bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of the immune microenvironment of high-risk ductal carcinoma in situ by intralesional pembrolizumab injection
Authors: Glencer Alexa C. , Wong Jasmine M. , Hylton Nola M. , Krings Gregor , McCune Emma , Rothschild Harriet T. , Loveday Tristan A. , Alvarado Michael D. , Esserman Laura J. , Campbell Michael J. 
Published: May 2021

AbstractDuctal carcinoma in situ (DCIS) is a risk factor for the subsequent development of invasive breast cancer. High-risk features include age <45 years, size >5 cm, high-grade, palpable mass, hormone receptor negativity, and HER2 positivity. We have previously shown that immune infiltrates are positively associated with these high-risk features, suggesting that manipulating the immune microenvironment in high-risk DCIS could potentially alter disease progression. Patients with high-risk DCIS were enrolled in this 3 × 3 phase 1 dose-escalation pilot study of 2, 4, and 8 mg intralesional injections of the PD-1 immune checkpoint inhibitor, pembrolizumab. Study participants received two intralesional injections, three weeks apart, prior to surgery. Tissue from pre-treatment biopsies and post-treatment surgical resections was analyzed using multiplex immunofluorescence (mIF) staining for various immune cell populations. The intralesional injections were easily administered and well-tolerated. mIF analyses demonstrated significant increases in total T cell and CD8+ T cell percentages in most patients after receiving pembrolizumab, even at the 2 mg dose. T cell expansion was confined primarily to the stroma rather than within DCIS-containing ducts. Neither cleaved caspase 3 (CC3) staining, a marker for apoptosis, nor DCIS volume (as measured by MRI) changed significantly following treatment. Intralesional injection of pembrolizumab is safe and feasible in patients with DCIS. Nearly all patients experienced robust total and CD8+ T cell responses. However, we did not observe evidence of cell death or tumor volume decrease by MRI, suggesting that additional strategies may be needed to elicit stronger anti-tumor immunity.
Reference SVA insertion polymorphisms are associated with Parkinson’s Disease progression and differential gene expression
Authors: Pfaff Abigail L. , Bubb Vivien J. , Quinn John P. , Koks Sulev 
Published: May 2021

AbstractThe development of Parkinson’s disease (PD) involves a complex interaction of genetic and environmental factors. Genome-wide association studies using extensive single nucleotide polymorphism datasets have identified many loci involved in disease. However much of the heritability of Parkinson’s disease is still to be identified and the functional elements associated with the risk to be determined and understood. To investigate the component of PD that may involve complex genetic variants we characterised the hominid specific retrotransposon SINE-VNTR-Alus (SVAs) in the Parkinson’s Progression Markers Initiative cohort utilising whole genome sequencing. We identified 81 reference SVAs polymorphic for their presence/absence, seven of which were associated with the progression of the disease and with differential gene expression in whole blood RNA sequencing data. This study highlights the importance of addressing SVA variants and potentially other types of retrotransposons in PD genetics, furthermore, these SVA elements should be considered as regulatory domains that could play a role in disease progression.
Parallel quantum simulation of large systems on small NISQ computers
Authors: Barratt F. , Dborin James , Bal Matthias , Stojevic Vid , Pollmann Frank , Green A. G. 
Published: May 2021

AbstractTensor networks permit computational and entanglement resources to be concentrated in interesting regions of Hilbert space. Implemented on NISQ machines they allow simulation of quantum systems that are much larger than the computational machine itself. This is achieved by parallelising the quantum simulation. Here, we demonstrate this in the simplest case; an infinite, translationally invariant quantum spin chain. We provide Cirq and Qiskit code that translates infinite, translationally invariant matrix product state (iMPS) algorithms to finite-depth quantum circuit machines, allowing the representation, optimisation and evolution of arbitrary one-dimensional systems. The illustrative simulated output of these codes for achievable circuit sizes is given.
Efficacy and tolerability of aripiprazole versus D2 antagonists in the early course of schizophrenia: a systematic review and meta-analysis
Authors: Kim David D. , Barr Alasdair M. , Lian Lulu , Yuen Jessica W. Y. , Fredrikson Diane , Honer William G. , Thornton Allen E. , Procyshyn Ric M. 
Published: May 2021

AbstractEarly intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D2 receptor (D2R) partial agonists and D2R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D2R partial agonists with D2R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D2R partial agonist, and was not significantly different from pooled D2R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D2R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D2R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole’s efficacy did not differ substantially from D2R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D2R partial agonists with D2R antagonists in early stages of schizophrenia.
Regional zircon U-Pb geochronology for the Maniitsoq region, southwest Greenland
Authors: Olierook Hugo K. H. , Kirkland Christopher L. , Hollis Julie A. , Gardiner Nicholas J. , Yakymchuk Chris , Szilas Kristoffer , Hartnady Michael I. H. , Barham Milo , McDonald Bradley J. , Evans Noreen J. , Steenfelt Agnete , Waterton Pedro 
Published: May 2021

