bluuebunny/crossref_metadata_2025_split huggingface dataset:
A hydraulic instability drives the cell death decision in the nematode germline
Authors: Chartier Nicolas T. , Mukherjee Arghyadip , Pfanzelter Julia , Fürthauer Sebastian , Larson Ben T. , Fritsch Anatol W. , Amini Rana , Kreysing Moritz , Jülicher Frank , Grill Stephan W. 
Published: May 2021

AbstractOocytes are large cells that develop into an embryo upon fertilization1. As interconnected germ cells mature into oocytes, some of them grow—typically at the expense of others that undergo cell death2–4. We present evidence that in the nematode Caenorhabditis elegans, this cell-fate decision is mechanical and related to tissue hydraulics. An analysis of germ cell volumes and material fluxes identifies a hydraulic instability that amplifies volume differences and causes some germ cells to grow and others to shrink, a phenomenon that is related to the two-balloon instability5. Shrinking germ cells are extruded and they die, as we demonstrate by artificially reducing germ cell volumes via thermoviscous pumping6. Our work reveals a hydraulic symmetry-breaking transition central to the decision between life and death in the nematode germline.
Spectroscopic and deep learning-based approaches to identify and quantify cerebral microhemorrhages
Authors: Crouzet Christian , Jeong Gwangjin , Chae Rachel H. , LoPresti Krystal T. , Dunn Cody E. , Xie Danny F. , Agu Chiagoziem , Fang Chuo , Nunes Ane C. F. , Lau Wei Ling , Kim Sehwan , Cribbs David H. , Fisher Mark , Choi Bernard 
Published: May 2021

AbstractCerebral microhemorrhages (CMHs) are associated with cerebrovascular disease, cognitive impairment, and normal aging. One method to study CMHs is to analyze histological sections (5–40 μm) stained with Prussian blue. Currently, users manually and subjectively identify and quantify Prussian blue-stained regions of interest, which is prone to inter-individual variability and can lead to significant delays in data analysis. To improve this labor-intensive process, we developed and compared three digital pathology approaches to identify and quantify CMHs from Prussian blue-stained brain sections: (1) ratiometric analysis of RGB pixel values, (2) phasor analysis of RGB images, and (3) deep learning using a mask region-based convolutional neural network. We applied these approaches to a preclinical mouse model of inflammation-induced CMHs. One-hundred CMHs were imaged using a 20 × objective and RGB color camera. To determine the ground truth, four users independently annotated Prussian blue-labeled CMHs. The deep learning and ratiometric approaches performed better than the phasor analysis approach compared to the ground truth. The deep learning approach had the most precision of the three methods. The ratiometric approach has the most versatility and maintained accuracy, albeit with less precision. Our data suggest that implementing these methods to analyze CMH images can drastically increase the processing speed while maintaining precision and accuracy.
Glucose and NAADP trigger elementary intracellular β-cell Ca2+ signals
Authors: Heister Paula Maria , Powell Trevor , Galione Antony 
Published: May 2021

