Miracle-dz/UniFAR-FTUs huggingface dataset:
Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change Two Novel Mutations and Literature Review

The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208C>G (p.Pro70Ala) and c.511C>T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.
Cell Fusion in Human Cancer: The Dark Matter Hypothesis

Current strategies to determine tumor × normal (TN)-hybrid cells among human cancer cells include the detection of hematopoietic markers and other mesodermal markers on tumor cells or the presence of donor DNA in cancer samples from patients who had previously received an allogenic bone marrow transplant. By doing so, several studies have demonstrated that TN-hybrid cells could be found in human cancers. However, a prerequisite of this cell fusion search strategy is that such markers are stably expressed by TN-hybrid cells over time. However, cell fusion is a potent inducer of genomic instability, and TN-hybrid cells may lose these cell fusion markers, thereby becoming indistinguishable from nonfused tumor cells. In addition, hybrid cells can evolve from homotypic fusion events between tumor cells or from heterotypic fusion events between tumor cells and normal cells possessing similar markers, which would also be indistinguishable from nonfused tumor cells. Such indistinguishable or invisible hybrid cells will be referred to as dark matter hybrids, which cannot as yet be detected and quantified, but which contribute to tumor growth and progression.
Usefulness of virtual bronchoscopic navigation combined with endobronchial ultrasound guided transbronchial lung biopsy for solitary pulmonary nodules

Background: The aim of this study was to evaluate the diagnostic utility of virtual bronchoscopic navigation (VBN) combined with endobronchial ultrasound (EBUS) guided transbronchial lung biopsy for solitary pulmonary nodules (SPN). Methods: A total of 115 patients with suspected SPN who underwent transbronchial lung biopsy were evaluated. The patients were randomly divided into an EBUS (EBUS) group and a virtual bronchoscopic navigation combined with endobronchial ultrasound (VBN+EBUS) group. The diagnostic yield and examination time were compared. Results: There was no significant difference in the diagnostic yield between the VBN+EBUS group and the EBUS group (83.6% vs 66.7%, P = .419). When the lesions less than 20 mm in diameter of the lesions were analyzed, the diagnostic yield was higher in the VBN+EBUS group than in the EBUS group (80.0% vs 53.6%, P = .041). The time for positioning lesions in VBN+EBUS group was less than that in EBUS group (5.67 ± 2.48 min vs 8.65 ± 2.23 min, P = .015). But the total examination time was not significantly different between the 2 groups (20.59 ± 2.12 min vs 21.53 ± 1.62 min, P = .236). The incidence of complications did not differ between the 2 groups. Conclusions: In conclusion, VBN can shorten the positioning time and it is a safe and effective technique for pulmonary nodules.
Genetics of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) has been seen to run in families and genetics help to understand its heritability. In this review, we summarize older studies which focused on establishing the familial nature of OCD, including its various dimensions of symptoms, and we focus on recent findings from studies using both the candidate gene approach and genome-wide association study (GWAS) approach. The family studies and twin studies establish the heritability of OCD. Candidate gene approaches have implicated genes in the serotonergic, glutamatergic, and dopaminergic pathways. GWAS has not produced significant results possibly due to the small sample size. Newer techniques such as gene expression studies in brain tissue, stem cell technology, and epigenetic studies may shed more light on the complex genetic basis of OCD.
Electrode–Electrolyte Interface Modeling and Impedance Characterizing of Tripolar Concentric Ring Electrode

Electrodes are used to convert ionic currents to electrical currents in biological systems. Modeling the electrode–electrolyte interface and characterizing the impedance of the interface could help to optimize the performance of the electrode interface to achieve higher signal to noise ratios. Previous work has yielded accurate models for single-element biomedical electrodes. This paper introduces a model for a tripolar concentric ring electrode (TCRE) derived from impedance measurements using electrochemical impedance spectroscopy with a Ten20 electrode impedance matching paste. It is shown that the model serves well to predict the performance of the electrode–electrolyte interface for TCREs as well as standard cup electrodes. In this paper, we also discuss the comparison between the TCRE and the standard cup electrode regarding their impedance characterization and demonstrate the benefit of using TCREs in biomedical applications. We have also conducted auditory evoked potential experiments using both TCRE and standard cup electrodes. The results show that electroencephalography (EEG) recorded from tripolar concentric ring electrodes is beneficial, acquiring the auditory brainstem response with less stimuli with respect to recoding EEG using standard cup electrodes.
The N-glycan structures of the antigenic variants of chlorovirus PBCV-1 major capsid protein help to identify the virus-encoded glycosyltransferases

The chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) is a large dsDNA virus that infects the microalga Chlorella variabilis NC64A. Unlike most other viruses, PBCV-1 encodes most, if not all, of the machinery required to glycosylate its major capsid protein (MCP). The structures of the four N-linked glycans from the PBCV-1 MCP consist of nonasaccharides, and similar glycans are not found elsewhere in the three domains of life. Here, we identified the roles of three virus-encoded glycosyltransferases (GTs) that have four distinct GT activities in glycan synthesis. Two of the three GTs were previously annotated as GTs, but the third GT was identified in this study. We determined the GT functions by comparing the WT glycan structures from PBCV-1 with those from a set of PBCV-1 spontaneous GT gene mutants resulting in antigenic variants having truncated glycan structures. According to our working model, the virus gene a064r encodes a GT with three domains: domain 1 has a β-l-rhamnosyltransferase activity, domain 2 has an α-l-rhamnosyltransferase activity, and domain 3 is a methyltransferase that decorates two positions in the terminal α-l-rhamnose (Rha) unit. The a075l gene encodes a β-xylosyltransferase that attaches the distal d-xylose (Xyl) unit to the l-fucose (Fuc) that is part of the conserved N-glycan core region. Last, gene a071r encodes a GT that is involved in the attachment of a semiconserved element, α-d-Rha, to the same l-Fuc in the core region. Our results uncover GT activities that assemble four of the nine residues of the PBCV-1 MCP N-glycans.
Objective evaluation of fat tissue induration after breast reconstruction using a deep inferior epigastric perforator (DIEP) flap

Abstract Problems in breast reconstruction with deep inferior epigastric perforator (DIEP) flaps include postoperative fat induration and necrosis. A resulting clinical symptom is palpable indurated tissue, but it is difficult to measure the stiffness of transplanted fat tissues objectively at a deep site. The ability to perform shear-wave elastography (SWE) was recently added to some common ultrasonic echo devices, enabling objective three-dimensional measurements of tissue stiffness. In this study, we measured the stiffness of transplanted DIEP flaps using SWE to examine the effects of measurement sites, flap size and perforator patterns on stiffness. The subjects were 26 patients who showed induration of a transplanted flap on palpation in follow-up observation performed more than 6 months after breast reconstruction with a DIEP flap. The effects of the weight of the transplanted flap, and the diameter, number and location of the perforators on the stiffness of fat tissue were also analyzed. Within each zone, distal regions showed higher values, but in Zone II, significantly higher stiffness was also found in the proximal region. Multivariate regression analysis including all measurement sites, the weight of transplanted flap, and diameter, number and location of perforators showed that the stiffness of fat tissue was significantly higher in subjects with a larger weight flap. For safe reconstruction, it will be useful to examine the stiffness of fat tissue in individual regions of a transplanted flap retrospectively, because the examination results can be used in actual clinical practice.
BRAFV600E mutation in papillary thyroid carcinoma: a potential target for therapy?

This article reviews the therapeutic significance of the close genotype–phenotype association in papillary thyroid carcinoma, namely regarding the association between genetic alterations in RET, BRAF or RAS genes and the histopathological variants of papillary thyroid carcinoma. Based upon the aforementioned review on morphology and molecular pathology, the most recent prognostic and therapeutic data are reviewed and the role of targeted therapies, namely those interfering with BRAF-activated pathways are discussed, which may play a role in the treatment of patients with papillary thyroid carcinoma unresponsive to radioactive iodine.
Interpreting Hashtag Politics: Policy Ideas in an Era of Social Media, by S. Jeffares

Twitter is becoming the default platform for policy-makers to communicate their branded policy ideas and initiatives and a space for policy actors to endorse, critique and deride such initiatives: this is hashtag politics. Gaining an interpretive understanding of shortform messages has until now posed a challenge for policy studies, with a preference among scholars to keep clean, to measure the quantifiable metadata rather than interpret the ‘messy’ nuances of the message itself. In response, Stephen Jeffares explores the potential of interpretive analysis of hashtag politics and combines systematic online text analytics (and some Q methodology) to understand how policy ideas fare in an era of social media. Worked examples include the death of the big society, the introduction of elected policy commissioners, bedroom tax and compassionate care. The book argues interpretive policy analysis has much to offer our understanding of hashtag politics but requires new methods to interpret the meaning of high volume, variety and the velocity of big data.
Making RUP agile

The Unified Development Process (USDP) and especially its implementation by Rational Software Corporation, the Rational Unified Process (RUP), is a comprehensive process covering almost all aspects of software development projects. However, due to the great level of detail provided by RUP, many professionals do not consider RUP practical for small, fast paced projects. This paper reports the experiences with RUP on two small projects with teams of 3 to 5 developers. RUP proved to be adaptable to the needs of small projects and was very effective in both projects. One key to the successful application of RUP in small projects is the careful selection of a proper subset of artifacts and keeping these artifacts very concise and free from unnecessary formalism. This paper goes into the details of what it takes to make RUP agile, how it was applied in the two projects, and how it was configured. Also covered is what elements of RUP contributed to the success of one project, and why RUP could not prevent that the outcome of the other project was less than optimal.
Effect of acute experimental hand pain on left–right discrimination response latency for hand recognition

