bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV service interruptions during the COVID-19 pandemic in China: the role of HIV service challenges and institutional response from healthcare professional’s perspective
Authors: Yang Xueying , Zeng Chengbo , Tam Cheuk Chi , Qiao Shan , Li Xiaoming , Shen Zhiyong , Zhou Yuejiao 
Published: March 2021

AbstractBackgroundThe healthcare system in China was largely overwhelmed during the unprecedented pandemic of coronavirus disease (COVID-19). HIV-related services have been unavoidably interrupted and impacted. However, the nature and scope of HIV service interruptions due to COVID-19 has rarely been characterized in China and how HIV service challenges affect the service interruptions are also unclear. The current study aimed at characterize HIV service interruption levels and analyzed its associated factors related to service challenges and institutional response from HIV healthcare providers’ viewpoint.MethodsA cross-sectional online survey was conducted among 1,029 HIV healthcare providers in Guangxi, China, from April to May 2020. Latent class analysis (LCA) was first used to identify HIV service interruption levels. Then hierarchical multinomial logistic regression was conducted to analyze the relationships of HIV care service challenges and institutional response with HIV service interruption levels. Simple slope analysis was employed to examine interaction effects between HIV service challenges and institutional response to COVID-19.ResultsFour classes of HIV service interruption were identified using LCA, with 22.0% complete interruption (class 1), 15.4% moderate interruption (class 2), 21.9% minor interruption (class 3) and 40.7% almost no interruption (class 4). Using class 4 as a reference group, HIV care service challenges were positively associated with the probabilities of service interruptions (Class 1: AOR=1.23, 95%CI: 1.19∼1.26; Class 2: AOR= 1.10, 95%CI: 1.08∼1.13; Class 3: AOR= 1.10, 95%CI: 1.08∼1.12). Institutional response to HIV healthcare delivery was negatively associated with the probabilities of being classified into Class 1 (“Complete interruption”) (AOR=0.97, 95%CI: 0.93∼1.00) and Class 3 (“minor interruption [Outreach service]”) (AOR=0.96, 95%CI: 0.93∼0.99) as compared to Class 4 (“almost no interruption”). Institutional response to HIV healthcare delivery moderated the association of HIV service challenges with complete interruption, but not with the moderate or minor interruption when comparing with no interruption group.ConclusionsA substantial HIV service interruptions occurs due to the COVID-19 pandemic, particularly services that require face-to-face interactions, such as VCT counselling, follow up and outreach services. HIV service challenges largely hinder the HIV service delivery. Institutional response to HIV healthcare delivery could marginally buffer the negative effect of service challenges on complete HIV service interruptions. To maintain continuity of core HIV services in face of a pandemic, build a resilient health care system with adequate preparedness is necessary.
Multiplexed single-cell proteomics using SCoPE2
Authors: Petelski Aleksandra A. , Emmott Edward , Leduc Andrew , Huffman R. Gray , Specht Harrison , Perlman David H. , Slavov Nikolai 
Published: March 2021

AbstractMany biological systems are composed of diverse single cells. This diversity necessitates functional and molecular single-cell analysis. Single-cell protein analysis has long relied on affinity reagents, but emerging mass-spectrometry methods (either label-free or multiplexed) have enabled quantifying over 1,000 proteins per cell while simultaneously increasing the specificity of protein quantification. Isobaric carrier based multiplexed single-cell proteomics is a scalable, reliable, and cost-effective method that can be fully automated and implemented on widely available equipment. It uses inexpensive reagents and is applicable to any sample that can be processed to a single-cell suspension. Here we describe an automated Single Cell ProtEomics (SCoPE2) workflow that allows analyzing about 200 single cells per 24 hours using only standard commercial equipment. We emphasize experimental steps and benchmarks required for achieving quantitative protein analysis.SCoPE2 Protocol
SARS-CoV-2 Nsp8 N-terminal domain dimerizes and harbors autonomously folded elements
Authors: Treviño Miguel Á. , Pantoja-Uceda David , Laurents Douglas V. , Mompeán Miguel 
Published: March 2021

