bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of orthodontic gap closure versus prosthetic replacement of missing maxillary lateral incisor on dental arch relationships and symmetry on 212 cleft patients: a retrospective study Missing lateral incisor gap in cleft patients (39/40 characters max)
Authors: QUENEL Léonie , KERIBIN Pierre , DURAND Thomas , SALAGNAC Jean-Michel , PERRIN Jean-Philippe , DELAIRE Jean , MERCIER Jacques , TALMANT Jean-Claude , CORRE Pierre , BERTIN Helios 
Published: July 2022

Background:
Maxillary lateral incisors (MLI) are frequently missing in cleft patients. The aim of this study was to assess how orthodontic gap closure or prosthetic rehabilitation of the missing MLI affected the dental arch relationships and symmetry at the end of treatment. We also aimed to determine the impact of the level of oral hygiene on the decision made to manage the missing MLI gap.

Methods:
A descriptive, retrospective cohort study including all cleft patients born between 1980 and 1999 treated at Nantes Cleft Center was performed. Patients presenting unilateral or bilateral missing MLI were reviewed. Data about management of the missing MLI gap, dental arch relationships, symmetry and level of oral hygiene were collected.

Results:
Four hundred and eighty-six cleft patients were reviewed, including 212 patients with unilateral or bilateral missing MLI. When compared to orthodontic gap closure, prosthetic replacement of the MLI gap was associated with better final dental arch relationships (59.8% vs. 10.3%; p<0.01) and better dental arch symmetry (88.1% vs. 44.0%; p<0.01) for unilateral missing MLI cases but not for bilateral missing MLI cases. A better level of oral hygiene was associated with more cases with prosthetic replacement for unilateral missing MLI cases (p=0.03) and had no impact for bilateral missing MLI cases.

Conclusion:
Prosthetic replacement of the missing MLI gap provided better functional and esthetic results for cleft patients presenting with unilateral missing MLI.
Prospective evaluation of the selective nonoperative management of abdominal stab wounds: When is it safe to discharge?
Authors: Owattanapanich Natthida , Cremonini Camilla , Schellenberg Morgan A. , Matsushima Kazuhide , Lewis Meghan R. , Lam Lydia , Martin Matthew J. , Inaba Kenji 
Published: July 2022

BACKGROUND
The optimal observation time required to exclude hollow viscus injury in patients undergoing selective nonoperative management (SNOM) for abdominal stab wounds (SWs) remains unclear. The aim of this study was to determine the safe period of observation required before discharge.

METHODS
In this prospective observational study, all patients who sustained an abdominal SW were screened for study inclusion (July 2018 to May 2021). The primary study outcome was time to SNOM failure, defined as the need for surgical intervention after an initial period of observation.

RESULTS
During the study period, 256 consecutive patients with an abdominal SW met the study criteria. The mean age was 33 (26–46) years, and 89% were male. Of all patients, 77% had single SW, and 154 (60%) had an anterior abdominal SW (most common site right upper quadrant, 31%). Forty-six (18%) underwent immediate laparotomy because of evisceration (59%), hemodynamic instability (33%), or peritonitis (24%). The remaining 210 patients (82%) were taken for computed tomography scan (n = 208 [99%]) or underwent clinical observation only (n = 2 [<1%]). Of the patients undergoing computed tomography scan, 27 (13%) triggered operative intervention, and 9 (4%) triggered angioembolization. The remaining 174 patients (83%) underwent SNOM. Of these, three patients (2%) failed SNOM and underwent laparotomy: two developed peritonitis at 10 and 20 hours after arrival, respectively, and at laparotomy had small bowel and gastric injuries. The third patient developed increasing leukocytosis but had nontherapeutic laparotomy.

