bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review and Critical Appraisal of Clinical Practice Guidelines of Modalities Used in the Diagnosis of Celiac Disease
Authors: Graham Kennedy , Gidrewicz Dominica , Turner Justine M , Duerksen Donald R , Pinto-Sanchez Maria Ines 
Published: April 2023

Abstract

Background
There is controversy over the recommendations for specific serological strategies implemented and the need for a biopsy to confirm celiac disease (CeD). We reviewed and appraised the current clinical practice guidelines (CPGs) to assess the quality and reliability of recommendations for CeD diagnosis in pediatric and adult populations.

Methods
We searched databases, including MEDLINE, EMBASE, Web of Science, and CINAHL, between December 2010 and January 2021 for CPGs. Four independent reviewers extracted data. Appraisal of Guidelines Research and Evaluation (AGREE II) criteria were applied by two reviewers, and a standardized score was calculated for each of the six domains. A cut-off of 60% was used to identify high-quality guidelines.

Results
A total of 654 records were identified, 10 of which were eligible for data extraction. Both adult and pediatric CPGs averaged above 70% for the domains of ‘scope and purpose’ and ‘clarity and presentation’. For ‘stakeholder involvement’, the mean adult and pediatric CPG scores were below the cut-off. Only one adult-focused guideline exceeded the cut-off for the ‘rigour of development’ domain. ‘Applicability’ scores were most alarming, with adult CPGs averaging 21% and pediatric CPGs averaging 23%.

Conclusion
Our review and appraisal of the CPGs for the diagnosis of CeD highlight significant discrepancies in clinical recommendations and some concerns regarding methodological rigour, particularly in stakeholder engagement, rigour, and applicability. Creating a Canadian guideline of high methodological quality that overcomes these weaknesses is critical to optimize patient care and ensuring accurate diagnoses in CeD.
Inspiring Regime Change
Authors: Morris Stephen , Shadmehr Mehdi 
Published: April 2023

Abstract
We consider the problem of a leader who can assign rewards for citizens for different anti-regime actions. Citizens face a coordination problem in which each citizen has a private, endogenous degree of optimism about the likelihood of regime change. Because more optimistic citizens are easier to motivate, the choice of optimal rewards entails optimal screening. This leads to a distribution of anti-regime actions. A key result is the emergence of a vanguard, consisting of citizens who engage in the endogenous, maximum level of action. Other citizens participate at varying degrees, with less optimistic citizens contributing less. We explore how the regime’s strength or the maximum reward available to the leader influences the distribution of actions. Moreover, we show that more heterogeneity (e.g., higher inequality) among potential revolutionaries reduces the likelihood of regime change. Our methodological contribution is that we deliver a sharp and novel marriage of screening and global games.
The Military Medical Officer’s Current-Day Professional Identity: An Enhanced Model
Authors: Cole Rebekah , Williamson Samantha S , Hughes Joshua R , Rudinsky Sherri L 
Published: April 2023

ABSTRACT

Background
As the landscapes of war have evolved, so too has the role of the military medical officer (MMO). Colonel (Retired) Barry Wolcott developed a “vector” model in the 1990s, illustrating the dual professional role of the MMO. Since then, propelled by the War on Terror, MMOs have adapted to treating patients in volatile, uncertain, complex, and ambiguous operational environments. This study, therefore, aimed to explore modern-day aspects of the MMO’s role in order to enhance Wolcott’s depiction of the MMO’s professional identity in contemporary operational environments.

Materials and Methods
We used the qualitative phenomenological tradition to design our study. We interviewed military physicians from a variety of specialties in order to explore their experiences and professional identity as MMOs. Our research team then coded each of these interview transcripts. We organized these codes into categories, which served as the themes of our study.

Results
The following themes emerged from our data regarding the role of the MMO in the operational environment: Primary roles (officer, physician, educator, and diplomat) and aptitudes (innovation, advocacy, cultural competency, and leadership). The MMO’s roles as officer and physician often intersect, with dual foci on the mission and the patient. The MMO also serves as an educator to medics and line officers. In addition, they act as diplomats both outside and within the military. Within each of these primary roles, the MMO innovatively prepares for future landscapes of war and advocates for both the individual warfighter and the unit/command. Finally, the MMO navigates both foreign and internal cultural differences and demonstrates leadership in enabling the military’s mission.

