bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bio-Inspired Attentive Segmentation of Retinal OCT imaging
Authors: Lazaridis Georgios , Xu Moucheng , Afgeh Saman Sadeghi , Montesano Giovanni , Garway-Heath David 
Published: August 2020

AbstractAlbeit optical coherence imaging (OCT) is widely used to assess ophthalmic pathologies, localization of intra-retinal boundaries suffers from erroneous segmentations due to image artifacts or topological abnormalities. Although deep learning-based methods have been effectively applied in OCT imaging, accurate automated layer segmentation remains a challenging task, with the flexibility and precision of most methods being highly constrained. In this paper, we propose a novel method to segment all retinal layers, tailored to the bio-topological OCT geometry. In addition to traditional learning of shift-invariant features, our method learns in selected pixels horizontally and vertically, exploiting the orientation of the extracted features. In this way, the most discriminative retinal features are generated in a robust manner, while long-range pixel dependencies across spatial locations are efficiently captured. To validate the effectiveness and generalisation of our method, we implement three sets of networks based on different backbone models. Results on three independent studies show that our methodology consistently produces more accurate segmentations than state-of-the-art networks, and shows better precision and agreement with ground truth. Thus, our method not only improves segmentation, but also enhances the statistical power of clinical trials with layer thickness change outcomes.
Wide-based Foveal Pit: A Predisposition to Idiopathic Epiretinal Membrane
Authors: Ma I-Hsin , Yang Chung-May , Hsieh Yi-Ting 
Published: August 2020

AbstractAimsTo report the anatomical characteristics of wide-based foveal pit and its associations with macular diseases.MethodsWide-based foveal pit was defined as a foveal base width (FBW) larger than the mean value plus one standard deviation of normal population. Eyes with a wide-based foveal pit were retrospectively collected as the study group, and age- and sex-matched subjects with a normal FBW were recruited as the control group. FBW, area of foveal avascular zone (FAZ) and retinal artery trajectory (RAT) were compared between two groups. The characteristics of the fellow eyes in the study group were also described.ResultsFifty two eyes from 52 patients were identified as having a wide-based foveal pit; 43 (82.7%) were female. Both their FBW (474.7 ± 84.6μm) and area of FAZ (0.50 ± 0.11mm2) were significantly larger than in the control group (297.6 ± 42.3 μm and 0.29 ± 0.10 mm2, respectively; p < 0.001 for both), and they also had a wider RAT than the control group (p < 0.001). During follow-up, three eyes had developed idiopathic epiretinal membrane. As for their fellow eyes, they either also had a wide-based foveal pit (11 eyes) or had various macular diseases including idiopathic epiretinal membrane (27 eyes), macular hole (5 eyes) and others (16 eyes).ConclusionsEyes with a wide-based foveal pit also had a large FAZ and a wide RAT, and they might have a predisposition to idiopathic epiretinal membrane formation. Their fellow eyes also had a predisposition to epiretinal membrane and macular hole.SynopsisEyes with a wide-based foveal pit had a predisposition to idiopathic epiretinal membrane formation. Their fellow eyes might also have a wide-based foveal pit and had a predisposition to epiretinal membrane and macular hole.
Influence of adherence to social distancing due to the COVID-19 pandemic on physical activity level in post-bariatric patients
Authors: Rezende Diego Augusto Nunes , Pinto Ana Jéssica , Goessler Karla Fabiana , Nicoletti Carolina Ferreira , Sieczkowska Sofia Mendes , Meireles Kamila , Esteves Gabriel Perri , Genario Rafael , de Oliveira Gersiel Nascimento , Santo Marco Aurélio , de Cleva Roberto , Roschel Hamilton , Gualano Bruno 
Published: August 2020

