bluuebunny/crossref_metadata_2025_split huggingface dataset:
National adherence to the ASGE-SAGES guidelines for managing suspected choledocholithiasis: An EAST multicenter study
Authors: Tracy Brett M. , Poulose Benjamin K. , Paterson Cameron W. , Mendoza April E. , Gaitanidis Apostolos , Saxe Jonathan M. , Young Andrew J. , Zielinski Martin D. , Sims Carrie A. , Gelbard Rondi B. 
Published: November 2021

BACKGROUND
The American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons provide guidelines for managing suspected common bile duct (CBD) stones. We sought to evaluate adherence to the guidelines among patients with choledocholithiasis and/or acute biliary pancreatitis (ABP) and to evaluate the ability of these guidelines to predict choledocholithiasis.

METHODS
We prospectively identified patients undergoing same-admission cholecystectomy for choledocholithiasis and/or ABP from 2016 to 2019 at 12 United States medical centers. Predictors of suspected CBD stones were very strong (CBD stone on ultrasound; bilirubin >4 mg/dL), strong (CBD > 6 mm; bilirubin ≥1.8 to ≤4 mg/dL), or moderate (abnormal liver function tests other than bilirubin; age >55 years; ABP). Patients were grouped by probability of CBD stones: high (any very strong or both strong predictors), low (no predictors), or intermediate (any other predictor combination). The management of each probability group was compared with the recommended management in the guidelines.

RESULTS
The cohort was comprised of 844 patients. High-probability patients had 64.3% (n = 238/370) deviation from guidelines, intermediate-probability patients had 29% (n = 132/455) deviation, and low-probability patients had 78.9% (n = 15/19) deviation. Acute biliary pancreatitis increased the odds of deviation for the high- (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.06–2.8; p = 0.03) and intermediate-probability groups (OR, 1.6; 95% CI, 1.07–2.42; p = 0.02). Age older than 55 years (OR, 2.19; 95% CI, 1.4–3.43; p < 0.001) also increased the odds of deviation for the intermediate group. A CBD greater than 6 mm predicted choledocholithiasis in the high (adjusted OR (aOR), 2.16; 95% CI, 1.17–3.97; p = 0.01) and intermediate group (aOR, 2.78; 95% CI, 1.59–4.86; p < 0.001). Any very strong predictor (aOR, 2.43; 95% CI, 1.76–3.37; p < 0.0001) and both strong predictors predicted choledocholithiasis (aOR, 2; 95% CI, 1.35–2.96; p < 0.001).

CONCLUSION
Almost 45% of patients with suspected CBD stones were managed discordantly from the American Society for Gastrointestinal Endoscopy and Society of American Gastrointestinal and Endoscopic Surgeons guidelines. We believe these guidelines warrant revision to better reflect the ability of the clinical variables at predicting choledocholithiasis.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
Advanced neuroimaging techniques in epilepsy
Authors: Duncan John S. , Trimmel Karin 
Published: November 2021

Purpose of review
We review significant advances in epilepsy imaging in recent years.

Recent findings
Structural MRI at 7T with optimization of acquisition and postacquisition image processing increases the diagnostic yield but artefactual findings remain a challenge. MRI analysis from multiple sites indicates different atrophy patterns and white matter diffusion abnormalities in temporal lobe and generalized epilepsies, with greater abnormalities close to the presumed seizure source. Structural and functional connectivity relate to seizure spread and generalization; longitudinal studies are needed to clarify the causal relationship of these associations. Diffusion MRI may help predict surgical outcome and network abnormalities extending beyond the epileptogenic zone. Three-dimensional multimodal imaging can increase the precision of epilepsy surgery, improve seizure outcome and reduce complications. Language and memory fMRI are useful predictors of postoperative deficits, and lead to risk minimization. FDG PET is useful for clinical studies and specific ligands probe the pathophysiology of neurochemical fluxes and receptor abnormalities.

