bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sweetspot mapping in deep brain stimulation: Strengths and limitations of current approaches
Authors: Dembek Till A. , Baldermann Juan Carlos , Petry-Schmelzer Jan-Niklas , Jergas Hannah , Treuer Harald , Visser-Vandewalle Veerle , Dafsari Haidar S. , Barbe Michael T. 
Published: September 2020

AbstractObjectiveOpen questions remain regarding the optimal target, or sweetspot, for deep brain stimulation (DBS) in e.g. Parkinson’s Disease. Previous studies introduced different methods of mapping DBS effects to determine sweetspots. While having a direct impact on surgical targeting and postoperative programming in DBS, these methods so far have not been investigated in ground-truth data.Materials & MethodsThis study investigated five previously published DBS mapping methods regarding their potential to correctly identify a ground-truth sweetspot. Methods were investigated in silico in eight different use-case scenarios, which incorporated different types of clinical data, noise, and differences in underlying neuroanatomy. Dice-coefficients were calculated to determine the overlap between identified sweetspots and the ground-truth. Additionally, out-of-sample predictive capabilities were assessed using the amount of explained variance R2.ResultsThe five investigated methods resulted in highly variable sweetspots. Methods based on voxel-wise statistics against average outcomes showed the best performance overall. While predictive capabilities were high, even in the best of cases Dice-coefficients remained limited to values around 0.5, highlighting the overall limitations of sweetspot identification.ConclusionsThis study highlights the strengths and limitations of current approaches to DBS sweetspot mapping. Those limitations need to be taken into account when considering the clinical implications. All future approaches should be investigated in silico before being applied to clinical data.
Patterns of age disparities in colon and lung cancer survival: a systematic narrative literature review
Authors: Pilleron Sophie , Gower Helen , Janssen-Heijnen Maryska , Signal Virginia , Gurney Jason , Morris Eva JA , Cunningham Ruth , Sarfati Diana 
Published: September 2020

AbstractObjectiveTo identify patterns of age disparities in cancer survival, using colon and lung cancer as exemplars.MethodsWe conducted a systematic review of literature published in EMBASE, MEDLINE, Scopus, and Web of Science according to PRISMA guidelines. We included population-based studies in patients with colon or lung cancer. We assessed the quality of included studies against selected evaluation domains from the QUIPS Tool, and items concerning statistical reporting. We evaluated age disparities using the absolute difference in survival or mortality rates between middle-aged group and the oldest age group, or by describing survival curves.ResultsOut of 2,162 references reviewed, we retained 35 studies (15 for colon, 18 for lung, 2 for both sites). Regardless of the cancer site, included studies were highly heterogeneous and often of poor quality. The magnitude of age disparities in survival varied greatly by sex, ethnicity, socio-economic status, stage at diagnosis, cancer site and morphology, the number of nodes examined, and by treatment strategy. Although results were inconsistent for most characteristics, we consistently observed greater age disparities for females with lung cancer compared to males. Also, age disparities increased with more advanced stages for colon cancer, and decreased with more advanced stages for lung cancer.ConclusionsAlthough age is one of the most important prognostic factors in cancer survival, age disparities in colon and lung cancer survival have so far been understudied in population-based research. Further studies are needed to better understand age disparities in colon and lung cancer survival. (PROSPERO registration number: CRD42020151402).Article SummaryStrengths and limitations of this studyFor the first time, we conducted a systematic review of population-based studies relating to differences in cancer survival between middle-aged and older patients, using colon and lung cancer as exemplar cancers.We limited our search to peer-reviewed original articles and letters to Editors published in English up until 30 September 2019.We excluded clinical studies and trials because of the strict selection of patients and the common underrepresentation of older patients in these studies.We could not conduct any quantitative analysis (such as meta-analysis) because of the vast heterogeneity of studies included, which prevented us from quantifying the relationship between increasing age and cancer survival.
Comparative evaluation of six immunoassays for the detection of antibodies against SARS-CoV-2
Authors: Pérez-García Felipe , Pérez-Tanoira Ramón , Esther Iglesias María , Romanyk Juan , Arroyo Teresa , Gómez-Herruz Peña , González Rosa , Cuadros-González Juan 
Published: September 2020

