Miracle-dz/UniFAR-FTUs huggingface dataset:
Ganglionic acetylcholine receptor autoantibodies in patients with autoimmune diseases including primary biliary cirrhosis

Abstract Objectives: Autonomic dysfunction is closely associated with autoimmune diseases (AID) including primary biliary cirrhosis (PBC). The objective of this study was to determine the prevalence of anti-ganglionic (nicotinic) acetylcholine receptor (gAChR) antibodies in patients with AID. Methods: We determined the presence of gAChR antibodies in serum samples from 146 patients (systemic lupus erythematosus [SLE] = 32; rheumatoid arthritis [RA] = 43; systemic sclerosis [SSc] = 38; PBC= 33) without information regarding autonomic symptoms, as well as 34 patients with other neurological diseases [OND], and 73 healthy controls [HC]. We specifically analyzed sera for anti-gAChRα3 and -β4 antibodies using the luciferase immunoprecipitation system (LIPS) assay. Results: LIPS assay detected anti-gAChRα3 and -β4 antibodies in the sera from patients with SLE (12.5%, 4/32), RA (18.6%, 8/43), SSc (13.2%, 5/38), PBC (9.1%, 3/33), OND (2.9%, 1/34), and HC (0.0%, 1/73). There were no significant correlations between the levels of anti-gAChRα3 and -β4 antibodies, and the total titers of autoantibodies in AID. Conclusions: The results demonstrated a significant prevalence of anti-gAChR antibodies in patients with AID, which is independent of the production of other autoantibodies in patients with autoimmune diseases. These anti-gAChR antibodies could mediate the autonomic dysfunction involved in the autoimmune mechanisms of AID.
A 10-bit 1.2 GS/s 45 mW time-interleaved SAR ADC with background calibration

: A 10-bit 1.2GS/s power efficient time-interleaved successive-approximation-register (SAR) analog-to-digital converter (ADC) is present in this paper. Substrate bias effect depression and output resistance stabilization techniques are provided to enhance the linearity of input buffer. Further, meta-stability restrained trigger comparator is used to enhance the ENOB (effective number of bits) of SAR ADC. Additionally, a digital background calibration technique is proposed to suppress the inter-channel gain, offset and timing skew mismatches. To demonstrate the proposed techniques, a design of time-interleaved SAR ADC is fabricated in 55-nm CMOS technology, consuming 45mW from 1.2V power supply with a SNDR of 50dB and SFDR of 60dB. The proposed ADC core occupies an active area of 0.84mm 2 , and the corresponding FoM is 145 fJ/conversion-step with Nyquist rate.
Regulation of the vasomotor activity of lymph microvessels by nitric oxide and prostaglandins.

It was shown previously that the presence of endothelium modulates spontaneous vasomotion of small lymphatic vessels. In the present study, we aimed to elucidate the nature of endothelium-derived factors, produced in basal conditions and in response to agonists, that affect the smooth muscle tone of lymph microvessels in vitro. Afferent lymph microvessels were isolated from rat iliac lymph nodes, cannulated with glass micropipettes, and pressurized (6 cmH2O), and changes in their diameter were investigated with video microscopy. In resting conditions, isolated lymph vessels exhibited spontaneous constrictions and dilations. The maximum and minimum diameters ( D max and D min) were 149.8 ± 2.9 and 85.8 ± 3.6 μm, respectively. Acetylcholine (ACh, 10-7 to 10-5 M) and sodium nitroprusside (SNP, 10-8 to 10-6 M) temporarily abolished diameter oscillations, increasing the diameter of lymphatics dose dependently. For example, 10-5 M ACh and 10-6 M SNP increased the diameter ( D max) by 15.2 ± 2.2 and 25.0 ± 2.7 μm, respectively. Treatment of vessels with N G-nitro-l-arginine (10-4 M) significantly reduced the amplitude of diameter oscillations and nearly completely eliminated ACh-induced dilation of lymph microvessels, whereas SNP (10-6 M) elicited a significantly greater dilation (55.6 ± 7.5 μm). Arachidonic acid (AA, 10-8 to 10-6 M) constricted (up to 50 μm), whereas prostaglandin E2(PGE2, 10-9 to 10-7 M) dilated (up to 40 μm), lymphatic vessels. Indomethacin (10-5 M) increased both D max and D min and completely inhibited AA-induced constrictions, but did not affect PGE2-induced dilations of lymph microvessels. AA-induced constrictions of lymphatics were converted into dilations after treatment with SQ-29,548, a selective PGH2-thromboxane A2(PGH2-TxA2, 10-6 M) receptor antagonist, whereas PGE2-induced dilations were not affected. We conclude that endothelial nitric oxide and prostaglandins are important modulators of lymphatic vasomotion, hence pumping activity of lymph microvessels in vivo.
Synthesis of Biogenic Silver Nanoparticles Using Sesamum laciniatum Klein ex Willd

