bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Should COVID-19 Vaccines be Distributed between the Global North and South? A Discrete Choice Experiment in Six European Countries
Authors: Steinert JI , Sternberg H , Veltri GA , Büthe T 
Published: May 2022

AbstractBackgroundThe global distribution of COVID-19 vaccinations remains highly unequal. We examine public preferences in six European countries regarding the allocation of COVID-19 vaccines between the Global South and Global North.MethodsWe conducted online discrete choice experiments with adult participants in France (n=766), Germany (n=1964), Italy (n=767), Poland (n=670), Spain (n=925), and Sweden (n=938). Respondents were asked to decide which one of two candidates, who varied along four attributes: age, mortality risk, employment, and living in a low- or high-income country, should receive the vaccine first. We analysed the relevance of each attribute in allocation decisions using a conditional logit regression.ResultsAcross countries, respondents selected candidates with a high mortality and infection risk, irrespective of whether the candidate lived in their own country. All else equal, respondents in Italy, France, Spain, and Sweden gave priority to a candidate from a low-income country, whereas German respondents were significantly more likely to choose the candidate from their own country. Female, younger, and more educated respondents were more favourable of an equitable vaccine distribution.ConclusionsGiven these preferences for global solidarity, European governments should promote vaccine transfers to poorer world regions.FundingFunding was provided by the European Union’s Horizon H2020 research and innovation programme under grant agreement 101016233 (PERISCOPE).
Assessing Cellular and Transcriptional diversity of IIeal Mucosa amongst Treatment Naïve and Treated Crohn’s disease
Authors: Maddipatla Sushma Chowdary , Kolachala Vasantha L , Venkateswaran Suresh , Dodd Anne F , Pelia Ranjit Singh , Geem Duke , Yin Hong , Sun Yutong , Xu Congmin , Mo Angela , Kosters Astrid , Yang Junkai , Matthews Jason D. , Ghosn Eliver , Kugathasan Subra , Qiu Peng 
Published: May 2022

AbstractBackground and AimsCrohn’s disease is a life-long disease characterized by chronic inflammation of the gastrointestinal tract. Defining the cellular and transcriptional composition of the mucosa at different stages of disease progression is needed for personalized therapy in Crohn’s.MethodsIleal biopsies were obtained from (i) controls (n=6), (ii) treatment-naïve (n=7), and (iii) established (n=14) Crohn’s patients along with remission (n=3) and refractory (n=11) treatment groups. The biopsies were processed using 10x Genomics single cell 5’ yielded 139,906 cells. Gene expression count matrices of all samples were analyzed by reciprocal principal component integration, followed by clustering analysis. Manual annotations of the clusters were performed using canonical gene markers. Cell-type proportions, differential expression analysis and gene ontology enrichment were carried out for each cell type.ResultsWe identified 3 cellular compartments with 9 epithelial, 1 stromal, and 5 immune cell subtypes. We observed differences in the cellular composition between ctrl, treatment-naive and established groups, with the significant changes in the epithelial subtypes of the treatment-naive patients, including microfold, tuft, goblet, enterocytes and BEST4+ cells. Surprisingly, fewer changes in the composition of the immune compartment were observed, however gene expression in the epithelial and immune compartment was different between Crohn’s phenotypes indicating changes in cellular activity.ConclusionsOur study identified cellular and transcriptional signatures associated with treatment-naive that collectively points to dysfunction of the intestinal barrier with an increase in inflammatory cellular activity. Our analysis also highlights the heterogeneity amongst patients within the same disease phenotype, shinning new light on personalized treatment responses and strategies.
Shift work and evening chronotype are related to prevalent non-alcoholic fatty liver disease in 282,303 UK biobank participants
Authors: Maidstone Robert , Rutter Martin K. , Marjot Thomas , Ray David W. , Baxter Matthew 
Published: May 2022