AbstractPancreatic β-cells release insulin upon a rise in blood glucose. The precise mechanisms of stimulus-secretion coupling, and its failure in Diabetes Mellitus Type 2, remain to be elucidated. The consensus model, as well as a class of currently prescribed anti-diabetic drugs, are based around the observation that glucose-evoked ATP production in β-cells leads to closure of cell membrane ATP-gated potassium (KATP) channels, plasma membrane depolarisation, Ca2+ influx, and finally the exocytosis of insulin granules. However, it has been demonstrated by the inactivation of this pathway using genetic and pharmacological means that closure of the KATP channel alone may not be sufficient to explain all β-cell responses to glucose elevation. We have previously proposed that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells. Here we show using total internal reflection fluorescence (TIRF) microscopy that glucose as well as the Ca2+ mobilising messenger nicotinic acid adenine dinucleotide phosphate (NAADP), known to operate in β-cells, lead to highly localised elementary intracellular Ca2+ signals. These were found to be obscured by measurements of global Ca2+ signals and the action of powerful SERCA-based sequestration mechanisms at the endoplasmic reticulum (ER). Building on our previous work demonstrating that NAADP-evoked Ca2+ release is an important step in stimulus-secretion coupling in pancreatic β-cells, we provide here the first demonstration of elementary Ca2+ signals in response to NAADP, whose occurrence was previously suspected. Optical quantal analysis of these events reveals a unitary event amplitude equivalent to that of known elementary Ca2+ signalling events, inositol trisphosphate (IP3) receptor mediated blips, and ryanodine receptor mediated quarks. We propose that a mechanism based on these highly localised intracellular Ca2+ signalling events mediated by NAADP may initially operate in β-cells when they respond to elevations in blood glucose.
Indications, feasibility and outcome of robotic retroperitoneal lymph node dissection for metastatic testicular germ cell tumours
Authors: Ohlmann Carsten-Henning , Saar Matthias , Pierchalla Laura-Christin , Zangana Miran , Bonaventura Alena , Stöckle Michael , Siemer Stefan , Heinzelbecker Julia 
Published: May 2021

AbstractData on robotic retroperitoneal lymph node dissection (R-RPLND) for metastatic testicular germ cell tumours (mTGCTs) are scarce and the use of R-RPLND itself is still under debate. The aim of our study was to evaluate the indications, feasibility and outcomes of R-RPLND, with special emphasis on differences between primary R-RPLND (pR-RPLND) and post-chemotherapeutic R-RPLND (pcR-RPLND) in mTGCTs. We retrospectively analysed the data of patients who underwent R-RPLND for mTGCT between November 2013 and September 2019 in two centres in Germany. Indications, operative technique, intra- and postoperative complications and oncologic outcome were analysed. Twenty-three mTGCT patients underwent R-RPLND (7 pR-RPLND, 16 pcR-RPLND). For pR-RPLND versus pcR-RPLND, median time of surgery was 243 min [interquartile range (IQR) 123–303] versus 359 min (IQR 202–440, p = 0.154) and median blood loss 100 mL (IQR 50–200) versus 275 mL (IQR 100–775, p = 0.018). Intra- and postoperative complications were more frequent in pcR-RPLND (pcR-RPLND: intra/post: 44%/44%; pR-RPLND: intra/post: 0%/29%). However, these were only statistically significant in the case of intraoperative complications (intra: p = 0.036, post: p = 0.579). Intraoperative complications (n = 7), conversions (n = 4) and transfusions (n = 4) occurred in pcR-RPLND patients only. After a median follow-up of 16.3 months (IQR 7.5–35.0) there were no recurrences or deaths. R-RPLND displays a valuable, minimally invasive treatment option in mTGCT. However, R-RPLND is challenging and pcR-RPLND especially bears a considerable risk of complications. This operation should be limited to patients with an easily accessible residual tumour mass and to surgeons experienced in robotic surgery and TGCT treatment.
PapRIV, a BV-2 microglial cell activating quorum sensing peptide
Authors: Janssens Yorick , Debunne Nathan , De Spiegeleer Anton , Wynendaele Evelien , Planas Marta , Feliu Lidia , Quarta Alessandra , Claes Christel , Van Dam Debby , De Deyn Peter Paul , Ponsaerts Peter , Blurton-Jones Matthew , De Spiegeleer Bart 
Published: May 2021

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.
Anapole-assisted giant electric field enhancement for surface-enhanced coherent anti-Stokes Raman spectroscopy
Authors: Ghahremani Maryam , Habil Mojtaba Karimi , Zapata-Rodriguez Carlos J. 
Published: May 2021

