Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Disability Related to Hip Dysplasia Using Objective Measures of Physical Performance

Background: Lower extremity physical performance measures (PPMs), which can objectively quantify functional ability, are an attractive adjuvant to patient-reported outcome (PRO) instruments. However, few tests have been validated for use in hip instability. Purpose: To evaluate 4 different PPMs for their ability to differentiate between young adults with hip dysplasia indicated for treatment with periacetabular osteotomy (PAO) and asymptomatic controls and to test inter- and intratest reliability and relationship with popular hip PRO instruments. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A total of 24 symptomatic patients aged 15 to 39 years (100% female) with hip dysplasia (lateral center-edge angle <25°) indicated for treatment with PAO completed the visual analog scale (VAS) for pain, Hip disability and Osteoarthritis Outcome (HOOS) Pain subscale, HOOS Short Version (HOOS PS), International Hip Outcome Tool Short Version (iHOT-12), modified Harris Hip Score (mHHS), Patient Reported Outcome Measurement Information System (PROMIS) physical function (PF) and pain interference (PI), and 4 physical function tests: (1) self-selected walking speed (SSWS), sit-to-stand 5 times (STS5), (3) 4-square step test (FSST), and (4) timed stair ascent (TSA). A further 21 young, asymptomatic adults aged 18 to 39 years (91% female) also underwent testing. Between-group comparisons were made with unpaired t test with Bonferroni-Holm correction. Inter- and intrarater reliability was assessed in 38 participants by repeating PPMs at a second visit and using 2 raters. Spearman rank correlation coefficients were used to determine associations between PPMs and PRO instruments. Results: Significant differences between patients with hip dysplasia and controls were observed for all PRO instruments (HOOS Pain, 47.8 vs 99.2; HOOS PS, 61.9 vs 99.2; iHOT-12, 32.2 vs 99.2; mHHS, 54.5 vs 90.6; PROMIS PF, 41.4 vs 65.6; and PROMIS PI, 62.0 vs 39.1 [all P < .001]), and all PPMs (SSWS, 1.21 vs 1.53 m/s; STS5, 10.85 vs 5.95 s; FSST, 6.59 vs 4.03 s [all P < .001]; and TSA, 4.58 vs 3.29 s [P = .002]). All 4 PPMs demonstrated excellent intra- and intertest reliability (intraclass correlation coefficient, 0.83-0.99). STS5, FSST, and TSA were correlated highly (r > 0.5) with physical function PRO instruments, including PROMIS PF, mHHS, and iHOT-12. Conclusion: Patients with symptomatic hip dysplasia demonstrated significant impairment on functional testing compared with asymptomatic controls, and performance measure testing demonstrated excellent test-retest reliability. Timed stair ascent and sit-to-stand testing in particular were correlated strongly with physical function PRO instruments. PPMs may be a viable and well-received adjuvant to PRO instrument administration for patients with nonarthritic hip conditions, and investigation of the ability of PPMs to assess surgical outcomes for hip dysplasia is warranted.
Characterization of Oxytocin Receptor Expression Within Various Neuronal Populations of the Mouse Dorsal Hippocampus

Oxytocin, acting through the oxytocin receptor (Oxtr) in the periphery, is best known for its roles in regulating parturition and lactation. However, it is also now known to possess a number of important social functions within the central nervous system, including social preference, memory and aggression, that vary to different degrees in different species. The Oxtr is found in both excitatory and inhibitory neurons within the brain and research is focusing on how, for example, activation of the receptor in interneurons can enhance the signal-to-noise of neuronal transmission. It is important to understand which neurons in the mouse dorsal hippocampus might be activated during memory formation. Therefore, we examined the colocalization of transcripts in over 5,000 neurons for Oxtr with those for nine different markers often found in interneurons using hairpin chain reaction in situ hybridization on hippocampal sections. Most pyramidal cell neurons of CA2 and many in the CA3 express Oxtr. Outside of those excitatory neurons, over 90% of Oxtr-expressing neurons co-express glutamic acid decarboxylase-1 (Gad-1) with progressively decreasing numbers of co-expressing cholecystokinin, somatostatin, parvalbumin, neuronal nitric oxide synthase, the serotonin 3a receptor, the vesicular glutamate transporter 3, calbindin 2 (calretinin), and vasoactive intestinal polypeptide neurons. Distributions were analyzed within hippocampal layers and regions as well. These findings indicate that Oxtr activation will modulate the activity of ~30% of the Gad-1 interneurons and the majority of the diverse population of those, mostly, interneuron types specifically examined in the mouse hippocampus.
Crucial Role of the Accessory Genome in the Evolutionary Trajectory of Acinetobacter baumannii Global Clone 1

