Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel SLC9A6 mutations in two families with Christianson syndrome

To the Editor : Mutations in SLC9A6 are associated with Christianson syndrome, a syndromic form of X-linked intellectual disability characterized by severe intellectual disability, acquired microcephaly, seizures and ataxia (1, 2). Only nine mutations and two genomic aberrations involving SLC9A6 have been reported to date (1–7). Here, we report on two German families with novel SLC9A6 mutations. The index patient (IV:3, Fig. 1a–c) of family 1 was born with normal birth measurements. He suffered from feeding difficulties in the first weeks of life and had seizures starting from 10 months. At the age of 18 months, he had microcephaly [OFC, occipitofrontal circumference 44 cm (<3rd centile), height 82 cm (25th centile), weight 10 kg (10th centile)] and could neither walk nor talk. His sister (IV:1) had slightly delayed language
Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1

One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.
Design, Implementation and Analysis of Composite Material Dampers for Turning Operations

With advances in material technology, allowing, for instance, engines to withstand higher combustion pressure and consequently improving performance, comes challenges to productivity. These materials are, in fact, more difficult to machine with regards to tool wear and especially machine tool stability. Machining vibrations have historically been one of the major limitations to productivity and product quality and the cost of machining vibration for cylinder head manufacturing has been estimated at 0.35 euro per part.The literature review shows that most of the research on cutting stability has been concentrating on the use of the stability limits diagram (SLD), addressing the limitations of this approach. On the other hand, research dedicated to development of machine tool components designed for chatter avoidance has been concentrating solely on one component at the time.This thesis proposes therefore to extend the stability limits of the machining system by enhancing the structure’s damping capability via a unified concept based on the distribution of damping within the machining system exploiting the joints composing the machine tool structure. The design solution proposed is based on the enhancement of damping of joint through the exploitation of viscoelastic polymers’ damping properties consciously designed as High Damping Interfaces (HDI). The tool-turret joint and the turret-lathe joint have been analysed. The computational models for dimensioning the HDI’s within these joints are presented in the thesis and validated by the experiments. The models offer the possibility of consciously design damping in the machining system structure and balance it with regards to the needed stiffness.These models and the experimental results demonstrate that the approach of enhancing joint damping is viable and effective. The unified concept of the full chain of redesigned components enables the generation of the lowest surface roughness over the whole range of tested cutting parameters. The improved machining system is not affected by instability at any of the tested cutting parameters and offers an outstanding surface quality.The major scientific contribution of this thesis is therefore represented by the proposed unified concept for designing damping in a machining system alongside the models for computation and optimisation of the HDIs.From the industrial application point of view, the presented approach allows the end user to select the most suitable parameters in terms of productivity as the enhanced machine tool system becomes less sensitive to stability issues provoked by difficult-to-machine materials or fluctuations of the work material properties that may occur in ordinary production processes.
Success Stories In Simulation In Health Care

Healthcare is a rapidly changing industry, and facilities are struggling to find tools to enhance their ability to keep up with the change. Healthcare staff have generally adapted well, however are rarely in agreement as to how to migrate to a new environment, whether physical, functional or both. Simulation allows significant exploration of multiple options, without spending enormous amounts of money on staff, training, equipment, and most importantly, without risking possible degradation in the level of healthcare. This paper will describe the use of simulation in pre-op procedures, space utilization and outpatient studies. 1 PRE-OPERATION PROCEDURES
Precision of a photogrammetric method to perform 3D wound measurements compared to standard 2D photographic techniques in the horse.

REASONS FOR PERFORMING STUDY Methods of 3D wound imaging in man play an important role in monitoring of healing and determination of the prognosis. Standard photographic assessments in equine wound management consist of 2D analyses, which provide little quantitative information on the wound bed. HYPOTHESES 3D imaging of equine wounds is feasible using principles of stereophotogrammetry. 3D measurements differ significantly and are more precise than results with standard 2D assessments. METHODS Repeated specialised photographic imaging of 4 clinical wounds left to heal by second intention was performed. The intraoperator variability in measurements due to imaging and 3D processing was compared to that of a standard 2D technique using descriptive statistics and multivariate repeated measures ANOVA. RESULTS Using a custom made imaging system, 3D analyses were successfully performed. Area and circumference measurements were significantly different between imaging modalities. The intraoperator variability of 3D measurements was up to 2.8 times less than that of 2D results. On average, the maximum discrepancy between repeated measurements was 5.8% of the mean for 3D and 17.3% of the mean for 2D assessments. CONCLUSIONS The intraoperator repeatability of 3D wound measurements based on principles of stereophotogrammetry is significantly increased compared to that of a standard 2D photographic technique indicating it may be a useful diagnostic and monitoring tool. POTENTIAL RELEVANCE The equine granulation bed plays an important role in equine wound healing. When compared to 2D analyses 3D monitoring of the equine wound bed allows superior quantitative characterisation, contributing to clinical and experimental investigations by offering potential new parameters.
Rescue of Monocrotaline-Induced Pulmonary Arterial Hypertension Using Bone Marrow–Derived Endothelial-Like Progenitor Cells: Efficacy of Combined Cell and eNOS Gene Therapy in Established Disease

Pulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance caused by narrowing and loss of pulmonary microvasculature, which in its late stages becomes refractory to traditional therapies. We hypothesized that bone marrow–derived endothelial progenitor cells (EPCs), which normally function to repair and regenerate blood vessels, would restore pulmonary hemodynamics and increase microvascular perfusion in the rat monocrotaline (MCT) model of PAH. Mononuclear cells were isolated from the bone marrow of syngeneic Fisher-344 rats by Ficoll gradient centrifugation and cultured for 7 to 10 days in endothelial growth medium. Fluorescently labeled endothelial-like progenitor cells (ELPCs) engrafted at the level of the distal pulmonary arterioles and incorporated into the endothelial lining in the MCT-injured lung. The administration of ELPCs 3 days after MCT nearly completely prevented the increase in right ventricular systolic pressure seen at 3 weeks with MCT alone (31.5±0.95 versus 48±3 mm Hg, respectively; P<0.001), whereas injection of skin fibroblasts had no protective effect (50.9±5.4 mm Hg). Delayed administration of progenitor cells 3 weeks after MCT prevented the further progression of PAH 2 weeks later (ie, 5 weeks after MCT), whereas only animals receiving ELPCs transduced with human endothelial NO-synthase (eNOS) exhibited significant reversal of established disease at day 35 (31±2 mm Hg, P<0.005) compared with day 21 (50±3 mm Hg). Fluorescent microangiography revealed widespread occlusion of pulmonary precapillary arterioles 3 weeks after MCT, whereas arteriolar-capillary continuity and microvascular architecture was preserved with the administration of syngeneic ELPCs. Moreover, the delivery of ELPCs to rats with established PAH resulted in marked improvement in survival, which was greatest in the group receiving eNOS-transduced cells. We conclude that bone marrow–derived ELPCs can engraft and repair the MCT-damaged lung, restoring microvasculature structure and function. Therefore, the regeneration of lung vascular endothelium by injection of progenitor cells may represent a novel treatment paradigm for patients with PAH.
Obesity Is an Adverse Factor on Laparoscopic Radical Nephrectomy for T2 but Not T1 Renal Cell Carcinoma

Purpose Laparoscopic radical nephrectomy (LRN) is more challenging with increases in body mass index (BMI). Several recent studies have shown, however, that LRN can be safely performed even in obese patients. The influence of obesity on the perioperative outcomes of LRN has not been well elucidated for large renal tumors (>7 cm), however. We estimated the impact of obesity on LRN for stage T1 and T2 renal cell carcinoma (RCC). Materials and Methods From January 2004 to March 2011, 266 patients underwent LRN (T1: 195, T2: 71). These patients were subdivided into the following two groups according to BMI: the nonobese group (BMI less than 25 kg/m2) and the obese group (BMI greater than 25 kg/m2). Perioperative outcomes were retrospectively compared between these two groups in T1 and T2 RCC patients. Results There were no significant differences in perioperative outcomes between the obese and nonobese groups of T1 RCC patients. However, in T2 RCC patients, operative time and complication rate were significantly increased in the obese group. Conclusions Our results suggest that LRN can be safely performed in Korean patients with T1 RCC regardless of obesity. In T2 RCC patients, however, LRN may become more difficult with increasing BMI considering a longer operation time as well as a higher complication rate. We suggest that LRN for obese patients with T2 RCC be carefully considered.
ParaSense or How to Use Parallel Corpora for Word Sense Disambiguation

This paper describes a set of exploratory experiments for a multilingual classification-based approach to Word Sense Disambiguation. Instead of using a predefined monolingual sense-inventory such as WordNet, we use a language-independent framework where the word senses are derived automatically from word alignments on a parallel corpus. We built five classifiers with English as an input language and translations in the five supported languages (viz. French, Dutch, Italian, Spanish and German) as classification output. The feature vectors incorporate both the more traditional local context features, as well as binary bag-of-words features that are extracted from the aligned translations. Our results show that the ParaSense multilingual WSD system shows very competitive results compared to the best systems that were evaluated on the SemEval-2010 Cross-Lingual Word Sense Disambiguation task for all five target languages.
DYRK1A: A Promising Drug Target for Islet Transplant–Based Diabetes Therapies

