bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centred approach. Consensus Guidance Using a Delphi Process
Authors: Maggiolo Franco , Caputo Sergio Lo , Bonora Stefano , Borderi Marco , Cingolani Antonella , D’Ettorre Gabriella , Di Biagio Antonio , Di Giambenedetto Simona , Gervasoni Cristina , Guaraldi Giovanni , Maggi Paolo , Taramasso Lucia 
Published: May 2022

ABSTRACTBackgroundModern antiretroviral therapy (ART) offers several treatment options characterized by high efficacy and tolerability, and new strategies with new drugs are now available for the treatment of HIV infection. As definitive data on the long-term success of these new strategies are lacking, a panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow in time a person-centered ART approach.MethodsPanelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round through 2 subsequent rounds of voting.ResultsNinety infectious diseases specialists from different Infectious Diseases Centres in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need of an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality of life monitoring during the standard follow up of people living with HIV.ConclusionsThe consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.Key pointsA panel of experts in the care of HIV infection expressed their consensus on which could be the best strategy to achieve and maintain long-term effectiveness in course of antiretroviral therapy, using Delphi methodology.
A hospital-based study to assess various biomarkers for prognostic prediction of clinical outcome in COVID-19 disease
Authors: Padhi Abhishek , Shaw Dipika , Khatoon Shagufta , Ranjan Swekcha , Bhargava Anudita , Negi Sanjay Singh 
Published: May 2022

AbstractCOVID-19 pandemic has inflicted a painful unforgettable number of deaths throughout the world. Hematological inflammatory and organ-specific biomarkers are universally practiced in helping clinical decisions in various infectious diseases. Accordingly, their role in predicting progression and severity, and fatal outcome of COVID-19 was investigated to take initial appropriate treatment measures to reduce associated mortality.MethodsThe retrospective analysis of a total of 126 COVID-19 cases representing mild, moderate, severe, and succumbed cases were assessed for the pattern of hematological, inflammatory, and organ-specific biomarkers.ResultsA total of 126 proven cases of SARS-CoV-2 infection were retrospectively analyzed for the association of various biomarkers with the COVID-19 disease progression. The CBC analysis showed that the median TLC was high for the severe group of both males (12.49 × 103/μl) and females (14.23 x103/μl). Similarly, the neutrophil count was also found high in the severe group, whereas the monocytes count showed low median values in severe cases, but both these parameters had no significant difference among the males and the females. The platelet count showed a significant difference (p=0.018) among the non-severe and severe groups between males and females. Among inflammatory markers, D-dimer, CRP, LDH, and APTT showed a higher median value in severe cases among both the males and females while ESR value was higher in non-severe cases and ferritin showed similar values in both severe and non-severe cases. The liver and kidney function parameters were also analyzed and a significant P-value was found for ALP (p=0.004), ALT (p=0.032), and AST (p=0.009) in the non-severe vs. severe category of COVID-19 patients.DiscussionHigh TLC, neutrophilia, lymphopenia, thrombocytopenia, and eosinopenia are the potential risk factor for the progression of COVID-19 disease for severe and fatal outcomes. Inflammatory markers of D-dimer, CRP, LDH, APTT, and ferritin above normal range also carries the potential risk of severe and fatal outcome in COVID-19 disease. Higher ALT, AST, and serum creatinine may also carry a poor prognosis.
COVID-19 pandemic impact on preterm birth and stillbirth rates associated with socioeconomic disparities: A quasi-experimental study
Authors: Aboulatta Laila , Kowalec Kaarina , Leong Christine , Delaney Joseph , Falk Jamie , Alessi-Severini Silvia , Chateau Dan , Tan Qier , Kearns Katherine , Raimondi Christina , Lavu Alekhya , Haidar Lara , Vaccaro Christine , Eltonsy Sherif 
Published: May 2022

AbstractBackgroundConflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES).MethodsUsing the linked administrative health databases from Manitoba, Canada, we conducted a quasi-experimental study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used interrupted time series analysis using autoregressive integrated moving average models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the lower and higher SES (average annual household income) using subgroup analysis and interaction models.ResultsWe examined 70,931 pregnancies in Manitoba during the study period. Following the implementation of COVID-19 restrictions in March 2020, there were no statistically significant changes in the rates of both PTB (p=0.094) and stillbirths (p=0.958). However, over the pandemic, the PTB rate significantly decreased as a rebound effect by 0.63% per quarter(p=0.005); whereas the stillbirth rate did not change significantly (p=0.878) compared to pre-pandemic period. During the first quarter of 2021, the absolute differences in the observed and expected PTB and stillbirth percentages were 2.05% and 0.04%, respectively. We observed a statistically significant effect modification by SES for PTB rates (p=0.047).ConclusionWhile the onset of COVID-19 pandemic restrictions was not associated with significant effects on PTB and stillbirth rates, we observed a statistically significant rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
Effects of Hormone Therapy on survival, cancer, cardiovascular and dementia risks in 7 million menopausal women over age 65: a retrospective observational study
Authors: Baik Seo H. , Baye Fitsum , McDonald Clement J. 
Published: May 2022