Acinetobacter baumannii is one of the most important nosocomial pathogens able to rapidly develop extensive drug resistance. Here, we study the role of accessory genome in the success of the globally disseminated clone 1 (GC1) with functional and genomic approaches. Comparative genomics was performed with available GC1 genomes (n = 106) against other A. baumannii high-risk and sporadic clones. Genetic traits related to accessory genome were found common and conserved along time as two novel regions of genome plasticity, and a CRISPR-Cas system acquired before clonal diversification located at the same loci as “sedentary” modules. Although identified within hotspot for recombination, other block of accessory genome was also “sedentary” in lineage 1 of GC1 with signs of microevolution as the AbaR0-type genomic island (GI) identified in A144 and in A155 strains which were maintained one month in independent experiments without antimicrobial pressure. The prophage YMC/09/02/B1251_ABA_BP was found to be “mobile” since, although it was shared by all GC1 genomes, it showed high intrinsic microevolution as well as mobility to different insertion sites. Interestingly, a wide variety of Insertion Sequences (IS), probably acquired by the flow of plasmids related to Rep_3 superfamily was found. These IS showed dissimilar genomic location amongst GC1 genomes presumably associated with promptly niche adaptation. On the other hand, a type VI secretion system and three efflux pumps were subjected to deep processes of genomic loss in A. baumannii but not in GC1. As a whole, these findings suggest that preservation of some genetic modules of accessory genome harbored by strains from different continents in combination with great plasticity of IS and varied flow of plasmids, may be central features of the genomic structure of GC1. Competition of A144 and A155 versus A118 (ST 404/ND) without antimicrobial pressure suggested a higher ability of GC1 to grow over a clone with sporadic behavior which explains, from an ecological perspective, the global achievement of this successful pandemic clone in the hospital habitat. Together, these data suggest an essential role of still unknown properties of “mobile” and “sedentary” accessory genome that is preserved over time under different antibiotic or stress conditions.
The C291R Tau Variant Forms Different Types of Protofibrils

Mutations in the MAPT gene can lead to disease-associated variants of tau. However, the pathological mechanisms behind these genetic tauopathies are poorly understood. Here, we characterized the aggregation stages and conformational changes of tau C291R, a recently described MAPT mutation with potential pathogenic functions. The C291R variant of the tau four-repeat domain (tau-K18; a functional fragment with increased aggregation propensity compared with the full-length protein), aggregated into a mix of granular oligomers, amorphous and annular pore-like aggregates, in native-state and heparin-treated reactions as observed using atomic force microscopy (AFM) and negative-stained electron microscopy. On extended incubation in the native-state, tau-K18 C291R oligomers, unlike wild type (WT) tau-K18, aggregated to form protofibrils of four different phenotypes: (1) spherical annular; (2) spherical annular encapsulating granular oligomers; (3) ring-like annular but non-spherical; and (4) linear protofibrils. The ring-like tau-K18 C291R aggregates shared key properties of annular protofibrils previously described for other amyloidogenic proteins, in addition to two unique features: irregular/non-spherical-shaped annular protofibrils, and spherical protofibrils encapsulating granular oligomers. Tau-K18 C291R monomers had a circular dichroism (CD) peak at ~210 nm compared with ~199 nm for tau-K18 WT. These data suggest mutation-enhanced β-sheet propensity. Together, we describe the characterization of tau-K18 C291R, the first genetic mutation substituting a cysteine residue. The aggregation mechanism of tau-K18 C291R appears to involve β-sheet-rich granular oligomers which rearrange to form unique protofibrillar structures.
Single-Molecule Force Spectroscopy on the N2A Element of Titin: Effects of Phosphorylation and CARP