AbstractThe SARS-CoV-2 Nsp8 protein is a critical component of the RNA replicase, as its N-terminal domain (NTD) anchors Nsp12, the RNA, and Nsp13. Whereas its C-terminal domain (CTD) structure is well resolved, there is an open debate regarding the conformation adopted by the NTD as it is predicted as disordered but found in a variety of complex-dependent conformations or missing from many other structures. Using NMR spectroscopy, we show that the SARS CoV-2 Nsp8 NTD features both well folded secondary structure and disordered segments. Our results suggest that while part of this domain corresponding to two long α-helices forms autonomously, the folding of other segments would require interaction with other replicase components. When isolated, the α-helix population progressively declines towards the C-termini, and dynamics measurements indicate that the Nsp8 NTD behaves as a dimer under our conditions.
Massively parallel characterization of CYP2C9 variant enzyme activity and abundance
Authors: Amorosi Clara J. , Chiasson Melissa A. , McDonald Matthew G. , Wong Lai Hong , Sitko Katherine A. , Boyle Gabriel , Kowalski John P. , Rettie Allan E. , Fowler Douglas M. , Dunham Maitreya J. 
Published: March 2021

ABSTRACTCYP2C9encodes a cytochrome P450 enzyme responsible for metabolizing up to 15% of small molecule drugs, andCYP2C9variants can alter the safety and efficacy of these therapeutics. In particular, the anti-coagulant warfarin is prescribed to over 15 million people annually and polymorphisms inCYP2C9can affect patient response leading to an increased risk of hemorrhage. We developed Click-seq, a pooled yeast-based activity assay to test thousands of variants. Using Click-seq, we measured the activity of 6,142 missense variants expressed in yeast. We also measured the steady-state cellular abundance of 6,370 missense variants expressed in a human cell line using Variant Abundance by Massively Parallel sequencing (VAMP-seq). These data revealed that almost two-thirds of CYP2C9 variants showed decreased activity, and that protein abundance accounted for half of the variation in CYP2C9 function. We also measured activity scores for 319 previously unannotated human variants, many of which may have clinical relevance.
Ecophysiological differentiation between life stages in filmy ferns (Hymenophyllaceae)
Authors: Nitta Joel H. , Watkins James E. , Holbrook N. Michele , Wang Tristan W. , Davis Charles C. 
Published: March 2021

AbstractDesiccation tolerance was a key trait that allowed plants to colonize land. However, little is known about the transition from desiccation tolerant non-vascular plants to desiccation sensitive vascular ones. Filmy ferns (Hymenophyllaceae) represent a useful system to investigate how water-stress strategies differ between non-vascular and vascular stages within a single organism because they have vascularized sporophytes and nonvascular gametophytes that are each capable of varying degrees of desiccation tolerance. To explore this, we surveyed sporophytes and gametophytes of 19 species (22 taxa including varieties) of filmy ferns on Moorea (French Polynesia) and used chlorophyll fluorescence to measure desiccation tolerance and light responses. We conducted phylogenetically informed analyses to identify differences in physiology between life stages and growth habits. Gametophytes had similar or less desiccation tolerance (ability to recover from 2 d desiccation at -86 MPa) and lower photosynthetic optima (maximum electron transport rate of photosystem II and light level at 95% of that rate) than sporophytes. Epiphytes were more tolerant of desiccation than terrestrial species in both life stages. Despite their lack of greater physiological tolerances, gametophytes of several species occurred over a wider elevational range than conspecific sporophytes. Our results demonstrate that filmy fern gametophytes and sporophytes differ in their physiology and niche requirements, and point to the importance of microhabitat in shaping the evolution of water-use strategies in vascular plants.
Persisting Salivary IgG against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys
Authors: Alkharaan Hassan , Bayati Shaghayegh , Hellström Cecilia , Olsson Annika , Lindahl Karin , Bogdanovic Gordana , Aleman Soo , Tsilingaridis Georgios , De Palma Patricia , Hober Sophia , Månberg Anna , Nilsson Peter , Pin Elisa , Sällberg Chen Margaret 
Published: March 2021