AbstractBackground & AimsNon-alcoholic fatty liver disease (NAFLD) is globally prevalent and confers a high risk of morbidity via progression to non-alcoholic steatohepatitis (NASH). Circadian disruption in mouse models contributes to the development of hepatic steatosis and inflammation, however evidence in humans is lacking. We investigated how shift working and chronotype were associated with NAFLD/NASH in UK Biobank participants.MethodsWe stratified 282,303 UK Biobank participants into day, irregular-shift, and permanent night-shift workers. We compared the likelihood of NAFLD/NASH in these groups using: a) Dallas Steatosis Index (DSI), b) NAFLD/NASH ICD10 codes, and c) liver proton density fat fraction (PDFF) after serially adjusting for age, sex, ethnicity, sleep, alcohol, smoking, and body mass index. We further assessed the relationship of baseline chronotype with likelihood of NAFLD/NASH using the same outcomes and covariates.ResultsCompared to day workers, irregular-shift workers were more likely to have NAFLD/NASH defined by high DSI (odds ratio (OR) 1.29 (95% CI 1.18–1.4)) after adjusting for all covariates excluding BMI, with some attenuation after additional adjustment for BMI (OR 1.12 (1.03-1.22)). Likelihood of DSI-defined NAFLD/NASH was also higher in permanent night-shift workers (OR 1.08 (0.9–1.29)) in the fully-adjusted model. Compared to participants with intermediate chronotype, those with extreme late chronotype had a higher likelihood of DSI-defined NAFLD/NASH (OR 1.45 (1.34–1.56)) and a higher likelihood of NAFLD/NASH by ICD10 code (OR 1.23 (1.09–1.39)). Liver PDFF was elevated in irregular shift workers, but not permanent night shift workers.ConclusionsIrregular-shift work and chronotype are associated with NAFLD/NASH, suggesting circadian misalignment as an underlying mechanism. These findings have implications for health interventions to mitigate the detrimental effect of shift work.
Optimizing next-generation RSV prevention in Mali: a cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis
Authors: Laufer Rachel S. , Baral Ranju , Buchwald Andrea G. , Campbell James D. , Coulibaly Flanon , Diallo Fatoumata , Doumbia Moussa , Driscoll Amanda J. , Galvani Alison P. , Keita Adama M. , Neuzil Kathleen M. , Sow Samba , Pecenka Clint , Ortiz Justin R. , Fitzpatrick Meagan C. 
Published: May 2022

ABSTRACTBackgroundRespiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children.MethodsWe conducted an analysis of both health and economic impacts of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years of life, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios.FindingWe found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. In an optimization analysis incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months.InterpretationAt prices comparable to existing vaccine products, public health programs using extended half-life RSV mAbs alone or in combination with pediatric RSV vaccines would be impactful and efficient components of prevention strategies in LMICs such as Mali.
Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian Multiple Sclerosis patients, a follow-up study
Authors: Idda Maria Laura , Pitzalis Maristella , Lodde Valeria , Loizedda Annalisa , Frau Jessica , Lobina Monia , Zoledziewska Magdalena , Virdis Francesca , Delogu Giuseppe , Marini Maria Giuseppina , Mingoia Maura , Masala Marco , Lorefice Lorena , Fronza Marzia , Carmagnini Daniele , Carta Elisa , Pilotto Silvy , Castiglia Paolo , Chessa Paola , Uzzau Sergio , Farina Gabriele , Solla Paolo , Steri Maristella , Devoto Marcella , Fiorillo Edoardo , Floris Matteo , Zarbo Roberto Ignazio , Cocco Eleonora , Cucca Francesco 
Published: May 2022

AbstractMonitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations of the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and a month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. And although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.
The time is ripe to harmonize global acute febrile illness etiologic investigations
Authors: Moreira José , Fernando-Carballo B. Leticia , Escadafal Camille , Dittrich Sabine , Brasil Patrícia , M Siqueira André 
Published: May 2022

AbstractWe investigated the impact of considering different case definitions of fever as inclusion criteria among participants enrolling in an acute febrile illness investigation and observed that adopting a subjective assessment of fever regardless of specific fever cut-off value accounted for the diversity of clinical fever phenotypes and did not mischaracterize the febrile population.
A DSM-5 AMPD and ICD-11 compatible measure for an early identification of personality disorders in adolescence – LoPF-Q 12-18 latent structure and short form
Authors: Zimmermann Ronan , Steppan Martin , Zimmermann Johannes , Oeltjen Lara , Birkhölzer Marc , Schmeck Klaus , Goth Kirstin 
Published: May 2022

