bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV-1 Recent Infection Testing Algorithm With Antiretroviral Drug Detection to Improve Accuracy of Incidence Estimates
Authors: Voetsch Andrew C. , Duong Yen T. , Stupp Paul , Saito Suzue , McCracken Stephen , Dobbs Trudy , Winterhalter Frieda S. , Williams Daniel B. , Mengistu Assegid , Mugurungi Owen , Chikwanda Prisca , Musuka Godfrey , Ndongmo Clement B. , Dlamini Sindisiwe , Nuwagaba-Biribonwoha Harriet , Pasipamire Munyaradzi , Tegbaru Belete , Eshetu Frehywot , Biraro Samuel , Ward Jennifer , Aibo Dorothy , Kabala Andrew , Mgomella George S. , Malewo Optatus , Mushi Jeremiah , Payne Danielle , Mengistu Yohannes , Asiimwe Fred , Shang Judith D. , Dokubo Emily K. , Eno Laura T. , Zoung-Kanyi Bissek Anne-Cécile , Kingwara Leonard , Junghae Muthoni , Kiiru John N. , Mwesigwa Richard C.N. , Balachandra Shirish , Lobognon Roger , Kampira Elizabeth , Detorio Mervi , Yufenyuy Ernest L. , Brown Kristin , Patel Hetal K. , Parekh Bharat S. 
Published: June 2021

Background:
HIV-1 incidence calculation currently includes recency classification by HIV-1 incidence assay and unsuppressed viral load (VL ≥ 1000 copies/mL) in a recent infection testing algorithm (RITA). However, persons with recent classification not virally suppressed and taking antiretroviral (ARV) medication may be misclassified.

Setting:
We used data from 13 African household surveys to describe the impact of an ARV-adjusted RITA on HIV-1 incidence estimates.

Methods:
HIV-seropositive samples were tested for recency using the HIV-1 Limiting Antigen (LAg)-Avidity enzyme immunoassay, HIV-1 viral load, ARVs used in each country, and ARV drug resistance. LAg-recent result was defined as normalized optical density values ≤1.5. We compared HIV-1 incidence estimates using 2 RITA: RITA1: LAg-recent + VL ≥ 1000 copies/mL and RITA2: RITA1 + undetectable ARV. We explored RITA2 with self-reported ARV use and with clinical history.

Results:
Overall, 357 adult HIV-positive participants were classified as having recent infection with RITA1. RITA2 reclassified 55 (15.4%) persons with detectable ARV as having long-term infection. Those with detectable ARV were significantly more likely to be aware of their HIV-positive status (84% vs. 10%) and had higher levels of drug resistance (74% vs. 26%) than those without detectable ARV. RITA2 incidence was lower than RITA1 incidence (range, 0%–30% decrease), resulting in decreased estimated new infections from 390,000 to 341,000 across the 13 countries. Incidence estimates were similar using detectable or self-reported ARV (R2 > 0.995).

Conclusions:
Including ARV in RITA2 improved the accuracy of HIV-1 incidence estimates by removing participants with likely long-term HIV infection.
Analysis of the Positional Relationship Among the Operator, Camera, and Monitor: Overcoming the Difficulties of Mirror-image Conditions During Laparoscopic Surgery
Authors: Inagaki Yuriko , Kawai Kazushige , Nishikawa Takeshi , Ishii Hiroaki , Emoto Shigenobu , Murono Koji , Kaneko Manabu , Sasaki Kazuhito , Nozawa Hiroaki , Ishihara Soichiro 
Published: June 2021

Background:
Although methods to overcome difficulties associated with mirror-image conditions have been investigated, the ideal spatial relationship among the operator line of sight, monitor location, and camera location remains unclear. Moreover, the best training method for improving laparoscopic surgical skills under varying operator line of sight, camera, and monitor positions is unknown. We aimed to investigate the role of laparoscopic training under mirror-image conditions in improving surgical efficiency and whether prior surgical experience affects such training.