CONCLUSION
Selective nonoperative management of stab wounds to the abdomen commonly avoids nontherapeutic operative intervention and its resultant complications. A small percentage of patients will fail SNOM, and therefore, close clinical observation of these patients in hospital is critical. All patients in this series who failed SNOM did so within 24 hours of presentation. Therefore, we recommend a period of 24 hours of close clinical monitoring to exclude a hollow viscus injury before discharge of patients with abdominal stab wounds who do not meet the criteria for immediate operative intervention.

LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level III.
Postsecondary Education and Late-life Cognitive Outcomes Among Black and White Participants in the Project Talent Aging Study
Authors: Thomas Marilyn D. , Calmasini Camilla , Seblova Dominika , Lapham Susan , Peters Kelly , Prescott Carol A. , Mangurian Christina , Glymour Medellena Maria , Manly Jennifer J. 
Published: July 2022

Background:
Higher education consistently predicts improved late-life cognition. Racial differences in educational attainment likely contribute to inequities in dementia risk. However, few studies of education and cognition have controlled for prospectively measured early-life confounders or evaluated whether the education late-life cognition association is modified by race/ethnicity.

Methods:
Among 2343 Black and White Project Talent Aging Study participants who completed telephone cognitive assessments, we evaluated whether the association between years of education and cognition (verbal fluency, memory/recall, attention, and a composite cognitive measure) differed by race, and whether these differences persisted when adjusting for childhood factors, including the cognitive ability.

Results:
In fully adjusted linear regression models, each additional year of education was associated with higher composite cognitive scores for Black [β=0.137; 95% confidence interval (CI)=0.068, 0.206] and White respondents (β=0.056; CI=0.034, 0.078) with an interaction with race (P=0.03). Associations between education and memory/recall among Black adults (β=0.036; CI=−0.037, 0.109) and attention among White adults (β=0.022; CI=−0.002, 0.046) were nonsignificant. However, there were significant race-education interactions for the composite (P=0.03) and attention measures (P<0.001) but not verbal fluency (P=0.61) or memory/recall (P=0.95).

Conclusion:
Education predicted better overall cognition for both Black and White adults, even with stringent control for prospectively measured early-life confounders.
Lesion network mapping for symptom localization: recent developments and future directions
Authors: Joutsa Juho , Corp Daniel T. , Fox Michael D. 
Published: July 2022

Purpose of review
Focal lesions causing specific neurological or psychiatric symptoms can occur in multiple different brain locations, complicating symptom localization. Here, we review lesion network mapping, a technique used to aid localization by mapping lesion-induced symptoms to brain circuits rather than individual brain regions. We highlight recent examples of how this technique is being used to investigate clinical entities and identify therapeutic targets.

Recent findings
To date, lesion network mapping has successfully been applied to more than 40 different symptoms or symptom complexes. In each case, lesion locations were combined with an atlas of human brain connections (the human connectome) to map heterogeneous lesion locations causing the same symptom to a common brain circuit. This approach has lent insight into symptoms that have been difficult to localize using other techniques, such as hallucinations, tics, blindsight, and pathological laughter and crying. Further, lesion network mapping has recently been applied to lesions that improve symptoms, such as tremor and addiction, which may translate into new therapeutic targets.

Summary
Lesion network mapping can be used to map lesion-induced symptoms to brain circuits rather than single brain regions. Recent findings have provided insight into long-standing clinical mysteries and identified testable treatment targets for circuit-based and symptom-based neuromodulation.
Neural underpinnings of action adaptation in the subthalamic nucleus
Authors: Herz Damian M. , Bange Manuel , Gonzalez-Escamilla Gabriel , Auer Miriam , Muthuraman Muthuraman , Bogacz Rafal , Groppa Sergiu , Brown Peter 
Published: July 2022