Summary
Improved structural MRI increases detection of abnormalities that may underlie epilepsy. Diffusion, structural and functional MRI indicate the widespread associations of epilepsy syndromes. These can assist stratification of surgical outcome and minimize risk. PET has continued utility clinically and for research into the pathophysiology of epilepsies.
Learning from the comorbidities of epilepsy
Authors: Shlobin Nathan A. , Sander Josemir W. 
Published: November 2021

Purpose of reviewComorbidities are a common feature in epilepsy, but neither the entire spectrum nor the significance of such comorbidities has been fully explored. We review comorbidities associated with epilepsy and their associated burden, provide an overview of relationships, and discuss a new conceptualization of the comorbidities.Recent findingsThe epidemiology of the comorbidities of epilepsy and effects on health outcomes, healthcare use, and healthcare expenditures have been partly delineated. Distinct mechanisms of the associations have been suggested but not entirely ascertained. Movement from conceptualizing epilepsy as a condition to a symptom-complex has occurred.SummaryComorbidities are common among people with epilepsy and are associated with poorer clinical outcomes and quality of life, greater use of health resources, and increased expenditure. Becoming aware of the associated mechanisms and their uncertainty is central to understanding the relationships between epilepsy and comorbid health conditions, which have implications for diagnosis and screening, medical management, and surgical management. Conceptualizing comorbidities of epilepsy as precipitating factors and epilepsy as the symptom will improve the understanding of epilepsy and catalyze research and improvements in clinical practice.
Anemia and Idiopathic Intracranial Hypertension: A Systematic Review and Meta-analysis
Authors: Yu Caberry W. , Waisberg Ethan , Kwok Jason M. , Micieli Jonathan A. 
Published: November 2021

Background:
Idiopathic intracranial hypertension (IIH) is a condition typically affecting young, obese women. Although anemia is recognized as a risk factor of IIH from case reports, their relationship remains controversial as several comparative studies showed no significant association. This study aimed to examine the relationship between anemia and IIH.

Methods:
MEDLINE, Embase, Cochrane Library, and grey literature were searched to September 2020. Primary studies on patients with diagnoses of anemia of any kind and IIH were included. Primary outcomes included the total number of cases of anemia and IIH. A meta-analysis on the prevalence of anemia in IIH compared with control patients was conducted. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to rate the quality of evidence.

Results:
Overall, 62 cases and 5 observational or case–control studies were included. Pooled incidence of anemia in patients with IIH was 195/1,073 (18.2%). Patients with IIH (n = 774) had a significantly higher prevalence of anemia compared with controls (n = 230,981) (RR 1.44 [95% confidence interval 1.08–1.92]). Patients were 67.7% females and had a mean age of 22.4 years. The mean opening pressure was 37.9 cmH2O. Anemia was most commonly caused by iron deficiency (51.6%) and aplastic anemia (19.4%). Most patients (59.7%) showed improvement or resolution with anemia treatment only without intracranial pressure-lowering therapy. Evidence was limited because of high risk of reporting bias from the large number of case reports and case–control studies.

Conclusions:
Anemia is significantly more common in IIH compared with control patients, and case reports suggest a direct relationship. Complete blood counts should be considered in all patients with papilledema, particularly in atypical presentations (male, nonobese, nonperipapillary retinal hemorrhages, prominent risk factor for anemia) or in treatment-refractory IIH.
Sociodemographic and cultural determinants of mood disorders
Authors: D’cruz Migita M. , Chaturvedi Santosh K. 
Published: November 2021

Purpose of review
The present review aims to examine, summarize and update information on the sociodemographic and cultural determinants of mood disorders.

Recent findings
Known sociodemographic and cultural determinants continue to be good predictors of the risk of developing a mood disorder over the lifetime. Polygenic risk scores do not appear to offer any advantages over these determinants at present. There is also new and emerging understanding of the role of lifestyle and environmental factors in mediating vulnerability to mood disorder. The influence of ethnicity and migration, on the other hand, is far more complex than initially envisaged.

