Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechano‐energetic aspects of Barth syndrome

Energy‐demanding organs like the heart are strongly dependent on oxidative phosphorylation in mitochondria. Oxidative phosphorylation is governed by the respiratory chain located in the inner mitochondrial membrane. The inner mitochondrial membrane is the only cellular membrane with significant amounts of the phospholipid cardiolipin, and cardiolipin was found to directly interact with a number of essential protein complexes, including respiratory chain complexes I to V. An inherited defect in the biogenesis of cardiolipin causes Barth syndrome, which is associated with cardiomyopathy, skeletal myopathy, neutropenia and growth retardation. Energy conversion is dependent on reducing equivalents, which are replenished by oxidative metabolism in the Krebs cycle. Cardiolipin deficiency in Barth syndrome also affects Krebs cycle activity, metabolite transport and mitochondrial morphology. During excitation‐contraction coupling, calcium (Ca2+) released from the sarcoplasmic reticulum drives sarcomeric contraction. At the same time, Ca2+ influx into mitochondria drives the activation of Krebs cycle dehydrogenases and the regeneration of reducing equivalents. Reducing equivalents are essential not only for energy conversion, but also for maintaining a redox buffer, which is required to detoxify reactive oxygen species (ROS). Defects in CL may also affect Ca2+ uptake into mitochondria and thereby hamper energy supply and demand matching, but also detoxification of ROS. Here, we review the impact of cardiolipin deficiency on mitochondrial function in Barth syndrome and discuss potential therapeutic strategies.
Association of Dromedary Camels and Camel Ticks with Reassortant Crimean-Congo Hemorrhagic Fever Virus, United Arab Emirates

We previously detected a potentially novel reassortant of Crimean-Congo hemorrhagic fever virus in camels at the largest livestock market in the United Arab Emirates. A broader survey of large mammals at the site indicated zoonotic transmission is associated with dromedaries and camel ticks. Seroprevalence in cattle, sheep, and goats is minimal.
Altered regulation of BRCA1 exon 11 splicing is associated with breast cancer risk in carriers of BRCA1 pathogenic variants

Germline pathogenic variants in BRCA1 confer a high risk of developing breast and ovarian cancer. The BRCA1 exon 11 (formally exon 10) is one of the largest exons and codes for the nuclear localization signals of the corresponding gene product. This exon can be partially or entirely skipped during pre‐mRNA splicing, leading to three major in‐frame isoforms that are detectable in most cell types and tissue, and in normal and cancer settings. However, it is unclear whether the splicing imbalance of this exon is associated with cancer risk. Here we identify a common genetic variant in intron 10, rs5820483 (NC_000017.11:g.43095106_43095108dup), which is associated with exon 11 isoform expression and alternative splicing, and with the risk of breast cancer, but not ovarian cancer, in BRCA1 pathogenic variant carriers. The identification of this genetic effect was confirmed by analogous observations in mouse cells and tissue in which a loxP sequence was inserted in the syntenic intronic region. The prediction that the rs5820483 minor allele variant would create a binding site for the splicing silencer hnRNP A1 was confirmed by pull‐down assays. Our data suggest that perturbation of BRCA1 exon 11 splicing modifies the breast cancer risk conferred by pathogenic variants of this gene.
The discursive construction of HIV stigma in Irish print media

As interlocutors in national level discourse with the power to influence public opinion and inform policy, the news media are an important data source in understanding the constitutive roles played by culture and discourse in shaping health experiences and outcomes. This paper reports on a critical discourse analysis of news media coverage of HIV in the Republic of Ireland between 2006 and 2016. This period is significant because of the considerable increase in new HIV diagnoses that occurred in Ireland after the 2008 recession. Analysis of articles (n = 103) demonstrated a pattern of dividing practices whereby people living with or affected by HIV were frequently positioned as somatically and morally deficient via discourses of risk and responsibility. Little focus was given over to examination of the structural drivers of HIV, occluding the social context of the epidemic. The findings suggest that media discourses on HIV have the potential to other people living with HIV and generate stigma by invoking a dynamic of blame and shame frequently implicated in the stigma process.
Peer Assessment Rating (PAR) scoring of cleft patients treated within a regional cleft centre in the United Kingdom

