bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-Depth Characterization of Layer 5 Output Neurons of the Primary Somatosensory Cortex Innervating the Mouse Dorsal Spinal Cord
Authors: Frezel N , Platonova E , Voigt F F , Mateos J M , Kastli R , Ziegler U , Karayannis T , Helmchen F , Wildner H , Zeilhofer H U 
Published: August 2020

AbstractNeuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher central nervous system areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK + S1-corticospinal tract [CST] neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+ S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. Wheat germ agglutinin-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.
Morphologic Diversity of Merkel Cell Carcinoma
Authors: Ogawa Toru , Donizy Piotr , Wu Cheng-Lin , Cornejo Kristine M. , Ryś Janusz , Hoang Mai P. 
Published: August 2020

Abstract:Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of unknown origin. We performed a retrospective histologic review of primary cutaneous MCCs diagnosed from 1997 to 2018 in several clinical institutions and literature review to determine the frequency of various unusual morphologic appearances of MCC. Of the 136 primary MCCs identified, intraepidermal carcinoma or epidermotropism was noted in 11/136 (8%) cases. An association with pilar cyst in 1/136 (0.7%) case, with actinic keratosis in 2/136 (1.5%) cases, with either invasive or in situ squamous cell carcinoma (SCC) in 14/136 (10%) cases, with poroma in 1/136 (0.7%), and with basal cell carcinoma in 1/136 (0.7%) case was noted. Trabecular pattern and rosettes were noted in 7/136 (5%) and 3/136 (2%) cases, respectively. There was one case of metastatic MCC in a lymph node with chronic lymphocytic leukemia and one rare case of metastatic MCC and SCC in a lymph node. Although uncommon, differentiation toward other cell lineage can be observed in both primary and metastatic MCCs. The tumor can assume a variety of histologic appearances including association with SCC, basal cell carcinoma, melanocytic neoplasm, and follicular cyst; as well as exhibit glandular, sarcomatous, and mesenchymal differentiation. This diversity of morphologic appearance of MCC reflects the complexity of its underlying pathogenesis.
Fifty Years of Surgery for Pancreatic Cancer
Authors: Hackert Thilo , Klaiber Ulla , Pausch Thomas , Mihaljevic André L. , Büchler Markus W. 
Published: August 2020

Abstract
The surgical treatment of pancreatic cancer (PDAC) has seen sweeping changes during the past 5 decades. Up to the middle of the 20th century resection rates were below 5%, but the numbers of curative resections for PDAC are now continuously increasing due to improved neoadjuvant treatment concepts as well as progress in surgical techniques and perioperative management. During the same period, mortality rates after pancreatic surgery have decreased considerably and are now less than 5%. One of the most important cornerstones of reduced mortality has been the concentration of PDAC surgery in specialized centers. In addition, the management of postoperative complications has improved greatly as a result of optimized interdisciplinary teamwork. Adjuvant chemotherapy has become the reference treatment in resected PDAC, achieving significantly prolonged survival. Moreover, the concept of borderline resectable PDAC has emerged to characterize tumors with increased risk for tumor-positive resection margins or worse outcome. The best treatment strategy for borderline resectable PDAC is currently under debate, whereas neoadjuvant therapy has become established as a beneficial treatment option for patients with locally advanced PDAC, enabling conversion surgery in up to 60% of cases. This review article summarizes the principal changes in PDAC surgery during the past 50 years.
Halomonas rituensis sp. nov. and Halomonas zhuhanensis sp. nov., isolated from natural salt marsh sediment on the Tibetan Plateau
Authors: Gao Peixin , Lu Huibin , Xing Peng , Wu Qinglong L. 
Published: August 2020

Two novel Gram-stain-negative, aerobic and non-motile rods bacteria, designated TQ8ST and ZH2ST, were isolated from salt marsh sediment collected from the Tibetan Plateau. Strain TQ8ST was found to grow at 10–40 °C (optimum, 30 °C), pH 6.0–11.0 (optimum, pH 8.0–9.0) and in the presence of 2–12 % (w/v) NaCl (optimum, 6–8 %). Strain ZH2ST was found to grow at 15–40 °C (optimum, 30 °C), pH 7.0–10.0 (optimum pH 9.0) and in the presence of 2–10 % (w/v) NaCl (optimum, 4–6 %). Phylogenetic analysis based on the 16S rRNA gene sequences showed that strains TQ8ST and ZH2ST shared 99.07 % sequence similarity between each other and were affiliated with the genus