Biosynthesis of nanoparticles using higher plants is an emerging area of research in nanoscience and technology. In the present investigation, leaf mucilage of S. laciniatum was used for synthesis of silver nanoparticles. The biosynthesis of nanoparticles is a nontoxic and environmental friendly method. The change in the colour of reaction mixture from colorless to brown indicates the formation of silver nanoparticles. Further confirmed by characteristic UV-vis spectroscopy with a characteristic absorbance resonance peak at 436 nm. Fluorescence Spectroscopy is a powerful tool to study the tertiary structure of proteins. FTIR data reveals the various groups of biomolecules involved in bio reduction and capping for efficient stabilization silver nanoparticles. The SEM images showed spherical shaped nanoparticles and size ranges 10-20nm. XRD showed crystalline nature of nanosilver.
Data-driven subtyping of behavioural problems associated with ADHD in children

Many developmental disorders are associated with deficits in controlling and regulating behaviour. These difficulties are foremost associated with attention deficit hyperactivity disorder (ADHD), but are also frequently observed in other groups, including in children with diagnoses of specific learning difficulties, autistic spectrum disorder, or conduct disorder. The co-occurrence of these behavioural problems across disorders typically leads to comorbid diagnoses and can complicate intervention approaches. An alternative to classifying children on the basis of specific diagnostic criteria is to use a data-driven grouping that identifies dimensions of behaviour that meaningfully distinguish groups of children and become specific targets for intervention. The current study applies a novel data-driven clustering algorithm to group children by similarities in their ratings on a parent questionnaire that is commonly used to assess behavioural problems associated with ADHD. The sample consisted of 442 children identified by health and educational professionals as having difficulties in attention, learning and/or memory. The data-driven clustering yielded three distinct groups of children with symptoms of either: (1) elevated inattention, and hyperactivity/impulsivity, and poor executive function, (2) learning problems, and (3) aggressive behaviours and problems with peer relationships. These groups were associated with significant inter-individual variation in white matter connectivity of the prefrontal and anterior cingulate. In sum, data-driven classification of executive function difficulties identifies stable groups of children, provides a good account of inter-individual differences, and aligns closely with underlying neurobiological substrates.
Lung ultrasound: a novel technique for detecting fluid overload in children on dialysis

Background: Optimizing the target weight of infants and children on dialysis remains an important clinical challenge. The use of ultrasound to detect fluid overload in adult patients on dialysis is receiving growing attention. We hypothesized that fluid overload can be quantified in infants and children receiving dialysis using lung ultrasound. Methods: In this prospective observational study, infants and children receiving dialysis for end‐stage renal disease (ESRD) or acute kidney injury (AKI) in a regional paediatric nephrology centre were eligible. Lung ultrasound examinations were performed during in‐centre dialysis, on home visits or in an outpatient clinic. Fluid overload was assessed by quantifying B‐lines on ultrasound and compared with proportional (%) increase in patient weight from the target weight. Results: A total of 142 ultrasound assessments were performed in 23 children. In children with AKI, median B‐line score reduced from 5 (range 0‐22) at presentation to 1.5 (0‐4) at recovery (P = 0.04) with concurrent improvement in fluid overload judged by weight from 7.2 (−1.9 to 15.2)% to 0%. A linear correlation between lung ultrasound B‐line score and fluid overload judged by weight was observed in children with AKI (r = 0.83) and ESRD (r = 0.61). Inter‐observer variability was acceptable. Conclusions: Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited.
Cl- and K+ conductances activated by cell swelling in primary cultures of rabbit distal bright convoluted tubules.