Objective: To assess static occlusal outcomes for patients with cleft lip and/or palate (CLP) and cleft palate (CP) managed within a UK Regional Cleft Service and to compare with previously published Peer Assessment Rating (PAR) scores from a non-cleft population of patients treated within a UK consultant-led hospital service. Design: Retrospective multicentre study. Setting: Eight orthodontic hospital units within the Spires Cleft Service, UK. Participants: Patients born with CLP or CP between 1985 and 1995 treated within the service. Methods: Patients were assigned to groups by cleft type and whether they were treated by orthodontics only or a combination of orthodontics and orthognathic surgery. PAR was recorded before and after treatment from study models. Results: Data were collected for 171 patients included in the study. Median pre-treatment PAR was 42 and post-treatment 11. Median percentage change in PAR for all patients was 73%, although 12% of cleft patients had a PAR improvement that was worse or no different. Median change in PAR score was 71% for those treated with orthodontics only and 83% for those who had an osteotomy. Median PAR improvement for those treated with orthodontics only was 73% in the cleft lip group, 77% in the CP group, 66% in the unilateral CLP group and 53% in the bilateral CLP group. Median pre- and post-treatment PAR for the cleft group was higher and PAR reduction lower than those published for non-cleft patients. Conclusion: These data demonstrate high severity of malocclusion, complexity of orthodontic treatment and difficulty in achieving an ideal static occlusion for cleft patients. If PAR is to be used to assess orthodontic outcomes in cleft patients the findings of this study should be considered. A higher proportion of cases are likely to be classed as ‘worse or no different’, and a lower percentage change will be expected.
Is high-intensity focused ultrasound (HIFU) an option for neoadjuvant therapy for borderline resectable pancreatic cancer patients? – a systematic review

Abstract Introduction Pancreatic cancer is with the poorest prognosis of all common cancers worldwide. Despite the advances in treatment the results are poor throughout the different methods. Pancreatic resection still yields the best outcome. However only a quarter of the patients present at operable stage. HIFU is a noninvasive technique that can be used to treat pancreatic cancer. Aim The aim of this review is to perform a systematic review on the data about the resection rate after HIFU ablation in patients with borderline resectable pancreatic cancer (BRPC) and the impact of this technique over the oncological results. Materials and methods The PubMed and Wanfang databases were searched using keywords: pancreatic cancer, HIFU ablation and high-intensity focused ultrasound. All found articles were reviewed. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard guidelines. This study was financially supported by 2019 ‘Kuan-Ren Elite’ Program of 2nd Affiliated Hospital of Chongqing Medical University, China (Grant no. KY2019G019). Results The English database search showed 109 papers, of which 3 met the inclusion criteria. The Wanfang database resulted in 110 papers; however, none met the inclusion criteria of the review. From the included studies 97 patients underwent neoadjuvant HIFU ablation ± chemotherapy. Thirty-four patients reached resection (35.1%). In two patients, residual tumor (R) classification was not reported. R0 resection rate in all reported patients is 30.5% (29/95). R1 resection rate is 3.2% (3/95). Conclusion HIFU is found to be safe and feasible in locally advanced and metastatic pancreatic cancer with proven downstaging and downsizing effects. Further research on role of HIFU ablation as a neoadjuvant treatment for borderline resectable pancreatic cancer is needed.
Cytosolic and Mitochondrial Hsp90 in Cytokinesis, Mitochondrial DNA Replication, and Drug Action in Trypanosoma brucei

Trypanosoma brucei subspecies cause African sleeping sickness in humans, an infection that is commonly fatal if not treated, and available therapies are limited. Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors have potent and vivid activity against bloodstream-form trypanosomes. ABSTRACT Trypanosoma brucei subspecies cause African sleeping sickness in humans, an infection that is commonly fatal if not treated, and available therapies are limited. Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors have potent and vivid activity against bloodstream-form trypanosomes. Hsp90s are phylogenetically conserved and essential catalysts that function at the crux of cell biology, where they ensure the proper folding of proteins and their assembly into multicomponent complexes. To assess the specificity of Hsp90 inhibitors and further define the role of Hsp90s in African trypanosomes, we used RNA interference (RNAi) to knock down cytosolic and mitochondrial Hsp90s (HSP83 and HSP84, respectively). Loss of either protein led to cell death, but the phenotypes were distinctly different. Depletion of cytosolic HSP83 closely mimicked the consequences of chemically depleting Hsp90 activity with inhibitor 17-AAG. In these cells, cytokinesis was severely disrupted, and segregation of the kinetoplast (the massive mitochondrial DNA structure unique to this family of eukaryotic pathogens) was impaired, leading to cells with abnormal kinetoplast DNA (kDNA) structures. Quite differently, knockdown of mitochondrial HSP84 did not impair cytokinesis but halted the initiation of new kDNA synthesis, generating cells without kDNA. These findings highlight the central role of Hsp90s in chaperoning cell cycle regulators in trypanosomes, reveal their unique function in kinetoplast replication, and reinforce their specificity and value as drug targets.
Improved Inception V3 method and its effect on radiologists' performance of tumor classification with automated breast ultrasound system.

