bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training Characteristics, Academic Accomplishments, and Motivation of Current Chairs in Physical Medicine and Rehabilitation
Authors: Martinez Claudia I. , Sanchez Ashley N. , Knecht Kearstin , Frontera Joel , Escalon Miguel X. , Verduzco-Gutierrez Monica , Lee Michael Y. 
Published: August 2021

Objective
The aim of the study was to report the training characteristics, academic accomplishments, and motivation of current United States academic physical medicine and rehabilitation chairs.

Design
The authors developed a 23-question survey that was disseminated via e-mail to 86 current chairs who were members of the Chairs Council from the Association of Academic Physiatrists in May 2020. Follow-up e-mails were sent 2 and 4 wks after the initial distribution, and the survey closed after 6 wks in June 2020. The data collected were deidentified. Descriptive analysis was performed.

Results
Forty-nine chair responses were received, which had a response rate of 60%. A total of 69.4% of the chairs (32 of 49) were men and 30.6% (17 of 49) were women. A total of 75.5% (37 of 49) were White/Caucasian, 12.2% (6 of 49) Hispanic/Latinx, 10.2% (5 of 49) Asian, and 2% (1 of 49) were Black/African American. A total of 8.2% of the chairs (4 of 49) reported having a disability. Sixty-seven percent of the female chairs (10 of 15) reported experiencing gender discrimination in the workplace versus 3% of male chairs (1 of 34). Twenty-nine percent of the chairs were full professors in physical medicine and rehabilitation when first appointed, 57.1% associate professors, and 6% assistant professors. A total of 73.5% of the chairs had served as a reviewer for a peer-reviewed publication. Fifty-two percent of the chairs had a leadership role in a national physical medicine and rehabilitation organization. Fifty-eight percent of the chairs had at least 16 peer-reviewed publications when first appointed.

Conclusions
This survey provides insight to the training characteristics, accomplishments, and motivation of current chairs for physiatrists aspiring to enter these ranks. It also highlights the underrepresentation of women and minorities among leadership positions in physical medicine and rehabilitation.
Explainable Prediction of Dacryocystitis From Noninvasive Ocular Indicators Using Deep Stacked Network and The Shapley Additive Explanations Approach
Authors: Han Fuchang , Liao Shenghui , Song Xuefei , Chen Shaoqin , Li Lunhao , Liu Shu , Zhao Yuqian 
Published: August 2021

Abstract
Dacryocystitis diagnosis is important for preventing rapid blurring and vision loss. Existing state-of-the-art methods focus on routine clinical examinations and objective scattering index-based statistical analysis. Such approaches are invasive operations or lack quantitative indicators, and their application is limited. in addition, little attention has been paid to the explainability and clinical utility of models. This paper proposes an explainable dacryocystitis prediction model from noninvasive ocular indicators. The proposed model is based on an deep stacked network with 4 improvements: a multivariable feature extraction module, obtaining comprehensive predictive factors including the quantitative ocular indictors, conventional texture features, and deep learning features from shallow to deep convolutional layers; a multifeature fusion and attribute selection module based on the ReliefF method, guiding the network to focus on useful information at variables; Decision curve analysis the model is introduced into the model to evaluates the risks and benefits; and appending a SHapley Additive exPlanations (SHAP) module to the framework to automatically and efficiently interpret the prediction of the models. By integrating the above improvements in series, the models’ performances are gradually enhanced. Real labeled data samples are used to train and test the model, and our model achieves high accuracy and reliability.
Learning shapes cortical dynamics to enhance integration of relevant sensory input
Authors: Chadwick Angus , Khan Adil , Poort Jasper , Blot Antonin , Hofer Sonja , Mrsic-Flogel Thomas , Sahani Maneesh 
Published: August 2021