Methods:
This prospective study was conducted at the Department of Surgical Oncology, Tokyo University, Japan. Twenty-five surgeons participated. Novice (n=14), trained (n=7), and expert (n=4) participants performed the simulated task in a box trainer while varying the positional relationships among the surgeons, camera, and monitor. Five patterns were repeatedly performed 5 times per day for 4 days over 2 weeks.

Results:
The most significant differences in terms of the time required to complete the task under mirror-image conditions among the 3 groups were on day 1 (novices: 185.8 s, trained: 79.7 s, and experts: 46.5 s, P=0.009). However, after 4 days of training, the corresponding times did not differ among the 3 groups (26.0, 30.7, and 23.1 s, respectively; P=0.415). Laparoscopic training was sufficiently effective under mirror-image conditions.

Conclusions:
Mirror-image surgical conditions provided the most difficult setting, because surgeons and assistants often became disoriented, and task performance was most degraded. However, just 4 days of training was found to be sufficient to overcome the difficulties encountered while performing laparoscopic procedures under mirror-image conditions.
Blunt adrenal gland injury: The impact of extra-abdominal injury
Authors: Tanizaki Shinsuke , Maeda Shigenobu , Ishida Hiroshi 
Published: June 2021

BACKGROUND
Blunt adrenal gland injuries are considered uncommon. Moreover, the factors associated with the mechanisms of the injury following blunt trauma are unclear. In this study, we determined the factors associated with blunt adrenal gland injury (BAGI).

MATERIALS AND METHODS
A total of 315 patients with blunt abdominal trauma were admitted to our institution during a 12-year period. After excluding 26 patients who were under 18 years old and 27 patients who were in cardiopulmonary arrest on arrival, 262 eligible patients were retrospectively reviewed. Patient characteristics, mechanism of injury, intervention, and associated organ injuries were compared between those with and without BAGI.

RESULTS
Blunt adrenal gland injury was identified in 38 of 262 patients (14.5%). The right side was the predominant site of injury (68%). There were no differences in vital sign, in-hospital mortality, intervention, and concomitant abdominal organ injuries between those with and without adrenal gland injury. Patients with BAGI had a higher frequency of fall and motorcycle collision as mechanisms of injury. In addition, patients with BAGI had a higher injury severity score and a higher frequency of concomitant severe head, chest, and pelvic injuries.

CONCLUSION
The results of the present study suggest that the deceleration injury leading to concomitant head, chest, or pelvic injuries with blunt abdominal trauma may be associated with the mechanism of BAGI.

LEVEL OF EVIDENCE
Prognostic study, level IV.
Systematic single-variant and gene-based association testing of thousands of phenotypes in 426,370 UK Biobank exomes
Authors: Karczewski Konrad J. , Solomonson Matthew , Chao Katherine R. , Goodrich Julia K. , Tiao Grace , Lu Wenhan , Riley-Gillis Bridget M. , Tsai Ellen A. , Kim Hye In , Zheng Xiuwen , Rahimov Fedik , Esmaeeli Sahar , Grundstad A. Jason , Reppell Mark , Waring Jeff , Jacob Howard , Sexton David , Bronson Paola G. , Chen Xing , Hu Xinli , Goldstein Jacqueline I. , King Daniel , Vittal Christopher , Poterba Timothy , Palmer Duncan S. , Churchhouse Claire , Howrigan Daniel P. , Zhou Wei , Watts Nicholas A. , Nguyen Kevin , Nguyen Huy , Mason Cara , Farnham Christopher , Tolonen Charlotte , Gauthier Laura D. , Gupta Namrata , MacArthur Daniel G. , Rehm Heidi L. , Seed Cotton , Philippakis Anthony A. , Daly Mark J. , Davis J. Wade , Runz Heiko , Miller Melissa R. , Neale Benjamin M. 
Published: June 2021

