bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medium-chain acyl-CoA dehydrogenase deficiency: prevalence of ACADM pathogenic variants c.985A>G and c.199T>C in a healthy population in Rio Grande do Sul, Brazil
Authors: dos Santos Mariana Lopes , Randon Dévora Natalia , de Bitencourt Fernanda Hendges , Sperb-Ludwig Fernanda , Vianna Fernanda Sales Luiz , Vargas Carmen Regla , Sitta Angela , Schwartz Ida Vanessa Doederlein 
Published: July 2022

Abstract

Objectives:
To investigate the prevalence of ACADM pathogenic variants, c.985A>G and c.199T>C, for medium chain acyl CoA dehydrogenase deficiency (MCADD) in a healthy population in the southern region of Brazil.

Methods:
This was an observational cross-sectional study with a convenience sampling strategy. The participants were recruited from the blood bank of the Hospital de Clínicas of Porto Alegre, Brazil. A total of 1000 healthy individuals from the state of Rio Grande do Sul were included. Genotyping for the c.199T>C and c.985A>G variants was performed using real-time polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism (RFLP) technique, respectively. Individuals considered heterozygous for c.985A>G were subjected to additional acylcarnitine profile analysis using tandem mass spectrometry. Carrier frequency was obtained by calculating the ratio of heterozygous individuals to the total number of individuals analyzed and reported with a 95% confidence interval. Allele and genotype frequencies were calculated based on the Hardy–Weinberg equilibrium.

Results:
The c.985A>G variant was detected as heterozygotes in three individuals (frequency of the heterozygous genotype = 1:333, allele frequency = 0.0015, minimum frequency of MCADD = 1:444,444) whose acylcarnitine profiles were within normal limits. The c.199T>C variant was not identified.

Conclusions:
Considering the small sample size and associated allelic heterogeneity with MCADD, these findings are believed to denote the rarity or underdiagnosis of MCADD in southern Brazil. This study provides evidence for the need for further investigation to ascertain the contribution of these diseases to child morbidity and mortality in the country.
Virulence of Staphylococcus Infection in Surgically Treated Patients With Endocarditis
Authors: Luehr Maximilian , Weber Carolyn , Misfeld Martin , Lichtenberg Artur , Tugtekin Sems-Malte , Diab Mahmoud , Saha Shekhar , Li Yupeng , Matsche Klaus , Doenst Torsten , Borger Michael A. , Wahlers Thorsten , Akhyari Payam , Hagl Christian 
Published: July 2022

Objective:
Infective endocarditis (IE) caused by Staphylococcus species (spp.) is believed to be associated with higher morbidity and mortality rates. We hypothesize that Staphylococcus spp. are more virulent compared with other commonly causative bacteria of IE with regard to short-term and long-term mortality.

Background:
It remains unclear if patients suffering from IE due to Staphylococcus spp. should be referred for surgical treatment earlier than other IE patients to avoid septic embolism and to optimize perioperative outcomes.

Materials and Methods:
The database of the CAMPAIGN registry, comprising 4917 consecutive patients undergoing heart valve surgery, was retrospectively analyzed. Patients were divided into 2 groups with regard to the identified microorganisms: Staphylococcus group and the non-Staphylococcus group. The non-Staphylococcus group was subdivided for further analyses: Streptococcus group, Enterococcus group, and all other bacteria groups.

Results:
The respective mortality rates at 30 days (18.7% vs 11.8%; P<0.001), 1 year (24.7% vs 17.7%; P<0.001), and 5 years (32.2% vs 24.5%; P<0.001) were significantly higher in Staphylococcus patients (n=1260) compared with the non-Staphylococcus group (n=1787). Multivariate regression identified left ventricular ejection fraction <30% (P<0.001), chronic obstructive pulmonary disease (P=0.045), renal insufficiency (P=0.002), Staphylococcus spp. (P=0.032), and Streptococcus spp. (P=0.013) as independent risk factors for 30-day mortality. Independent risk factors for 1-year mortality were identified as: age (P<0.001), female sex (P=0.018), diabetes (P=0.018), preoperative stroke (P=0.039), chronic obstructive pulmonary disease (P=0.001), preoperative dialysis (P<0.001), and valve vegetations (P=0.004).

