bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Guillain-Barré syndrome following SARS-CoV-2 immunization in Mexico: A nation-wide registry of seven COVID-19 vaccines
Authors: García-Grimshaw Miguel , Galnares-Olalde Javier Andrés , Bello-Chavolla Omar Yaxmehen , Michel-Chávez Anaclara , Cadena-Fernández Arturo , Briseño-Godínez María Eugenia , Antonio-Villa Neftali Eduardo , Nuñez Isaac , Gutiérrez-Romero Alonso , Hernández-Vanegas Laura , del Mar Saniger-Alba María , Carrillo-Mezo Roger , Ceballos-Liceaga Santa Elizabeth , Carbajal-Sandoval Guillermo , Flores-Silva Fernando Daniel , Díaz-Ortega José Luis , López-Gatell Hugo , Cortes-Alcalá Ricardo , Pérez-Padilla José Rogelio , Chiquete Erwin , Reyes-Terán Gustavo , Arauz Antonio , Valdés-Ferrer Sergio Iván 
Published: April 2022

SummaryBackgroundGuillain-Barré syndrome (GBS) as an adverse event following immunization (AEFI) against SARS-CoV-2 has been linked to a few (ChAdOx1 nCov-19 and Ad26.COV2-S), but not all vaccines, including mRNA-based ones. Epidemiological information on GBS among recipients of other SARS-CoV-2-directed vaccines among Latinx/Hispanic recipients is scarce.MethodsWe report GBS incidence per million administered doses from a nationwide Mexican retrospective registry of adult (≥18 years) recipients of 81,842,426 doses of seven vaccines against SARS-CoV-2 immunized between December 24, 2020, and October 29, 2021. Cases were collected through a passive epidemiological surveillance system and defined as events occurring within 42 days from immunization. Vaccines were analyzed individually and by vector as either mRNA-based (mRNA-1273 and BNT162b2), adenovirus-vectored (ChAdOx1 nCov-19, rAd26-rAd5, Ad5-nCoV, and Ad26.COV2-S), or inactivated whole-virion-vectored (CoronaVac).FindingsWe identified 97 patients (52 [53.6%] males; median age 44 years (interquartile range 33–60), for an overall observed incidence of 1.19/1,000,000 doses (95% confidence interval [CI] 0.97–1.45), higher among Ad26.COV2-S (3.86/1,000,000 doses, 95% CI 1.50–9.93) and BNT162b2 (1.92/1,00,000 doses, 95% CI 1.36–2.71) recipients. The overall interval from vaccination-to-GBS symptoms onset was 10 days (interquartile range 3–17). Preceding diarrhea (≤ 4 weeks) was reported in 21.6%, and four (4.1%) more had mild COVID-19. Only 18 patients were tested for Campylobacter jejuni infection; 16 (88.9%) were positive. Electrophysiological examinations were performed in 76 (78.4%) patients (axonal in 46 [60.5%] and demyelinating in 25 [32.8%]); variants were similar between platforms. On initial evaluation, 91.8% had a GBS disability score ≥ 3. Seventy-five (77.3%) patients received intravenous immunoglobulin, seven (7.2%) plasma exchanges, and 15 (15.5%) were treated conservatively. There were 10 (10.3%) deaths, and 79.1% of survivors were unable to walk independently at discharge.InterpretationIn our population, GBS was an infrequent AEFI, observed in less than 1.2/1,000,000 administered doses of vaccines against SARS-CoV-2. Observed incidences were higher among Ad26.COV2.S and BNT162b2 recipients individually and for mRNA-vectored vaccines as a group.
Investigating the Consistency of Extracellular Vesicle Production from Breast Cancer Subtypes Using CELLine Adherent Bioreactors
Authors: Hisey Colin L. , Artuyants Anastasiia , Guo George , Chang Vanessa , Reshef Gabrielle , Middleditch Martin , Jacob Bincy , Chamley Lawrence W. , Blenkiron Cherie 
Published: April 2022

AbstractExtracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in-depth characterisation and validation of EVs produced using conventionalin vitrocultures can be challenging due to the large area of cell monolayers and volumes of culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but the consistency of EVs produced over time in these systems has not been reported previously. In this study, we demonstrate that several breast cancer cell lines of different subtypes can be cultured simultaneously in space, resource, and time efficient manner using CELLine AD 1000 systems, allowing the consistent production of vast amounts of EVs for downstream experimentation. We report an improved workflow used for inoculating, maintaining, and monitoring the bioreactors, their EV production, and the characterisation of the EVs produced. Lastly, our proteomic analyses of the EVs produced throughout the lifetime of the bioreactors show that core EV-associated proteins are relatively consistent, with few minor variations over time, and that tracking the production of EVs may be a convenient method for indirectly monitoring the bioreactors’ health. These findings will aid future studies requiring the simultaneous production of large amounts of EVs from several cell lines of different subtypes of a disease and other EV biomanufacturing applications.
A genetic and linguistic analysis of the admixture histories of the islands of Cabo Verde
Authors: Laurent Romain , Szpiech Zachary A. , da Costa Sergio S. , Thouzeau Valentin , Fortes-Lima Cesar A. , Dessarps-Freichey Françoise , Lémée Laure , Utgé José , Rosenberg Noah A. , Baptista Marlyse , Verdu Paul 
Published: April 2022

ABSTRACTFrom the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals’ birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants’ genomic diversity and structure on both sides of the Atlantic.
Modeling tactile pleasantness across skin types at the individual level reveals a reliable and stable basic function
Authors: Crucianelli Laura , Chancel Marie , Ehrsson H. Henrik 
Published: April 2022

AbstractTouch is perceived most pleasant when delivered at velocities known to optimally activate C Tactile afferents. At the group level, pleasantness ratings of touch delivered at velocities in the range 0.3-30 cm/s follows an inverted-U shape curve, with maximum pleasantness between 1 and 10 cm/s. However, the prevalence, reliability, and stability of this function at the individual level and across skin types remains unknown. Here, we tested a range of seven velocities delivered with a soft brush, on both hairy and non-hairy skin in 123 participants. We showed that the relationship between pleasantness and velocity of touch is significantly best described by a negative quadratic model at the individual level in the majority of participants both on hairy (67.1%) and non-hairy skin (62.6%). Higher interoceptive accuracy and self-reported depression were related to a better fit of the quadratic model and to the steepness of the curve, respectively. The prevalence of the quadratic model was stable across body sites (62.6%), across two experimental sessions (73-78%,), and regardless of the number of trials. Thus, the individual perception of tactile pleasantness follows a characteristic velocity-dependent function across skin types and shows trait characteristics, making it a possible biomarker for mental health disorders.
Single sample pathway analysis in metabolomics: performance evaluation and application
Authors: Wieder Cecilia , Lai Rachel PJ , Ebbels Timothy 
Published: April 2022

AbstractSingle sample pathway analysis (ssPA) transforms molecular level omics data to the pathway level, enabling the discovery of patient-specific pathway signatures. Compared to conventional pathway analysis, ssPA overcomes the limitations by enabling multi-group comparisons, alongside facilitating numerous downstream analyses such as pathway-based machine learning. While in transcriptomics ssPA is a widely used technique, there is little literature evaluating its suitability for metabolomics. Here we provide a thorough benchmark of established ssPA methods (ssGSEA, GSVA, SVD (PLAGE), and z-score) using semi-synthetic metabolomics data, alongside the evaluation of two novel methods we propose: ssClustPA and kPCA. While GSEA-based and z-score methods outperformed the others in terms of recall, clustering/dimensionality reduction-based methods provided higher precision at moderate-to-high effect sizes. A case study applying ssPA to inflammatory bowel disease demonstrates how these methods yield a much richer depth of interpretation than conventional approaches, for example by clustering pathway scores to visualise a pathway-based patient subtype-specific correlation network. We also developed the sspa python package (freely available at https://pypi.org/project/sspa/), providing implementations of all the methods benchmarked in this study. This work underscores the value ssPA methods can add to metabolomic studies and provides a useful reference for those wishing to apply ssPA methods to metabolomics data.Author summaryPathway analysis is a computational method used to draw insights from omics data by identifying groups of molecules (biological pathways) which are important in a study. Single-sample pathway analysis is based on the same principles as conventional pathway analysis but allows researchers to compute the enrichment of pathways at an individual-sample level. This enables pathway-based patient stratification and facilitates a multitude of downstream analyses based on pathways, such as machine learning, or pathway-based visualization which would not be possible using conventional approaches. In this work we investigated the application of single-sample pathway analysis to metabolomics data, a field in which it has not been widely used to date. We first evaluated the most popular methods for single-sample pathway analysis using simulated metabolomics data, as well as two novel methods we developed. Following these tests, we used metabolomics data from inflammatory bowel disease patients to demonstrate how single-sample pathway analysis methods can be used to infer novel pathway-based insights with the advantage of discriminating between disease subtypes. Overall, our analysis provides readers with information on the performance of single-sample pathway analysis methods, whilst highlighting the potential of such methods in metabolomics research.
Spatial Models of Pattern Formation During Phagocytosis
Authors: Herron J. Cody , Hu Shiqiong , Liu Bei , Watanabe Takashi , Hahn Klaus M. , Elston Timothy C. 
Published: April 2022