AbstractZircon U-Pb geochronology places high-temperature geological events into temporal context. Here, we present a comprehensive zircon U-Pb geochronology dataset for the Meso- to Neoarchean Maniitsoq region in southwest Greenland, which includes the Akia Terrane, Tuno Terrane, and the intervening Alanngua Complex. The magmatic and metamorphic processes recorded in these terranes straddle a key change-point in early Earth geodynamics. This dataset comprises zircon U-Pb ages for 121 samples, including 46 that are newly dated. A principal crystallization peak occurs across all three terranes at ca. 3000 Ma, with subordinate crystallization age peaks at 3200 Ma (Akia Terrane and Alanngua Complex only), 2720 Ma and 2540 Ma. Metamorphic age peaks occur at 2990 Ma, 2820–2700 Ma, 2670–2600 Ma and 2540 Ma. Except for one sample, all dated metamorphic zircon growth after the Neoarchean occurred in the Alanngua Complex or within 20 km of its boundaries. This U-Pb dataset provides an important resource for addressing Earth Science topics as diverse as crustal evolution, fluid–rock interaction and mineral deposit genesis.
Comprehensive ultrahigh resolution whole brain in vivo MRI dataset as a human phantom
Authors: Lüsebrink Falk , Mattern Hendrik , Yakupov Renat , Acosta-Cabronero Julio , Ashtarayeh Mohammad , Oeltze-Jafra Steffen , Speck Oliver 
Published: May 2021

AbstractHere, we present an extension to our previously published structural ultrahigh resolution T1-weighted magnetic resonance imaging (MRI) dataset with an isotropic resolution of 250 µm, consisting of multiple additional ultrahigh resolution contrasts. Included are up to 150 µm Time-of-Flight angiography, an updated 250 µm structural T1-weighted reconstruction, 330 µm quantitative susceptibility mapping, up to 450 µm structural T2-weighted imaging, 700 µm T1-weighted back-to-back scans, 800 µm diffusion tensor imaging, one hour continuous resting-state functional MRI with an isotropic spatial resolution of 1.8 mm as well as more than 120 other structural T1-weighted volumes together with multiple corresponding proton density weighted acquisitions collected over ten years. All data are from the same participant and were acquired on the same 7 T scanner. The repository contains the unprocessed data as well as (pre-)processing results. The data were acquired in multiple studies with individual goals. This is a unique and comprehensive collection comprising a “human phantom” dataset. Therefore, we compiled, processed, and structured the data, making them publicly available for further investigation.
Characterization of gross genome rearrangements in Deinococcus radiodurans recA mutants
Authors: Repar Jelena , Zahradka Davor , Sović Ivan , Zahradka Ksenija 
Published: May 2021

AbstractGenome stability in radioresistant bacterium Deinococcus radiodurans depends on RecA, the main bacterial recombinase. Without RecA, gross genome rearrangements occur during repair of DNA double-strand breaks. Long repeated (insertion) sequences have been identified as hot spots for ectopic recombination leading to genome rearrangements, and single-strand annealing (SSA) postulated to be the most likely mechanism involved in this process. Here, we have sequenced five isolates of D. radiodurans recA mutant carrying gross genome rearrangements to precisely characterize the rearrangements and to elucidate the underlying repair mechanism. The detected rearrangements consisted of large deletions in chromosome II in all the sequenced recA isolates. The mechanism behind these deletions clearly differs from the classical SSA; it utilized short (4–11 bp) repeats as opposed to insertion sequences or other long repeats. Moreover, it worked over larger linear DNA distances from those previously tested. Our data are most compatible with alternative end-joining, a recombination mechanism that operates in eukaryotes, but is also found in Escherichia coli. Additionally, despite the recA isolates being preselected for different rearrangement patterns, all identified deletions were found to overlap in a 35 kb genomic region. We weigh the evidence for mechanistic vs. adaptive reasons for this phenomenon.
Beauvericin potentiates the activity of pesticides by neutralizing the ATP-binding cassette transporters in arthropods
Authors: Al Khoury Charbel , Nemer Nabil , Nemer Georges 
Published: May 2021

AbstractMulti-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer’s recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.
Biological autoluminescence for assessing oxidative processes in yeast cell cultures
Authors: Vahalová Petra , Červinková Kateřina , Cifra Michal 
Published: May 2021