Conclusions:

Staphylococcus endocarditis is associated with an almost twice as high 30-day mortality and significantly inferior long-term outcome compared with IE by other commonly causative bacteria. Patients with Staphylococcus infection are more often female and critically ill, with >50% of these patients suffering from clinically relevant septic embolism. Early diagnosis and referral to a specialized center for surgical treatment are strongly recommended to reduce the incidence of preoperative deterioration and stroke due to septic embolism.
Evaluating the Accuracy and Design of Visual Abstracts in Academic Surgical Journals
Authors: Guidolin Keegan , Lin Justin , Zorigtbaatar Anudari , Nadeem Minahil , Ibrahim Tarek , Neilson Zdenka , Kim Kyung Young (Peter) , Rajendran Luckshi , Chadi Sami , Quereshy Fayez 
Published: July 2022

Objective:
The objective of this study was to assess the quality and accuracy of visual abstracts published in academic surgical journals.

Background:
Visual abstracts are commonly used to disseminate medical research findings. They distill the key messages of a research article, presenting them graphically in an engaging manner so that potential readers can decide whether to read the complete manuscript.

Methods:
We developed the Visual Abstract Assessment Tool based upon published guidelines. Seven reviewers underwent iterative training to apply the tool. We collected visual abstracts published by 25 surgical journals from January 2017 to April 2021; those corresponding to systematic reviews without meta-analysis, conference abstracts, narrative reviews, video abstracts, or nonclinical research were excluded. Included visual abstracts were scored on accuracy (as compared with written abstracts) and design, and were given a “first impression” score.

Results:
Across 25 surgical journals 1325 visual abstracts were scored. We found accuracy deficits in the reporting of study design (35.8%), appropriate icon use (49%), and sample size reporting (69.2%), and design deficits in element alignment (54.8%) and symmetry (36.1%). Overall scores ranged from 9 to 14 (out of 15), accuracy scores from 4 to 8 (out of 8), and design scores from 3 to 7 (out of 7). No predictors of visual abstract score were identified.

Conclusion:
Visual abstracts vary widely in quality. As visual abstracts become integrated with the traditional components of scientific publication, they must be held to similarly high standards. We propose a checklist to be used by authors and journals to standardize the quality of visual abstracts.
Pregnancy in trauma—A Western Trauma Association algorithm
Authors: Rizzo Anne , Martin Matthew , Inaba Kenji , Schreiber Martin , Brasel Karen , Sava Jack , Ciesla David , Sperry Jason , Kozar Rosemary , Brown Carlos , Moore Ernest 
Published: July 2022

BACKGROUND
The Western Trauma Association has undertaken publication of best practice clinical practice guidelines on multiple trauma topics. These guidelines are based on scientific evidence, case reports, and best practices per expert opinion. Some of the topics covered by this consensus group do not have the ability to have randomized controlled studies completed because of complexity, ethical issues, financial considerations or scarcity of experience. Care of the pregnant trauma patient is one of these clinically complex situations that is based on physiologic data, standard trauma care, trauma care experience, and outcomes.

METHODS
Review of multiple evidence- based guidelines, case reports, and expert opinion were compiled and reviewed.

RESULTS
The algorithm is attached with detailed explanation of each step, supported by data if available.

CONCLUSION
Resuscitative and trauma care of the mother is the utmost priority

Study Type
Algorithm, expert opinion, consensus

LEVEL OF EVIDENCE
Diagnostic Tests/Criteria; Level III.
Cross-attention PHV: Prediction of human and virus protein-protein interactions using cross-attention–based neural networks
Authors: Tsukiyama Sho , Kurata Hiroyuki 
Published: July 2022