Summary
Recent evidence on sociodemographic determinants of mood disorders confirms associations derived from existing literature. There is also new and emerging evidence on how quality of sleep, diet and the environment influence risk of mood disorders. Culture and ethnicity, depending on context, may contribute to both vulnerability and resilience. Socioeconomic deprivation may be the final common pathway through which several sociodemographic and cultural determinants of mood disorders act.
Immune escape facilitation by mutations of epitope residues in RdRp of SARS-CoV-2
Authors: Gupta Aayatti Mallick , Mandal SasthiCharan , Mandal Sukhendu , Chakrabarti Jaydeb 
Published: November 2021

ABSTRACTSARS-CoV-2 has considerably higher mutation rate. SARS-CoV-2 possesses a RNA dependent RNA polymerase (RdRp) which helps to replicate its genome. The mutation P323L in RdRp is associated with the loss of a particular epitope (321-327) from this protein which may influence the pathogenesis of the concern SARS-CoV-2 through the development of antibody escape variants. We consider the effect of mutations in some of the epitope regions including the naturally occurring mutation P323L on the structure of the epitope and their interface with paratope using all-atom molecular dynamics (MD) simulation studies. P323L mutations cause conformational changes in the epitope region by opening up the region associated with increase in the radius of gyration and intramolecular hydrogen bonds, making the region less accessible. Moreover, the fluctuations in the dihedral angles in the epitope:paratope (IgG) interface increase which destabilize the interface. Such mutations may help in escaping antibody mediated immunity of the host.
The impact of Fisher’s Reproductive Compensation on raising equilibrium frequencies of semi-dominant, non-lethal mutations under mutation/selection balance
Authors: Hastings Ian M. 
Published: November 2021

AbstractFisher’s reproductive compensation (fRC) occurs when a species’ demography means the death of an individual allows increased survival of his/her relatives, usually assumed to be full sibs. This likely occurs in many species, including humans. Several important recessive human genetic diseases cause early foetal/infant death allowing fRC to act on these mutations. The impact of fRC on these genetic conditions has been calculated and shown to be substantial as quantified by ω, the fold increase in equilibrium frequencies of the mutation under fRC compared to its absence i.e. ω=1.22 and ω=1.33 for autosomal and sex-linked loci, respectively. However, the impact of fRC on the frequency of the much large class of semi-dominant, non-lethal mutations is unknown. This is calculated here by a mixture of simulation and algebra and shown that ω=2-h*s and ω≈2-0.19s-0.85h*s for autosomal and sex-linked loci respectively where h is dominance (varied between 0.05 and 0.95) and s is selection coefficient (varied between 0.05 and 0.9). These results show that the actions of fRC can almost double equilibrium frequency of mutations with low values of h and/or s. The dynamics of fRC acting on this type of mutation are also identified and discussed.
Perceived facial happiness during conversation correlates with insular and hypothalamus activity for humans, not robots: An investigation of the somatic marker hypothesis applied to social interactions
Authors: Chaminade Thierry , Spatola Nicolas 
Published: November 2021

AbstractThe somatic marker hypothesis posits that perceiving emotions entails reenacting markers of self emotions, in particular in the autonomous nervous system. Well studied in decision-making tasks, it has not been tested in a social cognitive neuroscience framework, and in particular for the automatic processing of positive emotions during natural interactions. Here, we address this question using a unique corpus of brain activity recorded during unconstrained conversations between participants and a human or a humanoid robot. fMRI recordings are used to test whether activity in the most important brain regions in relation to the autonomic system, the amygdala, hypothalamus and insula, is affected by the level of happiness expressed by the human and robot agents. Results indicate that for the hypothalamus and the insula, in particular the anterior agranular region strongly involved in processing social emotions, activity in the right hemisphere increases with the level of happiness expressed by the human, but not the robot. Results indicate that perceiving positive emotions in social interactions induces the local brain responses predicted by the somatic marker hypothesis, but only when the interacting agent is a real human.
Effect of therapeutic ultrasound on the mechanical and biological properties of fibroblasts
Authors: Cárdenas-Sandoval Rosy P. , Pastrana-Rendón Homero F. , Ávila-Bernal Alba G. , Ramírez-Martínez Angélica M. , Navarrete-Jimenez Myriam L. , Ondo-Mendez Alejandro O. , Garzón-Alvarado Diego A. 
Published: November 2021

