bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competition for dominance within replicating quasispecies during prolonged SARS-CoV-2 infection in an immunocompromised host
Authors: Caccuri Francesca , Messali Serena , Bortolotti Daria , Di Silvestre Dario , De Palma Antonella , Cattaneo Chiara , Bertelli Anna , Zani Alberto , Milanesi Maria , Giovanetti Marta , Campisi Giovanni , Gentili Valentina , Bugatti Antonella , Filippini Federica , Scaltriti Erika , Pongolini Stefano , Tucci Alessandra , Fiorentini Simona , d’Ursi Pasqualina , Ciccozzi Massimo , Mauri Pierluigi , Rizzo Roberta , Caruso Arnaldo 
Published: May 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) emerge for their capability to better adapt to the human host aimed and enhance human-to-human transmission. Mutations in spike largely contributed to adaptation. Viral persistence is a prerequisite for intra-host virus evolution, and this likely occurred in immunocompromised patients who allow intra-host long-term viral replication. The underlying mechanism leading to the emergence of variants during viral persistence in the immunocompromised host is still unknown. Here, we show the existence of an ensemble of minor mutants in the early biological samples obtained from an immunocompromised patient and their dynamic interplay with the master mutant during a persistent and productive long-term infection. In particular, after 222 days of active viral replication, the original master mutant, named MB610, was replaced by a minor quasispecies (MB61222) expressing two critical mutations in spike, namely Q493K and N501T. Isolation of the two viruses allowed us to show that MB61222 entry into target cells occurred mainly by the fusion at the plasma membrane (PM), whereas endocytosis characterized the entry mechanism used by MB610. Interestingly, coinfection of two human cell lines of different origin with the SARS-CoV-2 isolates highlighted the early and dramatic predominance of MB61222 over MB610 replication. This finding may be explained by a faster replicative activity of MB61222 as compared to MB610 as well as by the capability of MB61222 to induce peculiar viral RNA-sensing mechanisms leading to an increased production of interferons (IFNs) and, in particular, of IFN-induced transmembrane protein 1 (IFITM1) and IFITM2. Indeed, it has been recently shown that IFITM2 is able to restrict SARS-CoV-2 entry occurring by endocytosis. In this regard, MB61222 may escape the antiviral activity of IFITMs by using the PM fusion pathway for entry into the target cell, whereas MB610 cannot escape this host antiviral response during MB61222 coinfection, since it has endocytosis as the main pathway of entry. Altogether, our data support the evidence of quasispecies fighting for host dominance by taking benefit from the cell machinery to restrict the productive infection of competitors in the viral ensemble. This finding may explain, at least in part, the extraordinary rapid worldwide turnover of VOCs that use the PM fusion pathway to enter into target cells over the original pandemic strain.
Implementing and Evaluating a Fellowship for Community-Based Physicians and Physician Assistants: Leadership, Practice Transformation, and Precepting
Authors: Casola Allison R. , Cunningham Amy , Crittendon Denine , Kelly Samantha , Sifri Randa , Arenson Christine 
Published: May 2022

Introduction:
Formal training in practice transformation, leadership, clinical education, and/or the time to gain these skills are limited postresidency for primary care physicians and physician assistants. Therefore, we created a novel Primary Care Champions fellowship program that provides practical experiences in education, practice transformation, and leadership for primary care physicians and physician assistants in community practice. The purpose of this study is to describe the fellowship and evaluate feedback from the first cohort.

Methods:
In the Jefferson Primary Care Champions Fellowship, fellows are provided protected time from clinical obligations to engage in didactic, informal, and experiential learning. They meet monthly and participate in student precepting training and receive mentorship from senior clinician administrators, scientists, educators, and population health researchers to hone skills for leadership and practice transformation endeavors. Cohort one began in September 2018. All fellows were family physicians from community-based practices in Philadelphia, PA (N = 4) and selected in collaboration with their practice leadership. Mixed-methods postprogram evaluations included Organizational Readiness Assessment and qualitative feedback.