ABSTRACT Background: Recent work has indicated that acute experimental pain affects left–right discrimination latency. This phenomenon highlights an effect of pain on the cortex that may have significant clinical importance in the form of pain state assessment. However, to date only limited study has further qualified this effect. A more thorough understanding of the magnitude and characteristics of this phenomenon is needed to determine its potential clinical utility. Objective: This study aimed to closely replicate previous studies investigating response latency changes for left–right discrimination judgements as a result of acute experimental pain. Methods: Twenty-two right-handed participants (n = 11 female, n = 11 male) free from pain, analgesia use, pain-related conditions, upper limb trauma/conditions, visual impairment, and dyslexia took part in this study. Participants completed a hand left–right discrimination judgement task before, during, and after an experimental pain stimulus was delivered to each hand separately. Experimental pain was achieved using an intramuscular injection of hypertonic (5%) saline into the thenar eminence of the left and right hands. Mean response times for the left–right discrimination task were determined and compared for pain location (right, left), pain condition (before, during, after), and image laterality (right, left). Pain intensity was rated at 20 s intervals during each left–right discrimination task. Results: A main effect of pain condition (p = 0.028) confirmed that pain intensity was significantly higher in the “during pain” condition compared to the “before pain” and “after pain” conditions. A main effect of image laterality (p = 0.002) further showed that response latency for right-hand pain was significantly shorter compared to left-hand pain. No significant interaction between the factors pain location and image laterality (p = 0.086) was found. For right-hand pain, response latencies for the unaffected hand were, however, descriptively greater compared to the affected hand, and this was not the case for left-hand pain. Furthermore, no main effect of pain stimulus or of pain location on response times was found (p = 1.00 and p = 0.202, respectively). Conclusion: Our results were not consistent with previous hand left–right discrimination response latency results and may cast doubt on the attentional bias hypothesis that is currently considered to underpin response latency changes during acute experimental hand pain. Individual responses to pain, subsets of participants, and differing mental rotation strategies during the left–right discrimination task may have influenced the results.
Environmental Sources of Bacteria and Genetic Variation in Behavior Influence Host-Associated Microbiota

An animal’s behavior can affect its risk of infection, but it is not well understood how behavior affects microbiome composition. The aquatic crustacean Daphnia exhibits genetic variation in the extent to which it browses in the sediment at the bottoms of ponds. We show that this behavior affects the Daphnia microbiome, indicating that genetic variation among individuals may affect microbiome composition and the movement of bacteria in different environments. ABSTRACT In many organisms, host-associated microbial communities are acquired horizontally after birth. This process is believed to be shaped by a combination of environmental and host genetic factors. We examined whether genetic variation in animal behavior could affect the composition of the animal’s microbiota in different environments. The freshwater crustacean Daphnia magna is primarily planktonic but exhibits variation in the degree to which it browses in benthic sediments. We performed an experiment with clonal lines of D. magna showing different levels of sediment-browsing intensity exposed to either bacteria-rich or bacteria-poor sediment or whose access to sediments was prevented. We found that the bacterial composition of the environment and genotype-specific browsing intensity together influence the composition of the Daphnia-associated bacterial community. Exposure to more diverse bacteria did not lead to a more diverse microbiome, but greater abundances of environment-specific bacteria were found associated with host genotypes that exhibited greater browsing behavior. Our results indicate that, although there is a great deal of variation between individuals, behavior can mediate genotype-by-environment interaction effects on microbiome composition. IMPORTANCE An animal’s behavior can affect its risk of infection, but it is not well understood how behavior affects microbiome composition. The aquatic crustacean Daphnia exhibits genetic variation in the extent to which it browses in the sediment at the bottoms of ponds. We show that this behavior affects the Daphnia microbiome, indicating that genetic variation among individuals may affect microbiome composition and the movement of bacteria in different environments.
Safety and accuracy of robot-assisted versus fluoroscopy-assisted pedicle screw insertion in thoracolumbar spinal surgery: a prospective randomized controlled trial.