SummaryAdaptive sensory behavior is thought to depend on processing in recurrent cortical circuits, but how dynamics in these circuits shapes the integration and transmission of sensory information is not well understood. Here, we study neural coding in recurrently connected networks of neurons driven by sensory input. We show analytically how information available in the network output varies with the alignment between feedforward input and the integrating modes of the circuit dynamics. In light of this theory, we analyzed neural population activity in the visual cortex of mice that learned to discriminate visual features. We found that over learning, slow patterns of network dynamics realigned to better integrate input relevant to the discrimination task. This realignment of network dynamics could be explained by changes in excitatory-inhibitory connectivity amongst neurons tuned to relevant features. These results suggest that learning tunes the temporal dynamics of cortical circuits to optimally integrate relevant sensory input.HighlightsA new theoretical principle links recurrent circuit dynamics to optimal sensory codingPredicts that high-SNR input dimensions activate slowly decaying modes of dynamicsPopulation dynamics in primary visual cortex realign during learning as predictedStimulus-specific changes in E-I connectivity in recurrent circuits explain realignment
Low amplitude burst detection of catecholamines
Authors: Eltahir Amnah , White Jason , Lohrenz Terry , Montague P. Read 
Published: August 2021

AbstractMachine learning advances in electrochemical detection have recently produced sub-second and concurrent detection of dopamine and serotonin during perception and action tasks in conscious humans. Here, we present a new machine learning approach to sub-second, concurrent separation of dopamine, norepinephrine, and serotonin. The method exploits a low amplitude burst protocol for the controlled voltage waveform and we demonstrate its efficacy by showing how it separates dopamine-induced signals from norepinephrine induced signals. Previous efforts to deploy electrochemical detection of dopamine in vivo have not separated the dopamine-dependent signal from a norepinephrine-dependent signal. Consequently, this new method can provide new insights into concurrent signaling by these two important neuromodulators.
Long-distance dispersal of pigeons and doves generated new ecological opportunities for host-switching and adaptive radiation by their parasites
Authors: Boyd Bret M. , Nguyen Nam-Phuong , Allen Julie M. , Waterhouse Robert M. , Vo Kyle B. , Sweet Andrew D. , Clayton Dale H. , Bush Sarah E. , Shapiro Michael D. , Johnson Kevin P. 
Published: August 2021

AbstractAdaptive radiation is an important mechanism of organismal diversification, and can be triggered by new ecological opportunities. Although poorly studied in this regard, parasites present an ideal system to study adaptive radiations because of their close associations with host species. Both experimental and comparative studies suggest that the ectoparasitic wing lice of pigeons and doves have undergone an adaptive radiation, resulting in differences in both body size and overall coloration. Here we show that long-distance dispersal by dove hosts was important for parasite diversification, providing new ecological opportunities for parasites to speciate by host-switching. We further show that these new opportunities for host-switching decreased over time, and cospeciation became the more dominant mode of parasite speciation. Taken together, our results suggest that host dispersal, followed by host-switching, provided novel ecological opportunities that facilitated adaptive radiation by parasites.
Modeling minimum viable population size with multiple genetic problems of small populations
Authors: Nabutanyi Peter , Wittmann Meike J. 
Published: August 2021

AbstractAn important goal for conservation is to define minimum viable population (MVP) sizes for long-term persistence. Although many MVP size estimates focus on ecological processes, with increasing evidence for the role of genetic problems in population extinction, conservation practitioners have also increasingly started to incorporate inbreeding depression (ID). However, small populations also face other genetic problems such as mutation accumulation (MA) and loss of genetic diversity through genetic drift that are usually factored into population viability assessments only via verbal arguments. Comprehensive quantitative theory on interacting genetic problems is missing. Here we develop eco-evolutionary quantitative models that track both population size and levels of genetic diversity. Our models assume a biallelic multilocus genome whose loci can be under either a single or interacting genetic forces. In addition to mutation-selection-drift balance (for loci facing ID and MA), we include three forms of balancing selection (for loci where variation is lost through genetic drift). We define MVP size as the lowest population size that avoids an eco-evolutionary extinction vortex after a time sufficient for an equilibrium allele frequency distribution to establish. Our results show that MVP size decreases rapidly with increasing mutation rates for populations whose genomes are only under balancing selection, while for genomes under mutation-selection-drift balance, the MVP size increases rapidly. MVP sizes also increase rapidly with increasing number of loci under the same or different selection mechanisms until a point is reached at which even arbitrarily large populations cannot survive anymore. In the case of fixed number of loci under selection, interaction of genetic problems did not necessarily increase MVP sizes. To further enhance our understanding about interaction of genetic problems, there is need for more empirical studies to reveal how different genetic processes interact in the genome.
ANDOR and beyond: dynamically switchable logic gates as modules for flexible information processing
Authors: Bahadorian Mohammadreza , Modes Carl D. 
Published: August 2021