AbstractThe coherent anti-Stokes Raman spectroscopy (CARS) techniques are recognized for their ability to detect and identify vibrational coherent processes down to the single-molecular levels. Plasmonic oligomers supporting full-range Fano-like line profiles in their scattering spectrum are one of the most promising class of substrates in the context of surface-enhanced (SE) CARS application. In this work, an engineered assembly of metallic disk-shaped nanoparticles providing two Fano-like resonance modes is presented as a highly-efficient design of SECARS substrate. We show that the scattering dips corresponding to the double-Fano spectral line shapes are originated from the mutual interaction of electric and toroidal dipole moments, leading to the so-called non-trivial first- and second-order anapole states. The anapole modes, especially the higher-order ones, can result in huge near-field enhancement due to their light-trapping capability into the so-called “hot spots”. In addition, independent spectral tunability of the second Fano line shape is exhibited by modulating the gap distance of the corner particles. This feature is closely related to the electric current loop associated with the corner particles in the second-order anapole state and provides a simple design procedure of an optimum SECARS substrate, where the electric field hot spots corresponding to three involved wavelengths, i.e., anti-Stokes, pump, and Stokes, are localized at the same spatial position. These findings yield valuable insight into the plasmonic substrate design for SECARS applications as well as for other nonlinear optical processes, such as four-wave mixing and multi-photon surface spectroscopy.
Comparison of cine and real-time cardiac MRI in rhesus macaques
Authors: Moussavi Amir , Mißbach Sophie , Serrano Ferrel Claudia , Ghasemipour Hasti , Kötz Kristin , Drummer Charis , Behr Rüdiger , Zimmermann Wolfram-Hubertus , Boretius Susann 
Published: May 2021

AbstractCardiac MRI in rhesus macaques, a species of major relevance for preclinical studies on biological therapies, requires artificial ventilation to realize breath holding. To overcome this limitation of standard cine MRI, the feasibility of Real-Time (RT) cardiac MRI has been tested in a cohort of ten adult rhesus macaques using a clinical MR-system. In spite of lower tissue contrast and sharpness of RT-MRI, cardiac functions were similarly well assessed by RT-MRI compared to cine MRI (similar intra-subject repeatability). However, systematic underestimation of the end-diastolic volume (31 ± 9%), end-systolic volume (20 ± 11%), stroke volume (40 ± 12%) and ejection fraction (13 ± 9%) hamper the comparability of RT-MRI results with those of other cardiac MRI methods. Yet, the underestimations were very consistent (< 5% variability) for repetitive measurements, making RT-MRI an appropriate alternative to cine MRI for longitudinal studies. In addition, RT-MRI enabled the analysis of cardio-respiratory coupling. All functional parameters showed lower values during expiration compared to inspiration, most likely due to the pressure-controlled artificial ventilation. In conclusion, despite systematic underestimation of the functional parameters, RT-MRI allowed the assessment of left ventricular function in macaques with significantly less experimental effort, measurement time, risk and burden for the animals compared to cine MRI.
CoolMomentum: a method for stochastic optimization by Langevin dynamics with simulated annealing
Authors: Borysenko Oleksandr , Byshkin Maksym 
Published: May 2021

AbstractDeep learning applications require global optimization of non-convex objective functions, which have multiple local minima. The same problem is often found in physical simulations and may be resolved by the methods of Langevin dynamics with Simulated Annealing, which is a well-established approach for minimization of many-particle potentials. This analogy provides useful insights for non-convex stochastic optimization in machine learning. Here we find that integration of the discretized Langevin equation gives a coordinate updating rule equivalent to the famous Momentum optimization algorithm. As a main result, we show that a gradual decrease of the momentum coefficient from the initial value close to unity until zero is equivalent to application of Simulated Annealing or slow cooling, in physical terms. Making use of this novel approach, we propose CoolMomentum—a new stochastic optimization method. Applying Coolmomentum to optimization of Resnet-20 on Cifar-10 dataset and Efficientnet-B0 on Imagenet, we demonstrate that it is able to achieve high accuracies.
Infection with Borrelia afzelii and manipulation of the egg surface microbiota have no effect on the fitness of immature Ixodes ricinus ticks
Authors: Hurry Georgia , Maluenda Elodie , Sarr Anouk , Belli Alessandro , Hamilton Phineas T. , Duron Olivier , Plantard Olivier , Voordouw Maarten J. 
Published: May 2021

