bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deaza-modification of MR1 ligands modulates recognition by MR1-restricted T cells
Authors: Jin Haihong , Ladd Nicole A. , Peev Andrew M. , Swarbrick Gwendolyn M. , Cansler Meghan , Null Megan , Boughter Christopher T. , McMurtrey Curtis , Nilsen Aaron , Dobos Karen M. , Hildebrand William H. , Lewinsohn Deborah A. , Adams Erin J. , Lewinsohn David M. , Harriff Melanie J. 
Published: December 2022

AbstractMR1-restricted T (MR1T) cells recognize microbial small molecule metabolites presented on the MHC Class I-like molecule MR1 and have been implicated in early effector responses to microbial infection. As a result, there is considerable interest in identifying chemical properties of metabolite ligands that permit recognition by MR1T cells, for consideration in therapeutic or vaccine applications. Here, we made chemical modifications to known MR1 ligands to evaluate the effect on MR1T cell activation. Specifically, we modified 6,7-dimethyl-8-d-ribityllumazine (DMRL) to generate 6,7-dimethyl-8-d-ribityldeazalumazine (DZ), and then further derivatized DZ to determine the requirements for retaining MR1 surface stabilization and agonistic properties. Interestingly, the IFN-γ response toward DZ varied widely across a panel of T cell receptor (TCR)-diverse MR1T cell clones; while one clone was agnostic toward the modification, most displayed either an enhancement or depletion of IFN-γ production when compared with its response to DMRL. To gain insight into a putative mechanism behind this phenomenon, we used in silico molecular docking techniques for DMRL and its derivatives and performed molecular dynamics simulations of the complexes. In assessing the dynamics of each ligand in the MR1 pocket, we found that DMRL and DZ exhibit differential dynamics of both the ribityl moiety and the aromatic backbone, which may contribute to ligand recognition. Together, our results support an emerging hypothesis for flexibility in MR1:ligand-MR1T TCR interactions and enable further exploration of the relationship between MR1:ligand structures and MR1T cell recognition for downstream applications targeting MR1T cells.
A genome-wide association study of tinnitus reveals shared genetic links to neuropsychiatric disorders
Authors: Bhatt Ishan Sunilkumar , Wilson Nicholas , Dias Raquel , Torkamani Ali 
Published: December 2022

AbstractTinnitus, a phantom perception of sound in the absence of any external sound source, is a prevalent health condition often accompanied by psychiatric comorbidities. Recent genome-wide association studies (GWAS) highlighted a polygenic nature of tinnitus susceptibility. A shared genetic component between tinnitus and psychiatric conditions remains elusive. Here we present a GWAS using the UK Biobank to investigate the genetic processes linked to tinnitus and tinnitus-related distress, followed by gene-set enrichment analyses. The UK Biobank sample comprised 132,438 individuals with tinnitus and genotype data. Among the study sample, 38,525 individuals reported tinnitus, and 26,889 participants mentioned they experienced tinnitus-related distress in daily living. The genome-wide association analyses were conducted on tinnitus and tinnitus-related distress. We conducted enrichment analyses using FUMA to further understand the genetic processes linked to tinnitus and tinnitus-related distress. A genome-wide significant locus (lead SNP: rs71595470) for tinnitus was obtained in the vicinity of GPM6A. Nineteen independent loci reached suggestive association with tinnitus. Fifteen independent loci reached suggestive association with tinnitus-related distress. The enrichment analysis revealed a shared genetic component between tinnitus and psychiatric traits, such as bipolar disorder, feeling worried, cognitive ability, fast beta electroencephalogram, and sensation seeking. Metabolic, cardiovascular, hematological, and pharmacological gene sets revealed a significant association with tinnitus. Anxiety and stress-related gene sets revealed a significant association with tinnitus-related distress. The GWAS signals for tinnitus were enriched in the hippocampus and cortex, and for tinnitus-related distress were enriched in the brain and spinal cord. This study provides novel insights into genetic processes associated with tinnitus and tinnitus-related distress and demonstrates a shared genetic component underlying tinnitus and psychiatric conditions. Further collaborative attempts are necessary to identify genetic components underlying the phenotypic heterogeneity in tinnitus and provide biological insight into the etiology.
Pictograms to aid laypeople in identifying the addictiveness of gambling products (PictoGRRed study)
Authors: Luquiens Amandine , Guillou Morgane , Giustiniani Julie , Barrault Servane , Caillon Julie , Delmas Helena , Achab Sophia , Bento Bruno , Billieux Joël , Brevers Damien , Brody Aymeric , Brunault Paul , Challet-Bouju Gaëlle , Chóliz Mariano , Clark Luke , Cornil Aurélien , Costes Jean-Michel , Devos Gaetan , Díaz Rosa , Estevez Ana , Grassi Giacomo , Hakansson Anders , Khazaal Yasser , King Daniel L. , Labrador Francisco , Lopez-Gonzalez Hibai , Newall Philip , Perales José C. , Ribadier Aurélien , Sescousse Guillaume , Sharman Stephen , Taquet Pierre , Varescon Isabelle , Von Hammerstein Cora , Bonjour Thierry , Romo Lucia , Grall-Bronnec Marie 
Published: December 2022

