bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma
Authors: Langendonk Myra , de Jong Mathilde R. W. , Smit Nienke , Seiler Jonas , Reitsma Bart , Ammatuna Emanuele , Glaudemans Andor W. J. M. , van den Berg Anke , Huls Gerwin A. , Visser Lydia , van Meerten Tom 
Published: March 2022

AbstractDiffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Despite the proven efficacy of combined immunochemotherapy (R-CHOP) in the majority of patients, ~40% of DLBCL patients do not respond or will relapse and consequently have a very poor prognosis. The development of targeted therapies has not improved patient survival, underscoring the need for new treatment approaches. Using an unbiased genome-wide CD20 guilt-by-association approach in more than 1800 DLBCL patients, we previously identified the estrogen receptor beta (ERβ) as a new target in DLBCL. Here, we demonstrate that ERβ is expressed at significantly higher levels in DLBCL compared to normal B cells, and ERβ plays a role in the protection against apoptosis in DLBCL. Targeting of the ERβ with the selective estrogen receptor modulator tamoxifen reduces cell viability in all tested DLBCL cell lines. Tamoxifen-induced cell death was significantly decreased in an ERβ knock-out cell line. The activity of tamoxifen was confirmed in a xenograft human lymphoma model, as tumor growth decreased, and survival significantly improved. Finally, tamoxifen-treated breast cancer (BC) patients showed a significantly reduced risk of 38% for DLBCL compared to BC patients who did not receive tamoxifen. Our findings provide a rationale to investigate tamoxifen, a hormonal drug with a good safety profile, in DLBCL patients.
Heterogeneity induced GZMA-F2R communication inefficient impairs antitumor immunotherapy of PD-1 mAb through JAK2/STAT1 signal suppression in hepatocellular carcinoma
Authors: Gao Yuxue , Xu Qingguo , Li Xinqiang , Guo Yuan , Zhang Bowen , Jin Yan , zhu Cunle , Shen Yuntai , Yang Pengxiang , Shi Ying , Jin Rifeng , Liu Daojie , Ouyang Yabo , Liu Xiaoni , Wang Wenjing , Chen Dexi , Yang Tongwang 
Published: March 2022

AbstractTumor heterogeneity has been associated with immunotherapy and targeted drug resistance in hepatocellular carcinoma (HCC). However, communications between tumor and cytotoxic cells are poorly understood to date. In the present study, thirty-one clusters of cells were discovered in the tumor tissues and adjacent tissues through single-cell sequencing. Moreover, the quantity and function exhaustion of cytotoxic cells was observed to be induced in tumors by the TCR and apoptosis signal pathways. Furthermore, granzyme failure of cytotoxic cells was observed in HCC patients. Importantly, the GZMA secreted by cytotoxic cells was demonstrated to interact with the F2R expressed by the tumor cells both in vivo and in vitro. This interaction induced tumor suppression and T cell-mediated killing of tumor cells via the activation of the JAK2/STAT1 signaling pathway. Mechanistically, the activation of JAK2/STAT1 signaling promoted apoptosis under the mediating effect of the LDPRSFLL motif at the N-terminus of F2R, which interacted with GZMA. In addition, GZMA and F2R were positively correlated with PD-1 and PD-L1 in tumor tissues, while the expressions of F2R and GZMA promoted PD-1 mAb-induced tumor suppression in both mouse model and HCC patients. Finally, in HCC patients, a low expression of GZMA and F2R in the tumor tissues was correlated with aggressive clinicopathological characteristics and poor prognosis. Collectively, GZMA-F2R communication inefficient induces deficient PD-1 mAb therapy and provide a completely novel immunotherapy strategy for tumor suppression in HCC patients.
Geographically dispersed zoonotic tuberculosis in pre-contact South American human populations
Authors: Vågene Åshild J. , Honap Tanvi P. , Harkins Kelly M. , Rosenberg Michael S. , Giffin Karen , Cárdenas-Arroyo Felipe , Leguizamón Laura Paloma , Arnett Judith , Buikstra Jane E. , Herbig Alexander , Krause Johannes , Stone Anne C. , Bos Kirsten I. 
Published: March 2022