Results:
Fellows denoted individual time, small-group mentorship, protected project time, and open-robust discussions about primary care most useful. Three fellows reported that they plan to continue their practice-improvement projects postfellowship and one published her initial project findings and reflections.

Discussion:
Overall feedback from the first cohort was positive. Fellows greatly appreciated structured time to explore primary care interests, contemplated long-term career prospects, and considered leadership opportunities. Cohort two is currently underway and cohort three is in recruitment.
Protometabolism as out-of-equilibrium chemistry
Authors: Nader Serge , Sebastianelli Lorenzo , Mansy Sheref S. 
Published: May 2022

It is common to compare life with machines. Both consume fuel and release waste to run. In biology, the engine that drives the living system is referred to as metabolism. However, attempts at deciphering the origins of metabolism do not focus on this energetic relationship that sustains life but rather concentrate on nonenzymatic reactions that produce all the intermediates of an extant metabolic pathway. Such an approach is akin to studying the molecules produced from the burning of coal instead of deciphering how the released energy drives the movement of pistons and ultimately the train when investigating the mechanisms behind locomotion. Theories that do explicitly invoke geological chemical gradients to drive metabolism most frequently feature hydrothermal vent conditions, but hydrothermal vents are not the only regions of the early Earth that could have provided the fuel necessary to sustain the Earth's first (proto)cells. Here, we give examples of prior reports on protometabolism and highlight how more recent investigations of out-of-equilibrium systems may point to alternative scenarios more consistent with the majority of prebiotic chemistry data accumulated thus far.
This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Emergence as the conversion of information: a unifying theory
Authors: Varley Thomas F. , Hoel Erik 
Published: May 2022

Is reduction always a good scientific strategy? The existence of the special sciences above physics suggests not. Previous research has shown that dimensionality reduction (macroscales) can increase the dependency between elements of a system (a phenomenon called ‘causal emergence’). Here, we provide an umbrella mathematical framework for emergence based on information conversion. We show evidence that coarse-graining can convert information from one ‘type’ to another. We demonstrate this using the well-understood mutual information measure applied to Boolean networks. Using partial information decomposition, the mutual information can be decomposed into redundant, unique and synergistic information atoms. Then by introducing a novel measure of the synergy bias of a given decomposition, we are able to show that the synergy component of a Boolean network’s mutual information can increase at macroscales. This can occur even when there is no difference in the total mutual information between a macroscale and its underlying microscale, proving information conversion. We relate this broad framework to previous work, compare it to other theories, and argue it complexifies any notion of universal reduction in the sciences, since such reduction would likely lead to a loss of synergistic information in scientific models.
This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Effect of delay on the emergent stability patterns in generalized Lotka–Volterra ecological dynamics
Authors: Saeedian Meghdad , Pigani Emanuele , Maritan Amos , Suweis Samir , Azaele Sandro 
Published: May 2022

Understanding the conditions of feasibility and stability in ecological systems is a major challenge in theoretical ecology. The seminal work of May in 1972 and recent developments based on the theory of random matrices have shown the existence of emergent universal patterns of both stability and feasibility in ecological dynamics. However, only a few studies have investigated the role of delay coupled with population dynamics in the emergence of feasible and stable states. In this work, we study the effects of delay on generalized Loka–Volterra population dynamics of several interacting species in closed ecological environments. First, we investigate the relation between feasibility and stability of the modelled ecological community in the absence of delay and find a simple analytical relation when intra-species interactions are dominant. We then show how, by increasing the time delay, there is a transition in the stability phases of the population dynamics: from an equilibrium state to a stable non-point attractor phase. We calculate analytically the critical delay of that transition and show that it is in excellent agreement with numerical simulations. Finally, following a similar approach to characterizing stability in empirical studies, we investigate the coefficient of variation, which quantifies the magnitude of population fluctuations. We show that in the oscillatory regime induced by the delay, the variability at community level decreases for increasing diversity.This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Emergence of functional information from multivariate correlations
Authors: Adami Christoph , C G Nitash 
Published: May 2022