A hallmark of all forms of diabetes, including type 2, is abnormal insulin release by pancreatic islets. This occurs either through impaired β-cell function and/or a reduction in β-cell number resulting from apoptosis or dedifferentiation (1). Currently available drugs only temporally ameliorate these processes, and many patients need insulin injections to reduce hyperglycemia 10–15 years after diagnosis (2). Mass transplantation of islets is not feasible due to the low availability of donor islets and side effects caused by immunosuppression. Further, although notable progress in targeted differentiation of stem cells into functional β-cells has been made (3), this approach has not yet advanced into routine clinical practice. An obvious therapeutic approach to improve islet transplantation would be to pharmacologically stimulate the proliferation of β-cells (Fig. 1) (4). These pharmacological agents could be used either to treat human islets before transplantation or to supplement protocols that transform stem cells into transplantable human islets. Alternatively, they could be used as oral medication to enhance β-cell proliferation once safety concerns are fully addressed. Figure 1 Pancreatic islets are composed of different endocrine cells, in particular insulin-secreting β-cells (shown in pink). These cells secrete insulin into a dense microvascular network for distribution to peripheral tissues. Several structurally unrelated inhibitors of DYRK1A (e.g., 5-IT, harmine, and GNF4877) have been recently identified to …
Investigating microbial co-occurrence patterns based on metagenomic compositional data

MOTIVATION The high-throughput sequencing technologies have provided a powerful tool to study the microbial organisms living in various environments. Characterizing microbial interactions can give us insights into how they live and work together as a community. Metagonomic data are usually summarized in a compositional fashion due to varying sampling/sequencing depths from one sample to another. We study the co-occurrence patterns of microbial organisms using their relative abundance information. Analyzing compositional data using conventional correlation methods has been shown prone to bias that leads to artifactual correlations. RESULTS We propose a novel method, regularized estimation of the basis covariance based on compositional data (REBACCA), to identify significant co-occurrence patterns by finding sparse solutions to a system with a deficient rank. To be specific, we construct the system using log ratios of count or proportion data and solve the system using the l1-norm shrinkage method. Our comprehensive simulation studies show that REBACCA (i) achieves higher accuracy in general than the existing methods when a sparse condition is satisfied; (ii) controls the false positives at a pre-specified level, while other methods fail in various cases and (iii) runs considerably faster than the existing comparable method. REBACCA is also applied to several real metagenomic datasets. AVAILABILITY AND IMPLEMENTATION The R codes for the proposed method are available at http://faculty.wcas. northwestern.edu/∼hji403/REBACCA.htm CONTACT hongmei@northwestern.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
The effectiveness of a supportive educative group intervention on family caregiver burden of patients with heart failure

Background: Living with heart failure patients is a complex situation for family caregivers. Few studies have been conducted to examine the effects of interventional programs to ease this condition. The purpose of this study was to determine the effectiveness of a supportive educative group intervention in reducing family caregivers’ burden of caregiving. Materials and Methods: This randomized clinical trail was conducted at a selective teaching hospital in Isfahan, Iran in 2012. The intervention consisted of four weekly multimedia training sessions of 2 h that included education and family support for 50 family caregivers. Caregiver burden was measured using the Zarit Burden Interview (ZBI). Paired t-test, Student's t-tests, and repeated measures analysis of variance (ANOVA) were used to test for significant differences of the mean scores of burden between the intervention and control groups over a 3-month period. Results: The intervention was successful in reducing caregiver burden over time both at the end of the intervention period (P = 0.000) and 3 months after the intervention (P = 0.000). Conclusions: Nurses and other healthcare providers can use the findings of this study in order to implement effective programs to reduce family caregivers’ challenges and to provide them more support.
Unlock the Door to my Secrets, but don't Forget to Glitch A comprehensive analysis of flash erase suppression attacks

In this work, we look into an attack vector known as flash erase suppression. Many microcontrollers have a feature that allows the debug interface protection to be deactivated after wiping the entire flash memory. The flash erase suppression attack exploits this feature by glitching the mass erase, allowing unlimited access to the data stored in flash memory. This type of attack was presented in a confined context by Schink et al. at CHES 2021. In this paper, we investigate whether this generic attack vector poses a serious threat to real-world products. For this to be true, the success rate of the attack must be sufficiently high, as otherwise, device unique secrets might be erased. Further, the applicability to different devices, different glitching setups, cost, and limitations must be explored. We present the first in-depth analysis of this attack vector. Our study yields that realistic attacks on devices from multiple vendors are possible. As countermeasures can hardly be retrofitted with software, our findings should be considered by users when choosing microcontrollers for security-relevant products or for protection of intellectual property (IP), as well by hardware designers when creating next generation microcontrollers.
Coronary side-effect potential of current and prospective antimigraine drugs.