AbstractAdapting our actions to changing goals and environments is central to intelligent behavior. There is substantial evidence that the basal ganglia play a crucial role in reinforcing actions that have led to favorable outcomes. However, little is known about the neural mechanisms underlying action adaptation following unfavorable outcomes when change is warranted. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus (STN), a core area of the basal ganglia, in patients with Parkinson’s disease using deep brain stimulation electrodes. During a task where patients continuously had to adapt their force depending on changing action-value associations, decreases in STN beta (13-30 Hz) activity in two critical time windows were associated with poorer outcomes and stronger action adaptation. STN stimulation reduced beta activity and led to stronger action adaptation if applied within the time windows when STN activity reflected action evaluation and adaptation. These results suggest that dynamic modulation of STN activity facilitates adaptive behavior.
Major Histocompatibility Complex (MHC) I-induced Endoplasmic Reticulum (ER) Stress mediates the secretion of pro-inflammatory muscle-derived cytokines
Authors: Thoma Anastasia , Earl Kate E. , Cooper Robert G. , Goljanek-Whysall Katarzyna , Lightfoot Adam P. 
Published: July 2022

ABSTRACTMajor histocompatibility complex (MHC) I is an important component of intracellular antigen presentation. However, improper expression of MHC I upon the cell surface has been associated with several autoimmune diseases. Myositis is a rare acquired autoimmune diseases which targets skeletal muscle, and MHC I overexpression on the surface of muscle fibres and immune cell infiltration are clinical hallmarks. MHC I overexpression may have an important pathogenic role, mediated by the activation of the endoplasmic reticulum (ER) stress response. Given the evidence that muscle is a diverse source of cytokines, we aimed to investigate whether MHC I overexpression can modify the profile of muscle-derived cytokines and what role the ER stress pathway may play. Using C2C12 myoblasts we overexpressed MHC I with a H-2kb vector in the presence or absence of salubrinal an ER stress pathway modifying compound. MHC I overexpression induced ER stress pathway activation and elevated cytokine gene expression. MHC I overexpression caused significant release of cytokines and chemokines, which was attenuated in the presence of salubrinal. Conditioned media from MHC I overexpressing cells induced in vitro T-cell chemotaxis, atrophy of healthy myotubes and modified mitochondrial function, features which were attenuated in the presence of salubrinal. Collectively, these data suggest that MHC I overexpression can induce pro-inflammatory cytokine/chemokine release from C2C12 myoblasts, a process which appears to be mediated in-part by the ER stress pathway.
Genome-wide determination of barriers to horizontal gene transfer
Authors: Burch Christina L. , Romanchuk Artur , Kelly Michael , Wu Yingfang , Jones Corbin D. 
Published: July 2022

AbstractHorizontal gene transfer (HGT) is a major contributor to bacterial genome evolution, generating phenotypic diversity, driving the expansion of protein families, and facilitating the evolution of new phenotypes, new metabolic pathways, and new species. Comparative studies of gene gain in bacteria suggest that the frequency with which individual genes successfully undergo HGT varies considerably and may be associated with the number of protein-protein interactions in which the gene participates—its connectivity. Two non-exclusive hypotheses have emerged to explain why transferability should decrease with connectivity: the Complexity Hypothesis (Jain, Rivera, & Lake, 1999) and the Balance Hypothesis (Papp, Pál, & Hurst, 2003). These hypotheses predict that the functional costs of HGT arise from a failure of divergent homologues to make normal protein-protein interactions or from gene mis-expression, respectively. Here we describe genome-wide assessments of these hypotheses in which we used 74 existing prokaryotic whole genome shotgun libraries to estimate rates of horizontal transfer of genes from taxonomically diverse prokaryotic donors into E. coli. We show that transferability declines as connectivity increases, but that this effect is driven primarily by the ribosomal genes. We also show that transferability declines as the divergence (% amino acid difference) between donor and recipient orthologs increases and that this effect of divergence increases with connectivity. We explain how these results, even the stronger effect of connectivity on the transferability of ribosomal compared to non-ribosomal genes, provide strong support for both the Balance and Complexity Hypotheses.Significance StatementComparisons between prokaryotic genomes consistently show that genes with informational functions, e.g. in genome replication, transcription, and translation, have been subject to horizontal gene transfer between species more often than genes with operational functions, e.g. in metabolism and environmental sensing. In this study, we use a genome wide analysis of transferability data obtained from 74 genomes to provide the first experimental evidence that this pattern results from differences between informational and operational genes in the number of other proteins with which they interact, i.e., their connectivity, rather than from their functional differences. The importance of our exceptionally large dataset to the detection of connectivity effects on transferability explains why past experimental studies failed to replicate the consistent finding from comparative genomic studies.
Evaluating a Human/Machine Interface with Redundant Motor Modalities for Trajectory-Tracking
Authors: Chou Amber H.Y. , Yamagami Momona , Burden Samuel A. 
Published: July 2022