AbstractPrevious ancient DNA research has shown that Mycobacterium pinnipedii, which today causes tuberculosis (TB) primarily in pinnipeds, infected human populations living in the coastal areas of Peru prior to European colonization. Skeletal evidence indicates the presence of TB in several pre-colonial South and North American populations with minimal access to marine resources— a scenario incompatible with TB transmission directly from infected pinnipeds or their tissues. In this study, we investigate the causative agent of TB in ten pre-colonial, non-coastal individuals from South America. We reconstruct M. pinnipedii genomes (10- to 15-fold mean coverage) from three contemporaneous individuals from inland Peru and Colombia, demonstrating the widespread dissemination of M. pinnipedii beyond the coast, either through human-to-human and/or animal-mediated routes. Overall, our study suggests that TB transmission in the pre-colonial era Americas involved a more complex transmission pathway than simple pinniped-to-human transfer.
Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer
Authors: Lopez Andrea , Reyna Denis E. , Gitego Nadege , Kopp Felix , Zhou Hua , Miranda-Roman Miguel A. , Nordstrøm Lars Ulrik , Narayanagari Swathi-Rao , Chi Ping , Vilar Eduardo , Tsirigos Aristotelis , Gavathiotis Evripidis 
Published: March 2022

AbstractDeregulation of the BCL-2 family interaction network ensures cancer resistance to apoptosis and is a major challenge to current treatments. Cancer cells commonly evade apoptosis through upregulation of the BCL-2 anti-apoptotic proteins; however, more resistant cancers also downregulate or inactivate pro-apoptotic proteins to suppress apoptosis. Here, we find that apoptosis resistance in a diverse panel of solid and hematological malignancies is mediated by both overexpression of BCL-XL and an unprimed apoptotic state, limiting direct and indirect activation mechanisms of pro-apoptotic BAX. Both survival mechanisms can be overcome by the combination of an orally bioavailable BAX activator, BTSA1.2 with Navitoclax. The combination demonstrates synergistic efficacy in apoptosis-resistant cancer cells, xenografts, and patient-derived tumors while sparing healthy tissues. Additionally, functional assays and genomic markers are identified to predict sensitive tumors to the combination treatment. These findings advance the understanding of apoptosis resistance mechanisms and demonstrate a novel therapeutic strategy for cancer treatment.
Topological charge-entropy scaling in kagome Chern magnet TbMn6Sn6
Authors: Xu Xitong , Yin Jia-Xin , Ma Wenlong , Tien Hung-Ju , Qiang Xiao-Bin , Reddy P. V. Sreenivasa , Zhou Huibin , Shen Jie , Lu Hai-Zhou , Chang Tay-Rong , Qu Zhe , Jia Shuang 
Published: March 2022

AbstractIn ordinary materials, electrons conduct both electricity and heat, where their charge-entropy relations observe the Mott formula and the Wiedemann-Franz law. In topological quantum materials, the transverse motion of relativistic electrons can be strongly affected by the quantum field arising around the topological fermions, where a simple model description of their charge-entropy relations remains elusive. Here we report the topological charge-entropy scaling in the kagome Chern magnet TbMn6Sn6, featuring pristine Mn kagome lattices with strong out-of-plane magnetization. Through both electric and thermoelectric transports, we observe quantum oscillations with a nontrivial Berry phase, a large Fermi velocity and two-dimensionality, supporting the existence of Dirac fermions in the magnetic kagome lattice. This quantum magnet further exhibits large anomalous Hall, anomalous Nernst, and anomalous thermal Hall effects, all of which persist to above room temperature. Remarkably, we show that the charge-entropy scaling relations of these anomalous transverse transports can be ubiquitously described by the Berry curvature field effects in a Chern-gapped Dirac model. Our work points to a model kagome Chern magnet for the proof-of-principle elaboration of the topological charge-entropy scaling.
Tropical extreme droughts drive long-term increase in atmospheric CO2 growth rate variability
Authors: Luo Xiangzhong , Keenan Trevor F. 
Published: March 2022

AbstractThe terrestrial carbon sink slows the accumulation of carbon dioxide (CO2) in the atmosphere by absorbing roughly 30% of anthropogenic CO2 emissions, but varies greatly from year to year. The resulting variations in the atmospheric CO2 growth rate (CGR) have been related to tropical temperature and water availability. The apparent sensitivity of CGR to tropical temperature ($${{{{{{\rm{\gamma }}}}}}}_{{{{{{\rm{CGR}}}}}}}^{{{{{{\rm{T}}}}}}}$$

γ

CGR

T

) has changed markedly over the past six decades, however, the drivers of the observation to date remains unidentified. Here, we use atmospheric observations, multiple global vegetation models and machine learning products to analyze the cause of the sensitivity change. We found that a threefold increase in $${{{{{{\rm{\gamma }}}}}}}_{{{{{{\rm{CGR}}}}}}}^{{{{{{\rm{T}}}}}}}$$