ABSTRACTObjectivesTo assess physical activity levels in post-bariatric patients who adhered or not to social distancing measures due to the Covid-19 pandemic. Our secondary aim was to compare physical activity estimates between objectively measured and self-reported physical activity level.MethodsIn this descriptive, cross-sectional study, we assessed physical activity level using accelerometers and a validated questionnaire in 33 post-bariatric patients who reported to be adherent (n=15) or not (n=18) to social distancing measures.ResultsPatients adherent to social distancing measures spent more time in sedentary behavior (1.1 hours/day [95%CI: 0.1, 2.2]; p=0.045) and less time in moderate-to-vigorous physical activity (−12.2 min/day [95%CI: −23.8, −0.6]; p=0.040) compared to non-adherent ones. No difference was observed for light-intensity physical activity. Bland-Altman analysis comparing objective and subjective physical activity estimates showed a bias for time spent in sedentary behavior and moderate-to-vigorous physical activity of 2.8 hours/day and 8.5 min/day, respectively.ConclusionPost-bariatric patients who were adherent to social distancing measures due to the Covid-19 outbreak were more inactive and sedentary than non-adherent ones. Additionally, questionnaire data widely underestimated sedentary behavior. Strategies to increase or at least sustain physical activity levels in post-bariatric patients exposed to social distancing measures are necessary during the Covid-19 pandemic.What is already known about this subject?Reduced physical activity is associated with poor health-related outcomes in patient undergoing bariatric surgery.The impact of the social distancing measures due to Covid-19 pandemic on objectively-measured physical activity in this condition remains unknown.What are the new findings in your manuscript?Adherence to social distancing due to Covid-19 pandemic was associated with decreased objectively measured physical activity and increased sedentary behavior in patients who had undergone bariatric surgery.Questionnaire data widely underestimated sedentary behavior when compared to accelerometry data.How might your results change the direction of research or the focus of clinical practice?Given the increased burden of cardiovascular diseases related to inactivity and sedentary behavior, strategies to increase physical activity in post-bariatric patients are clinically relevant during the Covid-19 pandemic.The use of validated accelerometers is recommended to screen and track physical activity during the pandemic.
Assessment of Infection Prevention and Control Protocols, Procedures, and Implementation in Response to the COVID-19 Pandemic in Twenty-three Long-term Care Facilities in Fulton County, Georgia
Authors: Telford Carson T. , Bystrom Cyndra , Fox Teresa , Wiggins-Benn Sherry , McCloud Meshell , Holland David P. , Shah Sarita 
Published: August 2020

AbstractThrough infection prevention and control (IPC) site visits to 23 LTCFs in Fulton County, Georgia, comparison between the Higher- and Lower-prevalence groups revealed significant differences in PPE and Social Distancing, with five specific indicators driving these differences.
Comparison of COVID-19 Infections Among Healthcare Workers and Non-Healthcare Workers
Authors: Kim Rachel , Nachman Sharon , Fernandes Rafael , Meyers Kristen , Taylor Maria , LeBlanc Debra , Singer Adam J 
Published: August 2020

AbstractObjectivesHealthcare workers face distinct occupational challenges that affect their personal health, especially during a pandemic. In this study we compare the characteristics and outcomes of Covid-19 patients who are and who are not healthcare workers (HCW).MethodsWe retrospectively analyzed a cohort of adult patients with known HCW status and a positive SARS-CoV-2 PCR test presenting to a large academic medical center emergency department (ED) in New York State. We routinely collect data on occupation and exposures to suspected Covid-19. The primary outcome was hospital admission. Secondary outcomes were ICU admission, need for invasive mechanical ventilation (IMV), and mortality. We compared baseline characteristics and outcomes of Covid-19 adult patients based on whether they were or were not HCW using univariable and multivariable analyses.ResultsFrom March 1 2020 through June 2020, 2,842 adult patients (mean age 53+/-19 years, 53% male) with positive SARS-CoV-2 PCR tests and known HCW status visited the ED. This included 193 (6.8%) known HCWs and 2,649 (93.2%) non-HCWs. Compared with non-HCW, HCWs were younger (43 vs 53 years, P<0.001), more likely female (118/193 vs 1211/2649, P<0.001), and more likely to have a known Covid-19 exposure (161/193 vs 946/2649, P<0.001), but had fewer comorbidities. On presentation to the ED, HCW also had lower frequencies of tachypnea (12/193 vs 426/2649, P<0.01), hypoxemia (15/193 vs 564/2649, P<0.01), bilateral opacities on imaging (38/193 vs 1189/2649, P<0.001), and lymphocytopenia (6/193 vs 532/2649, P<0.01) compared to non-HCWs. Direct discharges home from the ED were more frequent in HCW 154/193: 80% vs 1275/2649: 48% p<0.001). Hospital admissions (38/193 20% vs 1264/2694 47%, P<0.001), ICU admissions (7/193 3% vs 321/2694 12%, P<0.001), need for IMV (6/193 3% vs 321/2694 12%, P<0.001) and mortality (2/193 1% vs 219/2694 8%, P<0.01) were lower than among non-HCW. After controlling for age, sex, comorbidities, presenting vital signs and radiographic imaging, HCW were less likely to be admitted (OR 0.6, 95%CI 0.3-0.9) than non HCW.ConclusionsCompared with non HCW, HCW with Covid-19 were younger, had less severe illness, and were less likely to be admitted.
SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry
Authors: Wei Congwen , Wan Luming , Yan Qiulin , Wang Xiaolin , Zhang Jun , Zhang Yanhong , Sun Jin , Yang Xiaopan , Gong Jing , Fan Chen , Yang Xiaoli , Wang Yufei , Wang Xuejun , Li Jianmin , Yang Huan , Li Huilong , Zhang Zhe , Wang Rong , Du Peng , Zong Yulong , Yin Feng , Zhang Wanchuan , Peng Yumeng , Lin Haotian , Zhang Rui , Chen Wei , Gao Qi , Cao Yuan , Zhong Hui 
Published: August 2020