AbstractBackgroundThe long-term influence of menopausal hormone therapy remains unanswered due to the termination of randomized clinical trials and discordant findings from observational studies.MethodsFrom 2007-2019 enrollment records of 100% Medicare beneficiaries, we identified 7 million female enrollees aged 65 or more. We identified type, route and strength of estrogen based on their prescription drug utilization records. Using vital status record and encounter records, we defined the first onset of thirteen patient outcomes; all-cause mortality; 5 cancers (breast, lung, endometrial, colorectal, ovarian cancers); 6 CV conditions (ischemic heart diseases, heart failure, venous thromboembolism, stroke, atrial fibrillation, acute myocardial infarction); and dementia. Then, we implemented an extended Cox regression analysis to examine the effects of type, route, and strength of estrogens on each of 13 study outcomes.FindingsEstrogen monotherapy (ET) exhibited a significant, 20% (aHR=0.80; 95% CI 0.78-0.82), relative risk reduction of mortality. The reduction was greater with estradiol (aHR=0.78; 95% CI 0.75-0.80) than conjugated estrogen (aHR=0.86; 95% CI 0.85-0.88), and with vaginal (aHR=0.69; 95% CI 0.65-0.74) than oral (aHR=0.89; 95% CI 0.87-0.90) and transdermal (aHR=0.78; 95% CI 0.75-0.81) preparations. ET also exhibited significant risk reductions for all study cancers, breast (aHR=0.82; 95% CI 0.80-0.84), lung (aHR=0.87; 95% CI 0.84-0.90), endometrial (aHR=0.65; 95% CI 0.62-0.69), colorectal (aHR=0.86; 95% CI 0.82-0.90) and ovarian (aHR=0.83; 95% CI 0.79-0.88). ET slightly increased risks of ischemic heart diseases (aHR=1.03; 95% CI 1.01-1.04). However, such risk was not observed with low dose ET (aHR=0.98; 95% CI 0.97-0.99). Both combination therapy (aHR=1.11; 95% CI 1.08-1.14) and progestogen monotherapy (aHR=1.09; 95% CI 1.05-1.13) exhibited a significantly increased risk of breast cancer. Oral HT exhibited a moderately increased risk of dementia.ConclusionsAmong female Medicare beneficiaries aged ≥65, the effect of menopausal hormone therapy varies by type, route, and strength but overall estrogen seemed beneficial.
Motivation, intention and action: wearing masks to prevent the spread of COVID-19
Authors: Kaine Geoff , Wright Vic , Greenhalgh Suzie 
Published: May 2022

AbstractGovernments around the world are seeking to slow the spread of COVID-19 by implementing measures that encourage, or mandate, changes in people’s behaviour. These changes include the wearing of face masks, social distancing, and testing and self-isolating when unwell. The success of these measures depends on (1) the willingness of individuals to change their behaviour and (2) their commitment and capacity to translate that intention into actions. Consequently, understanding and predicting the willingness of individuals to change their behaviour, and their enthusiasm to act on that willingness, is critical in assessing the likely effectiveness of these measures in slowing the spread of the virus.In this paper we analyse responses to two separate regional surveys about people’s intentions and behaviour with respect to preventing the spread of COVID-19 in New Zealand. While motivations and intentions were largely similar across the regions, there was marked difference in action across the regions, specifically with respect to the frequency of wearing face masks. Our analysis suggests that the translation of intention (preventing the spread of COVID-19) into action (as measured by self-reported frequency of face mask use) was strongly associated with perceptions of the risk of infection (as measured by regional case numbers).The results highlight the importance to policy design of distinguishing the factors that might influence the formation of behavioural intentions from those that might influence the implementation of those intentions.
First brain de-novo transcriptome of Tyrrenhian tree frog, Hyla sarda, for the study of dispersal-related behavioral variation
Authors: Libro Pietro , Bisconti Roberta , Chiocchio Andrea , Spadavecchia Giada , Castrignanò Tiziana , Canestrelli Daniele 
Published: May 2022