γ

CGR

T

emerged due to the long-term changes in the magnitude of CGR variability (i.e., indicated by one standard deviation of CGR; STDCGR), which increased 34.7% from 1960-1979 to 1985-2004 and subsequently decreased 14.4% in 1997-2016. We found a close relationship (r2 = 0.75, p < 0.01) between STDCGR and the tropical vegetated area (23°S – 23°N) affected by extreme droughts, which influenced 6-9% of the tropical vegetated surface. A 1% increase in the tropical area affected by extreme droughts led to about 0.14 Pg C yr−1 increase in STDCGR. The historical changes in STDCGR were dominated by extreme drought-affected areas in tropical Africa and Asia, and semi-arid ecosystems. The outsized influence of extreme droughts over a small fraction of vegetated surface amplified the interannual variability in CGR and explained the observed long-term dynamics of $${{{{{{\rm{\gamma }}}}}}}_{{{{{{\rm{CGR}}}}}}}^{{{{{{\rm{T}}}}}}}$$

γ

CGR

T

.
A bottom-up reward pathway mediated by somatostatin neurons in the medial septum complex underlying appetitive learning
Authors: Shen Li , Zhang Guang-Wei , Tao Can , Seo Michelle B. , Zhang Nicole K. , Huang Junxiang J. , Zhang Li I. , Tao Huizhong W. 
Published: March 2022

AbstractValence detection and processing are essential for the survival of animals and their life quality in complex environments. Neural circuits underlying the transformation of external sensory signals into positive valence coding to generate appropriate behavioral responses remain not well-studied. Here, we report that somatostatin (SOM) subtype of GABAergic neurons in the mouse medial septum complex (MS), but not parvalbumin subtype or glutamatergic neurons, specifically encode reward signals and positive valence. Through an ascending pathway from the nucleus of solitary tract and then parabrachial nucleus, the MS SOM neurons receive rewarding taste signals and suppress the lateral habenula. They contribute essentially to appetitive associative learning via their projections to the lateral habenula: learning enhances their responses to reward-predictive sensory cues, and suppressing their responses to either conditioned or unconditioned stimulus impairs acquisition of reward learning. Thus, MS serves as a critical hub for transforming bottom-up sensory signals to mediate appetitive behaviors.
Surface loss calculations and design of a superconducting transmon qubit with tapered wiring
Authors: Martinis John M. 
Published: March 2022

AbstractAnalytical formulas are presented for simplified but useful qubit geometries that predict surface dielectric loss when its thickness is much less than the metal thickness, the limiting case needed for real devices. These formulas can thus be used to precisely predict loss and optimize the qubit layout. Surprisingly, a significant fraction of surface loss comes from the small wire that connects the Josephson junction to the qubit capacitor. Tapering this wire is shown to significantly lower its loss. Also predicted are the size and density of the two-level state (TLS) spectrum from individual surface dissipation sites.
Experimental implementation of secure anonymous protocols on an eight-user quantum key distribution network
Authors: Huang Zixin , Joshi Siddarth Koduru , Aktas Djeylan , Lupo Cosmo , Quintavalle Armanda O. , Venkatachalam Natarajan , Wengerowsky Sören , Lončarić Martin , Neumann Sebastian Philipp , Liu Bo , Samec Željko , Kling Laurent , Stipčević Mario , Ursin Rupert , Rarity John G. 
Published: March 2022

AbstractAnonymity in networked communication is vital for many privacy-preserving tasks. Secure key distribution alone is insufficient for high-security communications. Often, knowing who transmits a message to whom and when must also be kept hidden from an adversary. Here, we experimentally demonstrate five information-theoretically secure anonymity protocols on an eight user city-wide quantum network using polarisation entangled photon pairs. At the heart of these protocols is anonymous broadcasting, which is a cryptographic primitive that allows one user to reveal one bit of information while keeping their identity anonymous. For a network of n users, the protocols retain anonymity for the sender, given that no more than n − 2 users are colluding. This is an implementation of genuine multi-user cryptographic protocols beyond standard QKD. Our anonymous protocols enhance the functionality of any fully-connected Quantum Key Distribution network without trusted nodes.
In vivo lensless microscopy via a phase mask generating diffraction patterns with high-contrast contours
Authors: Adams Jesse K. , Yan Dong , Wu Jimin , Boominathan Vivek , Gao Sibo , Rodriguez Alex V. , Kim Soonyoung , Carns Jennifer , Richards-Kortum Rebecca , Kemere Caleb , Veeraraghavan Ashok , Robinson Jacob T. 
Published: March 2022