AbstractBackgroundDeclining humoral immunity in COVID-19 patients and possibility of reinfections has raised concern. Mucosal immunity particularly salivary antibodies could be short-lived. However, long-term studies are sparse.MethodsUsing a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n=74, Cohort 1), undiagnosed individuals with self-reported questionnaires (n=147, Cohort 2), and individuals sampled pre-pandemic time (n= 35, Cohort 3).ResultsSalivary IgG antibody responses in Cohort 1 (mainly mild COVID-19) were detectable up to 9 month recovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in saliva in majority as seen in blood serology. Salivary IgA was rarely detected at this timepoint. In Cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19 like symptoms. Salivary IgG also tolerated temperature and detergent pre-treatments.ConclusionsUnlike SARS-CoV-2 salivary IgA that appeared short-lived, the specific IgG in saliva appears stable even after mild COVID-19 as noted for blood serology. The non-invasive saliva-based SARS-Cov-2 antibody testing with self-collection at homes may thus serve as a complementary alternative to conventional blood serology.
A Preliminary Characterization of Canonicalized and Non-Canonicalized Section Headers Across Variable Clinical Note Types
Authors: Wang Junjie , Yu Shun , Davoudi Anahita , Mowery Danielle L. 
Published: March 2021

AbstractIn the electronic health record, the majority of clinically relevant information is stored within clinical notes. Most clinical notes follow a set organizational structure composed of canonicalized section headers that facilitate clinical review and information gathering. Standardized section header terminologies such as the SecTag terminology permit the identification and standardization of headers to a canonicalized form. Although the SecTag terminology has been evaluated extensively for history & physical notes, the coverage of canonical section header terms has not been assessed across other note types. For this pilot study, we conducted a coverage study and characterization of canonical section headers across 5 common, clinical note types and a generalizability study of canonical section headers detected within two types of clinical notes from Penn Medicine.
Age-related increase in matrix stiffness downregulates α-Klotho in chondrocytes and induces cartilage degeneration
Authors: Iijima Hirotaka , Gilmer Gabrielle , Wang Kai , Bean Allison , He Yuchen , Lin Hang , Evans Christopher , Ambrosio Fabrisia 
Published: March 2021

ABSTRACTEnhanced mechanistic insight into age-related knee osteoarthritis (KOA) is an essential step to promote successful translation of animal research to bedside interventions. To this end, the goal of these studies was to interrogate molecular mechanisms driving age-related KOA in a mouse model and correspond findings to human knee cartilage. Unbiased mass spectrometry proteomics of cartilage tissue revealed PI3K/Akt signaling was the predominant pathway disrupted over time in male, but not female, mice. This finding was consistent with a significantly accelerated KOA progression in males when compared to female counterparts. In probing for upstream regulators of these age-dependent alterations, we found that α-Klotho, a suppressor of PI3K/Akt signaling and potent longevity protein, significantly decreased with aging in both mouse and human knee cartilage. Upstream of these alterations, we found that age-related increases in matrix stiffness initiated a cascade of altered nuclear morphology and downregulated α-Klotho expression, ultimately impairing chondrocyte health. Conversely, reducing matrix stiffness increased α-Klotho expression in chondrocytes, thus enhancing their chondrogencity and cartilage integrity. Collectively, our findings establish a novel mechanistic link between age-related alterations in ECM biophysical properties and regulation of cartilage health by α-Klotho.
Langerhans islets induce anti-tumor immunity at the expense of glycemic control and predict chemotherapy response in pancreatic cancer
Authors: Ahmed Azaz , Charoentong Pornpimol , Klotz Rosa , Köhler Sophia , Suarez-Carmona Meggy , Valous Nektarios A. , Ferber Dyke , Heikenwälder Mathias , Giese Nathalia , Hackert Thilo , Klupp Fee , Schneider Martin , Schmidt Thomas , Springfeld Christoph , Tanriver Yakup , Falk Christine S. , Zitvogel Laurence , Zörnig Inka , Jäger Dirk , Halama Niels 
Published: March 2021