Conclusions
The role of the MMO is complex and multifaceted. The recognition of the contemporary MMO’s unique skill set is essential for the effective education and training of future military health care leaders. The value of capitalizing on this unique skill set has been demonstrated in recent civ-mil responses. Because their intricate skill set is specialized for the operational environment, long-term retention of MMOs is key to force readiness.
The Internal Morality of Criminal Law
Authors: Edwards James , Yusari Tarek 
Published: April 2023

Abstract
According to a popular picture, criminal law lives up to the demands of its internal morality when its norms have counterparts with the same content in morality—when it conforms to what we call the mirror principle. This article argues that the popular picture must be redrawn by relying on a second principle, which we call the instrumental principle. Criminal law conforms to the instrumental principle when the existence of its norms helps to prevent or ameliorate moral wrongdoing. Our argument is that the instrumental principle forms part of the internal morality of criminal law, and supplies a justification for criminal laws that depart from the mirror principle. We further suggest that criminal law’s internal morality is asymmetrical: though departures from the mirror principle are sometimes justified by the instrumental principle, departures from the latter are not justified by the former.
Model of Human Fallibility: Traveling Behavioral Assumptions in Public Governance
Authors: Pallesen Trine , Pedersen Kirstine Zinck 
Published: April 2023

Abstract
Over the past decades, insights from behavioral sciences have gained traction as sources for designing public policy and for governing areas of collective concerns. It has become increasingly common to ascribe ‘flawed’ decision-making to systematic heuristics and cognitive biases of citizens and experts. This popular behavioral approach to public organizing is anchored in a very particular model of human behavior, namely what we label homo fallibilis or the model human fallibility. This model grew out of a critique of neoclassical economics’ homo economicus but ended as a new recipe for predicting and regulating human behavior. To conceptualize the model of human fallibility and to understand its ability to travel intellectually and empirically, we trace it historically to Simon’s bounded rationality, over Tversky and Kahneman’s systematic biases and to recent nudge literature. Next, we illustrate how and by what means the model travels into different areas of public service provision in strikingly similar ways. We finally suggest that the model of human fallibility risks giving way to an “anti-human stance” that promotes a particular type of behavioral design in ever more areas of public governance at the expense of alternative ways of governing that enhance discretion, expertise, training, and habituation.
High fat diet allows food-predictive stimuli to energize action performance in the absence of hunger, without distorting insulin signaling on accumbal cholinergic interneurons
Authors: Gladding Joanne M. , Lingawi Nura W. , Leung Beatrice , Kendig Michael D. , Chieng Billy C. , Laurent Vincent 
Published: April 2023

AbstractObesity can disrupt how food-predictive stimuli control action performance and selection. These two forms of control recruit cholinergic interneurons (CIN) located in the nucleus accumbens core (NAcC) and shell (NAcS), respectively. Given that obesity is associated with insulin resistance in this region, we examined whether interfering with CIN insulin signaling disrupts how food-predictive stimuli control actions. To interfere with insulin signaling we used a high-fat diet (HFD) or genetic excision of insulin receptor (InsR) from cholinergic cells. HFD left intact the capacity of food-predictive stimuli to energize performance of an action earning food when mice were tested hungry. However, it allowed this energizing effect to persist when the mice were tested sated. This persistence was linked to NAcC CIN activity but was not associated with distorted CIN insulin signaling. Accordingly, InsR excision had no effect on how food-predicting stimuli control action performance. Next, we found that neither HFD nor InsR excision altered the capacity of food-predictive stimuli to guide action selection. Yet, this capacity was associated with changes in NAcS CIN activity. These results indicate that insulin signaling on accumbal CIN does not modulate how food-predictive stimuli control action performance and selection. However, they show that HFD allows food-predictive stimuli to energize performance of an action earning food in the absence of hunger.
Stress-induced clustering of the UPR sensor IRE1α is driven by disordered regions within its ER lumenal domain
Authors: Kettel Paulina , Marosits Laura , Spinetti Elena , Rechberger Michael , Radler Philipp , Niedermoser Isabell , Fischer Irmgard , Versteeg Gijs A , Loose Martin , Covino Roberto , Karagöz G Elif 
Published: April 2023

AbstractUpon accumulation of unfolded proteins at the endoplasmic reticulum (ER), IRE1 activates the unfolded protein response (UPR) to restore protein-folding homeostasis. During ER stress, IRE1’s ER lumenal domain (LD) drives its clustering on the ER membrane to initiate signaling. How IRE1’s LD assembles into high-order oligomers remains largely unknown. Byin vitroreconstitution experiments we show that human IRE1α LD forms dynamic biomolecular condensates. IRE1α LD condensates were stabilized when IRE1α LD was tethered to model membranes and upon binding of unfolded polypeptide ligands. Molecular dynamics simulations suggested that weak multivalent interactions are involved in IRE1α LD assemblies. Mutagenesis showed that disordered regions in IRE1α LD control its clusteringin vitroand in cells. Importantly, dysregulated clustering led to defects in IRE1α signaling. Our results reveal that membranes and unfolded polypeptides act as scaffolds to assemble dynamic IRE1α condensates into stable, signaling competent clusters.
Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration
Authors: Bryson Noah , Lombardi Lorenzo , Hawthorn Rachel , Fei Jie , Keesey Rodolfo , Peiffer J.D. , Seáñez Ismael 
Published: April 2023

AbstractObjectiveTranscutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation.ApproachIn this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS.ResultsAnalysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode’s position.SignificanceImprovements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.
Carnosine synthase deficiency aggravates neuroinflammation in multiple sclerosis
Authors: Spaas Jan , Van der Stede Thibaux , de Jager Sarah , van de Waterweg Berends Annet , Tiane Assia , Baelde Hans , Baba Shahid P. , Eckhardt Matthias , Wolfs Esther , Vanmierlo Tim , Hellings Niels , Eijnde Bert O. , Derave Wim 
Published: April 2023

AbstractMultiple sclerosis (MS) pathology features autoimmune-driven neuroinflammation, demyelination, and failed remyelination. Carnosine is a histidine-containing dipeptide (HCD) with pluripotent homeostatic properties that is able to improve outcomes in an animal MS model (EAE) when supplied exogenously. To uncover if endogenous carnosine is involved in, and protects against, MS-related neuroinflammation, demyelination or remyelination failure, we here studied the HCD-synthesizing enzyme carnosine synthase (CARNS1) in human MS lesions and two preclinical mouse MS models (EAE, cuprizone). We demonstrate that due to its presence in oligodendrocytes, CARNS1 expression is diminished in demyelinated MS lesions and mouse models mimicking demyelination/inflammation, but returns upon remyelination.Carns1-KO mice that are devoid of endogenous HCDs display exaggerated neuroinflammation and clinical symptoms during EAE, which could be partially rescued by exogenous carnosine treatment. Worsening of the disease appears to be driven by a central, not peripheral immune-modulatory, mechanism possibly linked to impaired clearance of the reactive carbonyl acrolein inCarns1-KO mice. In contrast, the presence of CARNS1 and endogenous HCDs does not protect against cuprizone-induced demyelination, and is not required for normal oligodendrocyte precursor cell differentiation and (re)myelin to occur. Exogenously administered carnosine is not effective in blunting demyelination or accelerating remyelination. In conclusion, we show that CARNS1 is diminished in demyelinated MS lesions, which may have detrimental effects on disease progression through weakening the endogenous protection against neuroinflammation.
Handedness and its association with education and spatial navigation assessed in over 400,000 participants across 41 countries
Authors: Fernandez-Velasco P. , Coutrot A. , Oloye H. , Wiener J.M. , Dalton R.C. , Hoelscher C. , Manley E. , Hornberger M. , Spiers H.J 
Published: April 2023

AbstractThere is an active debate concerning the association of handedness and spatial ability. Past studies used small sample sizes within a single country. Determining the effect of handedness on spatial ability requires a large, cross-cultural sample of participants, and a navigation task with real-world validity. Here, we overcome these challenges via the mobile app Sea Hero Quest. We analysed the navigation performance from 422,772 participants from 41 countries and found no reliable evidence for any difference in spatial ability between left- and right-handers across all countries. Using 749,037 participants from the larger sample, we replicate previous findings that age, gender, and country of residence have an impact on the prevalence of left-handedness, and found an effect of education on left-handedness prevalence in China, Indonesia, India, Taiwan, and Hong Kong. Our study clarifies the factors associated with spatial ability and outlines new ways in which cultural patterns influence handedness.Statement of RelevanceWhat is the relation between handedness and navigation ability? Evidence so far has been mixed, and findings from small-scale and large-scale tasks seem to point in opposite directions. Part of the reason is that cultural and sociodemographic differences have a significant impact on both spatial ability and handedness. Tackling the question requires a large, cross-cultural sample of participants performing an ecologically valid navigation task. Here, we employ a mobile app, Sea Hero Quest, to test the navigation ability of a large number of participants across many different countries. What we find is that there is no reliable connection between handedness and navigation ability. Then, we use our data to explore the prevalence of left-handedness across countries, and find that age, gender, and country of residency all have an effect on the ratio of left-handedness. Moreover, we find an effect of education on left-handedness in China, Indonesia, India, Taiwan, and Hong Kong.
Sodium-mediated plateau potentials in an identified decisional neuron contribute to feeding-related motor pattern genesis inAplysia
Authors: Bédécarrats Alexis , Simmers John , Nargeot Romuald 
Published: April 2023