Ionic currents induced by cell swelling were characterized in primary cultures of rabbit distal bright convoluted tubule (DCTb) by the whole cell patch-clamp technique. Cl- currents were produced spontaneously by whole cell recording with an isotonic pipette solution or by exposure to a hypotonic stress. Initial Cl- currents exhibited outwardly rectifying current-voltage relationship, whereas steady-state currents showed strong decay with depolarizing pulses. The ion selectivity sequence was I-= Br- > Cl- ≫ glutamate. Currents were inhibited by 0.1 mM 5-nitro-2-(3-phenylpropylamino)benzoic acid and 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and strongly blocked by 1 mM diphenylamine-2-carboxylate. Currents were insensitive to intracellular Ca2+but required the presence of extracellular Ca2+. They were not activated in cells pretreated with 200 nM staurosporine, 50 μM LaCl3, 10 μM nifedipine, 100 μM verapamil, 5 μM tamoxifen, and 50 μM dideoxyforskolin. Staurosporine, tamoxifen, verapamil, or the absence of external Ca2+ was without effect on the fully developed Cl-currents. Osmotic shock also activated K+ currents in Cl--free conditions. These currents were time independent, activated at depolarized potentials, and inhibited by 5 mM BaCl2. The activation of Cl- and K+ currents by an osmotic shock may be implicated in regulatory volume decrease in DCTb cells.
Universal linear and nonlinear electrodynamics of a Dirac fluid

Significance Electrons in pristine solids behave as a hydrodynamic fluid in a certain range of temperatures and frequencies. We show that the response of such a fluid to an electromagnetic field is different from what is predicted by the usual kinetic theory. Certain aspects of this response are universal, for example, a direct relation between the linear and second-order nonlinear optical conductivities. Discovery of this relation enriches our understanding of the light–matter interaction in diverse electron systems and new materials such as graphene. A general relation is derived between the linear and second-order nonlinear ac conductivities of an electron system in the hydrodynamic regime of frequencies below the interparticle scattering rate. The magnitude and tensorial structure of the hydrodynamic nonlinear conductivity are shown to differ from their counterparts in the more familiar kinetic regime of higher frequencies. Due to universality of the hydrodynamic equations, the obtained formulas are valid for systems with an arbitrary Dirac-like dispersion, ranging from solid-state electron gases to free-space plasmas, either massive or massless, at any temperature, chemical potential, or space dimension. Predictions for photon drag and second-harmonic generation in graphene are presented as one application of this theory.
Live Quantitative Monitoring of Mineral Deposition in Stem Cells Using Tetracycline Hydrochloride

The final stage of in vitro osteogenic differentiation is characterized by the production of mineral deposits containing calcium cations and inorganic phosphates, which populate the extracellular matrix (ECM) surrounding the cell monolayer. Conventional histological techniques for the assessment of mineralization, such as Von Kossa and Alizarin Red S staining, are end point techniques requiring cell fixation. Moreover, in both cases staining quantitation requires dye extraction, which irreversibly alters the ECM conformation and structure, therefore preventing the use of the sample for further analysis. In this study, the use of tetracycline hydrochloride (TC) is proposed for the nondestructive staining, quantitation, and imaging of mineralizing bone-like nodules in live cultures of human bone marrow mesenchymal stem cells cultured under osteogenic conditions. Overnight administration of TC to living cells was shown not to alter the metabolic activity or the progression of cell differentiation. When applied to differentiating cultures, cell exposure to serial doses of TC was found to produce quantifiable fluorescence emission specifically in osteogenic cultures. Incubation with TC enabled fluorescence imaging of mineralized areas in live cultures and the combination with other fluorophores using appropriate filters. These results demonstrate that serial TC administration over the differentiation time course provides a qualitative and quantitative tool for the monitoring and evaluation of the differentiation process in live cells.
The therapeutic validity and effectiveness of physiotherapeutic exercise following total hip arthroplasty for osteoarthritis: A systematic review