Halomonas

, sharing 97.48 % and 97.41 % of sequence similarity to their closest neighbour

Halomonas sulfidaeris

Esulfide1T, respectively. DNA–DNA hybridization analyses showed 61.0 % relatedness between strains TQ8ST and ZH2ST. The average nucleotide identity and the average amino acid identity values between the two genomes were 92.33 and 92.84 %, respectively. The values between the two strains and their close phylogenetic relatives were all below 95 %. The major respiratory quinones of strain TQ8ST were Q-9 and Q-8, while that of ZH2ST was Q-9. The main fatty acids shared by the two strains were C18 : 1
ω6c and/or C18 : 1
ω7c, C16 : 1
ω6c and/or C16 : 1
ω7c, C16 : 0 and C12 : 0 3-OH. Strain ZH2ST can be distinguished from TQ8ST by a higher proportion of C19 : 0 cyclo ω8c. The G+C content of the genomic DNA of strains TQ8ST and ZH2ST were 57.20 and 57.14 mol%, respectively. On the basis of phenotypic distinctiveness and phylogenetic divergence, the two isolates are considered to represent two novel species of the genus

Halomonas

, for which the names Halomonas rituensis sp. nov (type strain TQ8ST=KCTC 62530T=CICC 24572T) and Halomonas zhuhanensis sp. nov (type strain ZH2ST=KCTC 62531T=CICC 24505T) are proposed.
Air pollution, SARS-CoV-2 transmission, and COVID-19 outcomes: A state-of-the-science review of a rapidly evolving research area
Authors: Bhaskar A , Chandra J , Braun D , Cellini J , Dominici F 
Published: August 2020

AbstractBackgroundAs the coronavirus pandemic rages on, 692,000 (August 7, 2020) human lives and counting have been lost worldwide to COVID-19. Understanding the relationship between short- and long-term exposure to air pollution and adverse COVID-19 health outcomes is crucial for developing solutions to this global crisis.ObjectivesTo conduct a scoping review of epidemiologic research on the link between short- and long-term exposure to air pollution and COVID-19 health outcomes.MethodWe searched PubMed, Web of Science, Embase, Cochrane, MedRxiv, and BioRxiv for preliminary epidemiological studies of the association between air pollution and COVID-19 health outcomes. 28 papers were finally selected after applying our inclusion/exclusion criteria; we categorized these studies as long-term studies, short-term time-series studies, or short-term cross-sectional studies. One study included both short-term time-series and a cross-sectional study design.Results27 studies of the 28 reported evidence of statistically significant positive associations between air pollutant exposure and adverse COVID-19 health outcomes; 11 of 12 long-term studies and all 16 short-term studies reported statistically significant positive associations. The 28 identified studies included various confounders, spatial and temporal resolutions of pollution concentrations, and COVID-19 health outcomes.DiscussionWe discuss methodological challenges and highlight additional research areas based on our findings. Challenges include data quality issues, ecological study design limitations, improved adjustment for confounders, exposure errors related to spatial resolution, geographic variability in testing, mitigation measures and pandemic stage, clustering of health outcomes, and a lack of publicly available data and code.
RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study
Authors: Walsh Edward E. , Frenck Robert , Falsey Ann R. , Kitchin Nicholas , Absalon Judith , Gurtman Alejandra , Lockhart Stephen , Neuzil Kathleen , Mulligan Mark J. , Bailey Ruth , Swanson Kena A. , Li Ping , Koury Kenneth , Kalina Warren , Cooper David , Fontes-Garfias Camila , Shi Pei-Yong , Türeci Özlem , Tompkins Kristin R. , Lyke Kirsten E. , Raabe Vanessa , Dormitzer Philip R. , Jansen Kathrin U. , Şahin Uğur , Gruber William C. 
Published: August 2020

ABSTRACTBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally. Multiple vaccine candidates are under development, but no vaccine is currently available.MethodsHealthy adults 18–55 and 65–85 years of age were randomized in an ongoing, placebo-controlled, observer-blinded dose-escalation study to receive 2 doses at 21-day intervals of placebo or either of 2 lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor-binding domain, or BNT162b2, which encodes a prefusion stabilized membrane-anchored SARS-CoV-2 full-length spike. In each of 13 groups of 15 participants, 12 received vaccine and 3 received placebo. Groups were distinguished by vaccine candidate, age of participant, and vaccine dose level. Interim safety and immunogenicity data of BNT162b1 in younger adults have been reported previously from US and German trials. We now present additional safety and immunogenicity data from the US Phase 1 trial that supported selection of the vaccine candidate advanced to a pivotal Phase 2/3 safety and efficacy evaluation.ResultsIn both younger and older adults, the 2 vaccine candidates elicited similar dose- dependent SARS-CoV-2-neutralizing geometric mean titers (GMTs), comparable to or higher than the GMT of a panel of SARS-CoV-2 convalescent sera. BNT162b2 was associated with less systemic reactogenicity, particularly in older adults.ConclusionThese results support selection of the BNT162b2 vaccine candidate for Phase 2/3 large-scale safety and efficacy evaluation, currently underway.
DNA oxidation induced by fetal exposure to BPA agonists impairs female meiosis
Authors: Abdallah Sonia , Moison Delphine , Wieckowski Margaux , Messiaen Sébastien , Martini Emmanuelle , Campalans Anna , Radicella J. Pablo , Habert René , Livera Gabriel , Rouiller-Fabre Virginie , Guerquin Marie-Justine 
Published: August 2020

SummaryMany endocrine disruptors have been proven to impair the meiotic process that is mandatory to produce healthy gametes. Bisphenol A is emblematic as it impairs meiotic prophase I and causes oocyte aneuploidy followingin uteroexposure. However, the mechanisms underlying these deleterious effects remain poorly understood. Furthermore, the increasing uses of BPA analogs raise concerns for public health. Here, we investigated the effect on oogenesis in mouse of fetal exposure to two BPA analogs, Bisphenol A Diglycidyl Ether (BADGE) or Bisphenol AF (BPAF). These analogs delay meiosis initiation, increase MLH1 focipercell and induce oocyte aneuploidy. We further demonstrate that these defects are accompanied by a deregulation of gene expression and aberrant mRNA splicing in fetal premeiotic germ cells. Interestingly, we observed an increase in DNA oxidation after exposure to BPA analogs. Specific induction of oxidative DNA damages during fetal germ cell differentiation causes similar defects during oogenesis, as observed in 8-Oxoguanine DNA Glycosylase (OGG1) deficient mice or afterin uteroexposure to potassium bromate (KBrO3), an inducer of oxidative DNA damages. Moreover, the supplementation of N-acetylcysteine (NAC) with BPA analogs counteracts the bisphenol-induced meiotic effect. Together our results position oxidative stress as a central event that negatively impacts the female meiosis with major consequences on oocyte quality. This could be a common mechanism of action for so called endocrine disruptors pollutants and it could lead to novel strategies for reprotoxic compounds.
Correlated decision making across multiple phases of olfactory guided search in Drosophila
Authors: van Breugel Floris 
Published: August 2020

AbstractAll motile organisms must search for food, often requiring the exploration of heterogeneous environments across a wide range of spatial scales. Recent field and laboratory experiments with the fruit fly,Drosophila, have revealed that they employ different strategies across these regimes, including kilometer scale straight-path flights between resource clusters, zig-zagging trajectories to follow odor plumes, and local search on foot after landing. However, little is known about the extent to which experiences in one regime might influence decisions in another. To determine how a flies’ odor plume tracking during flight is related to their behavior after landing, I tracked the behavior of individually labelled fruit flies as they explored an array of three odor emitting, but food-barren, objects. The distance flies travelled on the objects in search of food was correlated with the time elapsed between their visits, suggesting that their in-flight plume tracking and on-foot local search behaviors are interconnected through a lossy memory-like process.
A Practical Alzheimer Disease Classifier via Brain Imaging-Based Deep Learning on 85,721 Samples
Authors: Lu Bin , Li Hui-Xian , Chang Zhi-Kai , Li Le , Chen Ning-Xuan , Zhu Zhi-Chen , Zhou Hui-Xia , Li Xue-Ying , Wang Yu-Wei , Cui Shi-Xian , Deng Zhao-Yu , Fan Zhen , Yang Hong , Chen Xiao , Thompson Paul M. , Castellanos Francisco Xavier , Yan Chao-Gan ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2020