AbstractThe structural addictive characteristics of gambling products are important targets for prevention, but can be unintuitive to laypeople. In the PictoGRRed (Pictograms for Gambling Risk Reduction) study, we aimed to develop pictograms that illustrate the main addictive characteristics of gambling products and to assess their impact on identifying the addictiveness of gambling products by laypeople. We conducted a three-step study: (1) use of a Delphi consensus method among 56 experts from 13 countries to reach a consensus on the 10 structural addictive characteristics of gambling products to be illustrated by pictograms and their associated definitions, (2) development of 10 pictograms and their definitions, and (3) study in the general population to assess the impact of exposure to the pictograms and their definitions (n = 900). French-speaking experts from the panel assessed the addictiveness of gambling products (n = 25), in which the mean of expert’s ratings was considered as the true value. Participants were randomly provided with the pictograms and their definitions, or with a standard slogan, or with neither (control group). We considered the control group as representing the baseline ability of laypeople to assess the addictiveness of gambling products. Each group and the French-speaking experts rated the addictiveness of 14 gambling products. The judgment criterion was the intraclass coefficients (ICCs) between the mean ratings of each group and the experts, reflecting the level of agreement between each group and the experts. Exposure to the pictograms and their definition doubled the ability of laypeople to assess the addictiveness of gambling products compared with that of the group that read a slogan or the control group (ICC = 0.28 vs. 0.14 (Slogan) and 0.14 (Control)). Laypeople have limited awareness of the addictive characteristics of gambling products. The pictograms developed herein represent an innovative tool for universally empowering prevention and for selective prevention.
The uptake pattern of 18F-sodium fluoride radioligand in brain tissue after cerebral infarction
Authors: Kim Jeong-Min , Lee Reeree , Jeong Hae-Bong , Park Kwang-Yeol , Seok Ju Won 
Published: December 2022

AbstractPositron emission tomography with 18F-sodium fluoride (NaF) radioligand has been actively investigated in atherosclerosis research because it is known to detect microcalcification activity within atheroma. We studied whether NaF shows any uptake in the brain tissue of patients with acute ischemic stroke. This is a post-hoc analysis of previously reported cerebral atherosclerosis research with positron emission tomography which applied the two radioligands, 18F-fluorodeoxyglucose and NaF for the detection of culprit atheroma among 20 acute cerebral infarction patients (mean age = 75.1 ± 9.0 years; 10 women). In this study, we measured the maximum and mean standardized uptake value (SUVmax and SUVmean) of NaF uptake level in the cerebral infarct region between lesions with and without diffusion weighted image (DWI) positivity, indicating acute ischemic cell death. Correlation analysis was performed between NaF uptake levels and imaging and clinical variables, including neurological severity. The NaF uptake levels were significantly higher in DWI positive lesions than in negative lesions (SUVmax: 2.0 [0.60–4.2] versus 0.20 [0.10–0.40], p = 0.021 by Mann–Whitney U test). The intensity of NaF uptake (SUVmax) was significantly correlated with the initial neurological severity (Spearman's ρ = 0.579, p= 0.007) and white blood cell count (Spearman's ρ = 0.626, p p 0.003). During ischemic stroke NaF was concentrated in brain tissue undergoing acute cell death and its uptake intensity was correlated with neurological severity, suggesting that NaF could reflect acute ischemic cell death after stroke.
Global urban homogenization and the loss of emotions
Authors: Grêt-Regamey Adrienne , Galleguillos-Torres Marcelo 
Published: December 2022