AbstractViral infections represent a major health concern worldwide. The alarming rate at which SARS-CoV-2 spreads, for example, led to a worldwide pandemic. Viruses incorporate genetic material into the host genome to hijack host cell functions such as the cell cycle and apoptosis. In these viral processes, protein-protein interactions (PPIs) play critical roles. Therefore, the identification of PPIs between humans and viruses is crucial for understanding the infection mechanism and host immune responses to viral infections and for discovering effective drugs. Experimental methods such as yeast two-hybrid assays and mass spectrometry are widely used to identify human-virus PPIs, but these experimental methods are time-consuming, expensive, and laborious. To overcome this problem, we developed a novel computational predictor, named cross-attention PHV, by implementing two key technologies of the cross-attention mechanism and a one- dimensional convolutional neural network (1D-CNN). The cross-attention mechanisms were very effective in enhancing prediction and generalization abilities. Application of 1D-CNN to the word2vec-generated feature matrices reduced computational costs, thus extending the allowable length of protein sequences to 9000 amino acid residues. Cross- attention PHV outperformed existing state-of-the-art models using a benchmark dataset and accurately predicted PPIs for unknown viruses. Cross-attention PHV also predicted human–SARS-CoV-2 PPIs with area under the curve values >0.95.
Assessment of the Human Placental Microbiome in Early Pregnancy
Authors: Sharlandjieva Vassilena , Beristain Alexander G. , Terry Jefferson 
Published: July 2022

AbstractBacteria derived from the maternal circulation have been suggested to seed the human placenta during development leading to an intrinsic placental microbiome. This concept has become controversial as numerous studies suggest that the apparent placental microbiome is mostly, if not completely, comprised of contaminants. If the maternal circulation seeds the placenta then there should be an increase in abundance and diversity of detectable bacteria with onset of maternal perfusion of the placenta around 10 weeks gestational age; however, if only contaminants are present then there should be no significant evolution of the placental microbiome with increasing gestational age. This pilot study addresses whether bacterial abundance and diversity increases in human placenta and whether there is an associated shift in the immunophenotype of the decidual immune cell complement before and after initiation of placental perfusion. Human placental and decidual tissue from 5-19 weeks gestational age are assessed by quantitative 16S polymerase chain reaction (PCR), 16S gene sequencing, and immunological flow cytometry studies. A weak positive correlation between placental bacterial abundance and gestational age is identified but is not statistically significant. No significant changes in bacterial diversity are found with increasing gestational age. The proportion of decidual activated memory T helper cells increases with gestational age but no change was observed in other lymphocyte subsets. This pilot study does not strongly support bacterial colonization of the placenta after initiation of maternal perfusion; however, the minor trends towards increases in bacterial abundance and activated memory T helper cells may represent an early stage of this process. Additional investigations in larger cohorts are warranted.
Decoding the mouse spinal cord locomotor neural network using tissue clearing, tissue expansion and tiling light sheet microscopy techniques
Authors: Feng Ruili , Xie Jiongfang , Lu Jing , Hu Huijie , Chen Yanlu , Wang Dongyue , Gao Liang 
Published: July 2022

AbstractDecoding a biological neural network requires the structural information regarding the spatial organization, dendritic morphology, axonal projection and synaptic connection of the neurons in the network. Imaging physically sectioned nervous tissues using electron microscopy (EM) has been the only method to acquire such information. However, EM is inefficient for imaging and reconstructing large neural networks due to the low throughput and inability to target neural circuits of interest by labeling specific neuron populations genetically. Here, we present a method to image large nervous tissues from the cellular to synaptic level with high throughput using tiling light sheet microscopy combined with tissue clearing and tissue expansion techniques. We describe the method, demonstrate its capability and explore its utility for decoding large biological neural networks by studying the spinal cord locomotor neural network in genetically labeled fluorescent mice. We show our method could advance the decoding of large neural networks significantly.
Meta-analysis of the effects of clinically-effective therapeutics in the preclinical migraine model as a tool for design optimisation
Authors: Dolgorukova Antonina , Protsenko Ekaterina , Isaeva Julia , Gagloeva Victoria , Verbitskaya Elena , Sokolov Alexey Y. 
Published: July 2022