AbstractThe recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.
Lineage transcription factors co-regulate subtype-specific genes providing a roadmap for systematic identification of small cell lung cancer vulnerabilities
Authors: Pozo Karine , Kollipara Rahul K. , Kelenis Demetra P. , Rodarte Kathia E. , Zhang Xiaoyang , Minna John D. , Johnson Jane E. 
Published: August 2020

ABSTRACTLineage-defining transcription factors (LTFs) play key roles in tumor cell growth, making them highly attractive, but currently “undruggable”, small cell lung cancer (SCLC) vulnerabilities. Delineating LTF genomic binding sites and associated chromatin features would provide important insights into SCLC dependencies. Here we map super-enhancers (SEs) across multiple patient-derived SCLC preclinical models, and find SE patterns are sufficient to classify the models into the recently defined, LTF-based, SCLC subtypes. 3D-chromatin conformation analysis identified genes associated with SEs that define subtype-specific tumor signatures with genes functioning in diverse processes. Focusing on ASCL1-high SCLC (SCLC-A), we found ASCL1 physically interacts with NKX2-1 and PROX1. These factors bind overlapping genomic regions, and co-regulate a set of genes, including genes encoding cell surface proteins, SCN3A and KCNB2 enriched in SCLC-A. Genetic depletion of NKX2-1 or PROX1 alone, or in combinations with ASCL1, did not inhibit SCLC growth more than that achieved by depleting ASCL1 alone. We demonstrate the SE signature supports the LTF classification of SCLC, identify NKX2-1 and PROX1 as ASCL1 co-factors, and substantiate the central importance of ASCL1 as a key dependency factor in the majority of SCLC. The LTF and SE gene sets provide a molecular roadmap for future ASCL1 therapeutic targeting studies.
Ex vivodetection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory
Authors: Schulien Isabel , Kemming Janine , Oberhardt Valerie , Wild Katharina , Seidel Lea M. , Killmer Saskia , Sagar  , Daul Franziska , Lago Marilyn Salvat , Decker Annegrit , Luxenburger Hendrik , Binder Benedikt , Bettinger Dominik , Sogukpinar Oezlem , Rieg Siegbert , Panning Marcus , Huzly Daniela , Schwemmle Martin , Kochs Georg , Waller Cornelius F. , Nieters Alexandra , Duerschmied Daniel , Emmerich Florian , Mei Henrik , Schulz Axel , Llewellyn-Lacey Sian , Price David A. , Boettler Tobias , Bengsch Bertram , Thimme Robert , Hofmann Maike , Neumann-Haefelin Christoph 
Published: August 2020