Background The automated breast ultrasound system (ABUS) is recognized as a valuable detection tool in addition to mammography. The purpose of this study was to propose a novel computer-aided diagnosis (CAD) system by extracting the textural features from ABUS images and to investigate the efficiency of using this CAD for breast cancer detection. Methods This retrospective study involved 149 breast nodules [maximum diameter: mean size 18.89 mm, standard deviation (SD) 10.238, and range 5-59 mm] in 135. We assigned 3 novice readers (<3 years of experience and 3 experienced readers (≥10 years of experience to review the imaging data and stratify the 149 breast nodules as either malignant or benign. The Improved Inception V3 (II3) method was developed and used as an assistant tool to help the 6 readers to re-interpret the images. Results Our method (II3) achieved an accuracy of 88.6% for the final result. The 3 novice readers had an average accuracy of 71.37%±4.067% while the 3 experienced readers was 83.03%±3.371% on the first-reading. With the help of II3 on the second-reading, the average accuracy of the novice readers increased to 84.13%±1.662% and the experienced readers increased to 89.50%±0.346%. The areas under the curve (AUCs) were similar compared with linear algorithms. The mean AUC of the novice readers was improved from 0.7751 (without II3) to 0.8232 (with II3). The mean AUC of the experienced readers was improved from 0.8939 (without II3) to 0.9211 (with II3). The mean AUC for all readers improved in both the second-reading mode (from 0.8345 to 0.8722, P=0.0081<0.05). Conclusions With the help of the II3, the diagnostic accuracy of the two groups were both improved, and II3 was more helpful for novice readers than for experienced readers. Our results showed that II3 is valuable in the differentiation of benign and malignant breast nodules and it also improves the experience and skill of some novice radiologists. The II3 cannot completely replace the influence of experience in the diagnostic process and will retain an auxiliary role in the clinic at present.
Association between individual surgeon volume and outcome in mitral valve surgery: a systematic review

Background Surgeon volume has been identified as a possible factor that influences outcomes in mitral valve (MV) surgery. The aim of this study was to systematically review all published studies on the association between individual surgeon volume and outcome in MV surgery. Methods PubMed was searched last on 19 November 2020. The reporting of this systematic review was done in accordance with PRISMA guidelines. Manuscripts were eligible when these studied individual surgeon volumes and its association with repair rate, mortality or reoperation. The methodological quality of the studies was assessed with the Newcastle-Ottawa Scale (NOS). Absolute numbers and percentages of the outcome measures, odds ratios (ORs), P values and threshold values regarding surgeon volume were collected. Results A total of 7 retrospective cohort studies were included in the qualitative analysis with total of 158488 patients. Definitions of surgeon volumes were found to be heterogenic and therefore pooling of data was not possible. Surgeon volume was significantly associated with repair rate (OR =1.25–5.5) and mortality (OR =0.46–0.84 and OR =1.50–2.27 depending on the reference group). Regarding reoperation, results were not consistent and did not always show a significant lower reoperation rate when surgeon volume increased. A mean threshold of minimally 30 MV surgeries per year was found. Discussion Higher surgeon volume is significantly associated with improved outcomes of repair rate and mortality. MV should preferentially be performed by high-volume surgeons and centralization of MV surgery might be necessary.
Heparin Monitoring with an Anti-Xa Protocol Compared to Activated Clotting Time in Patients on Temporary Mechanical Circulatory Support

Background: Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established. Objective: To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients. Methods: A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range. Results: There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group (P = 0.017). An anti-Xa–based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups. Conclusion and Relevance: Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.
Novel electrodes for precise and accurate droplet dispensing and splitting in digital microfluidics

Abstract Digital microfluidics (DMF) is a versatile fluid handling tool that is widely used in the biochemical field. There are very high requirements for the volume of single droplet in many biochemical applications. Droplet dispensing and splitting are two main operations to generate a single droplet in DMF. Therefore, the generation of droplets with high volume precision and accuracy in the two droplet operations is one of the keys to the efficient application of DMF in biochemical analysis. We have developed a novel droplet dispensing and splitting scheme where electrode geometry is optimized. The liquid column can contract in a regular shape, which keep the neck shape uniform and stable, and the position of pinch-off point was fixed; meanwhile, the liquid tail is eliminated before pinching off, so that the precision and accuracy of droplet volume were greatly improved. The increase in the radius of the cutting electrodes elongated the droplet neck and increased the neck curvature at the pinch-off point, which further effectively improved the precision and accuracy of droplet volume. The optimized droplet splitting scheme can also be applied to the droplet splitting with unequal volume effectively.
The G protein-first activation mechanism of opioid receptors by Gi protein and agonists