AbstractGenome-wide association studies have successfully discovered thousands of common variants associated with human diseases and traits, but the landscape of rare variation in human disease has not been explored at scale. Exome sequencing studies of population biobanks provide an opportunity to systematically evaluate the impact of rare coding variation across a wide range of phenotypes to discover genes and allelic series relevant to human health and disease. Here, we present results from systematic association analyses of 4,529 phenotypes using single-variant and gene tests of 426,370 individuals in the UK Biobank with exome sequence data. We find that the discovery of genetic associations is tightly linked to frequency as well as correlated with metrics of deleteriousness and natural selection. We highlight biological findings elucidated by these data and release the dataset as a public resource alongside the Genebass browser for rapidly exploring rare variant association results.
Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial – BCPP/ Ya Tsie trial
Authors: Magosi Lerato E. , Zhang Yinfeng , Golubchik Tanya , De Gruttola Victor , Tchetgen Eric Tchetgen , Novitsky Vlad , Moore Janet , Bachanas Pam , Segolodi Tebogo , Lebelonyane Refeletswe , Holme Molly Pretorius , Moyo Sikhulile , Makhema Joseph , Lockman Shahin , Fraser Christophe , Essex Max , Lipsitch Marc 
Published: June 2021

AbstractMathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence. To elucidate patterns of HIV spread in universal test-and-treat trials we quantified the contribution of geographic-location, gender, age and randomized-HIV- intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana (estimated trial population: 175,664). Deep-sequence phylogenetic analysis revealed that most inferred HIV transmissions within the trial occurred within the same or between neighboring communities, and between similarly-aged partners. Transmissions into intervention communities from control communities were more common than the reverse post-baseline (30% [12.2 – 56.7] versus 3% [0.1 – 27.3]) than at baseline (7% [1.5 – 25.3] versus 5% [0.9 – 22.9]) compatible with a benefit from treatment-as-prevention. Our findings suggest that population mobility patterns are fundamental to HIV transmission dynamics and to the impact of HIV control strategies.
First identification of SARS-CoV-2 Lambda (C.37) variant in Southern Brazil
Authors: Wink Priscila Lamb , Zempulski Volpato Fabiana Caroline , Monteiro Francielle Liz , Willig Julia Biz , Zavascki Alexandre Prehn , Luís Barth Afonso , Martins Andreza Francisco 
Published: June 2021

AbstractIn June 15, 2021, the lineage Lambda (C.37) of SARS-CoV-2 was considered a variant of interest (VOI) by the World Health Organization. This lineage has high prevalence in some South America countries but it was described only occasionally in Brazil. Here we describe the first report of the SARS-CoV-2 Lambda variant in Southern Brazil. The sequence described in this paper presented all the eight C.37 defining lineage mutations (ORF1a gene: Δ3675-3677; Spike gene: Δ246-252, G75V, T76I, L452Q, F490S, D614G, and T859N) in addition to other 19 mutations. Considering that this VOI has been associated with high rates of transmissibility, the possible spread in the Southern Brazilian community is a matter of concern.
Social return on investment of home exercise and community referral for people with early dementia
Authors: Hartfiel Ned , Gladman John , Harwood Rowan , Edwards Rhiannon Tudor 
Published: June 2021

AbstractBackgroundExercise can improve physical function and slow the progression of dementia. However, uncertainty exists around the cost-effectiveness of exercise programmes for people with early dementia.ObjectiveThe aim is to determine whether a home-based supervised exercise programme (PrAISED – promoting activity, independence, and stability in early dementia) can generate a positive social return on investment (SROI).MethodsSROI was conducted as part of a randomised controlled feasibility trial comparing PrAISED with usual care. Wellbeing valuation was used to compare the costs of the programme with the monetised benefits to participants, carers, and healthcare service providers.ResultsThe PrAISED programme generated SROI ratios ranging from £3.46 to £5.94 for every £1 invested. Social value was created from improved physical activity, increased confidence, more social connection and PrAISED participants using healthcare services less often than usual care.ConclusionHome-based supervised exercise programmes can generate a positive SROI for people with early dementia.Trial registrationClinicalTrials.gov: NCT02874300 (first posted 22nd August 2016), ISRCTN: 10550694 (date assigned 31st August 2016)
Moving Beyond the ‘CAP’ of the Iceberg: Intrinsic Connectivity Networks in fMRI are Continuously Engaging and Overlapping
Authors: Iraji A. , Faghiri A. , Fu Z. , Kochunov P. , Adhikari B. M. , Belger A. , Ford J.M. , McEwen S. , Mathalon D.H. , Pearlson G.D. , Potkin S.G. , Preda A. , Turner J.A. , van Erp T.G.M. , Chang C. , Calhoun V.D. 
Published: June 2021

