, tool to detect clinically actionable aberrations across numerous cancer types in real-time. With the development of new therapeutic agents in prostate cancer (PC) including DNA repair targeted therapies, this is especially attractive. However, there is unclarity on how best to screen for PC, improve risk stratification and ultimately how to treat advanced disease. Therefore, there is an urgent need to develop better biomarkers to help guide oncologists’ decisions in these settings. Circulating tumour cells (CTCs), exosomes and cell-free DNA/RNA (cfDNA/cfRNA) analysis, including epigenetic features such as methylation, have all shown potential in prognostication, treatment response assessment and detection of emerging mechanisms of resistance. However, there are still challenges to overcome prior to implementing liquid biopsies in routine clinical practice such as preanalytical considerations including blood collection and storage, the cost of CTC isolation and enrichment, low-circulating tumour content as a limitation for genomic analysis and how to better interpret the sequencing data generated. In this review, we describe an overview of the up-to-date clinical opportunities in the management of PC through blood-based liquid biopsies and the next steps for its implementation in personalised treatment guidance.
Direct observation of significant hot carrier cooling suppression in a two-dimensional silicon phononic crystal
Authors: Yan Wensheng , Long Liyuan , Zang Yue , Yang Gaoyuan , Liang Guijie 
Published: June 2022

AbstractFinding hot carrier cooling suppression in new material structures is fundamentally important for developing promising technological applications. These phenomenona have not been reported for crystalline silicon phononic crystals. Herein, we experimentally design two-dimensional (2D) silicon samples consisting of airy hole arrays in a crystalline silicon matrix. For reference, the determined hot carrier cooling times were 0.45 ps and 0.37 ps, respectively, at probe wavelengths of 1080 nm and 1100 nm. Surprisingly, when the 2D structured silicon possessed the properties of a phononic crystal, significant suppression of hot carrier cooling was observed. In these cases, the observed hot carrier cooling times were as long as 15.9 ps and 10.7 ps at probe wavelengths of 1080 nm and 1100 nm, respectively, indicating prolongation by orders of magnitude. This remarkable enhancement was also observed with other probe wavelengths. The present work presents experimental evidence for hot carrier cooling suppression in 2D silicon phononic crystals and opens opportunities for promising applications.
Addressing challenges with real-world synthetic control arms to demonstrate the comparative effectiveness of Pralsetinib in non-small cell lung cancer
Authors: Popat Sanjay , Liu Stephen V. , Scheuer Nicolas , Hsu Grace G. , Lockhart Alexandre , Ramagopalan Sreeram V. , Griesinger Frank , Subbiah Vivek 
Published: June 2022

AbstractAs advanced non-small cell lung cancer (aNSCLC) is being increasingly divided into rare oncogene-driven subsets, conducting randomised trials becomes challenging. Using real-world data (RWD) to construct control arms for single-arm trials provides an option for comparative data. However, non-randomised treatment comparisons have the potential to be biased and cause concern for decision-makers. Using the example of pralsetinib from a RET fusion-positive aNSCLC single-arm trial (NCT03037385), we demonstrate a relative survival benefit when compared to pembrolizumab monotherapy and pembrolizumab with chemotherapy RWD cohorts. Quantitative bias analyses show that results for the RWD-trial comparisons are robust to data missingness, potential poorer outcomes in RWD and residual confounding. Overall, the study provides evidence in favour of pralsetinib as a first-line treatment for RET fusion-positive aNSCLC. The quantification of potential bias performed in this study can be used as a template for future studies of this nature.
Topological phonon transport in an optomechanical system
Authors: Ren Hengjiang , Shah Tirth , Pfeifer Hannes , Brendel Christian , Peano Vittorio , Marquardt Florian , Painter Oskar 
Published: June 2022