Abstract G protein-first mechanism of activation for opioid receptors and their cognate Gi protein. Σ0: In the absence of ligand and Gi protein, the opioid receptors adopt the inactive conformation, featuring a tight hydrogen bond between the cytosolic ends of TM3 and TM6 that keeps the cytoplasmic region tightly closed. Σ1: Before agonist binding, the inactive Gi protein tightly bound to GDP couples to inactive opioid receptor, to form a pre-coupled opioid receptor-Gi (GDP) complex. Σ2: Interactions between inactive opioid receptor and inactive Gi (GDP) leads to breaking the TM3-TM6 hydrogen bond and opening the cytoplasmic region of the receptors to accommodate the Gi protein. As a result, the pre-activated state (Σ2) emerges, which remains at this resting state until an agonist binds the receptor. Σ3′: agonist bound to the pre-activated state induces the Gi (GDP) to be activated. Activation of the Gi protein is associated with a remarkable opening in the cleft between AH and Ras-like domains of Gα, providing an exit path for GDP release or exchange with a GTP. Σ4′: Upon GDP release of exchange, the agonist-opioid receptor-Gi protein evolves to its fully active state. Abstract We report the G protein-first mechanism for activation of G protein-coupled receptors (GPCR) for the three closest subtypes of the opioid receptors (OR), μOR, κOR and δOR. We find that they couple to the inactive Gi protein-bound guanosine diphosphate (GDP) prior to agonist binding. The inactive Gi protein forms anchors to the intracellular loops of the inactive apo-μOR, apo-κOR and apo-δOR, inducing opening of the cytoplasmic region to form a pre-activated state that holds Gi protein in place until agonist binds. Then, agonist binds to μOR, κOR and δOR already complexed with Gi protein, to trigger the Gαi to open up the tightly coupled GDP binding site, making GDP accessible for GTP exchange, an essential step for Gi signalling. We show that the agonist alone cannot open the intracellular region of μOR and κOR, requiring Gi protein to open the cytoplasmic region by itself. We consider that this G protein-first mechanism may apply to activation of other Class A GPCRs. However, for δOR, agonist binding can open up the intracellular region to encourage Gi protein recruitment. Thus, activation of Gi protein mediated by δOR favourably may proceed with either ligand-first or G protein-first activation mechanisms.
Discrete Optimization for Shape Matching

We propose a novel discrete solver for optimizing functional map‐based energies, including descriptor preservation and promoting structural properties such as area‐preservation, bijectivity and Laplacian commutativity among others. Unlike the commonly‐used continuous optimization methods, our approach enforces the functional map to be associated with a pointwise correspondence as a hard constraint, which provides a stronger link between optimized properties of functional and point‐to‐point maps. Under this hard constraint, our solver obtains functional maps with lower energy values compared to the standard continuous strategies. Perhaps more importantly, the recovered pointwise maps from our discrete solver preserve the optimized for functional properties and are thus of higher overall quality. We demonstrate the advantages of our discrete solver on a range of energies and shape categories, compared to existing techniques for promoting pointwise maps within the functional map framework. Finally, with this solver in hand, we introduce a novel Effective Functional Map Refinement (EFMR) method which achieves the state‐of‐the‐art accuracy on the SHREC'19 benchmark.
Multispectral hand features for secure biometric authentication systems

With rapid growth of mobile‐based computing, reliable security and user authentication methods are necessary. This article proposes a proof‐of‐concept biometric authentication method utilizing hand images collected in different light spectra. An analysis of similarity between pattern of blood vessels extracted from near‐infrared images and thermal images and assessment of the correlation between individual biometric features contained in each image type is also performed. Results indicate a large potential of using thermal images in biometrics more extensively than now. Also proposed and evaluated are biometric recognition methods based on images of the hand acquired in visible light, near infrared, and using thermal infrared sensors. Two approaches were used to assess information content in images of each type: one based on texture descriptor and one employing convolutional neural networks. In an evaluation gathering data from 104 subjects, the former yielded the lowest equal error rate (EER) of 7.44% , whereas the latter approach gave EER=0.03% for thermal images. Finally, fusion of different‐spectra modalities increases accuracy and further reduces EER to 0.01% . This is, to the authors' best knowledge, the first study exploring the concept of fusing different spectral representations of the human hand for the purpose of biometric recognition.