Titin is a large filamentous protein that forms a sarcomeric myofilament with a molecular spring region that develops force in stretched sarcomeres. The molecular spring has a complex make-up that includes the N2A element. This element largely consists of a 104-residue unique sequence (N2A-Us) flanked by immunoglobulin domains (I80 and I81). The N2A element is of interest because it assembles a signalosome with CARP (Cardiac Ankyrin Repeat Protein) as an important component; CARP both interacts with the N2A-Us and I81 and is highly upregulated in response to mechanical stress. The mechanical properties of the N2A element were studied using single-molecule force spectroscopy, including how these properties are affected by CARP and phosphorylation. Three protein constructs were made that consisted of 0, 1, or 2 N2A-Us elements with flanking I80 and I81 domains and with specific handles at their ends for study by atomic force microscopy (AFM). The N2A-Us behaved as an entropic spring with a persistence length (Lp) of ∼0.35 nm and contour length (Lc) of ∼39 nm. CARP increased the Lp of the N2A-Us and the unfolding force of the Ig domains; force clamp experiments showed that CARP reduced the Ig domain unfolding kinetics. These findings suggest that CARP might function as a molecular chaperone that protects I81 from unfolding when mechanical stress is high. The N2A-Us was found to be a PKA substrate, and phosphorylation was blocked by CARP. Mass spectrometry revealed a PKA phosphosite (Ser-9895 in NP_001254479.2) located at the border between the N2A-Us and I81. AFM studies showed that phosphorylation affected neither the Lp of the N2A-Us nor the Ig domain unfolding force (Funfold). Simulating the force-sarcomere length relation of a single titin molecule containing all spring elements showed that the compliance of the N2A-Us only slightly reduces passive force (1.4%) with an additional small reduction by CARP (0.3%). Thus, it is improbable that the compliance of the N2A element has a mechanical function per se. Instead, it is likely that this compliance has local effects on binding of signaling molecules and that it contributes thereby to strain- and phosphorylation- dependent mechano-signaling.
An Antennae-Specific Odorant-Binding Protein Is Involved in Bactrocera dorsalis Olfaction

Insect antennae are important olfactory organs that house high concentrations of odorant-binding proteins (OBPs) in the sensillum lymph. Previous studies in other insects have shown that OBPs play important roles in transporting odorants and enhancing the sensitivity of the olfactory system. However, the functions of OBPs in the oriental fruit fly, Bactrocera dorsalis, especially those specifically expressed in antennae, have not been fully elucidated. In this study, cDNA libraries were constructed from both the male and female antennal transcriptome, and twenty OBPs were identified in total. The expression profiles of these OBPs were examined in the adult antenna, head, thorax, leg, and abdomen of both sexes. Seven of the identified OBP genes had significantly higher expression in both the male and female antennae than in other tissues, while the transcript levels of the remaining OBPs varied across different tissues. Regarding the function of antenna-specific OBPs, we targeted Bdorsobp2 as a representative for further RNA interference (RNAi) and identified via electrophysiology a decrease in detection of a potential species-specific a potent attractant, methyl eugenol. Moreover, subsequent behavioral assay data showed that the behavioral response of B. dorsalis toward this odorant decreased when Bdorobp2 was silenced with injection of double-stranded RNA (dsRNA). Combined, these results support our initial hypothesis that antennae-specific OBPs are of critical importance for insect odorant detection, sensitivity, and behavior.
The Role of GI Peptides in Functional Dyspepsia and Gastroparesis: A Systematic Review