Dispersal is a key process in ecology and evolution as it contributes to shaping the spatial patterns of biological diversity at all its levels of organization. Growing evidence is unveiling the role of phenotypic trait variation in affecting dispersal dynamics of populations, and that substantial, rapid, and directional changes in the phenotypic makeup of populations would occur during range expansions by spatial sorting of dispersal-related traits. Accordingly, selective pressures at the front of a range expansion wave would actively promote individuals with higher dispersal abilities. Although many studies have been focusing on phenotypic trait evolution during range expansion, its genomic underpinnings are almost unexplored, hampering a thorough understanding of the evolutionary processes involved during dispersal.The Tyrrhenian tree frog Hyla sarda is a small amphibian endemic to the Tyrrhenian islands. According to previous phylogeographic studies, H. sarda underwent a northward range expansion from the north of Sardinia (western Mediterranean sea) during the last glacial phase. The colonization of the Corsica island was allowed by the temporary formation of a wide land bridge connecting Sardinia and Corsica, induced by the marine regression occurred during the last glacial maximum. The postglacial loss of this land bridge prevented any subsequent gene flow between Corsican and Sardinian populations. As a consequence, the genetic and phenotypic legacies of this range expansion event can still be detected in current populations, which makes H. sarda an interesting candidate species for the study of the genetic underpinnings of phenotypic trait evolution during range expansions.Here, we contribute to the investigation of the genetic underpinning phenotypic trait evolution during range expansion, by generating the first brain de-novo transcriptome of H. sarda. We focused on the brain transcriptome as behavioural variation at personality traits has been identified as a key component of the dispersal syndromes, substantial personality traits variation has been observed within H. sarda populations, and brain gene expression patterns have been linked to a vast number of behavioural responses to environmental stimuli.
Modeling Down syndrome neurodevelopment with isogenic cerebral organoids
Authors: Czerminski Jan T. , King Oliver D. , Lawrence Jeanne B. 
Published: May 2022

AbstractAs a model of early fetal brain development in Down syndrome, this study examines cortical organoids generated from isogenic trisomic and disomic iPSC lines. Initially pools of organoids from a trisomic versus disomic line found broad transcriptomic differences and modest differences in cell-type representation, suggesting a potential neurodevelopmental phenotype due to Trisomy 21. To better control for multiple sources of variation, we undertook a very robust study of ~1,200 organoids, using an expanded panel of six isogenic subclones (three disomic and three trisomic). The power of the experimental design was indicated by exceptionally strong detection of the ~1.5-fold difference in most chr21 genes. Despite some variability in secreted Aβ-40 levels between “identical” cell lines, this Alzheimer-related phenotype was detected as clearly correlated with Trisomy 21. However, the many statistically significant non-chr21 DEGs found in the small experiment fell away in the expanded study design, such that just three non-chr21 DEGs correlated to T21 status. Similarly, differences in cell-type representation of organoids varied somewhat between the six isogenic lines, but did not correlate with T21 status. Overall, our results indicate that even when organoid and batch variability are better controlled, common, subtle differences between isogenic cell lines (even subclones) may obscure, or be confused with, differences due to Trisomy 21. Interestingly, the neurodegenerative increase in Aβ due to T21 was strong enough to be evident in “fetal” organoids. In contrast, any neurodevelopmental phenotype that may be present in the ~2ndtrimester of DS brain development may be more subtle, and within the range of variability in neurodifferentiation potential (unrelated to Trisomy 21) of our isogenic iPSC lines. The potential significance of two non-Chr21 DEGs that results suggest correlate with T21 is discussed.
Astronauts Gaze Behavior in Visual Target Acquisition during Space Shuttle Flights
Authors: Kolev Ognyan I. , Reschke Millard F. , Clément Gilles 
Published: May 2022

AbstractWe explored how weightlessness during space flight altered the astronauts’ gaze behavior with respect to flight day and target eccentricity. Thirty-four astronauts of 20 Space Shuttle missions had to acquire visual targets with angular offsets of 20°, 30°, and 49°. Measurements of eye, head, and gaze positions collected before and during flight days 1 to 15 indicated changes during target acquisition that varied as a function of flight days and target eccentricity. The in-flight changes in gaze behavior were presumably the result of a combination of several factors, including a transfer from allocentric to egocentric reference for spatial orientation in absence of a gravitational reference, the generation of slower head movements to prevent space motion sickness, and a decrease in smooth pursuit and vestibulo-ocular reflex performance. These results confirm that humans have several strategies for gaze behavior, between which they switch depending on the environmental conditions.
Spatiotemporal Ecological Chaos Enables Gradual Evolutionary Diversification Without Niches or Tradeoffs
Authors: Mahadevan Aditya , Pearce Michael T. , Fisher Daniel S. 
Published: May 2022