AbstractNowadays, modern medicine is looking for new, more gentle, and more efficient diagnostic methods. A pathological state of an organism is often closely connected with increased amount of reactive oxygen species. They can react with biomolecules and subsequent reactions can lead to very low endogenous light emission (biological autoluminescence—BAL). This phenomenon can be potentially used as a non-invasive and low-operational-cost tool for monitoring oxidative stress during diseases. To contribute to the understanding of the parameters affecting BAL, we analyzed the BAL from yeast Saccharomyces cerevisiae as a representative eukaryotic organism. The relationship between the BAL intensity and the amount of reactive oxygen species that originates as a result of the Fenton reaction as well as correlation between spontaneous BAL and selected physical and chemical parameters (pH, oxygen partial pressure, and cell concentration) during cell growth were established. Our results contribute to real-time non-invasive methodologies for monitoring oxidative processes in biomedicine and biotechnology.
Preverbal infants expect agents exhibiting counterintuitive capacities to gain access to contested resources
Authors: Meng Xianwei , Nakawake Yo , Hashiya Kazuhide , Burdett Emily , Jong Jonathan , Whitehouse Harvey 
Published: May 2021

AbstractClaims to supernatural power have been used as a basis for authority in a wide range of societies, but little is known about developmental origins of the link between supernatural power and worldly authority. Here, we show that 12- to 16-month-old infants expect agents exhibiting counterintuitive capacities to win out in a two-way standoff over a contested resource. Infants watched two agents gain a reward using either physically intuitive or physically counterintuitive methods, the latter involving simple forms of levitation or teleportation. Infants looked longer, indicating surprise, when the physically intuitive agent subsequently outcompeted a physically counterintuitive agent in securing a reward. Control experiments indicated that infants’ expectations were not simply motived by the efficiency of agents in pursuing their goals, but specifically the deployment of counterintuitive capacities. This suggests that the link between supernatural power and worldly authority has early origins in development.
Variable coastal hypoxia exposure and drivers across the southern California Current
Authors: Low Natalie H. N. , Micheli Fiorenza , Aguilar Juan Domingo , Arce Daniel Romero , Boch Charles A. , Bonilla Juan Carlos , Bracamontes Miguel Ángel , De Leo Giulio , Diaz Eduardo , Enríquez Eduardo , Hernandez Arturo , Martinez Ramón , Mendoza Ramon , Miranda Claudia , Monismith Stephen , Ramade Mario , Rogers-Bennett Laura , Romero Alfonso , Salinas Carmina , Smith Alexandra E. , Torre Jorge , Villavicencio Gustavo , Woodson C. Brock 
Published: May 2021

AbstractDeclining oxygen is one of the most drastic changes in the ocean, and this trend is expected to worsen under future climate change scenarios. Spatial variability in dissolved oxygen dynamics and hypoxia exposures can drive differences in vulnerabilities of coastal ecosystems and resources, but documentation of variability at regional scales is rare in open-coast systems. Using a regional collaborative network of dissolved oxygen and temperature sensors maintained by scientists and fishing cooperatives from California, USA, and Baja California, Mexico, we characterize spatial and temporal variability in dissolved oxygen and seawater temperature dynamics in kelp forest ecosystems across 13° of latitude in the productive California Current upwelling system. We find distinct latitudinal patterns of hypoxia exposure and evidence for upwelling and respiration as regional drivers of oxygen dynamics, as well as more localized effects. This regional and small-scale spatial variability in dissolved oxygen dynamics supports the use of adaptive management at local scales, and highlights the value of collaborative, large-scale coastal monitoring networks for informing effective adaptation strategies for coastal communities and fisheries in a changing climate.
Effects of occipital-atlas stabilization in the upper cervical spine kinematics: an in vitro study
Authors: Hidalgo-García César , Lorente Ana I. , López-de-Celis Carlos , Lucha-López Orosia , Malo-Urriés Miguel , Rodríguez-Sanz Jacobo , Maza-Frechín Mario , Tricás-Moreno José Miguel , Krauss John , Pérez-Bellmunt Albert 
Published: May 2021