AbstractThe low reliability of the preclinical study’s findings is of critical concern. The possible sources include poor experimental design and a lack of measures to reduce the risk of bias. In this study, we focused on anti-migraine drug discovery and a particular animal model with the aim to contribute to the elimination of these sources in future research. We performed a systematic search of controlled studies testing established migraine treatments in the model of trigeminovascular nociception (EMTVN) and meta-analysis for the main outcomes to estimate the overall effect sizes. In 13 studies reporting on 21 experiments, anti-migraine drugs significantly decreased trigeminovascular nociceptive traffic compared with a control intervention. Considering these effects biologically relevant, we used them in sample size calculation for future experiments. To refine the EMTVN and inform its users, we explored the impact of methodological features on the outcome and revealed several factors potentially impacting the results obtained in this model. We also assessed the internal validity of the included studies and found that the selection bias, particularly, the lack of randomisation, is likely a main source of bias. Based on our findings, we discuss the translational potential of the EMTVN and suggest what should be addressed for its improvement. We believe that this work highlights the importance of systematic reviews and meta-analyses as tools for design optimisation in animal research.
A low-cost smartphone fluorescence microscope for research, life science education, and STEM outreach
Authors: Schaefer Madison A , Nelson Heather N , Butrum John L , Gronseth James R , Hines Jacob H 
Published: July 2022

AbstractMuch of our understanding of cell and tissue development, structure, and function stems from fluorescence microscopy. The acquisition of colorful and glowing images engages and excites users ranging from seasoned microscopists to STEM students. Fluorescence microscopes range in cost from several thousand to several hundred thousand US dollars. Therefore, the use of fluorescence microscopy is typically limited to well-funded institutions and biotechnology companies, research core facilities, and medical laboratories, but is financially impractical at many universities and colleges, primary and secondary schools (K-12), and in science outreach settings. In this study, we developed and characterized components that when used in combination with a smartphone or tablet, perform fluorescence microscopy at a cost of less than $50 US dollars per unit. We re-purposed recreational LED flashlights and theater stage lighting filters to enable viewing of green and red fluorophores including EGFP, DsRed, mRFP, and mCherry on a simple-to-build frame made of wood and plexiglass. These devices, which we refer to as glowscopes, were capable of 10 μm resolution, imaging fluorescence in live specimens, and were compatible with all smartphone and tablet models we tested. In comparison to scientific-grade fluorescence microscopes, glowscopes may have limitations to sensitivity needed to detect dim fluorescence and the inability to resolve subcellular structures. We demonstrate capability of viewing fluorescence within zebrafish embryos, including heart rate, rhythmicity, and regional anatomy of the central nervous system. Due to the low cost of individual glowscope units, we anticipate this device can help to equip K-12, undergraduate, and science outreach classrooms with fleets of fluorescence microscopes that can engage students with hands-on learning activities.
Covert detection of own-name and semantic violations in task-irrelevant speech, in a realistic Virtual Café
Authors: Brown Adi , Pinto Danna , Burgart Ksenia , Zvilichovsky Yair , Zion-Golumbic Elana 
Published: July 2022

AbstractDetecting that someone has said your name is one of the most famous examples for incidental processing of supposedly-unattended speech. However, empirical investigation of this so-called “cocktail party effect” has yielded conflicting results. We present a novel empirical approach for revisiting this effect under highly ecological conditions, by immersing participants in a multisensory virtual café environment and using realistic stimuli and tasks. Participants listened to conversational speech from a character sitting across from them, while a barista in the back of the café called out food orders. Unbeknownst to them, the barista sometimes called orders containing their own name or semantic violations. We used combined measurements of brain activity (EEG), eye-gaze and galvanic skin response to assess the response-profile to these two probes in the task-irrelevant barista-stream.Both probes elicited unique neural and physiological responses relative to control stimuli, indicating that the system indeed processed these words and detected their unique status, despite being task-irrelevant. Interestingly, these responses were covert in nature and were not accompanied by gaze-shifts towards the barista character. This pattern demonstrates that under these highly ecological conditions, listeners incidentally pick up information from task-irrelevant speech, emphasizing the dynamic and non-binary nature of attention in real-life environments.
Structural basis of botulinum neurotoxin serotype A1 binding to human SV2A or SV2C receptors
Authors: Azzaz Fodil , Hilaire Didier , Fantini Jacques 
Published: July 2022