ABSTRACTUnderstanding how complex (bio-)chemical pathways and regulatory networks may be capable of processing information in efficient, flexible, and robust ways is a key question with implications touching fields across biology, systems biology, biochemistry, synthetic biology, dynamical systems theory, and network science. Considerable effort has been focused on the identification and characterization of structural motifs in these signaling networks, and companion efforts have instead sought to cast their operation as controlled by dynamical modules that appear out of dynamical correlations during information processing. While both these approaches have been successful in many examples of biological information processing, cases in which the signaling or regulatory network exhibits multi-functionality or context dependence remain problematic. We here propose a small set of higher-order effective modules that simultaneously incorporate both network structure and the attendant dynamical landscape. In so doing, we render effective computational units that can perform different logical operations based purely on the basin of attraction in which the network dynamics resides or is steered to. These dynamically switchable biochemical logic gates require fewer chemical components or gene products overall than their traditional analogs where static, separate gates are used for each desired function. We demonstrate the applicability and limits of these flexible gates by determining a robust range of parameters over which they correctly operate and further characterize the resilience of their function against intrinsic noise of the constituent reactions using the theory of large deviations. We also show the capability of this framework for general computations by designing a binary adder/subtractor circuit composed of only six components.
Linking Individual Differences in Personalized Functional Network Topography to Psychopathology in Youth
Authors: Cui Zaixu , Pines Adam R. , Larsen Bart , Sydnor Valerie J. , Li Hongming , Adebimpe Azeez , Alexander-Bloch Aaron F. , Bassett Dani S. , Bertolero Max , Calkins Monica E. , Davatzikos Christos , Fair Damien A. , Gur Ruben C. , Gur Raquel E. , Moore Tyler M. , Shanmugan Sheila , Shinohara Russell T. , Vogel Jacob W. , Xia Cedric H. , Fan Yong , Satterthwaite Theodore D. 
Published: August 2021

ABSTRACTThe spatial layout of large-scale functional brain networks differs between individuals and is particularly variable in association cortex that has been implicated in a broad range of psychiatric disorders. However, it remains unknown whether this variation in functional topography is related to major dimensions of psychopathology in youth. Capitalizing on a large sample with 27-minutes of high-quality functional MRI data (n=790, ages 8-23 years) and advances in machine learning, we examined associations between functional topography and four correlated dimensions of psychopathology (fear, psychosis, externalizing, anxious-misery) as well as an overall psychopathology factor. We found that functional topography significantly predicted individual differences in dimensions of psychopathology, driven mainly by robust associations between topography and overall psychopathology. Reduced cortical representations of association networks were among the most important features of the model. Our results emphasize the value of considering systematic differences in functional neuroanatomy for personalized diagnostics and therapeutics in psychiatry.
Non-Viral Engineering of CAR-NK and CAR-T cells using theTc BusterTransposon System™
Authors: Pomeroy Emily J. , Lahr Walker S. , Chang Jae Woong , Krueger Joshua , Wick Bryce J. , Slipek Nicholas J. , Skeate Joseph G. , Webber Beau R. , Moriarity Branden S. 
Published: August 2021