AbstractThe simple and compact optics of lensless microscopes and the associated computational algorithms allow for large fields of view and the refocusing of the captured images. However, existing lensless techniques cannot accurately reconstruct the typical low-contrast images of optically dense biological tissue. Here we show that lensless imaging of tissue in vivo can be achieved via an optical phase mask designed to create a point spread function consisting of high-contrast contours with a broad spectrum of spatial frequencies. We built a prototype lensless microscope incorporating the ‘contour’ phase mask and used it to image calcium dynamics in the cortex of live mice (over a field of view of about 16 mm2) and in freely moving Hydra vulgaris, as well as microvasculature in the oral mucosa of volunteers. The low cost, small form factor and computational refocusing capability of in vivo lensless microscopy may open it up to clinical uses, especially for imaging difficult-to-reach areas of the body.
Single-nuclei isoform RNA sequencing unlocks barcoded exon connectivity in frozen brain tissue
Authors: Hardwick Simon A. , Hu Wen , Joglekar Anoushka , Fan Li , Collier Paul G. , Foord Careen , Balacco Jennifer , Lanjewar Samantha , Sampson Maureen McGuirk , Koopmans Frank , Prjibelski Andrey D. , Mikheenko Alla , Belchikov Natan , Jarroux Julien , Lucas Anne Bergstrom , Palkovits Miklós , Luo Wenjie , Milner Teresa A. , Ndhlovu Lishomwa C. , Smit August B. , Trojanowski John Q. , Lee Virginia M. Y. , Fedrigo Olivier , Sloan Steven A. , Tombácz Dóra , Ross M. Elizabeth , Jarvis Erich , Boldogkői Zsolt , Gan Li , Tilgner Hagen U. 
Published: March 2022

AbstractSingle-nuclei RNA sequencing characterizes cell types at the gene level. However, compared to single-cell approaches, many single-nuclei cDNAs are purely intronic, lack barcodes and hinder the study of isoforms. Here we present single-nuclei isoform RNA sequencing (SnISOr-Seq). Using microfluidics, PCR-based artifact removal, target enrichment and long-read sequencing, SnISOr-Seq increased barcoded, exon-spanning long reads 7.5-fold compared to naive long-read single-nuclei sequencing. We applied SnISOr-Seq to adult human frontal cortex and found that exons associated with autism exhibit coordinated and highly cell-type-specific inclusion. We found two distinct combination patterns: those distinguishing neural cell types, enriched in TSS-exon, exon-polyadenylation-site and non-adjacent exon pairs, and those with multiple configurations within one cell type, enriched in adjacent exon pairs. Finally, we observed that human-specific exons are almost as tightly coordinated as conserved exons, implying that coordination can be rapidly established during evolution. SnISOr-Seq enables cell-type-specific long-read isoform analysis in human brain and in any frozen or hard-to-dissociate sample.
Temporally dynamic neural correlates of drug cue reactivity, response inhibition, and methamphetamine-related response inhibition in people with methamphetamine use disorder
Authors: Jafakesh Sara , Sangchooli Arshiya , Aarabi Ardalan , Helfroush Mohammad Sadegh , Dakhili Amirhossein , Oghabian Mohammad Ali , Kazemi Kamran , Ekhtiari Hamed 
Published: March 2022