AbstractLight is a powerful tool for controlling mechanical motion, as shown by numerous applications in the field of cavity optomechanics. Recently, small scale optomechanical circuits, connecting a few optical and mechanical modes, have been demonstrated in an ongoing push towards multi-mode on-chip optomechanical systems. An ambitious goal driving this trend is to produce topologically protected phonon transport. Once realized, this will unlock the full toolbox of optomechanics for investigations of topological phononics. Here, we report the realization of topological phonon transport in an optomechanical device. Our experiment is based on an innovative multiscale optomechanical crystal design and allows for site-resolved measurements in an array of more than 800 cavities. The sensitivity inherent in our optomechanical read-out allowed us to detect thermal fluctuations traveling along topological edge channels. This represents a major step forward in an ongoing effort to downscale mechanical topological systems.
3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Authors: Zhao Yanhe , Wang Huafeng , Wiesehoefer Caroline , Shah Naman B. , Reetz Evan , Hwang Jae Yeon , Huang Xiaofang , Wang Tse-en , Lishko Polina V. , Davies Karen M. , Wennemuth Gunther , Nicastro Daniela , Chung Jean-Ju 
Published: June 2022

AbstractThe sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.
Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states
Authors: Jaber Mohammad , Radwan Ahmed , Loyfer Netanel , Abdeen Mufeed , Sebban Shulamit , Khatib Areej , Yassen Hazar , Kolb Thorsten , Zapatka Marc , Makedonski Kirill , Ernst Aurelie , Kaplan Tommy , Buganim Yosef 
Published: June 2022

AbstractFollowing fertilization, it is only at the 32-64-cell stage when a clear segregation between cells of the inner cell mass and trophectoderm is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro, by nuclear reprogramming, share similar dynamics/trajectories. Using a comparative parallel multi-omics analysis (i.e., bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, RRBS and CNVs) on cells undergoing reprogramming to pluripotency and TSC state we show that each reprogramming system exhibits specific trajectories from the onset of the process, suggesting ‘V’-shaped model. We describe in detail the various trajectories toward the two states and illuminate reprogramming stage-specific markers, blockers, facilitators and TSC subpopulations. Finally, we show that while the acquisition of the TSC state involves the silencing of embryonic programs by DNA methylation, during the acquisition of pluripotency these regions are initially defined but retain inactive by the elimination of H3K27ac.
The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin
Authors: Truch Julia , Downes Damien J. , Scott Caroline , Gür E. Ravza , Telenius Jelena M. , Repapi Emmanouela , Schwessinger Ron , Gosden Matthew , Brown Jill M. , Taylor Stephen , Cheong Pak Leng , Hughes Jim R. , Higgs Douglas R. , Gibbons Richard J. 
Published: June 2022

AbstractThe chromatin remodeller ATRX interacts with the histone chaperone DAXX to deposit the histone variant H3.3 at sites of nucleosome turnover. ATRX is known to bind repetitive, heterochromatic regions of the genome including telomeres, ribosomal DNA and pericentric repeats, many of which are putative G-quadruplex forming sequences (PQS). At these sites ATRX plays an ancillary role in a wide range of nuclear processes facilitating replication, chromatin modification and transcription. Here, using an improved protocol for chromatin immunoprecipitation, we show that ATRX also binds active regulatory elements in euchromatin. Mutations in ATRX lead to perturbation of gene expression associated with a reduction in chromatin accessibility, histone modification, transcription factor binding and deposition of H3.3 at the sequences to which it normally binds. In erythroid cells where downregulation of α-globin expression is a hallmark of ATR-X syndrome, perturbation of chromatin accessibility and gene expression occurs in only a subset of cells. The stochastic nature of this process suggests that ATRX acts as a general facilitator of cell specific transcriptional and epigenetic programmes, both in heterochromatin and euchromatin.
ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription
Authors: Yu Chunhong , Lei Xiaoyun , Chen Fang , Mao Song , Lv Lu , Liu Honglu , Hu Xueying , Wang Runhan , Shen Licong , Zhang Na , Meng Yang , Shen Yunfan , Chen Jiale , Li Pishun , Huang Shi , Lin Changwei , Zhang Zhuohua , Yuan Kai 
Published: June 2022

AbstractTransposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription.
Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion
Authors: Wang Li-Qiang , Ma Yeyang , Yuan Han-Ye , Zhao Kun , Zhang Mu-Ya , Wang Qiang , Huang Xi , Xu Wen-Chang , Dai Bin , Chen Jie , Li Dan , Zhang Delin , Wang Zhengzhi , Zou Liangyu , Yin Ping , Liu Cong , Liang Yi 
Published: June 2022

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3–55) and C-terminal segment (residues 86–153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Authors: Cao Yunlong , Yisimayi Ayijiang , Jian Fanchong , Song Weiliang , Xiao Tianhe , Wang Lei , Du Shuo , Wang Jing , Li Qianqian , Chen Xiaosu , Yu Yuanling , Wang Peng , Zhang Zhiying , Liu Pulan , An Ran , Hao Xiaohua , Wang Yao , Wang Jing , Feng Rui , Sun Haiyan , Zhao Lijuan , Zhang Wen , Zhao Dong , Zheng Jiang , Yu Lingling , Li Can , Zhang Na , Wang Rui , Niu Xiao , Yang Sijie , Song Xuetao , Chai Yangyang , Hu Ye , Shi Yansong , Zheng Linlin , Li Zhiqiang , Gu Qingqing , Shao Fei , Huang Weijin , Jin Ronghua , Shen Zhongyang , Wang Youchun , Wang Xiangxi , Xiao Junyu , Xie Xiaoliang Sunney 
Published: June 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
Functional HLA-C expressing trophoblast spheroids as a model to study placental–maternal immune interactions during human implantation
Authors: Alexandrova Marina , Manchorova Diana , You Yuan , Mor Gil , Dimitrova Violeta , Dimova Tanya 
Published: June 2022

AbstractIn healthy couples over half of the conceptions result in failed pregnancy and around 30% of them occur during implantation defining it as a rate-limiting step for the success of native and in vitro fertilization. The understanding of the factors regulating each step of implantation and immune recognition is critical for the pregnancy outcome. Creation of 3D-cell culture models, such as spheroids and organoids, is in the focus of placental tissue engineering in attempt to resemble the in vivo complexity of the maternal-fetal interface and to overcome the need of laboratory animals and human embryos. We constructed stable, reliable, and reproducible trophoblast Sw71 spheroids which are functional independently of the serum level in the culture media. These models resemble the hatched human blastocyst in size, shape and function and are useful for in vitro studies of the in vivo concealed human implantation. Since Sw71 spheroids produce HLA-C, the only classical MHC molecule indispensable for establishment of the immune tolerance and proper human implantation, they are applicable for the evaluation not only of implantation itself but also of maternal-trophoblasts immune interactions. In addition, Sw71-blastocyst-like spheroids are manipulable in low-volume platform, easy to monitor and analyze automatically under treatment with favorable/detrimental factors.
Dissolved oxygen isotope modelling refines metabolic state estimates of stream ecosystems with different land use background
Authors: Piatka David R. , Venkiteswaran Jason J. , Uniyal Bhumika , Kaule Robin , Gilfedder Benjamin , Barth Johannes A. C. 
Published: June 2022

AbstractDissolved oxygen (DO) is crucial for aerobic life in streams and rivers and mostly depends on photosynthesis (P), ecosystem respiration (R) and atmospheric gas exchange (G). However, climate and land use changes progressively disrupt metabolic balances in natural streams as sensitive reflectors of their catchments. Comprehensive methods for mapping fundamental ecosystem services become increasingly important in a rapidly changing environment. In this work we tested DO and its stable isotope (18O/16O) ratios as novel tools for the status of stream ecosystems. For this purpose, six diel sampling campaigns were performed at three low-order and mid-latitude European streams with different land use patterns. Modelling of diel DO and its stable isotopes combined with land use analyses showed lowest P rates at forested sites, with a minimum of 17.9 mg m−2 h−1. Due to high R rates between 230 and 341 mg m−2 h−1 five out of six study sites showed a general heterotrophic state with P:R:G ratios between 0.1:1.1:1 and 1:1.9:1. Only one site with agricultural and urban influences showed a high P rate of 417 mg m−2 h−1 with a P:R:G ratio of 1.9:1.5:1. Between all sites gross G rates varied between 148 and 298 mg m−2 h−1. In general, metabolic rates depend on the distance of sampling locations to river sources, light availability, nutrient concentrations and possible exchanges with groundwater. The presented modelling approach introduces a new and powerful tool to study effects of land use on stream health. Such approaches should be integrated into future ecological monitoring.
Applying convolutional neural networks to speed up environmental DNA annotation in a highly diverse ecosystem
Authors: Flück Benjamin , Mathon Laëtitia , Manel Stéphanie , Valentini Alice , Dejean Tony , Albouy Camille , Mouillot David , Thuiller Wilfried , Murienne Jérôme , Brosse Sébastien , Pellissier Loïc 
Published: June 2022