AbstractIn human/machine interfaces (HMI), humans can interact with dynamic machines through a variety of sensory and motor modalities. Redundant motor modalities are known to have advantages in both human sensorimotor control and human-computer interaction: motor redundancy in sensorimotor control provides abundant solutions to achieve tasks; and incorporating diverse features from different modalities has improved the performance of movement-, gesture-, and brain-controlled computer interfaces. Our objective is to investigate whether redundant motor modalities enhance performance for a continuous trajectory-tracking task. We designed a multimodal human/machine interface with combined manual (joystick) and muscle (surface electromyography, sEMG) inputs and evaluated its closed-loop performance for tracking trajectories through second-order machine dynamics. In a human subjects experiment with 15 participants, we found that the multimodal interface outperformed the manual-only interface while performing comparably to the muscle-only interface; and that the multimodal interface enabled users to coordinate individual modalities to attenuate noise. Multimodal human/machine interfaces could be beneficial in systems that require stability and robustness against perturbations such as motor rehabilitation and robotic manipulation.
Mid-life leukocyte telomere length and dementia risk: a prospective cohort study of 435,046 UK Biobank participants
Authors: Liu Rui , Xiang Meiruo , Pilling Luke C. , Melzer David , Wang Lihong , Manning Kevin J. , Steffens David C. , Bowden Jack , Fortinsky Richard H. , Kuchel George A. , Rhee Taeho G , Diniz Breno S. , Kuo Chia-Ling 
Published: July 2022

AbstractImportanceTelomere attribution is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD).ObjectiveTo assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes.Design, Setting, and ParticipantsData from European-ancestry participants in the UK Biobank (n=435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n=43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology.ExposuresRelative mean leukocyte TL at baseline was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction technique by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S).Main Outcomes and MeasuresAD/ADRD was confirmed by mapping multi-source data to 3-charcter ICD codes (G30; F00; F01; F03; G31), excluding other-cause dementias (F02).ResultsLonger TL was associated with a lower risk of incident AD/ADRD (adjusted HR [aHR] per SD=0.93, 95% CI 0.90 to 0.96, P=3.37×10−7). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume (adjusted standardized β [aβ] per SD=0.012, 95% CI 0.003 to 0.021, P=0.012), lower total volume of white matter hyperintensities (aβ per SD= -0.015, 95% CI -0.024 to -0.006, P=0.002), and higher fractional anisotropy (FA; aβ per SD=0.018, 95% CI 0.009 to 0.027, P=9.44×10−5) and lower mean diffusivity (MD; aβ per SD=0.045, 95% CI 0.035 to 0.056, P=1.07×10−17) in the fornix.Conclusions and RelevanceLonger TL is a protective factor against AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. A better understanding of underlying mechanisms may help improve diagnosis and management of AD/ADRD in older adults.Key PointsQuestionIs leukocyte telomere length (TL) associated with Alzheimer’s disease (AD) and AD related dementias (AD/ADRD) and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging phenotypes?FindingsLonger TL was associated with a lower risk of incident AD/ADRD, larger hippocampus volume, lower total volume of white matter hyperintensities, higher fractional anisotropy and lower mean diffusivity in the fornix.MeaningLonger TL in midlife may play a protective role against AD/ADRD, and a better understanding of underlying mechanisms may help improve diagnosis and management of AD/ADRD in older adults.
Long-range communication between transmembrane- and nucleotide-binding domains does not depend on drug binding to mutant P-glycoprotein
Authors: Bonito Cátia A. , Ferreira Ricardo J. , Ferreira Maria-José.U. , Gillet Jean-Pierre , Cordeiro M. Natália D. S. , dos Santos Daniel J. V. A. 
Published: July 2022

