Miracle-dz/UniFAR-FTUs huggingface dataset:
Physico-chemical stability of co-formulation of PEGylated human amylin with insulin

Abstract Since the discovery of amylin no combined formulation with insulin has been made available. Amylin or its triple proline analog pramlintide are not compatible in solution with insulin. The drug candidate hAmy-PEG5k is a novel monoPEGylated amylin derivative with improved physicochemical properties and retained similar pharmacological activity compared to free amylin and pramlintide. We have investigated the short- and long-term physicochemical compatibility of hAmy-PEG5k co-formulated with slow-acting human insulin analogs glargine or detemir. While human amylin promptly aggregates over a large range of pH, and both free and in the presence of regular, glargine or detemir insulin, the hAmy-PEG5k analog is stable at these conditions as shown by Thioflavin T (ThT) binding assay. When hAmy-PEG5k (100 or 500 µg/mL) was added to the commercial formulations of either insulin glargine or detemir (95 IU/mL), the combinations remained stable after 6 months stored at 4 °C, as probed by ThT, dynamic light scattering (DLS) measurements and high performance liquid chromatography (HPLC) analyses, confirming the absence of amyloid fibers, minor aggregation products or loss of material. These results suggest hAmy-PEG5k and the insulin analogs glargine and detemir are physicochemically compatible and are candidate ready-to-use fixed-dose combinations.
A Compact MIMO Antenna using CRLH Configuration Double-Layered Folded Ring Radiations with Planar Mushroom Decoupling Structure

This paper proposes a novel compact multiple-input-multiple-output (MIMO) antenna, which has miniaturized radiators and improved isolation, working for the long-term evolution (LTE) mobile communication. Each of the proposed radiators has a double-layered ring of the composite right- and left-handed transmission-line configuration, which has the footprint of λg/30 by λg/30, much smaller than the conventional MIMO antenna radiators. These radiators can be placed close to each other and have a planar modified mushroom structure between them for a higher isolation level. The design starts from the equivalent circuit for the LTE 1.7-GHz-band antenna, finds a physical structure suitable for the circuit, and is verified by comparing the circuit simulation with the 3-D EM simulation and measured data. The dispersion diagram shows that the zeroth-order resonance coincides with the center frequency of the band, and the fabricated antenna has the return loss less than -10 dB, the isolation over 12 dB, and the radiation efficiency over 50%.
Detection and isolation of Shiga Toxin‐producing Escherichia coli (STEC) strains in caecal samples from pigs at slaughter in Italy

Abstract Shiga toxin‐producing Escherichia coli (STEC) strains are food‐borne pathogens of public health concern. Despite ruminants are the most important reservoir, STEC human infections have also been attributed to pigs. We examined for the presence of STEC in 234 samples of swine caecal content collected during the year 2015 at Italian abattoirs in the framework of the harmonized monitoring of antimicrobial resistance (Decision 2013/652/EU). The presence of stx genes was detected in 122 (52.1%) samples, which were subsequently subjected to STEC isolation and characterization. The analysis of the 66 isolated STEC strains showed that the majority of the isolates (74.2%) possessed the stx2a gene subtype, in a few cases (16.7%) in combination with stx2b or stx2c. Only 25.8% of isolates possessed the stx2e subtype, typical of swine‐adapted STEC. None of the isolates possessed the intimin‐coding eae gene and the majority of them did not belong to serogroups commonly associated with human infections. The results of this study suggest that pigs can be considered as potential reservoir of certain STEC types.
A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis

Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective against Trypanosoma brucei in the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner. Antibodies were conjugated to a pyrrolobenzodiazepine (PBD) toxin and killed T. brucei in vitro at picomolar concentrations. A single therapeutic dose (0.25 mg/kg) of a HpHbR antibody-PBD conjugate completely cured a T. brucei mouse infection within 2 days with no re-emergence of infection over a subsequent time course of 77 days. These experiments provide a demonstration of how ADCs can be exploited to treat protozoal diseases that desperately require new therapeutics. Author Summary Here we show that antibody-drug conjugates (ADCs) can be re-purposed from cancer immunotherapeutics to anti-protozoals by changing the specificity of the immunoglobulin to target a trypanosome cell surface receptor. Trypanosomes were used as a model system due to the availability of receptor null cell lines that allowed the unambiguous demonstration that ADCs targeted to a parasite surface receptor could be specifically internalised via receptor-mediated endocytosis. A single low dose of the resulting ADC was able to cure a stage 1 mouse model of trypanosome infection. We have used toxins and conjugation chemistry that are identical to anti cancer ADCs demonstrating the ability to piggy-back onto the huge research efforts and resources that are being invested in the development of such ADCs. The potential for development of ADCs against a wide range of human pathogens is vast, where only epitope binding sites need vary in order to provide selectivity. This provides a far-reaching opportunity for the rapid development of novel anti-protozoals for the targeted killing of a wide range of pathogens that cause disease worldwide, especially in developing countries.
1.6kV, 2.9 mΩ cm2 normally-off p-GaN HEMT device