AbstractThis study compares upper cervical spine range of motion (ROM) in the three cardinal planes before and after occiput-atlas (C0–C1) stabilization. After the dissection of the superficial structures to the alar ligament and the fixation of C2, ten cryopreserved upper cervical columns were manually mobilized in the three cardinal planes of movement without and with a screw stabilization of C0–C1. Upper cervical ROM and mobilization force were measured using the Vicon motion capture system and a load cell respectively. The ROM without C0–C1 stabilization was 19.8° ± 5.2° in flexion and 14.3° ± 7.7° in extension. With stabilization, the ROM was 11.5° ± 4.3° and 6.6° ± 3.5°, respectively. The ROM without C0–C1 stabilization was 4.7° ± 2.3° in right lateral flexion and 5.6° ± 3.2° in left lateral flexion. With stabilization, the ROM was 2.3° ± 1.4° and 2.3° ± 1.2°, respectively. The ROM without C0–C1 stabilization was 33.9° ± 6.7° in right rotation and 28.0° ± 6.9° in left rotation. With stabilization, the ROM was 28.5° ± 7.0° and 23.7° ± 8.5° respectively. Stabilization of C0–C1 reduced the upper cervical ROM by 46.9% in the sagittal plane, 55.3% in the frontal plane, and 15.6% in the transverse plane. Also, the resistance to movement during upper cervical mobilization increased following C0–C1 stabilization.
Recommendation for management of patients with their first episode of primary spontaneous pneumothorax, using video-assisted thoracoscopic surgery or conservative treatment
Authors: Chiu Hsin-Yi , Ho Yi-Chia , Yang Pei-Chen , Chiang Chi-Ming , Chung Cheng-Chin , Wu Wei-Ciao , Lin Yu-Cih , Chen Chien-Yu , Wu Yu-Chung 
Published: May 2021

AbstractInternational guidelines do not recommend surgery for the first episode of primary spontaneous pneumothorax (PSP), except in cases of persistent air leak, hemopneumothorax, bilateral pneumothorax, or occupations at risk. However, these recommendations have been challenged because of a significant reduction in the recurrence rate in emerging studies. We evaluated the rationale of recommendations by systematically reviewing RCTs and observational studies by using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. We searched articles in PubMed, EMBASE, and Cochrane databases up to August 15, 2020. The primary outcomes were the recurrence rate and complication rate. The secondary outcomes were hospital stay and drainage duration. Nine eligible studies with 1121 patients were retrieved and analyzed. The recurrence rate was lower in the VATS than in conservative treatment with moderate evidence (OR 0.13, 95% CI 0.09 to 0.19, P < 0.001, I2 = 0%). We did not find significant differences in complication rate (Peto OR 1.17, 95% CI 0.33 to 4.12, P = 0.80), hospital stay duration (MD − 0.48 days, 95% CI − 2.84 to 1.87, P = 0.69, very low evidence), and in drainage duration (MD − 3.99 days, 95% CI − 9.06 to 1.08, P = 0.12, very low evidence) between the two groups. Our results would suggest VATS treatment as a weak recommendation for patients with the first episode of PSP, based on our systematic review of the current evidence by using the GRADE system, indicating that different treatments will be appropriate for different patients and that patients’ values and preferences should be incorporated through shared decision making.Trial REGISTRY: PROSPERO; No.: CRD42020162267.
Modeling cometabolism of hexavalent chromium by iron reducing bacteria in tertiary substrate system
Authors: Upadhyay Shivangi , Sinha Alok 
Published: May 2021

AbstractIn this study, a bacterial strain Serratia sp. was employed for the reduction of synthetically prepared different concentration of Cr(VI) solution (10, 25, 40, 50 and 100 mg/L). Cometabolism study have been carried out in the binary substrate system as well as in the tertiary substrate system. The results revealed that when glucose was added as a co-substrate, at low Cr(VI) concentration, complete reduction was achieved followed by increased biomass growth, but when Cr(VI) concentration was increased to 100 mg/L, the reduction decline to 93%. But in presence of high carbon iron filings (HCIF) as co-substrate even at higher Cr(VI) concentration i.e. 100 mg/L, 100% reduction was achieved and the cell growth continued till 124 h. The study was illustrated via Monod growth kinetic model for tertiary substrate system and the kinetic parameters revealed that the HCIF and glucose combination showed least inhibition to hexavalent chromium reduction by Serratia sp.
Changing friction at the base of an Alpine glacier
Authors: Gräff Dominik , Walter Fabian 
Published: May 2021

AbstractRepeating earthquakes are a global phenomenon of tectonic faults. Multiple ruptures on the same fault asperities lead to nearly identical waveforms characteristic for these seismic events. We identify their microseismic counterparts beneath an Alpine glacier, where basal sliding accounts for a significant amount of ice flow. In contrast to tectonic faults, Alpine glacier beds are subject to large variations in sliding velocity and effective normal stresses. This leads to inter- and sub-seasonal variations in released seismic moment from stick–slip asperities, which we explain with the rate-and-state friction formalism. During summer, numerically modelled effective normal stresses at asperities are three times higher than in winter, which increases the local shear resistance by the same factor. Stronger summer asperities therefore tend to form in bed regions well connected to the efficient subglacial drainage system. Moreover, asperities organise themselves into a state of subcriticality, transferring stresses between each other. We argue that this seismic stick–slip behavior has potentially far-reaching consequences for glacier sliding and in particular for catastrophic failure of unstable ice masses.