AbstractObjectives:Serologic techniques can serve as a complement to diagnose SARS-CoV-2 infection. The objective of our study was to compare the diagnostic performance of six immunoassays to detect antibodies against SARS-CoV-2: three lateral flow immunoassays (LFAs), one ELISA and two chemiluminescence assays (CLIAs).Methods:We evaluated three LFAs (Alltest, One Step and SeroFlash), one ELISA (Dia.Pro) and 34 two CLIAs (Elecsys and COV2T). To assess the specificity, 60 pre-pandemic sera were 35 used. To evaluate the sensitivity, we used 80 serum samples from patients with 36 positive PCR for SARS-CoV-2. Agreement between techniques was evaluated using the kappa score (k).ResultsAll immunoassays showed a specificity of 100% except for SeroFlash (96.7%). Overall sensitivity was 61.3%, 73.8%, 67.5%, 85.9%, 88.0% and 92.0% for Alltest, One Step, SeroFlash, Dia.Pro, Elecsys and COV2T, respectively. Sensitivity increased throughout the first two weeks from the onset of symptoms, reaching sensitivities over 85% from 14 days for all LFAs, being One Step the most sensitive (97.6%), followed by SeroFlash (95.1%). Dia.Pro, Elecsys and COV2T showed sensitivities over 97% from 14 days, being 100% for COV2T. One Step showed the best agreement results among LFAs, showing excellent agreement with Dia.Pro (agreement=94.2%, k=0.884), COV2T (99.1%, k=0.981) and Elecsys (97.3%, k=0.943). Dia.Pro, COV2T and Elecsys also showed excellent agreement between them.ConclusionOne Step, Dia.Pro, Elecsys and COV2T obtained the best diagnostic performanc e results. All these techniques showed a specificity of 100% and sensitivities over 97% from 14 days after the onset of symptoms, as well as excellent levels of agreement.
Systematic profiling of SARS-CoV-2 specific IgG epitopes at single amino acid resolution
Authors: Qi Huan , Ma Ming-liang , Jiang He-wei , Ling Jian-ya , Chen Ling-yun , Zhang Hai-nan , Lai Dan-yun , Li Yang , Guo Zi-wen , Hu Chuan-sheng , Guo Shu-Juan , Meng Qing-feng , Ren Yan , Wang Wei , Yang Xiao , Zhou Jie , Zhao Xiao-dong , Li Hua , Tao Sheng-ce 
Published: September 2020

AbstractSARS-CoV-2 specific IgG responses play critical roles for patients to recover from COVID-19, in-depth dissecting of the IgG responses on systems level is of great interest. Herein, we adopted a newly developed high-throughput epitope mapping technology (AbMap), analyzed 55 COVID-19 convalescent sera and 226 antibody samples enriched by specific proteins or peptides from these sera. We revealed three areas that are rich of IgG epitopes, two are on Spike protein but outside of RBD, and one is on Nucleocapsid protein. We identified 29 significant epitopes on Spike protein, from two of these significant epitopes, two critical epitope residues were found,i. e., D936 and P1263, which are highly related to the infectivity of SARS-CoV-2 In summary, we provided the first global map of IgG binding epitopes for SARS-CoV-2 at single amino acid resolution. This map will facilitate the precise development of therapeutic antibodies and vaccines.HIGHLIGHTSA map of SARS-CoV-2 specific IgG binding epitopes at single amino acid resolutionTwo areas outside of RBD that are rich of significant epitopes were identifiedOne area rich of significant epitopes was determined on Nucleocapsid proteinTwo critical epitope residues (D936 and P1263) on Spike protein are highly related to the infectivity of SARS-CoV-2
First report on the Latvian SARS-CoV-2 isolate genetic diversity
Authors: Zrelovs Nikita , Ustinova Monta , Silamiķelis Ivars , Birzniece Līga , Megnis Kaspars , Rovīte Vita , Freimane Lauma , Silamiķele Laila , Ansone Laura , Pjalkovskis Jānis , Fridmanis Dāvids , Vilne Baiba , Priedīte Marta , Caica Anastasija , Gavars Mikus , Perminovs Dmitrijs , Storoženko Jeļena , Savicka Oksana , Dimiņa Elīna , Dumpis Uga , Kloviņš Jānis 
Published: September 2020