Functional dyspepsia (FD) and gastroparesis (GP) are common disorders of the upper gastrointestinal tract. The pathophysiology of these conditions is likely to be heterogenous, and factors such as altered motility, sensitivity and response to nutrition have been identified as putative underlying mechanisms. Motility, sensitivity as well as responses to nutrition can be influenced or mediated by peptide hormones and serotonin released from the gastrointestinal mucosa. This review summarizes the role of GI peptides in functional dyspepsia and gastroparesis. In most studies, the levels of somatostatin, ghrelin, and motilin did not differ between healthy volunteers and FD or GP patients, but higher symptom burden was often correlated with higher peptide levels. Ghrelin and motilin receptor agonists showed promising results in improvement of the gastric emptying, but the link with improvement of symptoms is less predictable. Serotonin agonists have a potential to improve symptoms in both FD and idiopathic gastroparesis. Drugs acting on the GLP-1 and on the PYY receptors deserve further investigation. There is a need for systematic large scale studies.
LAceModule: Identification of Competing Endogenous RNA Modules by Integrating Dynamic Correlation

Competing endogenous RNAs (ceRNAs) regulate each other by competitively binding microRNAs they share. This is a vital post-transcriptional regulation mechanism and plays critical roles in physiological and pathological processes. Current computational methods for the identification of ceRNA pairs are mainly based on the correlation of the expression of ceRNA candidates and the number of shared microRNAs, without considering the sensitivity of the correlation to the expression levels of the shared microRNAs. To overcome this limitation, we introduced liquid association (LA), a dynamic correlation measure, which can evaluate the sensitivity of the correlation of ceRNAs to microRNAs, as an additional factor for the detection of ceRNAs. To this end, we firstly analyzed the effect of LA on detecting ceRNA pairs. Subsequently, we proposed an LA-based framework, termed LAceModule, to identify ceRNA modules by integrating the conventional Pearson correlation coefficient and dynamic correlation LA with multi-view non-negative matrix factorization. Using breast and liver cancer datasets, the experimental results demonstrated that LA is a useful measure in the detection of ceRNA pairs and modules. We found that the identified ceRNA modules play roles in cell adhesion, cell migration, and cell-cell communication. Furthermore, our results show that ceRNAs may represent potential drug targets and markers for the treatment and prognosis of cancer.
Genome-Wide Characterization of Alternative Splicing Events and Their Responses to Cold Stress in Tilapia

Alternative splicing (AS) is an important post-transcriptional regulatory mechanism for cells to generate transcript variability and proteome diversity. No systematic investigation of AS events among different tissues in response to stressors is available for tilapia currently. In this study, AS among different tissues was identified and the cold stress-related AS events were explored in a Nile tilapia (Oreochromis niloticus) line based on 42 RNA-seq datasets using a bioinformatics pipeline. 14,796 (82.76%; SD = 2,840) of the expression genes showed AS events. The two most abundant AS types were alternative transcription start site (TSS) and terminal site (TTS) in tilapia. Testis, brain and kidney possess the most abundant AS gene number, while the blood, muscle and liver possess the least number in each tissue. Furthermore, 208 differentially alternative splicing (DAS) genes in heart and 483 DAS in brain in response to cold stress. The number of AS types for alternative exon end, exon skipping and retention of single intron increased significantly under cold stress. GO enrichment and pathway overrepresentation analysis indicated that many DAS genes, e.g., genes in circadian clock pathway, may influence expression of downstream genes under cold stress. Our study revealed that AS exists extensively in tilapia and plays an important role in cold adaption.
Gross Total vs. Subtotal Resection on Survival Outcomes in Elderly Patients With High-Grade Glioma: A Systematic Review and Meta-Analysis