AbstractArthropod vectors carry vector-borne pathogens that cause infectious disease in vertebrate hosts, and arthropod-associated microbiota, which consists of non-pathogenic microorganisms. Vector-borne pathogens and the microbiota can both influence the fitness of their arthropod vectors, and hence the epidemiology of vector-borne diseases. The bacterium Borrelia afzelii, which causes Lyme borreliosis in Europe, is transmitted among vertebrate reservoir hosts by Ixodes ricinus ticks, which also harbour a diverse microbiota of non-pathogenic bacteria. The purpose of this controlled study was to test whether B. afzelii and the tick-associated microbiota influence the fitness of I. ricinus. Eggs obtained from field-collected adult female ticks were surface sterilized (with bleach and ethanol), which reduced the abundance of the bacterial microbiota in the hatched I. ricinus larvae by 28-fold compared to larvae that hatched from control eggs washed with water. The dysbiosed and control larvae were subsequently fed on B. afzelii-infected or uninfected control mice, and the engorged larvae were left to moult into nymphs under laboratory conditions. I. ricinus larvae that fed on B. afzelii-infected mice had a significantly faster larva-to-nymph moulting time compared to larvae that fed on uninfected control mice, but the effect was small (2.4% reduction) and unlikely to be biologically significant. We found no evidence that B. afzelii infection or reduction of the larval microbiota influenced the four other life history traits of the immature I. ricinus ticks, which included engorged larval weight, unfed nymphal weight, larva-to-nymph moulting success, and immature tick survival. A retrospective power analysis found that our sampling effort had sufficient power (> 80%) to detect small effects (differences of 5% to 10%) of our treatments. Under the environmental conditions of this study, we conclude that B. afzelii and the egg surface microbiota had no meaningful effects on tick fitness and hence on the R0 of Lyme borreliosis.
Withaferin A inhibits lymphocyte proliferation, dendritic cell maturation in vitro and prolongs islet allograft survival
Authors: Kumano Kenjiro , Kanak Mazhar A. , Saravanan Prathab Balaji , Blanck J. P. , Liu Yang , Vasu Srividya , Lawrence Michael , Naziruddin Bashoo 
Published: May 2021

AbstractThe immunosuppressive regimen for clinical allogeneic islet transplantation uses beta cell–toxic compounds such as tacrolimus that cause islet graft loss. Previously we reported that the plant-derived steroidal lactone Withaferin A (WA) can protect islet grafts by inhibiting nuclear factor-kappa B (NF-κB). Since the NF-κB signaling pathway is essential for T-cell activation, we hypothesized that long-term WA administration may also provide an immunosuppressive effect. Treatment of BALB/c donor islets and C57BL/6N recipients with WA alone resulted in 80% islet graft long-term survival vs. 40% in low-dose FK506-treated mice. In vitro, WA significantly blocked mouse and human T-cell proliferation by CD3/CD28 bead stimulation and in mixed lymphocyte reaction assay. Treatment of immature dendritic cells with WA prevented their maturation in response to inflammatory stimuli, as seen by decreased expression of CD83 and human leukocyte antigen–DR isotype. Exosomes released by islets treated with WA contained significantly fewer proinflammatory molecules interleukin-6, interleukin-8, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, inducible nitric oxide synthase, and cyclooxygenase-2. In conclusion, WA treatment not only reduced inflammation but also prolonged allograft survival, possibly through suppression of dendritic cell maturation and T-cell proliferation. WA has the potential to inhibit both the innate and adaptive immune response to prolong allograft survival.
Antimicrobial responses of peripheral and central nervous system glia against Staphylococcus aureus
Authors: Choudhury Indra N. , Chacko Anu , Delbaz Ali , Chen Mo , Basu Souptik , St John James A. , Huygens Flavia , Ekberg Jenny A. K. 
Published: May 2021