AbstractUrban expansion is generating unprecedented homogenization of landscapes across the world. This uniformization of urban forms brings along dramatic environmental, social, and health problems. Reverting such processes requires activating people’s sense of place, their feeling of caring for their surroundings, and their community engagement. While emotions are known to have a modulating effect on behavior, their role in urban transformation is unknown. Drawing on large cognitive-psychological experiments in two countries, we demonstrate for the first time that urban homogenization processes lower people’s affective bounds to places and ultimately their intentions to engage with their neighbourhoods. The dulled emotional responses in peri-urban areas compared to urban and rural areas can be explained by lower social cohesion and place attachment. The findings highlight the significance of considering emotions in shaping just, equitable, sustainable, and resilient cities.
Binding affinity estimation from restrained umbrella sampling simulations
Authors: Govind Kumar Vivek , Polasa Adithya , Agrawal Shilpi , Kumar Thallapuranam Krishnaswamy Suresh , Moradi Mahmoud 
Published: December 2022

AbstractThe protein–ligand binding affinity quantifies the binding strength between a protein and its ligand. Computer modeling and simulations can be used to estimate the binding affinity or binding free energy using data- or physics-driven methods or a combination thereof. Here we discuss a purely physics-based sampling approach based on biased molecular dynamics simulations. Our proposed method generalizes and simplifies previously suggested stratification strategies that use umbrella sampling or other enhanced sampling simulations with additional collective-variable-based restraints. The approach presented here uses a flexible scheme that can be easily tailored for any system of interest. We estimate the binding affinity of human fibroblast growth factor 1 to heparin hexasaccharide based on the available crystal structure of the complex as the initial model and four different variations of the proposed method to compare against the experimentally determined binding affinity obtained from isothermal titration calorimetry experiments.
Speech Error Variability and Phonological Awareness in Preschoolers
Authors: Roepke Elizabeth , Brosseau-Lapré Françoise 
Published: December 2022

Purpose:
The purpose of this article was to investigate the relationship between speech error variability and phonological awareness.

Method:
This article begins with a narrative review of the theoretical interpretation of speech error variability. The post hoc exploratory analysis of the relationship between speech error variability and phonological awareness included 40 children: 20 with typical speech and language and 20 with speech sound disorder and typical language. Groups were matched on gender, age, maternal education, receptive and expressive vocabulary, nonverbal intelligence, and expressive morphosyntax. Multiple regression was used to identify the best fit model for the relationship between vocabulary, speech errors, and phonological awareness.

Results:
Segmental variability was associated with poor phonological awareness in preschool-aged children.

Conclusion:
Children with high levels of segmental variability have poor phonological awareness, likely due to unstable phonological representations.
Fatigue-Related Change in Surface Electromyographic Activities of the Perilaryngeal Muscles
Authors: Yiu Edwin M.-L. , Lau Gary W. H. , Wang Feifan 
Published: December 2022

Purpose:
This study set out to quantify the fatigue-related changes in surface electromyographic (sEMG) activities of the perilaryngeal muscles following a vocal loading task.

Method:

Thirty-six young healthy participants (
M
age
= 22.4 years) with normal voice performed karaoke singing for at least 100 min. Before the singing task, all participants underwent the sEMG measure and completed a Perceived Vocal Fatigue Score (P-VFS) questionnaire. After the singing task, all participants were immediately measured with the P-VFS again. Half of the participants were then measured for their sEMG immediately after their karaoke singing task, and the other half were given 20 min of rest before undertaking the sEMG measure. The P-VFS and the median frequency (MDF) of the sEMG signals collected from the suprahyoid, infrahyoid, and sternocleidomastoid muscles before and after the singing task were compared using a linear mixed-effects model.

Results:
All participants reported a perceived vocal fatigue after singing, with a significantly increased P-VFS. Compared with the presinging baseline, the MDF of the sEMG signals in perilaryngeal muscles was significantly lower immediately after the singing task. Such a significant difference was also found after 20 min following the singing task.