ABSTRACTThe modulation of drug efflux by P-glycoprotein (P-gp, ABCB1) represents one of the most promising approaches to overcome multidrug resistance (MDR) in cancer cells, however the mechanisms of drug specificity and signal-transmission are still poorly understood, hampering the development of more selective and efficient P-gp modulators. In this study, the impact of four P-gp mutations (G185V, G830V, F978A and ΔF335) on drug-binding and efflux-related signal-transmission mechanism was comprehensively evaluated in the presence of ligands within the drug-binding pocket (DBP), which are experimentally related with changes in their drug efflux profiles. The severe repacking of the transmembrane helices (TMH), induced by mutations and exacerbated by the presence of ligands, indicates that P-gp is sensitive to perturbations in the transmembrane region. Alterations on drug-binding were also observed as a consequence of the TMH repacking, but were not always correlated with alterations on ligands binding mode and/or binding affinity. Finally, and although all P-gp variantsholosystems showed considerable changes in the intracellular coupling helices/nucleotide-binding domain (ICH-NBD) interactions, they seem to be primarily induced by the mutation itself rather than by the presence of ligands within the DBP. The data further suggest that the changes in drug efflux experimentally reported are mostly related with changes on drug specificity rather than effects on signal-transmission mechanism. We also hypothesize that an increase in the drug-binding affinity may also be related with the decreased drug efflux, while minor changes in binding affinities are possibly related with the increased drug efflux observed in transfected cells.
Serotyping Salmonella Enteritidis and Typhimurium Using Whole Cell Matrix Assisted Laser Desorption Ionization – Time of Flight Mass Spectrometry (MALDI-TOF MS) through Multivariate Analysis and Artificial Intelligence
Authors: Gao Anli , Fischer-Jenssen Jennifer , Slavic Durda , Rutherford Kimani , Lippert Sarah , Wilson Emily , Chen Shu , Leon-Velarde Carlos G. , Martos Perry 
Published: July 2022

AbstractSalmonella is one of the most frequent food-borne zoonoses, while Salmonella Typhimurium and Enteritidis are the major serovars of concern in public health. 113 Salmonella strains including 38 S. Enteritidis (SE), 38 S. Typhimurium (ST) and 37 strains of 32 other Salmonella serovars (SG) were tested in quadruplicate by whole-cell MALDI-TOF MS. Ions were studied and aligned from the raw data of mzXML files using Mass-Up (http://www.sing-group.org/mass-up), resulting in 1,741 aligned peaks. Datasets of ions (presence/absence) selected using a home-developed criteria on their specificity and detectability were subjected to multivariate analyses and artificial intelligence tools. Principle Component Analysis based on 88 selected ions separated SE, ST and SG without overlap on the first three principle components. The network and forest based deep learning tools were more sophisticated than the decision tree-based models. Neural Network carried out consistently well in training model, but no advantage was gained over the other models in validation results. HP (high performance) Neural, Support Vector Machine, HP Forest and Gradient Boasting were able to identify SE, ST and SG up to 100% correctly in both training and validation when 88 selected ions were used in analysis. Among them, HP Neural seemed to perform slightly better and relatively stable. Selection of serovar specific ions helps develop serotyping by increasing signal to noise. MALDI-TOF MS used with appropriate data processing strategies and classification tools could be applied to quickly alert when Salmonella serotypes of concern are suspected among routinely processed samples.