AbstractPhagocytosis, the biological process in which cells ingest large particles such as bacteria, is a key component of the innate immune response. Fcγ receptor (FcγR)-mediated phagocytosis is initiated when these receptors are activated after binding immunoglobulin G (IgG). Receptor activation initiates a signaling cascade that leads to the formation of the phagocytic cup and culminates with ingestion of the foreign particle. In the experimental system termed “frustrated phagocytosis”, cells attempt to internalize micropatterned disks of IgG. Cells that engage in frustrated phagocytosis form “rosettes” of actin-enriched structures called podosomes around the IgG disk. The mechanism that generates the rosette pattern is unknown. We present data that supports the involvement of Cdc42, a member of the Rho family of GTPases, in pattern formation. Cdc42 acts downstream of receptor activation, upstream of actin polymerization, and is known to play a role in polarity establishment. Reaction-diffusion models for GTPase spatiotemporal dynamics exist. We demonstrate how the addition of negative feedback and minor changes to these models can generate the experimentally observed rosette pattern of podosomes. We show that this pattern formation can occur through two general mechanisms. In the first mechanism, an intermediate species forms a ring of high activity around the IgG disk, which then promotes rosette organization. The second mechanism does not require initial ring formation but relies on spatial gradients of intermediate chemical species that are selectively activated over the IgG patch. Finally, we analyze the models to suggest experiments to test their validity.Author SummaryPhagocytosis, the process by which cells ingest foreign bodies, plays an important role in innate immunity. Phagocytosis is initiated when antibodies coating the surface of a foreign body are recognized by immune cells, such as macrophages. To study early events in phagocytosis, we used “frustrated phagocytosis”, an experimental system in which antibodies are micropatterned in disks on a cover slip. The cytoskeleton of cells attempting to phagocytose these disks organizes into “rosette” patterns around the disks. To investigate mechanisms that underlie rosette formation we turned to mathematical modeling based on reaction-diffusion equations. Building on existing models for polarity establishment, our analysis revealed two mechanisms for rosette formation. In the first scenario an initial ring of an intermediate signaling molecule forms around the disk, while in the second scenario rosette formation is driven by gradients of positive and negative pathway regulators that are activated over the disk. Finally, we analyze our models to suggest experiments for testing these mechanisms.
Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: A longitudinal analysis of 1,811 UK adults
Authors: Paul Elise , Fancourt Daisy 
Published: April 2022

AbstractBackgroundDemographic and infection-related characteristics have been identified as risk factors for long COVID, but research on the influence of health behaviours (e.g., exercise, smoking) immediately preceding the index infection is lacking.Methods1,811 UK adults from the UCL COVID-19 Social Study and who had previously been infected with COVID-19 were analysed. Health behaviours in the month before infection were weekly exercise frequency, days of fresh air per week, sleep quality, smoking, consuming more than the number of recommended alcoholic drinks per week (>14), and the number of mental health care behaviours (e.g., online mental health programme). Logistic regressions controlling for covariates (e.g., COVID-19 infection severity and pre-existing health conditions) examined the impact of health behaviours on long COVID and three long COVID symptoms (difficulty with mobility, cognition, and self-care).ResultsIn the month before infection with COVID-19, poor quality sleep increased the odds of long COVID (odds ratio [OR]: 3.53; (95% confidence interval [CI]: 2.01 to 6.21), as did average quality sleep (OR: 2.44; 95% CI: 1.44 to 4.12). Having smoked (OR: 8.39; 95% CI: 1.86 to 37.91) increased and meeting recommended weekly physical activity guidelines (3+ hours) (OR: 0.05; 95% CI: 0.01 to 0.39) reduced the likelihood of difficulty with self-care (e.g., washing all over or dressing) amongst those with long COVID.ConclusionResults point to the importance of sleep quality for long COVID, potentially helping to explain previously demonstrated links between stress and long COVID. Results also suggest that exercise and smoking may be modifiable risk factors for preventing the development of difficulty with self-care.FundingThe Nuffield Foundation [WEL/FR-000022583], the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and the Wellcome Trust [221400/Z/20/Z and 205407/Z/16/Z].What is already known on the topicLong COVID is rapidly becoming a public health concern. Although existing evidence to date has identified health characteristics such as obesity as risk factors, hardly any research on modifiable risk factors such as health behaviours has been conducted.What this study addsThis study adds to the dearth of evidence on modifiable risk factors occurring before COVID-19 infection. Findings suggest a role of poor sleep quality for the development of long COVID, and for meeting physical activity guidelines (3+ hours per week) and not smoking as modifiable risk factors for self-care difficulties amongst those with long COVID.
Change in methicillin-resistant Staphylococcus aureus testing in the Intensive Care Unit as an antimicrobial stewardship initiative
Authors: Smith Hayden L. , DuMontier Samuel P. , Bushman Amanda M. , Hurdelbrink Jonathan R. , Yost William J. , Craig Steven R. 
Published: April 2022

ABSTRACTBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) associated infections are a cause of morbidity/mortality in the Intensive Care Unit (ICU). Vancomycin is an option for treatment but is not without its own risks.PurposeTo institute a testing change to decrease time between ordering of MRSA tests and availability of results in patients admitted to the adult ICU.ProceduresA MRSA testing change was implemented at two adult (i.e., tertiary and community) ICUs located in a U.S. Midwestern health system. The change was implemented in 2018 and included the switch from culture to polymerase chain reaction (PCR) in ICU admitted patients. Study data were collected from 2016-2020 and a Bayesian quantile regression model was fit to examine median level change in time to results and to calculate a counterfactual estimate.Main FindingsDuring the 58-month period, 71% of 19,975 patients seen at the two ICUs received MRSA testing. In the pre-change period, 91% and 99% of patients at the tertiary and community hospitals received testing via culture, respectively. Culture was used 1% and ∼0% of the time at the hospitals in the post-change period. The counterfactual estimated 36 (95% CrI: 35, 37) and 32 fewer hours (95% CrI: 31, 33) until results were available at the tertiary and community hospital, respectively.ConclusionsStudy revealed MRSA results were available in less time at both facilities after testing change. This information can aid anti-microbial stewardship via possibly delaying initiation and/or quicker de-escalation of therapy when results are known.
Metabolic-imaging of human glioblastoma live tumors: a new precision-medicine approach to predict tumor treatment response early
Authors: Morelli Mariangela , Lessi Francesca , Barachini Serena , Liotti Romano , Montemurro Nicola , Perrini Paolo , Santonocito Orazio Santo , Gambacciani Carlo , Snuderl Matija , Pieri Francesco , Aquila Filippo , Farnesi Azzurra , Naccarato Antonio Giuseppe , Viacava Paolo , Cardarelli Francesco , Ferri Gianmarco , Mulholland Paul , Ottaviani Diego , Paiar Fabiola , Liberti Gaetano , Pasqualetti Francesco , Menicagli Michele , Aretini Paolo , Signore Giovanni , Franceschi Sara , Mazzanti Chiara Maria 
Published: April 2022

AbstractBackgroundGlioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy (RT) remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients.MethodsGB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were then performed to characterize tumor cases stratification.ResultsOur functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non Responder tumors were identified. FLIM-based metabolic tumor stratification was well-reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17 gene molecular signature associated with survival. The number of promoter methylated tumors for the MGMT gene was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker.ConclusionsFor the first time, FLIM-based metabolic imaging was used on ex-vivo live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.
Axonal plasticity in response to active forces generated through magnetic nanopulling
Authors: Falconieri Alessandro , De Vincentiis Sara , Cappello Valentina , Convertino Domenica , Ghignoli Samuele , Figoli Sofia , Luin Stefano , Català-Castro Frederic , Marchetti Laura , Borello Ugo , Krieg Michael , Raffa Vittoria 
Published: April 2022

SummaryMechanical force is crucial in guiding axon outgrowth, before and after synapse formation. This process is referred to as “stretch-growth”. However, how neurons transduce mechanical inputs into signaling pathways remains poorly understood. Another open question is how stretch-growth is coupled in time with the intercalated addition of new mass along the entire axon. Here, we demonstrate that active mechanical force generated by magnetic nano-pulling induces a remodeling of the axonal cytoskeleton. Specifically, the increase in the axonal density of microtubules leads to an accumulation of organelles and signaling vesicles which, in turn, promotes local translation by increasing the probability of assembly of the “translation factories”. The modulation of axonal transport and local translation sustains enhanced axon outgrowth and synapse maturation.