AbstractBotulinum neurotoxin A1 (BoNT/A1) is the most potent serotype in humans with the highest clinical duration. BoNT/A1 interacts with synaptic vesicle glycoprotein 2 (SV2) and gangliosides to be taken up by neurons. In this study, we present three molecular dynamics simulations in which BoNT/A1 is in complex with singly or doubly glycosylated SV2C or singly glycosylated SV2A, in a ganglioside rich (lipid raft) context. Our computational data suggest that the N-glycan at position 480 (N480g) in the luminal domain of SV2C (LD-SV2C) indirectly enhanced the contacts of the neurotoxin surface with the second N-glycan at position 559 (N559g) by acting as a shield to prevent N559g to interact with residues of LD-SV2C. The N-glycosylation at the position N573 (N573g) in the luminal domain of SV2A has a slightly lower affinity for the surface of BoNT/A1 compared to 559g because of possible intermolecular contacts between N573g and residues of the luminal domain of SV2A (LD-SV2A). In addition to the ganglioside binding site (GBS) conserved across serotypes B, E, F and G, the lipid-raft associated GT1b interacted with a structure we coined the ganglioside binding loop (GBL) which is homologous to the lipid binding loop (LBL) in serotypes B, C, D, D/C and G. Finally, we proposed a global model in which BoNT/A1 interacts with its glycosylated protein receptor, one molecule of GT1b interacting in the GBS and five molecules of GT1b interacting with the GBL and residue Y1133. These data solved the puzzle generated by mutational studies that could be only partially understood with crystallographic data that lack both a biologically relevant membrane environment and a full glycosylation of SV2.Brief statementWe propose a full molecular description of the initial binding of a microbial toxin (Botulinum neurotoxin A1) to the surface of neural cells. Our model includes a protein receptor (SV2) in its native environment, i.e. the periphery of a cluster of gangliosides belonging to a membrane microdomain (lipid raft). A major outcome of our study is the elucidation of the role of the full length glycans (previously resolved by MS spectroscopy) covalently attached to the protein receptor. These data solved the puzzle generated by mutational studies that could be only partially understood with crystallographic data that lack both a biologically relevant membrane environment and a full glycosylation of SV2.
Timesweeper: Accurately Identifying Selective Sweeps Using Population Genomic Time Series
Authors: Whitehouse Logan S. , Schrider Daniel R. 
Published: July 2022

ABSTRACTDespite decades of research, identifying selective sweeps, the genomic footprints of positive selection, remains a core problem in population genetics. Of the myriad methods that have been developed to tackle this task, few are designed to leverage the potential of genomic time-series data. This is because in most population genetic studies of natural populations only a single period of time can be sampled. Recent advancements in sequencing technology, including improvements in extracting and sequencing ancient DNA, have made repeated samplings of a population possible, allowing for more direct analysis of recent evolutionary dynamics. Serial sampling of organisms with shorter generation times has also become more feasible due to improvements in the cost and throughput of sequencing. With these advances in mind, here we present Timesweeper, a fast and accurate convolutional neural network-based tool for identifying selective sweeps in data consisting of multiple genomic samplings of a population over time. Timesweeper population genomic time-series data by first simulating training data under a demographic model appropriate for the data of interest, training a one-dimensional Convolutional Neural Network on said simulations, and inferring which polymorphisms in this serialized dataset were the direct target of a completed or ongoing selective sweep. We show that Timesweeper is accurate under multiple simulated demographic and sampling scenarios, identifies selected variants with high resolution, and estimates selection coefficients more accurately than existing methods. In sum, we show that more accurate inferences about natural selection are possible when genomic time-series data are available; such data will continue to proliferate in coming years due to both the sequencing of ancient samples and repeated samplings of extant populations with faster generation times, as well as experimentally evolved populations where time-series data are often generated. Methodological advances such as Timesweeper thus have the potential to help resolve the controversy over the role of positive selection in the genome. We provide Timesweeper as a Python package for use by the community.