AbstractThe LoPF-Q 12-18 (Levels of Personality Functioning Questionnaire) was designed for clinical use and to promote early detection of personality disorder (PD). It is a self-report measure with 97 items to assess personality functioning in adolescents from 12 years up. It operationalizes the dimensional concept of personality disorder (PD) severity used in the Alternative DSM-5 Model for Personality Disorders and the ICD-11. In this study, we investigated the factorial structure of the LoPF-Q 12-18. Additionally, a short version was developed to meet the need of efficient screening for PD in clinical and research applications.To investigate the factorial structure, several confirmatory factor analysis models were compared. A bifactor model with a strong general factor and four specific factors showed the best nominal fit (CFI = .91, RMSEA = .04, SRMR = .07).The short version was derived using the ant colony optimization algorithm. This procedure resulted in a 20-item version with excellent fit for a hierarchical model with four first order factors to represent the domains and a secondary higher order factor to represent personality functioning (CFI = .98, RMSEA = .05, SRMR = .04). Clinical validity (effect size d= 3.1 between PD patients and controls) and clinical utility (cutoff ≥ 36 providing 87.5% specificity and 80.2% sensitivity) for detecting patients with PD were high for the short version. Both, the long and short LoPF-Q 12-18 version are ready to be used for research and diagnostic purposes.
A single closed head injury in mice induces chronic, progressive white matter atrophy and increased phospho-tau expressing oligodendrocytes
Authors: Havlicek David F. , Furhang Rachel , Nikulina Elena , Smith-Salzberg Bayle , Lawless Siobhán , Sevarin Sasha A. , Mallaboeva Sevara , Nayab Fizza , Seifert Alan C. , Crary John F. , Bergold Peter J. 
Published: May 2022

AbstractTraumatic brain injury (TBI) acutely damages the brain; this injury can evolve into chronic neurodegeneration. While much is known about the chronic effects arising from multiple mild TBIs, far less is known about the long-term effects of a single moderate to severe TBI. We found that a single moderate closed head injury to mice induces diffuse axonal injury within 1-day post-injury (DPI). At 14 DPI, injured animals have atrophy of ipsilesional cortex, thalamus, and corpus callosum, with bilateral atrophy of the dorsal fornix. Atrophy of the ipsilesional corpus callosum is accompanied by decreased fractional anisotropy and increased mean and radial diffusivity that remains unchanged between 14 and 180 DPI. Injured animals increased density of phospho-tau immunoreactive (pTau+) cells in the ipsilesional cortex and thalamus, and bilaterally in corpus callosum. Between 14 and 180 DPI, atrophy occurs in the ipsilesional ventral fornix, contralesional corpus callosum, and bilateral internal capsule. Diffusion tensor MRI parameters remain unchanged in white matter regions with delayed atrophy. Between 14 and 180 DPI, pTau+cell density increases bilaterally in corpus callosum, but decreases in cortex and thalamus. The location of pTau+cells within the ipsilesional corpus callosum changes between 14 and 180 DPI; density of all cells increases including pTau+or pTau-cells. Greater than 90% of the pTau+cells are in the oligodendrocyte lineage in both gray and white matter. Density of thioflavin-S+cells in thalamus increases by 180 DPI. These data suggest a single closed head impact produces multiple forms of chronic neurodegeneration. Gray and white matter regions proximal to the impact site undergo rapid atrophy. More distal white matter regions undergo chronic, progressive white matter atrophy with an increasing density of oligodendrocytes containing pTau. These data suggest that the chronic neurodegeneration arising from a single moderate CHI differs greatly from the chronic traumatic encephalopathy produced by multiple mild head injuries.HighlightsGray and white matter atrophy begins within 14 days after a single closed head injuryWhite matter atrophy progresses between 14 and 180 days post injury with minimal changes in diffusion tensor MRI parameters.CHI increases the density of oligodendrocytes with perinuclear accumulation of phosphorylated tauThioflavin-S+cells increase in thalamus at 180 days post injury
Periostin+stromal cells guide lymphovascular invasion by cancer cells
Authors: Null Jamie L. , Kim Dae Joong , McCann James V. , Pramoonjago Patcharin , Fox Jay W. , Kumar Pankaj , Edatt Lincy , Pecot Chad V. , Dudley Andrew C. 
Published: May 2022