The information content of symbolic sequences (such as nucleic or amino acid sequences, but also neuronal firings or strings of letters) can be calculated from an ensemble of such sequences, but because information cannot be assigned to single sequences, we cannot correlate information to other observables attached to the sequence. Here we show that an informationscoreobtained from multivariate (multiple-variable) correlations within sequences of a ‘training’ ensemble can be used to predict observables of out-of-sample sequences with an accuracy that scales with the complexity of correlations, showing that functional information emerges from a hierarchy of multi-variable correlations.This article is part of the theme issue ‘Emergent phenomena in complex physical and socio-technical systems: from cells to societies’.
Factors Related to Stress in Children with Online Media Learning Methods during a Pandemic at Jaya Mulya 1 Elementary School, Karawang-Indonesia
Authors: Bayuningsih Ratih , Sidik Fajar 
Published: May 2022

ABSTRACTStress on students is a condition that occurs when there is pressure at school that makes students feel burdened. This study aims to determine the factors related to stress in students who attend school with online media during the covid-19 pandemic at SDN Jayamulya 1 Kab. Karawang. This study uses a descriptive analytic design with a cross sectional approach with a population of 57 respondents and the sample used is 57 respondents. The results of this study there is a relationship between high achievement pressure factors and stress with a p-value of 0.022 < 0.05, a busy schedule factor with stress with a p-value of 0.012 < 0.05, academic achievement factors with stress with a p-value of 0.000 <0.05, physical demands factor with stress with p-value 0.036 < 0.05.
Allogeneic Hematopoietic Cell Transplants as Dynamical Systems: Effect of Early-Term Immune Suppression Intensity on Long-Term T Cell Recovery
Authors: Zelikson Viktoriya , Sabo Roy , Serrano Myrna , Aqeel Younus , Ward Savannah , Juhaishi Taha Al , Aziz May , Krieger Elizabeth , Simmons Gary , Roberts Catherine , Reed Jason , Buck Gregory , Toor Amir 
Published: May 2022

AbstractReduced intensity conditioning (RIC) is fraught with risk for disease relapse. This may be overcome by donor T cell alloreactivity. Reducing the duration of intense immune suppression in the early term following transplantation may create an immunologic environment favoring rapid T cell reconstitution to influence longer term transplant outcomes. Twenty-six patients were adaptively randomized based on donor-derived T cell recovery, between 2 different dosing schedules of mycophenolate mofetil (MMF): MMF for 30 days post-transplant, with filgrastim for cytokine support (MMF30 arm, 11 patients), or MMF for 15 days post-transplant, with sargramostim (MMF15 arm, 15 patients). All patients were treated with anti-thymocyte globulin at a dose of 1.7 mg/kg/day from day - 9 through day -7 and total body irradiation, 450 cGy given in 3 fractions. Patients were well matched between the study arms and underwent HLA matched related and unrelated donor hematopoietic cell transplantation (HCT). The MMF15 arm demonstrated superior T cell recovery in the first month. This difference persisted through the first year for total T cells, T cell subsets and NK cells. T cell repertoire tended to be more diverse in the MMF15 arm. The long term superior immune recovery in the MMF15 arm is consistent with a disproportionate impact of early interventions in HCT. Clinically, shorter course MMF post-transplant was not associated with increased risk of acute or chronic graft vs. host disease (GVHD), and relapse and there was a trend toward improved overall survival in the MMF15 arm. Reducing the duration of intense immunosuppression in the early term and the use of sargramostim following allogeneic HCT is feasible and leads to superior long-term T cell recovery. This regimen should be studied to improve immune recovery in large cohorts of patients undergoing HCT with RIC.
Estimation of the Ascertainment Bias in Covid Case Detection During the Omicron Wave
Authors: Elbanna Ahmed 
Published: May 2022