AbstractRemaining a major healthcare concern with nearly 29 million confirmed cases worldwide at the time of writing, novel severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) has caused more than 920 thousand deaths since its outbreak in China, December 2019. First case of a person testing positive for SARS-CoV-2 infection within the territory of the Republic of Latvia was registered on 2ndof March 2020, nine days prior to the pandemic declaration by WHO. Since then, more than 277 000 tests were carried out confirming a total of 1464 cases of COVID-19 in the country as of 12thof September 2020. Rapidly reacting to the spread of the infection, an ongoing sequencing campaign was started mid-March in collaboration with the local testing laboratories, with an ultimate goal in sequencing as much local viral isolates as possible, resulting in first full-length SARS-CoV-2 isolate genome sequences from the Baltics region being made publicly available in early April. With 133 viral isolates representing ∼9.1% of the total COVID-19 cases in the country being completely sequenced as of today, here we provide a first report on the genetic diversity of Latvian SARS-CoV-2 isolates.
COVID-19 Transmission Dynamics and Effectiveness of Public Health Interventions in New York City during the 2020 Spring Pandemic Wave
Authors: Yang Wan , Shaff Jaimie , Shaman Jeffrey 
Published: September 2020

AbstractNew York City experienced a large COVID-19 pandemic wave during March – May 2020. We model the transmission dynamics of COVID-19 in the city during the pandemic and estimate the effectiveness of public health interventions (overall and for each major intervention separately) for the entire population and by age group. We estimate that the overall effective reproductive number was 2.99 at the beginning of the pandemic wave and reduced to 0.93 one week after the stay-at-home mandate. Most age groups experienced similar reductions in transmission. Interventions reducing contact rates were associated with a 70.7% (95% CI: 65.0 – 76.4%) reduction of transmission overall and > 50% for all age groups during the pandemic. Face covering was associated with a 6.6% (95% CI: 0.8 – 12.4%) reduction of transmission overall and up to 20% for 65+ year-olds during the first month of implementation. Accounting for the amount of time masks are in use (i.e. mainly outside homes), these findings indicate universal masking could reduce transmission by up to 28-32% when lockdown-like measures are lifted, if the high effectiveness estimated for older adults were achieved for all ages. These estimates are verified by out-of-fit projections and support the need for implementing multiple interventions simultaneously in order to effectively mitigate the spread of COVID-19.
A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates
Authors: Vogel Annette B. , Kanevsky Isis , Che Ye , Swanson Kena A. , Muik Alexander , Vormehr Mathias , Kranz Lena M. , Walzer Kerstin C. , Hein Stephanie , Güler Alptekin , Loschko Jakob , Maddur Mohan S. , Tompkins Kristin , Cole Journey , Lui Bonny G. , Ziegenhals Thomas , Plaschke Arianne , Eisel David , Dany Sarah C. , Fesser Stephanie , Erbar Stephanie , Bates Ferdia , Schneider Diana , Jesionek Bernadette , Sänger Bianca , Wallisch Ann-Kathrin , Feuchter Yvonne , Junginger Hanna , Krumm Stefanie A. , Heinen André P. , Adams-Quack Petra , Schlereth Julia , Kröner Christoph , Hall-Ursone Shannan , Brasky Kathleen , Griffor Matthew C. , Han Seungil , Lees Joshua A. , Mashalidis Ellene H. , Sahasrabudhe Parag V. , Tan Charles Y. , Pavliakova Danka , Singh Guy , Fontes-Garfias Camila , Pride Michael , Scully Ingrid L. , Ciolino Tara , Obregon Jennifer , Gazi Michal , Carrion Ricardo , Alfson Kendra J. , Kalina Warren V. , Kaushal Deepak , Shi Pei-Yong , Klamp Thorsten , Rosenbaum Corinna , Kuhn Andreas N. , Türeci Özlem , Dormitzer Philip R. , Jansen Kathrin U. , Sahin Ugur 
Published: September 2020