Objective To assess the therapeutic validity and effectiveness of physiotherapeutic exercise interventions following total hip arthroplasty (THA) for osteoarthritis. Data sources The databases Embase, MEDLINE, Cochrane Library, CINAHL and AMED were searched from inception up to February 2017. Eligibility criteria Articles reporting results of randomized controlled trials in which physiotherapeutic exercise was compared with usual care or with a different type of physiotherapeutic exercise were included, with the applied interventions starting within six months after THA. Only articles written in English, German or Dutch were included. Study appraisal Therapeutic validity (using the CONTENT scale) and risk of bias (using both the PEDro scale and the Cochrane Collaboration’s tool) were assessed by two researchers independently. Characteristics of the physiotherapeutic exercise interventions and results about joint and muscle function, functional performance and self-reported outcomes were extracted. Results Of the 1124 unique records retrieved, twenty articles were included. Only one article was considered to be of high therapeutic validity. Description and adequacy of patient selection were the least reported items. The majority of the articles was considered as having potentially high risk of bias, according to both assessment tools. The level of therapeutic validity did not correspond with the risk of bias scores. Because of the wide variety in characteristics of the physiotherapeutic exercise and control interventions, follow-up length and outcome measures, limited evidence was found on the effectiveness of physiotherapeutic exercise following THA. Conclusion The insufficient therapeutic validity and potentially high risk of bias in studies involving physiotherapeutic exercise interventions limit the ability to assess the effectiveness of these interventions following THA. Researchers are advised to take both quality scores into account when developing and reporting studies involving physiotherapeutic exercise. Uniformity in intervention characteristics and outcome measures is necessary to enhance the comparability of clinical outcomes between trials.
Effects of Add-On Therapy with NDC-052, an Extract from Magnoliae Flos, in Adult Asthmatic Patients Receiving Inhaled Corticosteroids

Background/Aims There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS). Methods In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting β2-agonist usage, and adverse events. Results After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of β2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously. Conclusions The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma.
Evaluation of Low-Level Laser Therapy on Orthodontic Tooth Movement: A Randomized Control Study

Background: Fixed orthodontic treatment is time-consuming procedure. Pain is usually associated with orthodontic treatment. The aim of the present study was to evaluate the role of low-level laser therapy (LLLT) on orthodontic tooth movement (OTM) duration and pain perception. Materials and Methods: This randomized double-blind splint-mouth controlled clinical study includes 20 (8 males and 12 females) orthodontic patients requiring bilateral canine retraction. Time taken for canine retraction with LLLT (Group A) over control (Group B) quadrant on the same patient was assessed along with pain experience using facial pain scale. The data were tabulated and statistically evaluated using SPSS 20 for windows (Microsoft, Chicago, IL, USA) and t-test with P < 0.05. The difference in pain was evaluated with Wilcoxon signed-rank test. Results: There was no difference in values for age and sex of patient for tooth movement and pain (P > 0.05). There was statistically significant decrease in rate of canine retraction in Group A compared to Group B. There was statistically significant difference for maxillary and mandibular arches in Group A whereas it was not significant in Group B. Pain experience was statistically significant till 2nd day, and after 3rd day, it was not significant between the groups. Conclusion: LLLT can reduce the fixed OTM timing and pain experience.
Optimization of the tumor microenvironment and nanomedicine properties simultaneously to improve tumor therapy