Background: The optimal strategy for the management of high-grade glioma in the elderly (≥60.0 years) remains controversial, especially regarding the effects of surgical extent on survival outcomes. The purpose of this study was to compare gross total resection (GTR) with subtotal resection (STR) for treatment effects in elderly patients with high-grade glioma. Methods: Three electronic databases were systematically searched, including PubMed, EmBase, and the Cochrane library, from inception to August 2018. Hazard ratios (HRs) or odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to express summary effect estimates using the random-effects model. Nineteen retrospective observational studies involving a total of 10,815 elderly patients with high-grade glioma were included in this meta-analysis. Results: The summary results indicated that GTR was associated with a significant improvement in overall survival (OS) compared with STR (HR = 0.70, 95% CI = 0.64–0.77). In addition, elderly patients administered GTR showed lower risk of 3-month mortality (OR = 0.47, 95% CI = 0.24–0.93), 6-month mortality (OR = 0.38, 95% CI = 0.26–0.56), 9-month mortality (OR = 0.35, 95% CI = 0.25–0.49), and 1-year mortality (OR = 0.40, 95% CI = 0.29–0.56). Pooled OS data differed when stratified by publication year, country, sample size, disease status, and study quality. Conclusion: GTR seems to be more effective than STR in achieving longer survival in elderly patients with high-grade glioma.
Investigate the Variations of the Head and Brain Response in a Rodent Head Impact Acceleration Model by Finite Element Modeling

Diffuse axonal injury (DAI) is a severe form of traumatic brain injury and often induced by blunt trauma. The closed head impact acceleration (IA) model is the most widely used rodent DAI model. However, this model results in large variations of injury severity. Recently, the impact device/system was modified to improve the consistency of the impact energy, but variations of the head kinematics and subsequent brain injuries were still observed. This study was aimed to utilize a Finite Element (FE) model of a rat head/body and simulation to investigate the potential biomechanical factors influencing the impact energy transfer to the head. A detailed FE rat head model containing detailed skull and brain anatomy was developed based on the MRI, microCT and atlas data. The model consists of over 722,000 elements, of which 310,000 are in the brain. The white matter structures consisting of highly aligned axonal fibers were simulated with transversely isotropic material. The rat body was modeled to provide a realistic boundary at the spine-medulla junction. Rodent experiments including dynamic cortical deformation, brain-skull displacement, and IA kinematics were simulated to validate the FE model. The model was then applied to simulate the rat IA experiments. Parametric studies were conducted to investigate the effect of the helmet inclination angles (0°–5°) and skull stiffness (varied 20%) on the resulting head kinematics and maximum principal strain in the brain. The inclination angle of the helmet at 5° could vary head linear acceleration by 8–31%. The change in head rotational velocity was inversely related to the change in linear acceleration. Varying skull stiffness resulted in changes in head linear acceleration by 3% but with no effect on rotational velocity. The brain strain in the corpus callosum was only affected by head rotation while the strain in the brainstem was influenced by the combined head kinematics, local skull deformation, and head-neck position. Validated FE models of rat impact head injury can assist in exploring various biomechanical factors influencing the head impact response and internal brain response. Identification of these variables may help explain the variability of injury severity observed among experiments and across different labs.
Biodiversity, systematics, and new taxa of cladid crinoids from the Ordovician Brechin Lagerstätte

Abstract. Upper Ordovician (Katian) strata of the Lake Simcoe region of Ontario record a spectacularly diverse and abundant echinoderm fauna known as the Brechin Lagerstätte. Despite recognition as the most taxonomically diverse Katian crinoid paleocommunity, the Brechin Lagerstätte has received relatively little taxonomic study since Frank Springer published his classic monograph on the “Kirkfield fauna” in 1911. Using a new collection of exceptionally preserved material, we evaluate all dicyclic inadunate crinoids occurring in the Brechin Lagerstätte, which is predominantly comprised of cladids (Eucladida and Flexibilia). We document 15 species across 11 genera, including descriptions of two new genera and four new species. New taxa include Konieckicrinus brechinensis n. gen. n. sp. , K. josephi n. gen. n. sp. , Simcoecrinus mahalaki n. gen. n. sp. , and Dendrocrinus simcoensis n. sp. Although cladids are not commonly considered major components of the Early Paleozoic Crinoid Macroevolutionary Fauna, which is traditionally conceived as dominated by disparids and diplobathrid camerates, they are the most diverse major lineage of crinoids occurring in the Brechin Lagerstätte. This unexpected result highlights the important roles of specimen-based taxonomy and systematic revisions in the study of large-scale diversity patterns.