ABSTRACTInduction of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDA) is an unresolved challenge. Systematic investigation of the microenvironment of primary pancreatic tumors revealed a role of endocrine Langerhans islets in the coordination of immune activation. We found that intratumoral β-cells, regulated via STAT3, secrete C-C motif chemokine ligand 27 (CCL27) and thereby promote a TH1 phenotype in the microenvironment resulting in an enhanced T cell infiltration and prolonged patient survival. The local effect can be abrogated in a patient-based human explant model by inhibition of the CCL27 receptor CCR10. This defense mechanism is paralleled by an impaired metabolic function of Langerhans islets with reduced insulin levels resulting in a dysregulation of glycemic control in patients. Based on these findings, screening of PDA cases (n= 2264) led to the identification of type 2 diabetes mellitus (T2DM) and extractable glycated haemoglobin (HbA1c) levels as response markers for neoadjuvant chemotherapy with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Collectively these data provide insights into the interconnection of T2DM and PDA, and link declining glycemic control to therapeutic efficacy, which can be utilized as a tool for clinical decision-making and improve patient management.
Individualized precision targeting of dorsal attention and default mode networks with rTMS in traumatic brain injury-associated depression
Authors: Siddiqi Shan H. , Kandala Sridhar , Hacker Carl D. , Trapp Nicholas T. , Leuthardt Eric C. , Carter Alexandre R. , Brody David L. 
Published: March 2021

AbstractBackgroundAt the group level, antidepressant efficacy of rTMS targets is inversely related to their normative connectivity with subgenual anterior cingulate cortex (sgACC). Individualized connectivity may yield better targets, particularly in patients with neuropsychiatric disorders who may have aberrant connectivity. However, sgACC connectivity shows poor test-retest reliability at the individual level. Individualized resting-state network mapping (RSNM) can reliably map inter-individual variability in brain network organization.ObjectiveTo identify individualized RSNM-based rTMS targets that reliably target the sgACC connectivity profile.MethodsWe used RSNM to identify network-based rTMS targets in 10 healthy controls and 13 individuals with traumatic brain injury-associated depression (TBI-D). These “RSNM targets” were compared with consensus structural targets and targets based on individualized anti-correlation with a group-mean-derived sgACC region (“anti-group-mean sgACC targets”). The TBI-D cohort was randomized to receive active (n=9) or sham (n=4) rTMS to RSNM targets.ResultsThe group-mean sgACC connectivity profile was reliably estimated by individualized correlation with default mode network (DMN) and anti-correlation with dorsal attention network (DAN). Individualized RSNM targets were then identified based on DAN anti-correlation and DMN correlation. Counterintuitively, anti-correlation with the group-mean sgACC connectivity profile was stronger and more reliable for RSNM-derived targets than for “anti-group-mean sgACC targets”. Improvement in depression after RSNM-targeted rTMS was predicted by target anti-correlation with the portions of sgACC. Active treatment led to increased connectivity within and between several relevant regions.ConclusionsRSNM may enable reliable individualized rTMS targeting, although further research is needed to determine whether this personalized approach can improve clinical outcomes.
The Neurodata Without Borders ecosystem for neurophysiological data science
Authors: Rübel Oliver , Tritt Andrew , Ly Ryan , Dichter Benjamin K. , Ghosh Satrajit , Niu Lawrence , Soltesz Ivan , Svoboda Karel , Frank Loren , Bouchard Kristofer E. 
Published: March 2021

AbstractThe neurophysiology of cells and tissues are monitored electrophysiologically and optically in diverse experiments and species, ranging from flies to humans. Understanding the brain requires integration of data across this diversity, and thus these data must be findable, accessible, interoperable, and reusable (FAIR). This requires a standard language for data and metadata that can coevolve with neuroscience. We describe design and implementation principles for a language for neurophysiology data. Our open-source software (Neurodata Without Borders, NWB) defines and modularizes the interdependent, yet separable, components of a data language. We demonstrate NWB’s impact through unified description of neurophysiology data across diverse modalities and species. NWB exists in an ecosystem, which includes data management, analysis, visualization, and archive tools. Thus, the NWB data language enables reproduction, interchange, and reuse of diverse neurophysiology data. More broadly, the design principles of NWB are generally applicable to enhance discovery across biology through data FAIRness.
Co-variation between glucocorticoids, behaviour and immunity supports the pace-of-life syndrome hypothesis: an experimental approach
Authors: Carbillet Jeffrey , Rey Benjamin , Palme Rupert , Monestier Chloé , Börger Luca , Lavabre Typhaine , Maublanc Marie-Line , Cebe Nicolas , Rames Jean-Luc , Loc’h Guillaume Le , Wasniewski Marine , Rannou Benoit , Gilot-Fromont Emmanuelle , Verheyden Hélène 
Published: March 2021