AbstractBeyond detecting brain lesions or tumors, comparatively little success has been attained in identifying brain disorders such as Alzheimer’s disease (AD), based on magnetic resonance imaging (MRI). Many machine learning algorithms to detect AD have been trained using limited training data, meaning they often generalize poorly when applied to scans from previously unseen populations. Therefore, we built a practical brain MRI-based AD diagnostic classifier using deep learning/transfer learning on a dataset of unprecedented size and diversity. A retrospective MRI dataset pooled from more than 217 sites/scanners constituted one of the largest brain MRI samples to date (85,721 scans from 50,876 participants) between January 2017 and August 2021. Next, a state-of-the-art deep convolutional neural network, Inception-ResNet-V2, was built as a sex classifier with high generalization capability. The sex classifier achieved 94.9% accuracy and served as a base model in transfer learning for the objective diagnosis of AD. After transfer learning, the model fine-tuned for AD classification achieved 90.9% accuracy in leave-sites-out cross-validation on the Alzheimer’s Disease Neuroimaging Initiative (ADNI, 6,857 samples) dataset and 94.5%/93.6%/91.1% accuracy for direct tests on three unseen independent datasets (AIBL, 669 samples / MIRIAD, 644 samples / OASIS, 1,123 samples). When this AD classifier was tested on brain images from unseen mild cognitive impairment (MCI) patients, MCI patients who converted to AD were 3 times more likely to be predicted as AD than MCI patients who did not convert (65.2% vs 20.6%). Predicted scores from the AD classifier showed significant correlations with illness severity. In sum, the proposed AD classifier offers a medical-grade marker that has potential to be integrated into AD diagnostic practice.
Myanmar’s terrestrial ecosystems: status, threats and conservation opportunities
Authors: Murray Nicholas J. , Keith David A. , Duncan Adam , Tizard Robert , Ferrer-Paris Jose R. , Worthington Thomas A. , Armstrong Kate , Hlaing Nyan , Htut Win Thuya , Oo Aung Htat , Ya Kyaw Zay , Grantham Hedley 
Published: August 2020

AbstractMyanmar is highly biodiverse, with more than 16,000 plant, 314 mammal, 1131 bird, 293 reptile, and 139 amphibian species. Supporting this biodiversity is a variety of natural ecosystems—mostly undescribed—including tropical and subtropical forests, savannas, seasonally inundated wetlands, extensive shoreline and tidal systems, and alpine ecosystems. Although Myanmar contains some of the largest intact natural ecosystems in Southeast Asia, remaining ecosystems are under threat from accelerating land use intensification and over-exploitation. In this period of rapid change, a systematic risk assessment is urgently needed to estimate the extent and magnitude of human impacts and identify ecosystems most at risk to help guide strategic conservation action. Here we provide the first comprehensive conservation assessment of Myanmar’s natural terrestrial ecosystems using the IUCN Red List of Ecosystems categories and criteria. We identified 64 ecosystem types for the assessment, and used models of ecosystem distributions and syntheses of existing data to estimate declines in distribution, range size, and functioning of each ecosystem. We found that more than a third (36.9%) of Myanmar’s area has been converted to anthropogenic ecosystems over the last 2-3 centuries, leaving nearly half of Myanmar’s ecosystems threatened (29 of 64 ecosystems). A quarter of Myanmar’s ecosystems were identified as Data Deficient, reflecting a paucity of studies and an urgency for future research. Our results show that, with nearly two-thirds of Myanmar still covered in natural ecosystems, there is a crucial opportunity to develop a comprehensive protected area network that sufficiently represents Myanmar’s terrestrial ecosystem diversity.
Design of synthetic human gut microbiome assembly and function
Authors: Clark Ryan L. , Connors Bryce M. , Stevenson David M. , Hromada Susan E. , Hamilton Joshua J. , Amador-Noguez Daniel , Venturelli Ophelia S. 
Published: August 2020