AbstractResting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns.We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.
Unsupervised classification of SARS-CoV-2 genomic sequences uncovers hidden genetic diversity and suggests an efficient strategy for genomic surveillance
Authors: Chiara Matteo , Horner David S. , Ferrandi Erika , Gissi Carmela , Pesole Graziano 
Published: June 2021

AbstractAccurate and timely monitoring of emerging genomic diversity is crucial for limiting the spread of potentially more transmissible/pathogenic strains of SARS-CoV-2. At the time of writing, over 1.8M distinct viral genome sequences have been made publicly available, and a sophisticated nomenclature system based on phylogenetic evidence and expert manual curation has allowed the relatively rapid classification of emerging lineages of potential concern.Here, we propose a complementary approach that integrates fine-grained spatiotemporal estimates of allele frequency with unsupervised clustering of viral haplotypes, and demonstrate that multiple highly frequent genetic variants, arising within large and/or rapidly expanding SARS-CoV-2 lineages, have highly biased geographic distributions and are not adequately captured by current SARS-CoV-2 nomenclature standards.Our results advocate a partial revision of current methods used to track SARS-CoV-2 genomic diversity and highlight the importance of the application of strategies based on the systematic analysis and integration of regional data. Here we provide a complementary, completely automated and reproducible framework for the mapping of genetic diversity in time and across different geographic regions, and for the prioritization of virus variants of potential concern. We believe that the approach outlined in this study will contribute to relevant advances to current genomic surveillance methods.
Predator avoidance and foraging for food shape synchrony and response to perturbations in trophic metacommunities
Authors: Quévreux Pierre , Pigeault Rémi , Loreau Michel 
Published: June 2021

AbstractThe response of species to perturbations strongly depends on spatial aspects in populations connected by dispersal. Asynchronous fluctuations in biomass among populations lower the risk of simultaneous local extinctions and thus reduce the regional extinction risk. However, dispersal is often seen as passive diffusion that balances species abundance between distant patches, whereas ecological constraints, such as predator avoidance or foraging for food, trigger the movement of individuals. Here, we propose a model in which dispersal rates depend on the abundance of the species interacting with the dispersing species (e.g., prey or predators) to determine how density-dependent dispersal shapes spatial synchrony in trophic metacommunities in response to stochastic perturbations. Thus, unlike those with passive dispersal, this model with density-dependent dispersal bypasses the classic vertical transmission of perturbations due to trophic interactions and deeply alters synchrony patterns. We show that the species with the highest coefficient of variation of biomass governs the dispersal rate of the dispersing species and determines the synchrony of its populations. In addition, we show that this mechanism can be modulated by the relative impact of each species on the growth rate of the dispersing species. Species affected by several constraints disperse to mitigate the strongest constraints (e.g., predation), which does not necessarily experience the highest variations due to perturbations. Our approach can disentangle the joint effects of several factors implied in dispersal and provides a more accurate description of dispersal and its consequences on metacommunity dynamics.
Increased lung cell entry of B.1.617.2 and evasion of antibodies induced by infection and BNT162b2 vaccination
Authors: Arora Prerna , Kempf Amy , Nehlmeier Inga , Sidarovich Anzhalika , Krüger Nadine , Graichen Luise , Moldenhauer Anna-Sophie , Winkler Martin S. , Schulz Sebastian , Jäck Hans-Martin , Stankov Metodi V. , Behrens Georg M. N. , Pöhlmann Stefan , Hoffmann Markus 
Published: June 2021