Conclusions:
The MDF analysis of the sEMG signals could identify and quantify the performance vocal fatigue contributed by perilaryngeal muscles following a vocal loading task. The findings also showed that such fatigue in perilaryngeal muscles, as far as sEMG activities are concerned, can last for at least 20 min.
Multi‐feature fusion attention network for single image super‐resolution
Authors: Chen Jiacheng , Wang Wanliang , Xing Fangsen , Tu Hangyao 
Published: December 2022

AbstractSingle Image Super‐Resolution algorithms have made enormous progress in recent years. However, many previous Convolution Neural Network (CNN) based Super‐Resolution algorithms only stack uniform convolution layers of fixed kernel size, and frequently ignore inherent multi‐scale properties of the images, resulting in unsatisfactory reconstruction results. Here, a multi‐feature fusion attention network (MFFAN) is proposed for capturing information at diverse scales. MFFAN is composed of multiple efficient sparse residual group (ESRG) modules. Several multi‐scale feature fusion blocks (MSFFB) are constructed using a cascade manner in each ESRG module and it is capable of exploiting various cross scales information. Subsequently, a local‐global spatial attention block (LGSAB) is inserted at the tail of the ESRG module for further improving the interaction of inter‐pixel, which strengths essential features and suppresses irrelevant information. Additionally, owing to the fact that only feeding final output into the reconstruction layer has exacerbated the long‐range dependency problems, an enhanced hierarchy feature fusion block (EHFFB) is designed to fuse low‐level information and high‐level semantic information. Experiment results indicate that the proposed MFFAN is competitive in comparison to several state‐of‐the‐art algorithms.
Infantile Spasms without Hypsarrhythmia and Paroxysmal Eye–Head Movements in an Infant with a Pyridoxine-Dependent Epilepsy due to PLPBP/PLPHP Deficiency
Authors: Kalser Judith , Giuliano Fabienne , Peralta Maria , Plecko Barbara , Bölsterli Bigna K. 
Published: December 2022

AbstractTo describe a new phenotype and the diagnostic workup of a vitamin-B6-dependent epilepsy due to pyridoxal 5′-phosphate-binding protein (PLPBP) deficiency in an infant with early-onset epilepsy at the age of 5 years 6 months. Following immediate and impressive clinical response to treatment with pyridoxine, metabolic screening for vitamin-B6-dependent epilepsies and targeted next-generation sequencing (NGS)-based gene panel analysis were performed. Potentially pathogenic variants were confirmed by Sanger sequencing in the patient, and variants were analyzed in both parents to confirm biallelic inheritance. The clinical phenotype and course of disease were compared to the 44 cases reported in the literature, harboring variants in pyridoxal phosphate homeostasis protein (PLPHP) and with cases of vitamin-B6-dependent epilepsy due to other known causative genes. Levels of alpha-aminoadipic semialdehyde in urine and amino acids were normal. Two inherited pathogenic variations in PLPHP were found in compound heterozygosity, including one novel deletion. We here describe a previously unreported individual harboring biallelic pathogenic PLPHP variants presenting with paroxysmal eye–head movements followed by epileptic spasms and an almost normal interictal electroencephalogram, thus expanding the clinical spectrum of PLPBP deficiency. This warrants consideration of vitamin-B6-dependent epilepsies in patients with early-onset epilepsy, including epileptic spasms, and eye movement disorders also beyond the neonatal period even when metabolic screening for vitamin-B6-dependent epilepsies is negative. PLPHP should be included systematically in NGS epilepsy gene panels.
Forty-Eight Hour Ex Vivo Perfusion and Two-Hour Simulated Reperfusion after a Major Traumatic Upper Extremity Amputation
Authors: Stögner Viola Antonia , Neubert Lavinia , Kaltenborn Alexander , Wiegmann Bettina , Krettek Christian , Vogt Peter Maria , Krezdorn Nicco 
Published: December 2022