AbstractCancer immunotherapy using T cells and NK cells modified with viral vectors to express a chimeric antigen receptor (CAR) has shown remarkable efficacy in treating hematological malignancies in clinical trials. However, viral vectors are limited in their cargo size capacity, and large-scale manufacturing for clinical use remains complex and cost prohibitive. As an alternative, CAR delivery via DNA transposon engineering is a superior and cost-effective production method. Engineering via transposition is accomplished using a two-component system: a plasmid containing a gene expression cassette flanked by transposon inverted terminal repeats (ITRs) paired with a transposase enzyme that binds to the ITRs, excises the transposon from the plasmid, and stably integrates the transposon into the genome.Here, we used the newly developed hyperactiveTc Buster(Bio-Techne) transposon system to deliver a transposon containing a multicistronic expression cassette (CD19-CAR, mutant DHFR, and EGFP) to primary human peripheral blood (PB) NK cells and T cells. We optimized methods to avoid DNA toxicity and maximize efficiency. Our cargo contained a mutant dihydrofolate reductase (DHFR) which allowed us to enrich for stable transposon integration using methotrexate (MTX) selection. We then tested CAR-NK and CAR-T cells in functional assays against CD19-expressing Raji cells. CAR-expressing NK and T cells produced significantly more cytokines than CAR-negative controls and efficiently killed target cells. We recognize that cryopreservation manufactured CAR-expressing cells will be necessary for clinical translation. We observed reduced cytotoxicity of CAR-NK cells immediately after thaw, but increasing the NK dose overcame this loss of function.Our work provides a platform for robust delivery of multicistronic, large cargo via transposition to primary human NK and T cells. We demonstrate that CAR-expressing cells can be enriched using MTX selection, while maintaining high viability and function. This non-viral approach represents a versatile, safe, and cost-effective option for the manufacture of CAR-NK and CAR-T cells compared to viral delivery.
Dynamic evolution of bacterial ligand recognition by formyl peptide receptors
Authors: Paterson Nicole M. , Al-Zubieri Hussein , Ragona Joseph , Tirado Juan , Geisbrecht Brian V. , Barber Matthew F. 
Published: August 2021

ABSTRACTThe detection of invasive pathogens is critical for host immune defense. Cell surface receptors play a key role in the recognition of diverse microbe-associated molecules, triggering leukocyte recruitment, phagocytosis, release of antimicrobial factors, and cytokine production. The intense selective forces acting on innate immune receptor genes has led to their rapid diversification across plant and animal species. However, the impacts of this genetic variation on immune functions are often unclear. Formyl peptide receptors (FPRs) are a family of animal G-protein coupled receptors which are activated in response to a variety of ligands including formylated bacterial peptides, microbial virulence factors, and host-derived peptides. Here we investigate patterns of gene loss, sequence diversity, and ligand recognition among primate and carnivore FPRs. We observe that FPR1, which plays a critical role in innate immune defense in humans, has been lost in New World primates. Patterns of amino acid variation in FPR1 and FPR2 suggest a history of repeated positive selection acting on extracellular domains involved in ligand binding. To assess the consequences of FPR variation on bacterial ligand recognition, we measured interactions between primate FPRs and the FPR agonist Staphylococcus aureus enterotoxin B, as well as S. aureus FLIPr-like which functions as an FPR inhibitor. We find that comparatively few sequence differences between great ape FPRs are sufficient to modulate recognition of S. aureus ligands, further demonstrating how genetic variation can act to tune FPR activation in response to diverse microbial binding partners. Together this study reveals how rapid evolution of host immune receptors shapes the detection of diverse microbial molecules.
Isolation and characterization of human monoclonal antibodies to pneumococcal capsular polysaccharide 3
Authors: Babb Rachelle , Doyle Christopher R , Pirofski Liise-anne 
Published: August 2021