AbstractStaphylococcus aureusinfections of the central nervous system are serious and can be fatal.S. aureusis commonly present in the nasal cavity, and after injury to the nasal epithelium it can rapidly invade the brain via the olfactory nerve. The trigeminal nerve constitutes another potential route of brain infection. The glia of these nerves, olfactory ensheathing cells (OECs) and trigeminal nerve Schwann cells (TgSCs), as well as astrocytes populating the glia limitans layer, can phagocytose bacteria. Whilst some glial responses toS. aureushave been studied, the specific responses of different glial types are unknown. Here, we compared how primary mouse OECs, TgSCs, astrocytes and microglia responded toS. aureus. All glial types internalized the bacteria within phagolysosomes, andS. aureus-conjugated BioParticles could be tracked with subtle but significant differences in time-course of phagocytosis between glial types. Live bacteria could be isolated from all glia after 24 h in culture, and microglia, OECs and TgSCs exhibited better protection against intracellularS. aureussurvival than astrocytes. All glial types responded to the bacteria by cytokine secretion. Overall, OECs secreted the lowest level of cytokines, suggesting that these cells, despite showing strong capacity for phagocytosis, have immunomodulatory functions that can be relevant for neural repair.
Comparing machine learning algorithms for predicting ICU admission and mortality in COVID-19
Authors: Subudhi Sonu , Verma Ashish , Patel Ankit B. , Hardin C. Corey , Khandekar Melin J. , Lee Hang , McEvoy Dustin , Stylianopoulos Triantafyllos , Munn Lance L. , Dutta Sayon , Jain Rakesh K. 
Published: May 2021

AbstractAs predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O2 saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m2, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.
Cryptic developmental events determine medulloblastoma radiosensitivity and cellular heterogeneity without altering transcriptomic profile
Authors: Malawsky Daniel Shiloh , Weir Seth J. , Ocasio Jennifer Karin , Babcock Benjamin , Dismuke Taylor , Cleveland Abigail H. , Donson Andrew M. , Vibhakar Rajeev , Wilhelmsen Kirk , Gershon Timothy R. 
Published: May 2021

AbstractIt is unclear why medulloblastoma patients receiving similar treatments experience different outcomes. Transcriptomic profiling identified subgroups with different prognoses, but in each subgroup, individuals remain at risk of incurable recurrence. To investigate why similar-appearing tumors produce variable outcomes, we analyzed medulloblastomas triggered in transgenic mice by a common driver mutation expressed at different points in brain development. We genetically engineered mice to express oncogenic SmoM2, starting in multipotent glio-neuronal stem cells, or committed neural progenitors. Both groups developed medulloblastomas with similar transcriptomic profiles. We compared medulloblastoma progression, radiosensitivity, and cellular heterogeneity, determined by single-cell transcriptomic analysis (scRNA-seq). Stem cell-triggered medulloblastomas progressed faster, contained more OLIG2-expressing stem-like cells, and consistently showed radioresistance. In contrast, progenitor-triggered MBs progressed slower, down-regulated stem-like cells and were curable with radiation. Progenitor-triggered medulloblastomas also contained more diverse stromal populations, with more Ccr2+ macrophages and fewer Igf1+ microglia, indicating that developmental events affected the subsequent tumor microenvironment. Reduced mTORC1 activity in M-Smo tumors suggests that differential Igf1 contributed to differences in phenotype. Developmental events in tumorigenesis that were obscure in transcriptomic profiles thus remained cryptic determinants of tumor composition and outcome. Precise understanding of medulloblastoma pathogenesis and prognosis requires supplementing transcriptomic/methylomic studies with analyses that resolve cellular heterogeneity.