AbstractHigh-throughput DNA sequencing is becoming an increasingly important tool to monitor and better understand biodiversity responses to environmental changes in a standardized and reproducible way. Environmental DNA (eDNA) from organisms can be captured in ecosystem samples and sequenced using metabarcoding, but processing large volumes of eDNA data and annotating sequences to recognized taxa remains computationally expensive. Speed and accuracy are two major bottlenecks in this critical step. Here, we evaluated the ability of convolutional neural networks (CNNs) to process short eDNA sequences and associate them with taxonomic labels. Using a unique eDNA data set collected in highly diverse Tropical South America, we compared the speed and accuracy of CNNs with that of a well-known bioinformatic pipeline (OBITools) in processing a small region (60 bp) of the 12S ribosomal DNA targeting freshwater fishes. We found that the taxonomic labels from the CNNs were comparable to those from OBITools, with high correlation levels for the composition of the regional fish fauna. The CNNs enabled the processing of raw fastq files at a rate of approximately 1 million sequences per minute, which was about 150 times faster than with OBITools. Given the good performance of CNNs in the highly diverse ecosystem considered here, the development of more elaborate CNNs promises fast deployment for future biodiversity inventories using eDNA.
Active surveillance versus initial surgery in the long-term management of Bosniak IIF–IV cystic renal masses
Authors: Luomala Lassi , Rautiola Juhana , Järvinen Petrus , Mirtti Tuomas , Nisén Harry 
Published: June 2022

AbstractThere may be surgical overtreatment of complex cystic renal masses (CRM). Growing evidence supports active surveillance (AS) for the management for Bosniak IIF–III CRMs. We aimed to evaluate and compare oncological and pathological outcomes of Bosniak IIF–IV CRMs treated by initial surgery (IS) or AS. We identified retrospectively 532 patients with CRM counseled during 2006–2017. IS and AS were delivered to, respectively, 1 and 286 patients in Bosniak IIF, to 54 and 85 patients in III and to 85 and 21 patients in Bosniak IV. Median follow-up was 66 months (IQR 50–96). Metastatic progression occurred for 1 (0.3%) AS patient in Bosniak IIF, 1 IS (1.8%) and 1 AS (1.2%) patient in Bosniak III and 5 IS (3.5%) patients in Bosniak IV, respectively. Overall 5-year metastasis-free survival was 98.9% and cancer-specific survival was 99.6% without statistically significant difference between IS and AS in Bosniak IIF–IV categories. AS did not increase the risk of metastatic spread or cancer-specific mortality in patients with Bosniak IIF–IV. Our data indicate AS in Bosniak IIF and III is safe. Surgery is the primary treatment for Bosniak IV due to its high malignancy rate.
A clock synchronization method based on quantum entanglement
Authors: Shi Jianxin , Shen Shanshan 
Published: June 2022

AbstractThis study presents a clock synchronization method based on quantum entanglement which is simple and reliable and more efficient. The clock synchronization method based on quantum entanglement scheme can greatly improve the accuracy and precision of measurement. More importantly, the proposed method avoids synchronization error caused by traditional method due to the asymmetry of two-way delay. The probability of measuring the quantum state oscillates in cosine or sine fashion with propagation delay. The final experimental and simulation results are basically consistent with the theoretical results. The clock synchronization method based on quantum entanglement scheme can greatly imrprove the accuracy and precision of measurement.