AbstractCovid cases in the general population have been historically underreported due to a variety of reasons including limited access to PCR testing at the start of the pandemic, lack of nation-wide surveillance testing, and discouraged testing unless symptomatic. Concerns about underreporting have increased during the Omicron surge due to the expanded use of at-home rapid tests which are not required to be officially reported. For the state of Illinois, we have found that reported cases constituted only 50%-70% of the actual cases during the pre-Omicron waves (August 2020-December 2021). During the first Omicron (BA1) wave, this fraction dropped to 20-29% (i.e., only 1 in 4 to 1 in 5 cases are reported). During the ongoing second Omicron (BA2) surge, this fraction has further decreased to 12-18% (i.e., only 1 in 6 to 1 in 8 cases are reported). These estimates have important implications on understanding the extent of the Omicron surge at the state and national levels.
Factors influencing Blacks and Whites’ participation in Alzheimer’s disease biomarker research
Authors: Eliacin Johanne , Hathaway Elizabeth , Wang Sophia , O’Connor Caitlin , Saykin Andrew J. , Cameron Kenzie A. 
Published: May 2022

INTRODUCTIONAlzheimer’s disease (AD) is a public health priority. AD biomarkers may vary based on race, but recruitment of diverse participants has been challenging.METHODSThree groups of Black and White participants with and without prior research advocacy or participation were interviewed individually or in focus groups to better understand perspectives related to AD biomarker research participation. Thematic analytic approach was used to analyze the data.RESULTSIdentified barriers to AD biomarker research participation included hesitancy due to fear, distrust of research and researchers, lack of relevant knowledge, and lack of research test results disclosure. Drivers for engagement in biomarker research procedures included knowledge about research, AD, and related clinical procedures, perceived benefits of participation, and outreach from trusted sources.DISCUSSIONParticipants’ comments related to the need for diversity in research and desire for results disclosure suggest opportunities to engage Black individuals.
Trends in Diabetes Biomarkers and Treatment Statuses of Non-Institutionalized Canadians: Canadian Health Measures Survey 2007 to 2015
Authors: Chao Yi-Sheng 
Published: May 2022

AbstractBackgroundDiabetes has been a major source of disease burden in Canada. Moreover, untreated diabetes can lead to complications and severe conditions. A few studies exist on the prevalence of diabetes and the adequacy of diabetes management for the Canadian population, and so this study aims to estimate the diabetes prevalence rates using biomarkers and the treatment statuses of non-institutionalized Canadian patients.MethodsThe Canadian Health Measures Survey (CHMS) cycles 1 to 4 were conducted between 2007 and 2015 as interviews with non-institutionalized Canadians. Four blood diabetic markers were measured: insulin, glycosylated hemoglobin percentages, random-spot glucose, and fasting glucose. Subjects with levels higher than normal ranges were considered to have pre-diabetes or diabetes. Treatment statuses were categorized into treated (using anti-diabetic agents or diagnosed with diabetes), probably treated (taking prescriptions or diagnosed with chronic conditions), potentially treated (taking any medications or diagnosed with chronic conditions), and untreated (not taking any medications and not diagnosed with chronic conditions). Weights were applied to generate nationally representative statistics.ResultsThe blood insulin levels in cycle 4 were significantly higher than those in cycle 1 (ratio = 1.42, 95% CI = 1.04 to 1.79). The proportions of patients with pre-diabetes and diabetes were estimated differently at 0.75% using random-spot glucose and 42.17% using glycosylated hemoglobin percentages, respectively. The proportions of Canadians with uncontrolled pre-diabetes or diabetes varied from 0.59% using random-spot glucose levels to 4.63% using fasting glucose levels, respectively. Through cycles 1 to 4, the proportions of untreated Canadians with pre-diabetes or diabetes ranged from 3.86% to 3.73%. More than 93% of those with high fasting glucose levels were taking prescription medications or had been diagnosed with chronic conditions (probably treated). Less than 33% of those with high fasting glucose levels were diagnosed or actively being treated with anti-diabetic agents (treated).ConclusionDiabetes biomarkers might be useful for screening untreated and undertreated patients with pre-diabetes or diabetes. The treatment categories we used indicated different intensities of intervention that might be useful for determining levels of patient outreach and for planning targeted screening in Canada.
Acetylation of Adenine Nucleotide Translocase, Fuel Selection, and Metabolic Flexibility in Human Skeletal Muscle
Authors: Barakati Neusha , Bustos Rocio Zapata , Coletta Dawn K. , Langlais Paul R. , Kohler Lindsay N. , Luo Moulun , Funk Janet L. , Willis Wayne T. , Mandarino Lawrence J. 
Published: May 2022