ABSTRACTMotivated behaviors such as feeding depend on the functional properties of decision neurons which provide the flexibility required for behavioral adaptation. Here, we analyzed the ionic basis of the endogenous membrane properties of an identified decision neuron (B63) that drive radula biting cycles underlying food-seeking behavior inAplysia. Each spontaneous bite cycle arises from the irregular triggering of a plateau-like potential and resultant bursting by rhythmic subthreshold oscillations in B63’s membrane potential. In isolated buccal ganglion preparations, and after synaptic isolation, the expression of B63’s plateau potentials persisted after removal of extracellular calcium, but was completely suppressed in a TTX-containing bath solution, thereby indicating the contribution of a transmembrane Na+influx. Potassium outward efflux through TEA- and calcium-sensitive channels was found to contribute to each plateau’s active termination. This intrinsic plateauing capability, in contrast to B63’s membrane potential oscillation, was blocked by theICANblocker flufenamic acid (FFA). Conversely, the SERCA blocker cyclopianozic acid (CPA), which abolished the neuron’s oscillation, did not prevent the expression of experimentally evoked-plateau potentials. These results therefore indicate that the dynamic properties of the decision neuron B63 rely on two distinct mechanisms involving different sub-populations of ionic conductances.NEW & NOTEWORTHYHere, we report an endogenous plateau property underlying bursting in a bilateral pair of buccal ganglion pacemaker neurons (B63) which trigger individual motor pattern cycles for food-seeking behavior in the marine molluskAplysia. The ionic mechanisms of this membrane bistability in B63 rely critically on voltage-dependent sodium inward currents. The expression of these plateau properties and the underlying endogenous oscillatory pacemaker drive can be dissociated pharmacologically, indicating that the two intrinsic properties depend on different sets of conductances. Our results thus shed new light on the mechanisms of spontaneous decision making inAplysia.
Inferring interactions from microbiome data
Authors: Zapién-Campos Román , Bansept Florence , Traulsen Arne 
Published: April 2023

AbstractParameter inference of high-dimensional data is challenging and microbiome time series data is no exception. Methods aimed at predicting from point estimates exist, but often even fail to recover the true parameters from simulated data. Computational methods to robustly infer and quantify the uncertainty in model parameters are needed. Here, we propose a computational workflow addressing such challenges – allowing us to compare mechanistic models and identify the values and the certainty of inferred parameters. This approach allows us to infer which kind of interactions occur in the microbial community. In contrast to point-estimate inference, the distribution for the parameters, our outcome, reflects their uncertainty. To achieve this, we consider as many equations for the statistical moments of the microbiome as parameters. Our inference workflow, which builds upon a mechanistic foundation of microscopic processes, can take into account that commonly metagenomic datasets only provide information on relative abundances and hosts’ ensembles. With our framework, we move from qualitative prediction to quantifying the likelihood of certain interaction types in microbiomes.
Differentiation of vaginal cells from epidermal cells using morphological and autofluorescence properties: Implications for sexual assault casework involving digital penetration
Authors: Ingram Sarah , DeCorte Arianna , Gentry Amanda , Philpott M. Katherine , Moldenhauer Taylor , Stadler Sonja , Steinberg Cory , Millman Jonathan , Ehrhardt Christopher J. 
Published: April 2023

AbstractAnalysis of DNA mixtures from sexual assault evidence is an ongoing challenge for DNA casework laboratories. There is a significant need for new techniques that can provide information as to the source of DNA, particularly for sexual assault samples that do not involve semen. The goal of this study was to develop a new biological signature system that provides additional probative value to samples comprised of mixtures of epidermal and vaginal cells, as may be observed in cases involving digital penetration. Signatures were based on morphological and autofluorescence properties of individual cells collected through Imaging Flow Cytometry (IFC). Comparisons to reference cell populations from vaginal tissue and epidermal cells collected from hands showed strong multivariate differences across >80 cellular measurements. These differences were used to build a predictive framework for classifying unknown cell populations as originating from epithelial cells associated with digital penetration or epidermal tissue. As part of the classification scheme, posterior probabilities of specific tissue group membership were calculated for each cell, along with multivariate similarity to that tissue type. We tested this approach on cell populations from reference tissue as well as mock casework samples involving digital penetration. Many more cells classifying as non-epidermal tissue were detected in digital penetration samples than control hand swabbings. Minimum interpretation thresholds were developed to minimize false positives; these thresholds were also effective when screening licked hands, indicating the potential utility of this method for a variety of biological mixture types and depositional events relevant to forensic casework. Results showed that samples collected subsequent to digital penetration possessed markedly higher numbers of cells classifying as vaginal tissue as well as higher posterior probabilities for vaginal tissue (≥ 0.90) compared to cell populations collected from hands without prior contact with vaginal tissue. Additionally, digital penetration cell populations may be resolved from saliva cell populations and other non-target tissue types.