A p-GaN/AlGaN/GaN based normally-off HEMT device has been demonstrated on a Si substrate. Our p-GaN based device shows not only a high threshold voltage of 3 V but also low gate leakage current. Buffer and device breakdown voltages exceed 1600 V with 5.2 um GaN buffer thickness and specific on-state resistance is 2. 9mΩ cm2. The calculated figure of merit is 921 MV2/Ωcm2, which is the highest value reported for the GaN E-mode devices.
A case of successful full-thickness resection using endoscopic submucosal dissection and transanal suturing of rectal cancer

Endoscopic resection techniques have been applied to full-thickness resection of gastrointestinal neoplasms as combination procedures with surgical resection [1, 2]. However, the applications of these procedures are mainly limited to the upper gastrointestinal tract owing to severe leakage complications in the lower gastrointestinal tract. Here we present a case of a successful full-thickness resection using endoscopic submucosal dissection (ESD) techniques to treat rectal adenocarcinoma [3, 4]. A 68-year-old man with a rectal flat elevated lesion, 20mm in diameter, was referred to our department (▶Fig. 1 a). We consulted surgeons for a radical resection because of the estimated depth of invasion. General anesthesia was judged to be risky because of the patient’s severe chronic obstructive pulmonary disease. After careful discussion with surgeons, we decided to resect the lesion by using a combination of ESD techniques and transanal suturing (▶Video 1). After creating a circumferential mucosal incision around the lesion, two clips were anchored directly to the muscular layer on one side of the lesion. One of the clips was tied with a line to pull from outside the body. Pulling the line, we incised the muscular layer around the lesion (▶Fig. 1b). Finally, the lesion was resected in an en bloc fashion that included the muscular layer (▶Fig. 1 c). The muscular defect was completely closed by transanal suturing (▶Fig. 1 d). Computed tomography immediately after the procedure revealed minimal leakage of air into the retroperitoneal space (▶Fig. 2). The patient recovered well without any complications. Histopathological assessment revealed that a well-differentiated adenocarcinoma had invaded beneath the muscular layer, with free vertical and lateral margins. E-Videos
Assessing the Optimal Cutpoint for Tumor Size in Patients with Lung Cancer Based on Linear Rank Statistics in a Competing Risks Framework

Purpose In clinical studies, patients may experience several types of events during follow up under the competing risks (CR) framework. Patients are often classified into low- and high-risk groups based on prognostic factors. We propose a method to determine an optimal cutpoint value for prognostic factors on censored outcomes in the presence of CR. Materials and Methods We applied our method to data collected in a study of lung cancer patients. From September 1, 1991 to December 31, 2005, 758 lung cancer patients received tumor removal surgery at Samsung Medical Center in Korea. The proposed statistic converges in distribution to that of the supremum of a standardized Brownian bridge. To overcome the conservativeness of the test based on an approximation of the asymptotic distribution, we also propose a permutation test based on permuted samples. Results Most cases considered in our simulation studies showed that the permutation-based test satisfied a significance level of 0.05, while the approximation-based test was very conservative: the powers of the former were larger than those of the latter. The optimal cutpoint value for tumor size (unit: cm) prior to surgery for classifying patients into two groups (low and high risks for relapse) was found to be 1.8, with decent significance reflected as p values less than 0.001. Conclusion The cutpoint estimator based on the maximally selected linear rank statistic was reasonable in terms of bias and standard deviation in the CR framework. The permutation-based test well satisfied type I error probability and provided higher power than the approximation-based test.
The computer-aided detection of inferior printing quality and errors

This paper describes a new approach which detects inferior printing quality and errors by using a regular PC and document scanner. Our method relies on the comparison of an inspected document with its referential version. It firstly registers the images of the two documents, and then detects any discrepancies between the aligned pixels or regions. Iterations of the two-step registrations with interim interpolations introduce a sort of elastic image correction. We confirmed experimentally that the error detection rate for those documents with simpler structures, mostly pictures, was about 95%, whereas with more complex documents containing a lot of text this figure is about 90%
Stereospecific modulation of dimeric rhodopsin