AbstractIntroductionHealthy, resting skeletal muscle primarily oxidizes lipid, but insulin resistant muscle oxidizes carbohydrate and shows metabolic inflexibility during hyperinsulinemia. It is unclear whether fuel selection and metabolic flexibility are dependent on insulin sensitivity in skeletal muscle performing mild exercise.Research Design and MethodsSedentary volunteers underwent a cycle exercise protocol using stepwise increments in power output (15, 30, and 45 watts) and indirect calorimetry to estimate fuel oxidation in working muscle. Euglycemic clamps, indirect calorimetry and muscle biopsies were used to measure insulin sensitivity and acetylation and content of Adenine Nucleotide Translocase 1 (ANT1), which might be involved in fuel selection via acetylation of lysine 23, which was quantified using mass spectrometry.ResultsMild exercise produced predicted rates of oxygen consumption (11-12 ml O2/min), with low and stable blood lactate, allowing use of indirect calorimetry to calculate a respiratory exchange ratio in working muscle (RERm). ANT1 acetylation varied from 0.6 to 21% (10.3 ± 1.2%). Exercising muscle mainly oxidized carbohydrate (45 ± 9, 62 ± 6, and 70 ± 5% of total at 15, 30, and 45watts). Multiple linear regression showed that RERm rose with increasing power output (P < 0.001) and was lower with greater protein content of ANT1 (P < 0.001). Insulin-stimulated glucose disposal, ANT acetylation, and VO2peak were not predictors of RERm.ConclusionsMildly exercising muscle in sedentary people prefers to oxidize carbohydrate independent of insulin sensitivity but depending on ANT1 protein content. The ability to oxidize lipid may be regulated by higher ANT1 content due to either higher mitochondrial abundance or greater ANT content per mitochondrial mass.
Partial and Radical cystectomy Provides Equivalent Oncologic Outcomes in T2 Bladder Cancer: a Population-Based Study
Authors: Long Gongwei , Hu Zhiquan , Liu Zheng , Ye Zhangqun , Wang Shaogang , Wang Dongwen , Yang Chunguang 
Published: May 2022

ABSTRACTPurposeTo compare the oncologic outcomes of T2 bladder cancer (BCa) patients after partial cystectomy (PC) or radical cystectomy (RC).Materials and MethodsRelevant data of T2 BCa patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database. After propensity score matching, the oncologic outcomes after PC or RC were compared in patients who underwent lymph node dissection (LND) or not. Additionally, the benefits of different LND strategies were also explored.ResultsEventually, 3834 T2 BCa cases were enrolled in the analysis, including 724 (18.9%) received PC cases and 3110 (81.1%) RC cases. The PC and RC groups presented entirely different profiles in clinical parameters such as age, number of lymph nodes (LNs) removed, and adjuvant therapy. Particularly, LNDs were performed in 92.0% of RC cases, while only in 45.4% of PC cases. After propensity score matching, PC and RC present similar oncologic outcomes regardless of the LND strategies. Further exploration found that LND could improve the prognosis of patients and the benefit is associated with the number of LNs removed.ConclusionPC and RC could provide equivalent oncologic outcomes in T2 BCa. LND is essential in curative surgery and could significantly affect the prognosis, but it was frequently neglected, especially in PC. The criteria for PC in T2 BCa need further exploration in future studies.