AbstractThe biomedical literature has consistently highlighted that long-term elevation of glucocorticoids might impair immune functions. In wild animals, patterns are less clear. Here, we re-explored the stress-immunity relationship considering the potential effects of behavioural profiles. Thirteen captive roe deer (Capreolus capreolus) were monitored over an eight-week period encompassing two capture events. We assessed how changes in baseline faecal cortisol metabolite (FCM) concentrations following a standardised capture protocol and vaccination affected changes in thirteen immune parameters of the innate and adaptive immunity, and whether behavioural profiles were linked to changes in baseline FCM levels and immune parameters. We found that individuals showing an increase in baseline FCM levels also exhibited an increase in immunity and were characterised by more reactive behavioural profiles (low activity levels, docility to manipulation and neophilia). Our results suggest that immunity of large mammals may be influenced by glucocorticoids, but also behavioural profiles, as it is predicted by the pace-of-life syndrome hypothesis. Our results highlight the need to consider co-variations between behaviour, immunity and glucocorticoids in order to improve our understanding of the among-individual variability in the stress-immunity relationships observed in wildlife, as they may be underpinned by different life-history strategies.
Crosstalk between enterocytes and innate lymphoid cell drives early IFN-γ-mediated control ofCryptosporidium
Authors: Gullicksrud Jodi , Sateriale Adam , Englies Julie , Gibson Alexis , Shaw Sebastian , Hutchins Zachary , Martin Lindsay , Christian David , Taylor Gregory A. , Yamamoto Masahiro , Beiting Daniel P. , Striepen Boris , Hunter Christopher A. 
Published: March 2021

SUMMARYThe intestinal parasite,Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance toCryptosporidium, which specifically invades enterocytes, is dependent on the production of IFN-γ, yet whether enterocytes contribute to parasite control is poorly understood. In this study, utilizing the natural mouse pathogen,Cryptosporidium tyzzeri, we show that epithelial-derived IL-18 synergized with IL-12 to stimulate innate lymphoid cell (ILC) production of IFN-γ. This innate IFN-γ was required for early parasite control. Loss of STAT1 in enterocytes, but not dendritic cells or macrophages, antagonized early parasite control. Transcriptional profiling of enterocytes from infected mice identified an IFN-γ signature and enrichment of anti-microbial effectors like IDO, GBP and IRG. Deletion experiments identified a role for Irgm1/m3 in parasite control. Thus, enterocytes promote ILC production of IFN-γ that acts on enterocytes to restrict the growth ofC. tyzzeri.
Spontaneous dimensional reduction and novel ground state degeneracy in a simple chain model
Authors: Škrbić Tatjana , Hoang Trinh Xuan , Giacometti Achille , Maritan Amos , Banavar Jayanth R. 
Published: March 2021

AbstractChain molecules play a key role in the polymer field and in living cells. Our focus is on a new homopolymer model of a linear chain molecule subject to an attractive self-interaction promoting compactness. We analyze the model using simple analytic arguments complemented by extensive computer simulations. We find several striking results: there is a first order transition from a high temperature random coil phase to a highly unusual low temperature phase; the modular ground states exhibit significant degeneracy; the ground state structures exhibit spontaneous dimensional reduction and have a two-layer structure; and the ground states are assembled from secondary motifs of helices and strands connected by tight loops. We discuss the similarities and notable differences between the ground state structures (we call these PoSSuM - Planar Structures with Secondary Motifs) in the novel phase and protein native state structures.