The classic concept that GPCRs function as monomers has been challenged by the emerging evidence of GPCR dimerization and oligomerization. Rhodopsin (Rh) is the only GPCR whose native oligomeric arrangement was revealed by atomic force microscopy demonstrating that Rh exists as a dimer. However, the role of Rh dimerization in retinal physiology is currently unknown. In this study, we identified econazole and sulconazole, two small molecules that disrupt Rh dimer contacts, by implementing a cell‐based high‐throughput screening assay. Racemic mixtures of identified lead compounds were separated and tested for their stereospecific binding to Rh using UV‐visible spectroscopy and intrinsic fluorescence of tryptophan (Trp) 265 after illumination. By following the changes in UV‐visible spectra and Trp265 fluorescence in vitro, we found that binding of R‐econazole modulates the formation of Meta III and quenches the intrinsic fluorescence of Trp265. In addition, electrophysiological ex vivo recording revealed that R‐econazole slows photoresponse kinetics, whereas S‐econazole decreased the sensitivity of rods without effecting the kinetics. Thus, this study contributes new methodology to identify compounds that disrupt the dimerization of GPCRs in general and validates the first active compounds that disrupt the Rh dimer specifically. —Getter, T. , Gulati, S. , Zimmerman, R. , Chen, Y. , Vinberg, F. , Palczewski, K. Stereospecific modulation of dimeric rhodopsin. FASEB J. 33, 9526–9539 (2019). www.fasebj. org
Microscopic / "Backwash" Ileitis and its Association with Colonic Disease in New Onset Pediatric Ulcerative Colitis.

BACKGROUND Microscopic ileitis and its association with pancolitis in adults with ulcerative colitis (UC) has been described. However, the incidence of ileitis and associations with colonic disease in pediatric UC have not been thoroughly investigated. This study was undertaken to examine the prevalence of microscopic ileal inflammation at the time of initial diagnosis in a cohort of children with UC. METHODS We reviewed colonoscopy and biopsy data at time of diagnosis from 105 children and young adults with treatment naïve ulcerative colitis; ileal and colonic mucosal biopsies were available on all patients. Ileal mucosal biopsies were examined for the presence and severity of ileal inflammation, as well as other histologic features. Concurrently obtained colonic mucosal biopsies were assessed to define the severity, distribution, and extent of disease; endoscopic and clinical follow-up data were reviewed. RESULTS 107 ileal mucosal biopsies and 693 corresponding colonic mucosal biopsies were examined. Seventeen of 105 patients (16%) were found to have ileal inflammation (mean age = 10.4 years, 59% female), 14 (82%) of whom had histologic pancolitis. The presence of ileal inflammation was significantly associated with endoscopic pancolitis (p = 0.02). The association between histologic pancolitis, severity of active inflammation in the cecum and ascending colon suggested a possible association with ileal inflammation (p = 0.06, 0.07, and 0.08 respectively), but did not reach statistical significance. CONCLUSION Patients with new onset ulcerative colitis may have microscopic ileal inflammation at time of diagnosis, even if the terminal ileum appears macroscopically normal. The presence of endoscopic pancolitis is associated with the presence of histologic ileitis. In contrast to existing studies in adults, an association between the presence of ileitis and the histologic severity or the histologic extent of colitis was not observed. Children with microscopic ileitis in the context of UC do not need to be reclassified as "indeterminate colitis" or Crohn's disease.
Aspergillus flavus as a Model System to Test the Biological Activity of Botanicals: An Example on Citrullus colocynthis L. Schrad. Organic Extracts

Citrullus colocynthis L. Schrader is an annual plant belonging to the Cucurbitaceae family, widely distributed in the desert areas of the Mediterranean basin. Many pharmacological properties (anti-inflammatory, anti-diabetic, analgesic, anti-epileptic) are ascribed to different organs of this plant; extracts and derivatives of C. colocynthis are used in folk Berber medicine for the treatment of numerous diseases—such as rheumatism arthritis, hypertension bronchitis, mastitis, and even cancer. Clinical studies aimed at confirming the chemical and biological bases of pharmacological activity assigned to many plant/herb extracts used in folk medicine often rely on results obtained from laboratory preliminary tests. We investigated the biological activity of some C. colocynthis stem, leaf, and root extracts on the mycotoxigenic and phytopathogenic fungus Aspergillus flavus, testing a possible correlation between the inhibitory effect on aflatoxin biosynthesis, the phytochemical composition of extracts, and their in vitro antioxidant capacities.
Increased risk of Bell palsy in patient with migraine