Effective delivery of nanomedicines to tumor tissues depends on both the tumor microenvironment and nanomedicine properties. Accordingly, tumor microenvironment modification or advanced design of nanomedicine was emerging to improve nanomedicine delivery to tumors. However, few studies have emphasized the necessity to optimize the tumor microenvironment and nanomedicine properties simultaneously to improve tumor treatment. In the present study, imatinib mesylate (IMA) was used to normalize the tumor microenvironment including platelet-derived growth factor receptor-β expression inhibition, tumor vessel normalization, and tumor perfusion improvement as demonstrated by immunofluorescence staining. In addition, the effect of tumor microenvironment normalization on tumor delivery of nanomedicines with different sizes was carefully investigated. It was shown that IMA treatment significantly reduced the accumulation of nanoparticles (NPs) around 110 nm but enhanced the accumulation of micelles around 23 nm by in vivo fluorescence imaging experiment. Furthermore, IMA treatment limited the distribution of NPs inside tumors but increased that of micelles with a more homogeneous pattern. Finally, the anti-tumor efficacy study displayed that IMA pretreatment could significantly increase the therapeutic effects of paclitaxel-loaded micelles. All-together, a new strategy to improve nanomedicine delivery to tumor was provided by optimizing both nanomedicine size and the tumor microenvironment simultaneously, and it will have great potential in clinics for tumor treatment.
A Quality Model for Actionable Analytics in Rapid Software Development

Background: Accessing relevant data on the product, process, and usage perspectives of software as well as integrating and analyzing such data is crucial for getting reliable and timely actionable insights aimed at continuously managing software quality in Rapid Software Development (RSD). In this context, several software analytics tools have been developed in recent years. However, there is a lack of explainable software analytics that software practitioners trust. Aims: We aimed at creating a quality model (called Q-Rapids quality model) for actionable analytics in RSD, implementing it, and evaluating its understandability and relevance. Method: We performed workshops at four companies in order to determine relevant metrics as well as product and process factors. We also elicited how these metrics and factors are used and interpreted by practitioners when making decisions in RSD. We specified the Q-Rapids quality model by comparing and integrating the results of the four workshops. Then we implemented the Q-Rapids tool to support the usage of the Q-Rapids quality model as well as the gathering, integration, and analysis of the required data. Afterwards we installed the Q-Rapids tool in the four companies and performed semi-structured interviews with eight product owners to evaluate the understandability and relevance of the Q-Rapids quality model. Results: The participants of the evaluation perceived the metrics as well as the product and process factors of the Q-Rapids quality model as understandable. Also, they considered the Q-Rapids quality model relevant for identifying product and process deficiencies (e.g., blocking code situations). Conclusions: By means of heterogeneous data sources, the Q-Rapids quality model enables detecting problems that take more time to find manually and adds transparency among the perspectives of system, process, and usage.
Erastin-Like Anti-Warburg Agents Prevent Mitochondrial Depolarization Induced by Free Tubulin and Decrease Lactate Formation in Cancer Cells

In Warburg metabolism, suppression of mitochondrial metabolism contributes to a low cytosolic ATP/ADP ratio favoring enhanced aerobic glycolysis. Flux of metabolites across the mitochondrial outer membrane occurs through voltage-dependent anion channels (VDAC). In cancer cells, free dimeric tubulin induces VDAC closure and dynamically regulates mitochondrial membrane potential (ΔΨ). Erastin, a small molecule that binds to VDAC, antagonizes the inhibitory effect of tubulin on VDAC and hyperpolarizes mitochondria in intact cells. Here, our aim was to identify novel compounds from the ChemBridge DIVERSet library that block the inhibitory effect of tubulin on ΔΨ using cell-based screening. HCC4006 cells were treated with nocodazole (NCZ) to increase free tubulin and decrease ΔΨ in the presence or absence of library compounds. Tetramethylrhodamine methylester (TMRM) fluorescence was assessed by high-content imaging to determine changes in ΔΨ. Compounds were considered positive if ΔΨ increased in the presence of NCZ. Using confocal microscopy, we identified and validated six lead molecules that antagonized the depolarizing effect of NCZ. Lead compounds and erastin did not promote microtubule stabilization, so changes in ΔΨ were independent of tubulin dynamics. The most potent lead compound also decreased lactate formation. These novel small molecules represent a potential new class of anti-Warburg drugs.