AbstractConventional doses of therapeutic ultrasound alter the mechanical behavior of ligament fibroblasts to improve the regenerative and remodeling stages of the wound healing process. Using a multidisciplinary approach, we applied ultrasound doses of 1.0 and 2.0 W/cm2at 1 MHz frequency for five days on ligament fibroblasts. Atomic force microscopy showed a decrease in cell elastic modulus for both doses, but the treated cells were still viable based on flow cytometry. Finite element method analysis exhibited visible cytoskeleton displacements and decreased harmonics in treated cells. Colorimetric assay revealed increased cell proliferation, while scratch assay showed increased migration at low doses. An increase in collagen and fibronectin was detected by enzyme-linked immunoassay at high doses, and β-actin expression for both treatments was visualized through immunofluorescence imaging. Both doses of ultrasound altered the fibroblast mechanical properties due to cytoskeletal reorganization and enhanced the early and late stages of cell repair.
A computationally efficient clustering linear combination approach to jointly analyze multiple phenotypes for GWAS
Authors: Wang Meida , Zhang Shuanglin , Sha Qiuying 
Published: November 2021

AbstractThere has been an increasing interest in joint analysis of multiple phenotypes in genome-wide association studies (GWAS) because jointly analyzing multiple phenotypes may increase statistical power to detect genetic variants associated with complex diseases or traits. Recently, many statistical methods have been developed for joint analysis of multiple phenotypes in genetic association studies, including the Clustering Linear Combination (CLC) method. The CLC method works particularly well with phenotypes that have natural groupings, but due to the unknown number of clusters for a given data, the final test statistic of CLC method is the minimum p-value among all p-values of the CLC test statistics obtained from each possible number of clusters. Therefore, a simulation procedure must be used to evaluate the p-value of the final test statistic. This makes the CLC method computationally demanding. We develop a new method called computationally efficient CLC (ceCLC) to test the association between multiple phenotypes and a genetic variant. Instead of using the minimum p-value as the test statistic in the CLC method, ceCLC uses the Cauchy combination test to combine all p-values of the CLC test statistics obtained from each possible number of clusters. The test statistic of ceCLC approximately follows a standard Cauchy distribution, so the p-value can be obtained from the cumulative density function without the need for the simulation procedure. Through extensive simulation studies and application on the COPDGene data, the results demonstrate that the type I error rates of ceCLC are effectively controlled in different simulation settings and ceCLC either outperforms all other methods or has statistical power that is very close to the most powerful method with which it has been compared.
A flexible workflow for building spectral libraries from narrow window data independent acquisition mass spectrometry data
Authors: Heil Lilian R. , Fondrie William E. , McGann Christopher D. , Federation Alexander J. , Noble William S. , MacCoss Michael J. , Keich Uri 
Published: November 2021

AbstractAdvances in library-based methods for peptide detection from data independent acquisition (DIA) mass spectrometry have made it possible to detect and quantify tens of thousands of peptides in a single mass spectrometry run. However, many of these methods rely on a comprehensive, high quality spectral library containing information about the expected retention time and fragmentation patterns of peptides in the sample. Empirical spectral libraries are often generated through data-dependent acquisition and may suffer from biases as a result. Spectral libraries can be generated in silico but these models are not trained to handle all possible post-translational modifications. Here, we propose a false discovery rate controlled spectrum-centric search workflow to generate spectral libraries directly from gas-phase fractionated DIA tandem mass spectrometry data. We demonstrate that this strategy is able to detect phosphorylated peptides and can be used to generate a spectral library for accurate peptide detection and quantitation in wide window DIA data. We compare the results of this search workflow to other library-free approaches and demonstrate that our search is competitive in terms of accuracy and sensitivity. These results demonstrate that the proposed workflow has the capacity to generate spectral libraries while avoiding the limitations of other methods.
The effects of sequence length and composition of random sequence peptides on the growth of E. coli cells
Authors: Fajardo C. R. Johana , Tautz Diethard 
Published: November 2021