BACKGROUND The antimigraine drugs ergotamine and sumatriptan may cause angina-like symptoms, possibly resulting from coronary artery constriction. We compared the coronary vasoconstrictor potential of a number of current and prospective antimigraine drugs (ergotamine, dihydroergotamine, methysergide and its metabolite methylergometrine, sumatriptan, naratriptan, zolmitriptan, rizatriptan, avitriptan). METHODS AND RESULTS Concentration-response curves to the antimigraine drugs were constructed in human isolated coronary artery segments to obtain the maximum contractile response (Emax) and the concentration eliciting 50% of Emax (EC50). The EC50 values were related to maximum plasma concentrations (Cmax) reported in patients, obtaining Cmax/EC50 ratios as an index of coronary vasoconstriction occurring in the clinical setting. Furthermore, we studied the duration of contractile responses after washout of the acutely acting antimigraine drugs to assess their disappearance from the receptor biophase. Compared with sumatriptan, all drugs were more potent (lower EC50 values) in contracting the coronary artery but had similar efficacies (Emax <25% of K+-induced contraction). The Cmax of avitriptan was 7- to 11-fold higher than its EC50 value, whereas those of the other drugs were <40% of their respective EC50 values. The contractile responses to ergotamine and dihydroergotamine persisted even after repeated washings, but those to the other drugs declined rapidly after washing. CONCLUSIONS All current and prospective antimigraine drugs contract the human coronary artery in vitro, but in view of low efficacy, these drugs are unlikely to cause myocardial ischemia at therapeutic plasma concentrations in healthy subjects. In patients with coronary artery disease, however, these drugs must remain contraindicated. The sustained contraction by ergotamine and dihydroergotamine seems to be an important disadvantage compared with sumatriptan-like drugs.
Pulse Dose Methylprednisolone Therapy for Adult Idiopathic Inflammatory Myopathy

Idiopathic inflammatory myopathies (IIM) are a rare group of autoimmune diseases characterized by muscle inflammation. Typically high-dose daily oral corticosteroids are used as the first-line therapy of IIM. Pulse dose intravenous methylprednisolone (IVMP) has been used for serious or refractory cases. Here, we systematically analyze the therapeutic effect of pulse dose IVMP in patients with IIM in a large municipal safety net medical center and review the literature on pulse IVMP in adult IIM. We conducted a retrospective chart review of patients who were diagnosed with IIM in the rheumatology clinics of the Cook County Health and Hospital Systems. Data collected included patient demographics, diagnosis, immunosuppressive therapies, serial serum creatine kinase (CK) measurements, and serial muscle strength testing. Seven patients received pulse dose IVMP for active myositis. At the time of pulse dose IVMP, the mean strength in the weakest muscle group was rated as 3.1 of 5 (range, 2–4; SD, 0.9) and the mean peak CK was 5746 U/L (range, 1602–14,039; SD, 4911). Dysphagia was reported in 5 of the 7 patients at the time of IVMP. Four to six weeks after IVMP, the mean strength in the weakest muscle group was 3.3 of 5 (range, 1–5; SD, 1.5) and mean peak CK was 1064 U/L (range, 63–1788, SD, 712). Four to six weeks after IVMP, dysphagia had resolved in 2 and improved in 3. At the end of follow-up, mean strength in the weakest muscle group was 4.7 of 5 (range, 4–5; SD, 0.5), mean peak CK was 480 U/L (range, 37–1016; SD, 337), and the mean prednisone dosage was 15 mg (range, 2.5–60; SD, 21). Although our study has certain limitations, our cohort of adult patients with IIM had marked improvement in clinical and biochemical outcomes. Four to six weeks after IVMP infusion, there was a rapid improvement in muscle enzyme levels, muscle strength, and dysphagia. This therapy warrants further controlled trials.
Extraction of crude collagen from Pterygoplichthys pardalis skin and determination of functional properties of its hydrolysates

Collagen has a great demand and fish skin is a safe alternative source of collagen. Pterygoplichthys pardalis is an endemic, freshwater fish with no economic benefit. The study was conducted to extract crude collagen from the skin of P. pardalis using a simple method and identify the functional properties of its hydrolysates. Acid and pepsin soluble collagens were extracted from skin using citric acid (CA) and ethylene diamine tetraacetic acid (EDTA). Selected crude collagens were hydrolysed using pepsin, protease and trypsin enzymes (1:100). Extracted crude collagens and best hydrolysates were selected using 8 and 15% SDS-PAGE. Hydrolysates were analysed for antioxidant, Fe(II) chelating and antibacterial activities. CA treatment showed significantly (P<0.05) higher yield than EDTA treatment. Antioxidant properties, metal chelation and antibacterial activities were not significantly (P>0.05) different. Hydrolysates showed significantly (P<0.05) higher functional properties than crude collagen in both treatments. These results conclude that collagen hydrolysates from P. pardalis have good antioxidant, metal chelating and antibacterial properties.