AbstractCue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these phenomena develop and interact across time, the temporal dynamics of their underlying neural activity remain under-investigated. To explore these dynamics, an analysis of time-varying activation was applied to fMRI data from 62 men with methamphetamine use disorder in their first weeks of recovery in an abstinence-based treatment program. Using a mixed block-event, factorial cue-reactivity/Go-NoGo task and a sliding window across the task duration, dynamically-activated regions were identified in three linear mixed effects models (LMEs). Habituation to drug cues across time was observed in the superior temporal gyri, amygdalae, left hippocampus, and right precuneus, while response inhibition was associated with the sensitization of temporally-dynamic activations across many regions of the inhibitory frontoparietal network. Methamphetamine-related response inhibition was associated with temporally-dynamic activity in the parahippocampal gyri and right precuneus (corrected p-value < 0.001), which show a declining cue-reactivity contrast and an increasing response inhibition contrast. Overall, the declining craving-related activations (habituation) and increasing inhibition-associated activations (sensitization) during the task duration suggest the gradual recruitment of response inhibitory processes and a concurrent habituation to drug cues in areas with temporally-dynamic methamphetamine-related response inhibition. Furthermore, temporally dynamic cue-reactivity and response inhibition were correlated with behavioral and clinical measures such as the severity of methamphetamine use and craving, impulsivity and inhibitory task performance. This exploratory study demonstrates the time-variance of the neural activations undergirding cue-reactivity, response inhibition, and response inhibition during exposure to drug cues, and suggests a method to assess this dynamic interplay. Analyses that can capture temporal fluctuations in the neural substrates of drug cue-reactivity and response inhibition may prove useful for biomarker development by revealing the rate and pattern of sensitization and habituation processes, and may inform mixed cue-exposure intervention paradigms which could promote habituation to drug cues and sensitization in inhibitory control regions.
Modelling, characterization, and applications of silicon on insulator loop terminated asymmetric Mach Zehnder interferometer
Authors: El Shamy Raghi S. , Afifi Abdelrahman E. , Badr Mohamed M. , Swillam Mohamed A. 
Published: March 2022

AbstractThis work presents a loop terminated asymmetric Mach–Zehnder interferometer (LT-aMZI) structure based on the widespread silicon-on-insulator (SOI) platform. Four different path length differences of the LT-aMZI, which correspond to free spectral ranges (FSR) from 0.8 to 6.4 nm, are designed. These designs are compared to the common asymmetric Mach–Zehnder interferometer (C-aMZI) and are shown to be more compact. These devices are suitable for optical filtering as well as wavelength demultiplexing (WDM) applications. A compact analytical model is derived that accurately describe the operation of the LT-MZI devices. The designs are then fabricated using Electron Beam Lithography (EBL) and characterized. The experimental data show good agreement when compared to the simulation results. To our knowledge, this is the first time LT-aMZI fabrication and characterization. Moreover, the LT-MZI spectrum can be tuned not only by the interferometer arms phase difference like C-MZI, but also by using its directional couplers coefficients, forming a spectral tunable filter. Finally, we determine the performance parameters of optical sensors and modulators and show that our proposed LT-MZI structure will enhance the sensor figure of merit (FOM) and modulator speed, power consumption and Vπ × L compared to C-MZI. A comparison between symmetric and asymmetric MZI sensors and the advantage of the latter is also mentioned.
Quantity of IgG response to SARS-CoV-2 spike glycoprotein predicts pulmonary recovery from COVID-19
Authors: Nairz Manfred , Sahanic Sabina , Pizzini Alex , Böhm Anna , Tymoszuk Piotr , Mitterstiller Anna-Maria , von Raffay Laura , Grubwieser Philipp , Bellmann-Weiler Rosa , Koppelstätter Sabine , Schroll Andrea , Haschka David , Zimmermann Martina , Blunder Silvia , Trattnig Kristina , Naschberger Helene , Klotz Werner , Theurl Igor , Petzer Verena , Gehrer Clemens , Mindur John E. , Luger Anna , Schwabl Christoph , Widmann Gerlig , Weiss Günter , Löffler-Ragg Judith , Tancevski Ivan , Sonnweber Thomas 
Published: March 2022

AbstractThe CovILD study is a prospective, multicenter, observational cohort study to systematically follow up patients after coronavirus disease-2019 (COVID-19). We extensively evaluated 145 COVID-19 patients at 3 follow-up visits scheduled for 60, 100, and 180 days after initial confirmed diagnosis based on typical symptoms and a positive reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We employed comprehensive pulmonary function and laboratory tests, including serum concentrations of IgG against the viral spike (S) glycoprotein, and compared the results to clinical data and chest computed tomography (CT). We found that at the 60 day follow-up, 131 of 145 (90.3%) participants displayed S-specific serum IgG levels above the cut-off threshold. Notably, the highly elevated IgG levels against S glycoprotein positively correlated with biomarkers of immune activation and negatively correlated with pulmonary function and the extent of pulmonary CT abnormalities. Based on the association between serum S glycoprotein-specific IgG and clinical outcome, we generated an S-specific IgG-based recovery score that, when applied in the early convalescent phase, accurately predicted delayed pulmonary recovery after COVID-19. Therefore, we propose that S-specific IgG levels serve as a useful immunological surrogate marker for identifying at-risk individuals with persistent pulmonary injury who may require intensive follow-up care after COVID-19.