AbstractEcological and evolutionary dynamics are intrinsically entwined. On short time scales, ecological interactions determine the fate of new mutants and changes in the community they induce, while on longer time scales evolution shapes the whole community. How eco-evolutionary dynamics gives rise to the extensive coexisting diversity of strains found in many bacterial species is a major puzzle. In this paper we study the evolution of large numbers of closely related strains with generalized Lotka Volterra interactions but no niche structure. The host-pathogen-like interactions drive the ecological dynamics into a spatiotemporally chaotic state characterized by continual local blooms and busts. Upon the slow serial introduction of new strains, the community is found to diversify indefinitely, accommodating arbitrarily large numbers of strains in the absence of any kind of stabilizing niche interactions. This diversifying phase is robust to changes in evolutionary parameters, and persists even in the presence of a distribution of general, nonspecific fitness differences between individual strains, which explicitly break the assumption of tradeoffs inherent in much previous work. However, gradual increase of the general fitnesses in the ecosystem slows down the diversification. Quantitative analysis of the range of behaviors is carried out by a combination of analytical methods and simulations. Building on a dynamical-mean field-theory understanding of the ecological dynamics, an approximate effective model captures the effects of evolution on the distributions of key properties, such as strain abundances. This work establishes a potential scenario and a theoretical framework for understanding how the interplay between evolution and ecology can give rise to extensive fine-scale diversity. Future avenues for investigation are suggested, including the effects of the build-up of relatedness between strains, how conditioning on the evolutionary history affects the ecological interactions and dynamics, and application to coevolution of the diversity of a bacterial and a phage species.
AutoMorph: Automated Retinal Vascular Morphology Quantification via a Deep Learning Pipeline
Authors: Zhou Yukun , Wagner Siegfried K. , Chia Mark , Zhao An , Woodward-Court Peter , Xu Moucheng , Struyven Robbert , Alexander Daniel C. , Keane Pearse A. 
Published: May 2022

PurposeTo externally validate a deep learning pipeline (AutoMorph) for automated analysis of retinal vascular morphology on fundus photographs. AutoMorph has been made publicly available (https://github.com/rmaphoh/AutoMorph), facilitating widespread research in ophthalmic and systemic diseases.MethodsAutoMorph consists of four functional modules: image pre-processing, image quality grading, anatomical segmentation (including binary vessel, artery/vein, and optic disc/cup segmentation), and vascular morphology feature measurement. Image quality grading and anatomical segmentation use the most recent deep learning techniques. We employ a model ensemble strategy to achieve robust results and analyse the prediction confidence to rectify false gradable cases in image quality grading. We externally validate each module’s performance on several independent publicly available datasets.ResultsThe EfficientNet-b4 architecture used in the image grading module achieves comparable performance to the state-of-the-art for EyePACS-Q, with an F1-score of 0.86. The confidence analysis reduces the number of images incorrectly assessed as gradable by 76%. Binary vessel segmentation achieves an F1-score of 0.73 on AV-WIDE and 0.78 on DR-HAGIS. Artery/vein scores 0.66 on IOSTAR-AV, and disc segmentation achieves 0.94 in IDRID. Vascular morphology features measured from AutoMorph segmentation map and expert annotation show good to excellent agreement.ConclusionsAutoMorph modules perform well even when external validation data shows domain differences from training data, e.g., with different imaging devices. This fully automated pipeline can thus allow detailed, efficient and comprehensive analysis of retinal vascular morphology on colour fundus photographs.Translational RelevanceBy making AutoMorph publicly available and open source, we hope to facilitate ophthalmic and systemic disease research, particularly in the emerging field of ‘oculomics’.
Long Covid stigma: estimating burden and validating scale in a UK-based sample
Authors: Pantelic Marija , Ziauddeen Nida , Boyes Mark , O’Hara Margaret E , Hastie Claire , Alwan Nisreen A 
Published: May 2022

AbstractBackgroundStigma can be experienced as perceived or actual disqualification from social and institutional acceptance on the basis of one or more physical, behavioural or other attributes deemed to be undesirable. Long Covid is a predominantly multisystem condition that occurs in people with a history of SARSCoV2 infection, often resulting in functional disability.AimTo develop and validate a Long Covid Stigma Scale (LCSS); and to quantify the burden of Long Covid stigma.Design and SettingFollow-up of a co-produced community-based Long Covid online survey using convenience non-probability sampling.MethodThirteen questions on stigma were designed to develop the LCSS capturing three domains – enacted (overt experiences of discrimination), internalised (internalising negative associations with Long Covid and accepting them as self-applicable) and anticipated (expectation of bias/poor treatment by others) stigma. Confirmatory factor analysis tested whether LCSS consisted of the three hypothesised domains. Model fit was assessed and prevalence was calculated.Results966 UK-based participants responded (888 for stigma questions), with mean age 48 years (SD: 10.7) and 85% female. Factor loadings for enacted stigma were 0.70-0.86, internalised 0.75-0.84, anticipated 0.58-0.87, and model fit was good. The prevalence of experiencing stigma at least ‘sometimes’ and ‘often/always’ was 95% and 76% respectively. Anticipated and internalised stigma were more frequently experienced than enacted stigma. Those who reported having a clinical diagnosis of Long Covid had higher stigma prevalence than those without.ConclusionThis study establishes a scale to measure Long Covid stigma and highlights common experiences of stigma in people living with Long Covid.