ABSTRACTThe assembly of microbial communities and functions emerge from a complex and dynamic web of interactions. A major challenge in microbiome engineering is identifying organism configurations with community-level behaviors that achieve a desired function. The number of possible subcommunities scales exponentially with the number of species in a system, creating a vast experimental design space that is challenging to even sparsely traverse. We develop a model-guided experimental design framework for microbial communities and apply this method to explore the functional landscape of the health-relevant metabolite butyrate using a 25-member synthetic human gut microbiome community. Based on limited experimental measurements, our model accurately forecasts community assembly and butyrate production at every possible level of complexity. Our results elucidate key ecological and molecular mechanisms driving butyrate production including inter-species interactions, pH and hydrogen sulfide. Our model-guided iterative approach provides a flexible framework for understanding and predicting community functions for a broad range of applications.
MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane
Authors: Matsuoka Risa , Miki Masateru , Mizuno Sonoko , Ito Yurina , Yamada Chihiro , Suzuki Atsushi 
Published: August 2020

AbstractThe Golgi complex plays an active role in organizing asymmetric microtubule arrays essential for polarized vesicle transport. The coiled-coil protein MTCL1 stabilizes microtubules nucleated from the Golgi membrane. Here, we report an MTCL1 paralog, MTCL2, which preferentially acts on the perinuclear microtubules accumulated around the Golgi. MTCL2 associates with the Golgi membrane through the N-terminal coiled- coil region and directly binds microtubules through the conserved C-terminal domain without promoting microtubule stabilization. Knockdown of MTCL2 significantly impaired microtubule accumulation around the Golgi as well as the compactness of the Golgi ribbon assembly structure. Given that MTCL2 forms parallel oligomers through homo-interaction of the central coiled-coil motifs, our results indicate that MTCL2 promotes asymmetric microtubule organization by crosslinking microtubules on the Golgi membrane. Results ofin vitrowound healing assays further suggest that this function of MTCL2 enables integration of the centrosomal and Golgi-associated microtubules on the Golgi membrane, supporting directional migration. Additionally, the results demonstrated the involvement of CLASPs and giantin in mediating the Golgi association of MTCL2.
Belowground plant-plant signaling of root infection by nematodes
Authors: Zhang Peihua , Bonte Dries , De Deyn Gerlinde B. , Vandegehuchte Martijn L. 
Published: August 2020

AbstractCommunication between plants mediated by herbivore-induced volatile organic compounds has been extensively studied aboveground. However, the role of root herbivory in belowground plant-plant communication is much less understood. We here investigated whether root herbivores can trigger plant roots to emit warning signals to neighbouring plants that are not yet in direct contact with them.We used a split-root system and infected half of the roots ofAgrostis stoloniferaplants with root-knot nematodes (Meloidogyne minor) and left the other half uninfected. As a control, we grew plants without nematodes in separate pots. Leachates from each split-root soil compartment and from soils with control plants were applied to separate pots withA. stoloniferaplants, of which biomass allocation and morphological traits were measured one month after leachate addition.Plants receiving leachates from the soil with the nematode-free roots of the nematode-infected plants showed a significantly larger total biomass, more root branches, and deeper rooting than plants receiving leachates from the soil with the nematode-infected roots or from soil with control plants. Plants were taller and the root/shoot ratio was higher in plants receiving leachates from soil with the nematode-free roots than in plants receiving leachates from soil with nematode-infected roots. Shoot tiller number was higher in plants receiving leachates from either soil of the nematode-infected plants than in plants receiving control leachates.Our results suggest that an overcompensation response was triggered by systemically induced root-derived compounds from nematode-free roots of a plant locally infected with root-feeding nematodes. Signals from directly attacked roots of the same nematode-infected plant only caused receiver plants to develop more shoot tillers, possibly for future stolon development to grow away from the infected area. This may indicate an anticipatory tolerance response to root feeders that are still distant and an additional generalized escape response to root feeding.