AbstractTo contain the coronavirus disease 2019 (COVID-19) pandemic, a safe and effective vaccine against the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is urgently needed in quantities sufficient to immunise large populations. In this study, we report the design, preclinical development, immunogenicity and anti-viral protective effect in rhesus macaques of the BNT162b2 vaccine candidate. BNT162b2 contains an LNP-formulated nucleoside-modified mRNA that encodes the spike glycoprotein captured in its prefusion conformation. After expression of the BNT162b2 coding sequence in cells, approximately 20% of the spike molecules are in the one-RBD ‘up’, two-RBD ‘down’ state. Immunisation of mice with a single dose of BNT162b2 induced dose level-dependent increases in pseudovirus neutralisation titers. Prime-boost vaccination of rhesus macaques elicited authentic SARS-CoV-2 neutralising geometric mean titers 10.2 to 18.0 times that of a SARS-CoV-2 convalescent human serum panel. BNT162b2 generated strong TH1 type CD4+and IFNγ+CD8+T-cell responses in mice and rhesus macaques. The BNT162b2 vaccine candidate fully protected the lungs of immunised rhesus macaques from infectious SARS-CoV-2 challenge. BNT162b2 is currently being evaluated in a global, pivotal Phase 2/3 trial (NCT04368728).
Deep sea sediments associated with cold seeps are a subsurface reservoir of viral diversity
Authors: Li Zexin , Pan Donald , Wei Guangshan , Pi Weiling , Wang Jiang-Hai , Peng Yongyi , Zhang Lu , Wang Yong , Hubert Casey R.J. , Dong Xiyang 
Published: September 2020

AbstractIn marine ecosystems, viruses exert control on the composition and metabolism of microbial communities, thus influencing overall biogeochemical cycling. Deep sea sediments associated with cold seeps are known to host taxonomically diverse microbial communities, but little is known about viruses infecting these microorganisms. Here, we probed metagenomes from seven geographically diverse cold seeps across global oceans, to assess viral diversity, virus-host interaction, and virus-encoded auxiliary metabolic genes (AMGs). Gene-sharing network comparisons with viruses inhabiting other ecosystems reveal that cold seep sediments harbour considerable unexplored viral diversity. Most cold seep viruses display high degrees of endemism with seep fluid flux being one of the main drivers of viral community composition.In silicopredictions linked 14.2% of the viruses to microbial host populations, with many belonging to poorly understood candidate bacterial and archaeal phyla. Lysis was predicted to be a predominant viral lifestyle based on lineage-specific virus/host abundance ratios. Metabolic predictions of prokaryotic host genomes and viral AMGs suggest that viruses influence microbial hydrocarbon biodegradation at cold seeps, as well as other carbon, sulfur and nitrogen cycling via virus-induced mortality and/or metabolic augmentation. Overall, these findings reveal the global diversity and biogeography of cold seep viruses and indicate how viruses may manipulate seep microbial ecology and biogeochemistry.
Brain volumetric changes in the general population following the COVID-19 outbreak and lockdown
Authors: Salomon Tom , Cohen Adi , Barazany Daniel , Ben-Zvi Gal , Botvinik-Nezer Rotem , Gera Rani , Oren Shiran , Roll Dana , Rozic Gal , Saliy Anastasia , Tik Niv , Tsarfati Galia , Tavor Ido , Schonberg Tom , Assaf Yaniv 
Published: September 2020

AbstractThe COVID-19 outbreak introduced unprecedented health-risks, as well as pressure on the financial, social, and psychological well-being due to the response to the outbreak. Here, we examined the manifestations of the COVID-19 outbreak on the brain structure in the healthy population, following the initial phase of the pandemic in Israel. We pre-registered our hypothesis that the intense experience of the outbreak potentially induced stress-related brain modifications. Volumetric changes inn= 50 participants who were scanned before and after the COVID-19 outbreak and lockdown, were compared withn= 50 control participants who were scanned twice prior to the pandemic. The pandemic provided a rare opportunity to examine brain plasticity in a natural experiment. We found volumetric increases in bilateral amygdalae, putamen, and the anterior temporal cortices. Changes in the amygdalae diminished as time elapsed from lockdown relief, suggesting that the intense experience associated with the pandemic outbreak induced transient volumetric changes in brain regions commonly associated with stress and anxiety.
Scalable, multimodal profiling of chromatin accessibility and protein levels in single cells
Authors: Mimitou Eleni P. , Lareau Caleb A. , Chen Kelvin Y. , Zorzetto-Fernandes Andre L. , Takeshima Yusuke , Luo Wendy , Huang Tse-Shun , Yeung Bertrand , Thakore Pratiksha I. , Wing James Badger , Nazor Kristopher L. , Sakaguchi Shimon , Ludwig Leif S. , Sankaran Vijay G. , Regev Aviv , Smibert Peter 
Published: September 2020