AbstractCancer cell dissemination to the sentinel lymph node associates with poor patient outcomes, particularly in breast cancers. How cancer cells egress the primary tumor upon interfacing with the lymphatic vasculature is complex and driven by dynamic interactions between cancer cells and stromal cells including cancer associated fibroblasts (CAFs). The matricellular protein periostin can distinguish CAF subtypes in breast cancer and is associated with increased desmoplasia and disease recurrence in patients. However, since periostin is secreted, periostin-expressing CAFs are difficult to characterize in situ, limiting our understanding of their specific contribution to cancer progression. Here, we used in vivo genetic labelling and ablation to lineage trace periostin+cells and characterize their function(s) during tumor growth and metastasis. We report that periostin-expressing CAFs are spatially found at periductal and perivascular margins, are enriched at lymphatic vessel peripheries, and are differentially activated by highly-metastatic cancer cells versus low-metastatic counterparts. Surprisingly, genetically depleting periostin+CAFs slightly accelerated primary tumor growth but impaired intratumoral collagen organization and inhibited lymphatic, but not lung, metastases. Periostin ablation in CAFs impaired their ability to deposit aligned collagen matrices and inhibited cancer cell invasion through collagen and across lymphatic endothelial cell monolayers. Thus, highly-metastatic cancer cells mobilize periostin-expressing CAFs in the primary tumor site which promote collagen remodeling and collective cell invasion within lymphatic vessels and ultimately to sentinel lymph nodes.Significance StatementMetastatic disease causes the majority of cancer-related deaths but is challenging to treat as it is a complex multi-step process driven by heterotypic cell interactions. Cancer-associated fibroblasts (CAFs) are abundant in most solid tumors and display pro-tumorigenic and pro-metastatic functions, but extensive molecular diversity among CAFs has yielded contradictory results in previous attempts to target this population. Therefore, there is a need to identify markers of CAF subpopulations that promote or inhibit metastasis and functionally characterize them to understand their contributions during tumor progression. Our work identifies a population of CAFs, marked by expression of the matricellular protein periostin, that remodel the ECM to promote the escape of cancer cells into lymphatic vessels thereby driving colonization of proximal lymph nodes.
Epigenetic Age and Lung Cancer Risk in the CLUE II Prospective Cohort Study
Authors: Michaud Dominique S. , Chung Mei , Zhao Naisi , Koestler Devin C. , Lu Jiayun , Platz Elizabeth A. , Kelsey Karl T. 
Published: May 2022

AbstractBackgroundEpigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening.MethodsA nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at −70°C. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression.ResultsWe did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis.ConclusionFindings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.
Omicron and vaccines: An analysis on the decline in COVID-19 mortality
Authors: Larrauri Blas J. , Malbrán Alejandro , Larrauri José A. 
Published: May 2022

AbstractThe SARS-CoV-2 virus emerged in December 2019 infecting more than 430 million people worldwide and causing almost 6 million deaths until February 2022. Rapid vaccination efforts during this period coincided with a reduction in the mortality rate of the virus. A new genetic COVID-19 variant named Omicron appeared and widely spread by the end of 2021, after which the COVID-19 mortality rate showed a marked, albeit temporary, decline. The potential relationship between vaccines and omicron infection on the mortality rate of COVID-19 is analyzed in this article using online data from public sources from countries with relatively high incidence of infection. Mortality and incidence rates were compared before and after Omicron became the prevalent source of COVID-19 cases, as well as the effect of vaccination during these periods. Infection rates were higher during Omicron than in the pre-Omicron period (4.16% vs. 2%, respectively), whereas mortality rates showed the opposite trend both in deaths over population (0.021% vs. 0.171%) and deaths over positive cases (0.27% vs. 1.07%, respectively). The results suggest that vaccines, while significantly reducing mortality, did not prevent Omicron infection; and that during the Omicron period mortality decreased by a low aggressiveness of this variant.Key Messages*Vaccines do not appear to have prevented Omicron infection.*Infection rates were higher during the Omicron period than before it.*Mortality rates were lower during the Omicron period than before it.*Vaccines reduced mortality rates during both pre- and Omicron periods.*The sharp decrease in mortality rates during the Omicron period seems to be due to the low virulence of Omicron strains rather than vaccine efficacy.