ABSTRACTThe current pneumococcal capsular polysaccharide (PPS) conjugate vaccine (PCV13) is less effective againstStreptococcus pneumoniaeserotype 3 (ST3), which remains a major cause of pneumococcal disease and mortality. Therefore, dissecting structure-function relationships of human PPS3 antibodies may reveal characteristics of protective antibodies. Using flow cytometry, we isolated PPS3-binding memory B cells from pneumococcal vaccine recipients and generated seven human PPS3-specific monoclonal antibodies (humAbs). Five humAbs displayed ST3 opsonophagocytic activity, four induced ST3 agglutinationin vitro, and four mediated both activities. For two humAbs, C10 and C27, that used the same variable heavy (VH) and light (VL) chain domains (VH3-9*01/VL2-14*03), C10 had fewer VLsomatic mutations, higher PPS3 affinity, more ST3 opsonophagocytic and agglutinating activity, whilst both humAbs altered ST3 gene expressionin vitro. After VLswaps, C10VH/C27VLexhibited reduced ST3 binding and agglutination, but C27VH/C10VLbinding was unchanged. In C57Bl/6 mice, C10 and C27 reduced nasopharyngeal colonization with ST3 A66 and a clinical strain, B2, and prolonged survival following lethal A66 intraperitoneal infection, but only C10 protected against lethal intranasal infection with the clinical strain. Our findings, associate efficacy of PPS3-specific humAbs with ST3 agglutination and opsonophagocytic activity and reveal an unexpected role for the VLin functional activityin vitroandin vivo. These findings also provide insights that may inform antibody-based therapy and identification of surrogates of vaccine efficacy against ST3.IMPORTANCEDespite the global success of pneumococcal conjugate vaccination, serotype 3 (ST3) pneumococcus remains a leading cause of morbidity and mortality. In comparison to other vaccine-included serotypes, the ST3 pneumococcal capsular polysaccharide (PPS3) induces a weaker opsonophagocytic response, which is considered a correlate of vaccine efficacy. Previous studies of mouse PPS3 monoclonal antibodies identified ST3 agglutination as a correlate of reduced ST3 nasopharyngeal colonization in mice, however neither the agglutinating ability of human vaccine-elicited PPS3 antibodies nor their ability to prevent experimental murine nasopharyngeal colonization has been studied. We generated and analysed the functional andin vivoefficacy of human vaccine-elicited PPS3 monoclonal antibodies and found that ST3 agglutination associated with antibody affinity, protectionin vivo, and limited somatic mutations in the light chain variable region. These findings provide new insights that may inform the development of antibody-based therapies and next generation vaccines for ST3.
Disability Training for Health Workers: A Global Narrative Systematic Review
Authors: Rotenberg Sara , Gatta Rodríguez Danae , Wahedi Azizia , Loo Rachelle , McFadden Emily , Ryan Sara 
Published: August 2021

ABSTRACTBackgroundHealth worker training on disability is a recognized component of achieving high standards of health for people with disabilities, given that health worker’s lack of knowledge, stigma, and negative attitudes towards people with disabilities act as barriers to high quality health care.ObjectiveTo understand the published literature on training health workers about disability.MethodsWe searched five databases for relevant peer-reviewed articles published between January 2012 and January 2021. Studies that focused on training health care workers to improve knowledge, confidence, self-efficacy, and competence to support people with physical, sensory, or intellectual impairments were included. Data about the details of the intervention (setting, participants, format, impact assessments, etc.) and its effects were extracted.ResultsThere is an array of highly local tools to train health workers across stages of their training and careers (pre-service, in-service, and continuing professional development). Studies involving people with disabilities in the training, community placements, simulations, or interactive sessions were found to be most effective in improving knowledge, confidence, competency, and self-efficacy.ConclusionsAs part of initiatives to build inclusive health systems and improve health outcomes for people with disabilities, health workers around the world need to receive appropriate and evidence-based training that combine multiple methods and involve people with disabilities.