ABSTRACTRecent technological advances have enabled massively parallel chromatin profiling withsingle-cellAssay forTransposaseAccessibleChromatin bysequencing (scATAC-seq) in thousands of individual cells. Here, we extend these approaches and presentATAC withSelectAntigenProfiling bysequencing, ASAP-seq, a tool to simultaneously profile accessible chromatin and protein levels in thousands of single cells. Our approach pairs sparse scATAC-seq data with robust detection of hundreds of cell surface and intracellular protein markers and optional capture of mitochondrial DNA (mtDNA) for clonal tracking, thus concomitantly capturing three distinct modalities in single cells. Importantly, ASAP-seq uses a novel bridging approach that repurposes antibody:oligo conjugates designed for existing technologies that pair protein measurements with single cell RNA-seq. We demonstrate the utility of ASAP-seq by revealing coordinated and distinct changes in chromatin, RNA, and surface proteins during native hematopoietic differentiation, peripheral blood mononuclear cell stimulation, and as a combinatorial decoder and reporter of multiplexed perturbations in primary T cells.
An evolutionarily acquired microRNA shapes development of mammalian cortical projections
Authors: Diaz Jessica L , Siththanandan Verl B , Lu Victoria , Gonzalez-Nava Nicole , Pasquina Lincoln , MacDonald Jessica L , Woodworth Mollie B , Ozkan Abduladir , Nair Ramesh , He Zihuai , Sahni Vibhu , Sarnow Peter , Palmer Theo D , Macklis Jeffrey D , Tharin Suzanne 
Published: September 2020

AbstractThe corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are co-expressed across multiple projection neuron subtypes. Here, we discover seventeen CSMN-enriched microRNAs (miRNAs), fifteen of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development.In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is the first demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.Significance StatementThe mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills, including the corticospinal tract and corpus callosum. The neurons giving rise to these projections - corticospinal and callosal projection neurons - develop from the same progenitors, but acquire strikingly different fates. The broad evolutionary conservation of known genes controlling cortical projection neuron fates raises the question of how the more narrowly conserved corticospinal and callosal projections evolved. We identify a microRNA cluster selectively expressed by corticospinal projection neurons and exclusive to placental mammals. One of these microRNAs promotes corticospinal fate via regulation of the callosal gene LMO4, suggesting a mechanism whereby microRNA regulation during development promotes evolution of neuronal diversity.
Stochastic asymmetric repartition of lytic machinery in dividing CD8+T cells generates heterogeneous killing behavior
Authors: Lafouresse Fanny , Jugele Romain , Müller Sabina , Doineau Marine , Duplan-Eche Valérie , Espinosa Eric , Puissegur Marie-Pierre , Gadat Sébastien , Valitutti Salvatore 
Published: September 2020

AbstractCytotoxic immune cells are endowed with a high degree of heterogeneity in their lytic function, but how this heterogeneity is generated is still an open question. We therefore investigated if human CD8+T cells could segregate their lytic components during telophase, using imaging flow cytometry, confocal microscopy and live cell imaging. We show that CD107a+-intracellular vesicles, perforin and granzyme B unevenly segregate in a constant fraction of telophasic cells during each division round. Mathematical modeling posits that unequal lytic molecule inheritance by daughter cells results from the random distribution of lytic granules on the two sides of the cleavage furrow. Finally, we establish that the level of lytic compartment in individual CTL dictates CTL killing capacity. Together, our results show the stochastic asymmetric distribution of effector molecules in dividing CD8+T cells. They propose uneven mitotic repartition of pre-packaged lytic components as a mechanism generating non-hereditary functional heterogeneity in CTL.