AbstractWe study the potential for the de novo evolution of genes from random nucleotide sequences using libraries of E. coli expressing random sequence peptides. We assess the effects of such peptides on cell growth by monitoring frequency changes of individual clones in a complex library through four serial passages. Using a new analysis pipeline that allows to trace peptides of all lengths, we find that over half of the peptides have consistent effects on cell growth. Across nine different experiments, around 16 % of clones increase in frequency and 36 % decrease, with some variation between individual experiments. Shorter peptides (8–20 residues), are more likely to increase in frequency, longer ones are more likely to decrease. GC content, amino acid composition, intrinsic disorder and aggregation propensity show slightly different patterns between peptide groups. Sequences that increase in frequency tend to be more disordered with lower aggregation propensity. This coincides with the observation that young genes with more disordered structures are better tolerated in genomes. Our data indicate that random sequences can be a source of evolutionary innovation, since a large fraction of them are well tolerated by the cells or can provide a growth advantage.
Cholinergic control of striatal GABAergic microcircuits
Authors: Kocaturk S. , Shah F. , Guven B. , Tepper J.M. , Assous M. 
Published: November 2021

AbstractCholinergic interneurons (CINs) are essential elements of striatal circuits and behaviors. While acetylcholine signaling via muscarinic receptors (mAChRs) have been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on GABAergic interneurons (GINs) are equally critical. One demonstration is that CINs stimulation induces large disynaptic inhibition of SPNs mediated by nAChR activation of striatal GINs. While these circuits are ideally positioned to modulate striatal output activity, the neurons involved are not definitively identified due largely to an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs optogenetic activation evokes an intricate dual mechanism involving co-activation of pre- and postsynaptic mAChRs and nAChRs on four GINs populations. Using multi-optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs likely via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.
The energy requirements of ion homeostasis determine the lifespan of starving bacteria
Authors: Schink Severin , Polk Mark , Athaide Edward , Mukherjee Avik , Ammar Constantin , Liu Xili , Oh Seungeun , Chang Yu-Fang , Basan Markus 
Published: November 2021

AbstractThe majority of microbes on earth, whether they live in the ocean, the soil or in animals, are not growing, but instead struggling to survive starvation1–6. Some genes and environmental conditions affecting starvation survival have been identified7–13, but despite almost a century of study14–16, we do not know which processes lead to irreversible loss of viability, which maintenance processes counteract them and how lifespan is determined from the balance of these opposing processes. Here, we used time-lapse microscopy to capture and characterize the cell death process of E. coli during carbon starvation for the first time. We found that a lack of nutrients results in the collapse of ion homeostasis, triggering a positive-feedback cascade of osmotic swelling and membrane permeabilization that ultimately results in lysis. Based on these findings, we hypothesized that ion transport is the major energetic requirement for starving cells and the primary determinant of the timing of lysis. We therefore developed a mathematical model that integrates ion homeostasis and ‘cannibalistic’ nutrient recycling from perished cells16,17 to predict lifespan changes under diverse conditions, such as changes of cell size, medium composition, and prior growth conditions. Guided by model predictions, we found that cell death during starvation could be dramatically slowed by replacing inorganic ions from the medium with a non-permeating osmoprotectant, removing the cost of ion homeostasis and preventing lysis. Our quantitative and predictive model explains how survival kinetics are determined in starvation and elucidates the mechanistic underpinnings of starvation survival.