AbstractCD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in the current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific CD8+ T cells are detectable in the majority of individuals recovering from SARS-CoV-2 infection. However, optimal virus-specific epitopes, the role of pre-existing heterologous immunity as well as their kinetics and differentiation program during disease control have not been defined in detail. Here, we show that both pre-existing and newly induced SARS-CoV-2-specific CD8+ T-cell responses are potentially important determinants of immune protection in mild SARS-CoV-2 infection. In particular, our results can be summarized as follows: First, immunodominant SARS-CoV-2-specific CD8+ T-cell epitopes are targeted in the majority of individuals with convalescent SARS-CoV-2 infection. Second, MHC class I tetramer analyses revealed the emergence of phenotypically diverse and functionally competent pre-existing and newly induced SARS-CoV-2-specific memory CD8+ T cells that showed similar characteristics compared to influenza-specific CD8+ T cells. Third, SARS-CoV-2-specific CD8+ T-cell responses are more robustly detectable than antibodies against the SARS-CoV-2-spike protein. This was confirmed in a longitudinal analysis of acute-resolving infection that demonstrated rapid induction of the SARS-CoV-2-specific CD8+ T cells within a week followed by a prolonged contraction phase that outlasted the waning humoral immune response indicating that CD8+ T-cell responses might serve as a more precise correlate of antiviral immunity than antibody measurements after convalescence. Collectively, these data provide new insights into the fine specificity, heterogeneity, and dynamics of SARS-CoV-2-specific memory CD8+ T cells, potentially informing the rational development of a protective vaccine against SARS-CoV-2.
A power amplification dyad in seahorses
Authors: Avidan Corrine , Day Steven W , Holzman Roi 
Published: August 2020

AbstractUbiquitous constraints derived from the muscle’s structure limit the power capacity of fast contracting muscles. Correspondingly, organisms evolved elastic elements that store energy which, when released, can be used to rapidly accelerate appendages. Such latch-mediated spring actuation (LaMSA) systems comprise of a single elastic element and are used to actuate a single mass. Here we reveal a dual LaMSA system in seahorses, in which two elastic elements actuate two masses: the head as they rapidly swing it towards the prey, and the water mass sucked into the mouth to prevent the prey from escaping. This power-amplified system enhances the speeds of both head rotation and suction flows by x10 compared to similarly-sized fish. Furthermore, the dual system provides temporal coordination between head rotation and suction flows, a novel function for LaMSA. These findings extend the known function, capacity and design of LaMSA systems.
Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer
Authors: Siddiqui Mohammad Aarif , Gollavilli Paradesi Naidu , Ramesh Vignesh , Parma Beatrice , Schwab Annemarie , Vazakidou Maria Eleni , Natesan Ramakrishnan , Saatci Ozge , Rapa Ida , Bironzo Paolo , Schuhwerk Harald , Asangani Irfan Ahmed , Sahin Ozgur , Volante Marco , Ceppi Paolo 
Published: August 2020

AbstractBackgroundEpithelial-to-mesenchymal transition (EMT) enhances motility, stemness and chemoresistance of carcinomas and is an important determinant of metastasis. Little is known about how various pathways coordinate to elicit EMT’s different functional aspects. Even lesser has been studied in this context in non-small cell lung cancer (NSCLC), where EMT is a key event during early tumorigenesis. Thymidylate synthase (TS), a proliferation enzyme, has been previously correlated with EMT transcription factor ZEB1 in NSCLC and is associated with resistance against anti-folate chemotherapy. In this study we establish a functional correlation between TS, EMT, chemotherapy and metastasis and identify a network that might propel the TS mediated EMT phenotype.MethodsPublished datasets were analysed to evaluate significance of TS in NSCLC fitness and prognosis. mCherry based promoter reporter assay was used to sort Calu-1 and A549 NSCLC cells in TSHIGHand TSLOW. Metastatic potential of TS knock-down was assayed in syngeneic C57BL/6 mice.ResultsLow TS levels were prognostic and predicted chemotherapy response. NSCLC cell lines with higher TS promoter activity were more mesenchymal-like. RNA-seq from these cells, and shRNA mediated TS knocked down cells, identified EMT as one of the most differentially regulated pathways. EMT transcription factors HOXC6 and HMGA2 were identified as upstream regulator of TS whereas, AXL, SPARC and FOSL1 were identified as downstream effectors. TS knock-down reduced the metastatic colonisationin vivo.ConclusionThese results establish the role of TS as a theranostic NSCLC marker integrating survival, chemo-resistance and EMT, and identifies a regulatory network that could be exploited to target EMT-driven NSCLC.
Q-SNARE Syntaxin 7 confers actin-dependent rapidly replenishing synaptic vesicles upon high activity
Authors: Mori Yasunori , Takenaka Koichiro , Fukazawa Yugo , Takamori Shigeo 
Published: August 2020

AbstractReplenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained transmitter release during repetitive stimulation. Kinetics of replenishment and available pool size define synaptic performance. However, whether all SVs in the recycling pool are recruited for release with equal probability is unknown. Here, using comprehensive optical imaging for various presynaptic endosomal SNARE proteins in cultured hippocampal neurons, we demonstrate that part of the recycling pool bearing the endosomal Q–SNARE Syntaxin 7 (Stx7) is preferentially mobilized for release during high–frequency repetitive stimulation. Recruitment of the SV pool marked with the Stx7–reporter requires high intra–terminal Ca2+concentrations and actin polymerization. Furthermore, disruption of Stx7 function by overexpressing the N–terminal domain selectively abolished this pool. Thus, our data indicate that endosomal membrane fusion involving Stx7 is essential for adaptation of synapses to respond high-frequency repetitive stimulation.
Metabarcoding, direct stomach observation and stable isotope analysis reveal a highly diverse diet for the invasive green crab in Atlantic Patagonia
Authors: Cordone Georgina , Lozada Mariana , Vilacoba Elisabet , Thalinger Bettina , Bigatti Gregorio , Lijtmaer Darío A. , Steinke Dirk , Galván David E. 
Published: August 2020

AbstractThe European green crabCarcinus maenasand its sister speciesC. aestuariiare highly invasive species causing damage to coastal ecosystems and contributing to severe economic losses worldwide.C. maenaswas first detected at the Atlantic Patagonian coast in 2001. In this work, we studied the diet of the green crab in a recently invaded location in Golfo Nuevo, using three complementary techniques: direct stomach observation, metabarcoding of gut content and stable isotope analysis. Direct stomach observation and metabarcoding showed that green crabs have a broad omnivorous diet, ingesting most of the phyla present in the study area. Gut content metabarcoding allowed a detailed description of algal diversity and revealed other taxa that went unnoticed in the visual stomach analysis. Stable isotope analysis showed that the major contribution to the crabs’ diet was from the phytoplankton chain (by bivalve consumption) and not directly from algae. This study approach combining three complementary techniques also allowed us to detect some differences in the diet between sexes, which suggests that male and female crabs are not as ecologically equivalent as previously thought. Besides, we detected sequences corresponding toC. aestuariisuggesting that the green crab Patagonian population is a hybrid of both sister species. These findings are key to understanding the impacts green crabs can have on the local ecosystem.
Fibroblast Mechanotransduction Network Predicts Targets for Mechano-Adaptive Infarct Therapies
Authors: Rogers Jesse D. , Richardson William J. 
Published: August 2020

SummaryRegional control of fibrosis after myocardial infarction is critical for maintaining structural integrity in the infarct while preventing collagen accumulation in non-infarcted areas. Cardiac fibroblasts modulate matrix turnover in response to biochemical and biomechanical cues, but the complex interactions between signaling pathways confounds efforts to develop therapies for regional scar formation. Here, we employed a logic-based ordinary differential equation model of fibroblast mechano-chemo signal transduction to predict matrix protein expression in response to canonical biochemical stimuli and mechanical tension. Functional analysis of mechano-chemo interactions showed extensive pathway crosstalk with tension amplifying, dampening, or reversing responses to biochemical stimuli. Comprehensive drug target screens in low- and high-tension contexts identified 13 mechano-adaptive therapies that promote matrix accumulation in regions where it is needed and reduce matrix levels in regions where it is not needed. Our predictions demonstrate this approach’s utility for discovering context-specific mechanisms mediating fibrosis and druggable targets for spatially resolved therapies.
The dynamic nature of the human Origin Recognition Complex revealed through five cryoEM structures
Authors: Jaremko Matt J. , On Kin Fan , Thomas Dennis R. , Stillman Bruce , Joshua-Tor Leemor 
Published: August 2020

AbstractGenome replication is initiated from specific origin sites established by dynamic events. The Origin Recognition Complex (ORC) is necessary for orchestrating the initiation process by binding to origin DNA, recruiting CDC6, and assembling the MCM replicative helicase on DNA. Here we report five cryoEM structures of the human ORC (HsORC) that illustrate the native flexibility of the complex. The absence of ORC1 revealed a compact, stable complex of ORC2-5. Introduction of ORC1 opens the complex into several dynamic conformations. Two structures revealed dynamic movements of the ORC1 AAA+ and ORC2 winged-helix domains that likely impact DNA incorporation into the ORC core. Additional twist and pinch motions were observed in an open ORC conformation revealing a hinge at the ORC5·3 interface that may facilitate ORC binding to DNA. Finally, a structure of ORC was determined with endogenous DNA bound in the core revealing important differences between human and yeast origin recognition.