OBJECTIVEThe object of this study was to compare the safety and accuracy of pedicle screw placement using the TiRobot system versus conventional fluoroscopy in thoracolumbar spinal surgery.METHODSPatients with degenerative or traumatic thoracolumbar spinal disorders requiring spinal instrumentation were randomly assigned to either the TiRobot-assisted group (RG) or the freehand fluoroscopy-assisted group (FG) at a 1:1 ratio. The primary outcome measure was the accuracy of screw placement according to the Gertzbein-Robbins scale; grades A and B (pedicle breach < 2 mm) were considered clinically acceptable. In the RG, discrepancies between the planned and actual screw placements were measured by merging postoperative CT images with the trajectory planning images. Secondary outcome parameters included proximal facet joint violation, duration of surgery, intraoperative blood loss, conversion to freehand approach in the RG, postoperative hospital stay, and radiation exposure.RESULTSA total of 1116 pedicle screws were implanted in 234 patients (119 in the FG, and 115 in the RG). In the RG, 95.3% of the screws were perfectly positioned (grade A); the remaining screws were graded B (3.4%), C (0.9%), and D (0.4%). In the FG, 86.1% screws were perfectly positioned (grade A); the remaining screws were graded B (7.4%), C (4.6%), D (1.4%), and E (0.5%). The proportion of clinically acceptable screws was significantly greater in the RG than in the FG (p < 0.01). In the RG, the mean deviation was 1.5 ± 0.8 mm for each screw. The most common direction of screw deviation was lateral in the RG and medial in the FG. Two misplaced screws in the FG required revision surgery, whereas no revision was required in the RG. None of the screws in the RG violated the proximal facet joint, whereas 12 screws (2.1%) in the FG violated the proximal facet joint (p < 0.01). The RG had significantly less blood loss (186.0 ± 255.3 ml) than the FG (217.0 ± 174.3 ml; p < 0.05). There were no significant differences between the two groups in terms of surgical time and postoperative hospital stay. The mean cumulative radiation time was 81.5 ± 38.6 seconds in the RG and 71.5 ± 44.2 seconds in the FG (p = 0.07). Surgeon radiation exposure was significantly less in the RG (21.7 ± 11.5 μSv) than in the FG (70.5 ± 42.0 μSv; p < 0.01). CONCLUSIONSTiRobot-guided pedicle screw placement is safe and useful in thoracolumbar spinal surgery.Clinical trial registration no.: NCT02890043 (clinicaltrials.gov).
HBV T1719G mutation reduced HBV replication through mutant Enh II and HBx protein in vitro

It was repeatedly reported that the hepatitis B virus (HBV) T1719G mutation was very common and related to progression and malignancy of liver disease. However, its effect on viral replication efficiency remains unclear. In this study, we aimed to evaluate the function and mechanisms of the T1719G mutation on viral replication capacity. Wild‐type and T1719G mutation‐bearing HBV1.2× plasmids were transfected into Huh7 and HepG2 cells, respectively, and HBV total RNA, 3.5 kb RNA and supernatant HBV DNA were assessed using real‐time PCR, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured by time‐resolved fluoroimmunoassay. In order to assess Enh II activity and the binding capacity of HNF3β to Enh II sequence, dual‐luciferase assay and Chromatin immunoprecipitation (ChIP)‐PCR were employed, respectively. Simultaneously, the HBx or HBx‐mut (T1719G) plasmid was co‐transfected to evaluate the effect of HBx on viral replication. Our results showed that the T1719G mutation impaired viral replication efficacy compared with the wild type both by reducing Enh II activity and binding capacity of HNF3β with Enh II. And such reduction caused by T1719G mutation could be rescued by HBx protein. Our results show that the T1719G mutation decreases HBV viral replication capacity possibly by mutant HBx protein and altered Enh II activity.
Contemporary point of care cardiac troponin testing in suspected acute coronary syndrome

Around one million patients present to hospital with chest pain every year, accounting for approximately 5% of all emergency department attendances in the UK. However, only one in five patients are found to have had a myocardial infarction.1 Therefore, for several years, there has been a drive to develop diagnostic strategies which allow accurate identification of patients without myocardial infarction at an earlier stage, who may not require admission to hospital for serial cardiac biomarker testing. Such strategies have the potential to improve patient experience and optimise resource allocation both in the emergency department and in hospital, at a time of ever-increasing demands. Cardiac troponin is the biomarker of choice for the detection of myocardial injury, and international guidelines recommend concentrations are measured using a high-sensitivity assay.2 While high-sensitivity assays were first introduced in Europe in 2010, they have only recently become available for use in clinical practice in the USA. The higher precision and lower limits of detection afforded by these tests has facilitated the development of pathways which can rule out myocardial infarction at an earlier stage, the majority of which have demonstrated a magnitude of benefits in diagnostic accuracy compared with using the recommended diagnostic threshold (99th centile) alone.3 4 In practical terms, implementation of these approaches requires investment in infrastructure to deliver accurate and timely cardiac troponin results on a high-sensitivity platform which is not always available. One potential strategy to improve …