SUMMARYThe delta variant of SARS-CoV-2, B.1.617.2, emerged in India and has subsequently spread to over 80 countries. B.1.617.2 rapidly replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for COVID-19 therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although with lower efficiency as compared to B.1.351. Further, we found that B.1.617.2 is resistant against Bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3-lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.1.617.2 as an immune evasion variant with increased capacity to enter and fuse lung cells.
Dynamic Self-Reinforcement of Gene Expression Determines Acquisition and Retention of Cellular Mechanical Memory
Authors: Price Christopher C. , Mathur Jairaj , Boerckel Joel D. , Pathak Amit , Shenoy Vivek B. 
Published: June 2021

AbstractMechanotransduction describes activation of gene expression by changes in the cell’s physical microenvironment. Recent experiments show that mechanotransduction can lead to long-term “mechanical memory”, where cells cultured on stiff substrates for sufficient time (priming phase) maintain altered phenotype after switching to soft substrates (dissipation phase), as compared to unprimed controls. The timescale of memory acquisition and retention is orders of magnitude larger than the timescale of mechanosensitive cellular signaling, and memory retention time changes continuously with priming time. We develop a model that captures these features by accounting for positive reinforcement in mechanical signaling. The sensitivity of reinforcement represents the dynamic transcriptional state of the cell composed of protein lifetimes and 3D chromatin organization. Our model provides a single framework connecting microenvironment mechanical history to cellular outcomes ranging from no memory to terminal differentiation. Predicting cellular memory of environmental changes can help engineer cellular dynamics through changes in culture environments.
P2Y6 receptor signaling in natural killer cells impairs insulin sensitivity in obesity
Authors: Sieben Anna , Hausen Anne Christine , Klemm Paul , Jais Alexander , Heilinger Christian , Alber Jens , Folz-Donahue Kat , Schumacher Lena , Altmüller Janine , Franitza Marek , Giavalisco Patrick , Hinze Yvonne , Brodesser Susanne , Kukat Christian , Theurich Sebastian , Brüning Jens C. 
Published: June 2021

AbstractNatural killer (NK) cells contribute to the development of obesity-associated insulin resistance and have previously been shown to up-regulate the expression of the P2Y purinoreceptor 6 (P2Y6R) upon high fat diet (HFD)-induced obesity. Here, we reveal that NK cell-specific inactivation of the P2Y6R gene improves insulin sensitivity in obese mice and reduces the expression of chemokines in adipose tissue infiltrating NK-cells. Obese mice lacking P2Y6R specifically in NK cells exhibited a reduction in adipose tissue inflammation, exhibited improved insulin-stimulated suppression of lipolysis in adipose tissue and a reduction in hepatic glucose production, leading to an overall improvement of systemic insulin sensitivity. In contrast, myeloid lineage specific P2Y6R inactivation does not affect energy or glucose homeostasis in obesity. Collectively, we show that P2Y6R signaling in NK cells contributes to the development of obesity-associated insulin resistance and thus might be a future target for the treatment of obesity-associated insulin resistance and type 2 diabetes.
The Immune Factors Driving DNA Methylation Variation in Human Blood
Authors: Bergstedt Jacob , Azzou Sadoune Ait Kaci , Tsuo Kristin , Jaquaniello Anthony , Urrutia Alejandra , Rotival Maxime , Lin David T. S. , MacIsaac Julia L. , Kobor Michael S. , Albert Matthew L. , Duffy Darragh , Patin Etienne , Quintana-Murci Lluís ,   Milieu Intérieur Consortium
Published: June 2021

AbstractEpigenetic changes are required for normal development, yet the nature and respective contribution of factors that drive epigenetic variation in humans remain to be fully characterized. Here, we assessed how the blood DNA methylome of 884 adults is affected by DNA sequence variation, age, sex and 139 factors relating to life habits and immunity. Furthermore, we investigated whether these effects are mediated or not by changes in cellular composition, measured by deep immunophenotyping. We show that DNA methylation differs substantially between naïve and memory T cells, supporting the need for adjustment on these cell-types. By doing so, we find that latent cytomegalovirus infection drives DNA methylation variation and provide further support that the increased dispersion of DNA methylation with aging is due to epigenetic drift. Finally, our results indicate that cellular composition and DNA sequence variation are the strongest predictors of DNA methylation, highlighting critical factors for medical epigenomics studies.