Abstract Migraine is thought to be associated with Bell palsy. This study aimed to investigate the risk of Bell palsy in migraine patients. The Korean National Health Insurance Service-National Sample Cohort was collected from 2002 to 2013. A total of 45,164 migraine patients were matched for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia and compared with 180,656 controls. The migraine group included participants diagnosed with migraine [International Classification of Disease (ICD)-10: G43] who underwent treatment more than once. Participants with Bell palsy were included on the basis of the ICD-10 (G510) and treatment with steroids. A history of hypertension, diabetes, and dyslipidemia was determined using ICD-10 codes. Crude (simple) and adjusted hazard ratios (HRs) of Bell palsy in migraine patients were analyzed using the Cox proportional hazards model. Subgroup analyses were conducted based on age and sex. Bell palsy occurred in 0.6% (262/44,902) of the migraine group and 0.5% (903/179,753) of the control group. The adjusted HR of Bell palsy was 1.16 in the migraine group compared with the control group [95% confidence interval (95% CI) = 1.01–1.33, P = . 34]. Among age-related subgroups, participants ≥30 and <60 years old in the migraine subgroup demonstrated a 1.28-times higher risk of Bell palsy than the control group (95% CI = 1.05–1.57, P = .014). Migraine increased the risk of Bell palsy in the total population. Among age subgroups, migraine patients ≥30 and <60 years old had an increased risk of Bell palsy.
Endoscopic ultrasound-guided transmural approach versus ERCP-guided transpapillary approach for primary decompression of malignant biliary obstruction: a meta-analysis

Abstract Background Primary decompression in patients with malignant biliary obstruction can be achieved via endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary stenting, or, more recently, via transmural endoscopic ultrasound-guided biliary drainage (EUS-BD). It is unclear whether either approach is superior in terms of clinical success or adverse events in the primary setting. Methods A comprehensive systematic electronic search was performed for studies comparing EUS-BD and ERCP as the primary approach with respect to clinical success and any other outcome(s). Pooled relative risks (RRs) and weighted mean differences were obtained as appropriate using DerSimonian and Laird random effects models. Sensitivity analyses were also performed. Results 5 out of 776 studies with a total of 396 patients were included. Overall clinical success was not significantly different between EUS-BD and ERCP (RR 0.98, 95 % confidence interval [CI] 0.93 to 1.03). There was no significant difference in overall adverse events (RR 0.84, 95 %CI 0.35 to 2.01), though results suggested that EUS-BD may be associated with a reduced risk of pancreatitis (RR 0.22, 95 %CI 0.05 to 1.02). There were no significant differences between EUS-BD and ERCP in terms of procedure time or the risk of stent occlusion. Conclusions EUS-BD had similar clinical success rates and occlusion rates to ERCP in the primary decompression of malignant biliary obstruction from meta-analysis including a modest number of patients. EUS-BD may be a practical alternative to the ERCP-guided approach in such patients, but further well-designed prospective studies with larger numbers of patients are required to more clearly delineate potential differences in adverse events and cost.
Prevalence of overweight and obesity among adolescents in Bangladesh: do eating habits and physical activity have a gender differential effect?

Abstract The aim of this study was to examine the gender differential effects of eating habits and physical activity on overweight and obesity among school-aged adolescents in Bangladesh. Nationally representative data extracted from the 2014 Global School-based Student Health Survey (GSHS) were utilized. The survey collected information related to physical and mental health from 2989 school-aged adolescents in Bangladesh. An exploratory data analysis and multivariate logistic regression model were employed in this study. Female adolescents were at a lower risk of being overweight or obese (AOR=0.573) than males, with a prevalence of 7.4% (males: 9.9%). The results showed that high consumption of vegetables (both: AOR=0.454; males: AOR=0.504; females: AOR=0.432), high soft drink consumption (both: AOR=2.357; males: AOR=2.929; females: AOR=1.677), high fast food consumption (both: AOR=2.777; males: AOR=6.064; females: AOR=1.695), sleep disturbance (both: AOR=0.675; males: AOR=0.590; females: AOR=0.555) and regular walking or cycling to school (both: AOR=0.472; males: AOR=0.430; females: AOR=0.557) were vital influencing factors for being overweight or obese among adolescents for both sexes. Sedentary activities during leisure time were also identified as significant predictors of being overweight or obese for males. Regular fruit and vegetable consumption, the avoidance of soft drinks and fast food, an increase in vigorous physical activity, regular attendance at physical education classes and fewer sedentary leisure time activities could all help reduce the risk of being overweight or obese for both sexes.
Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits

Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography–mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs.
Epigenome-wide effects of vitamin D on asthma bronchial epithelial cells

ABSTRACT Vitamin D is a nutrient and a hormone with multiple effects on immune regulation and respiratory viral infections, which can worsen asthma and lead to severe asthma exacerbations. We set up a complete experimental and analytical pipeline for ATAC-Seq and RNA-Seq to study genome-wide epigenetic changes in human bronchial epithelial cells of asthmatic subjects, following treatment of these cells with calcitriol (vitamin D3) and Poly (I:C)(a viral analogue). This approach led to the identification of biologically plausible candidate genes for viral infections and asthma, such as DUSP10 and SLC44A1.