Abstract
Background Extremity replantation as well as allotransplantation aim to restore form and function of the amputated limb. Both approaches, however, are clearly limited by the ischemic time. Ex vivo perfusion (EVP), already well-established in the field of solid organ transplantation, represents a promising tool to overcome this restriction.
Methods We have currently established the technical requirements to provide EVP to severed limbs in a clinical hospital setting and hereby report of a 48-hour hypothermic EVP (EVP48) of an upper extremity amputated at the level of the proximal humerus, followed by a 2-hour simulated reperfusion (2SR) with donor blood.
Results Muscle biopsies revealed histopathologically well preserved, vital muscle tissue after EVP24, and partially grouped muscle fiber necrosis with predominantly vital muscle tissue after EVP48 and 2SR. Analyses of perfusate samples showed a marked decline of biochemical muscle damage markers during EVP48. Cytokine analysis disclosed an isolated increase of the proinflammatory cytokines, interleukine-6, monocyte chemotactic protein-1, and interferon-γ, during EVP and 2SR. Magnetic resonance imaging, performed after EVP48, indicated partial muscle necrosis of the intrinsic hand muscles only, while no signs for infection or inflammation were present.
Conclusion Our single case experience shows the general feasibility of an amputated limb ex vivo salvage perfusion setting to allow for delayed replantation up to 24 hours. Nevertheless, an accurate prior planning is crucial to ensure successful implementation of EVP in the acute clinical setting.
Evaluation of an Online Decision Aid for Selection of Contraceptive Methods
Authors: Redman Molly , Brian Jennifer , Wang Dongwen 
Published: December 2022

Abstract
Objectives Knowledge gaps in contraceptives led to their low adoption rates and misuse in young women. The existing online contraception decision aids missed certain decision factors deemed important to college-aged women and did not consistently provide clear and accurate recommendations. To address the needs of young women and the limitations in current tools, we developed a prototype contraception decision aid, My Contraceptive Choice (MCC). This article reports an evaluation study of the MCC tool.
Methods We conducted a mixed methods study: (1) to assess MCC's usefulness and usability through an online survey and a follow-up focus group, and (2) to provide a quantitative examination on the recommendations generated by MCC to match with individual user's needs and preferences through simulated test cases.
Results The survey of 150 college-aged women showed very positive responses (reflecting personal preferences, 75%; helping people learn more about birth control methods, 88%; easy to navigate, 91%). The follow-up focus group of 10 survey participants reconfirmed most findings from the survey and provided detailed feedback on certain system functions, such as the inclusion of an important decision factor of weight gain and the efficient hybrid design to integrate the customized recommendations with the side-by-side comparison of all contraceptive methods. Simulated test cases showed that the MCC tool achieved an accuracy of 72% in addressing user preferences and an accuracy of 72% in satisfying user needs, which were significantly better than the existing Planned Parenthood tool.
Conclusion The initial evaluations suggest that the MCC tool has achieved good levels of usefulness, usability, and appropriate recommendations to address user needs and preferences. Future research is required to assess the performance of the MCC tool in naturalistic settings and to examine the generalizability of the findings to other user populations.
Oncological Outcomes of Nipple-Sparing Mastectomy in an Unselected Population Evaluated in a Single Center
Authors: Cavalcante Francisco Pimentel , Araújo Mirella Macedo Parente , Veras Igor Moreira , Freitas-Junior Ruffo 
Published: December 2022

Abstract
Objective Nipple-sparing mastectomy (NSM) has been traditionally used in selected cases with tumor-to-nipple distance > 2 cm and negative frozen section of the base of the nipple. Recommending NSM in unselected populations remains controversial. The present study evaluated the oncological outcomes of patients submitted to NSM in an unselected population seen at a single center.
Methods This retrospective cohort study included unselected patients with invasive carcinoma or ductal carcinoma in situ (DCIS) who underwent NSM in 2010 to 2020. The endpoints were locoregional recurrence, disease-free survival (DFS), and overall survival (OS), irrespective of tumor size or tumor-to-nipple distance.
Results Seventy-six patients (mean age 46.1 years) (58 invasive carcinomas/18 DCIS) were included. The most invasive carcinomas were hormone-positive (60%) (HER2 overexpression: 24%; triple-negative: 16%), while 39% of DCIS were high-grade. Invasive carcinomas were T2 in 66% of cases, with axillary metastases in 38%. Surgical margins were all negative. All patients with invasive carcinoma received systemic treatment and 38% underwent radiotherapy. After a mean of 34.8 months, 3 patients with invasive carcinoma (5.1%) and 1 with DCIS (5.5%) had local recurrence. Two patients had distant metastasis and died during follow-up. The 5-year OS and DFS rates for invasive carcinoma were 98% and 83%, respectively.
Conclusion In unselected cases, the 5-year oncological outcomes following NSM were found to be acceptable and comparable to previous reports. Further studies are required.