Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoglycemia in Frail Elderly Patients With Type 2 Diabetes Mellitus Treated With Sulfonylurea

When glycemic control remains inadequate with metformin monotherapy, a sulfonylurea derivative (SU) can be added. Previous studies using a continuous glucose measurement system (CGMS) demonstrated that elderly patients with type 2 diabetes mellitus (T2DM) using SUs have unrecognized hypoglycemic events. Unfortunately, neither an appropriate control group (patients without diabetes or patients using metformin monotherapy) was used nor differences in hypoglycemia rate between different SUs were investigated. Therefore, this pilot study aimed to investigate the prevalence of (a)symptomatic hypoglycemia in frail elderly T2DM patients treated with metformin and a sulfonylurea, explicitly gliclazide and glimepiride. We included primary-care treated patients ≥ 70 years with T2DM, HbA1c < 58 mmol/mol (7.5%), and a Groningen Frailty Indicator (GFI) score ≥ 4. Patients used metformin monotherapy or metformin combined with gliclazide or glimepiride. A blinded CGMS (iPro2, Medtronic, Northridge, CA, USA) was worn for 5 consecutive days and patients were instructed to recorded symptoms of hypoglycemia. Primary outcome was the total number of hypoglycemic events (glucose levels < 3.0 mmol/L) persisting for at least 15 minutes with or without symptoms. The trial was approved by the medical ethics committee of the Isala hospital (Zwolle, Netherlands), registered in the local Dutch register (number: NTR 4952) and funded by the non-commercial Hein Hogerzeil Foundation. A total of 23 participants (47% male, 76 [72, 81] years old, with a GFI of 5 [4, 6], median diabetes duration of 9 [5, 11] years, and mean HbA1c 49 ± 4 mmol/mol [6.6 (0.4) %]) were monitored for a median period of 97 hours (range: 86 hours 15 minutes to 117 hours 25 minutes). Besides a lower GFI in the metformin and gliclazide group, there were no differences between groups. Five patients (22%) experienced a total of 15 events with a glucose level < 3.0 mmol/L recorded with CGMS. Eight patients (35%) experienced a total of 25 events with a glucose level < 3.5 mmol/L. None of these patients reported experiencing symptoms of hypoglycemia, all these patients used a SU, and there was no difference between gliclazide and glimepiride (see Table 1). On average, patients had significantly lower HbA1c levels (50 [3.4] vs 46 [4.1] mmol/mol (6.7 [0.3] vs 6.4 [0.4]%)) and higher GFI scores (4 [4, 5] vs 6 [4, 8]) if they experienced 1 or more hypoglycemic event(s) with a glucose level < 3.5 mmol/L than if they experienced no event. Although this pilot-study has (obvious) limitations and the clinical relevance of asymptomatic hypoglycemic events is unclear at present, we conclude that this study confirms the presence of hypoglycemia (<3.0 mmol/L) in well-controlled frail elderly T2DM patients using SUs and no events in patients treated with metformin only. All these events are asymptomatic and there are no relevant differences in frequency between gliclazide and glimepiride. 668873 DSTXXX10.1177/1932296816668873Journal of Diabetes Science and Technologyvan Dijk et al letter2016
A quantitative and automatic echographic method for real-time localization of endovascular devices

Current imaging methods for catheter position monitoring during minimally invasive surgery do not provide an effective support to surgeons, often resulting in the choice of more invasive procedures. This study was conducted to demonstrate the feasibility of non-ionizing monitoring of endovascular devices through embedded quantitative ultrasound (QUS) methods, providing catheter self-localization with respect to selected anatomical structures. QUS-based algorithms for real-time automatic tracking of device position were developed and validated on in vitro and ex vivo phantoms. A trans-esophageal ultrasound probe was adapted to simulate an endovascular device equipped with an intravascular ultrasound probe. B-mode images were acquired and processed in real time by means of a new algorithm for accurate measurement of device position. After off-line verification, automatic position calculation was found to be correct in 96% and 94% of computed frames in the in vitro and ex vivo phantoms, respectively. The average errors of distance measurements (bias ± 2SD) in a 41-step 10-cm-long parabolic pathway were 0.76 ± 3.75 mm or 0.52 ± 3.20 mm, depending on algorithm implementations. Our results showed the effectiveness of QUS-based tracking algorithms for real-time automatic calculation and display of endovascular system position. The method, validated for the case of an endoclamp balloon catheter, can be easily extended to most endovascular surgical systems.
Complete Genome Sequence of an H5N2 Avian Influenza Virus Isolated from a Parrot in Southern China

ABSTRACT We report the complete genome sequence of an H5N2 avian influenza virus (AIV) that was first isolated from a parrot in Guangdong in southern China in 2004. Genomic sequence and phylogenetic analyses showed that it was highly homologous with the North American H5N2 viruses and all eight genes of this virus belonged to the North American gene lineage. These data will help in the investigation of the epidemiology and host range of AIVs in southern China.
A Model of Self-Monitoring Blood Glucose Measurement Error

Background: A reliable model of the probability density function (PDF) of self-monitoring of blood glucose (SMBG) measurement error would be important for several applications in diabetes, like testing in silico insulin therapies. In the literature, the PDF of SMBG error is usually described by a Gaussian function, whose symmetry and simplicity are unable to properly describe the variability of experimental data. Here, we propose a new methodology to derive more realistic models of SMBG error PDF. Methods: The blood glucose range is divided into zones where error (absolute or relative) presents a constant standard deviation (SD). In each zone, a suitable PDF model is fitted by maximum-likelihood to experimental data. Model validation is performed by goodness-of-fit tests. The method is tested on two databases collected by the One Touch Ultra 2 (OTU2; Lifescan Inc, Milpitas, CA) and the Bayer Contour Next USB (BCN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ). In both cases, skew-normal and exponential models are used to describe the distribution of errors and outliers, respectively. Results: Two zones were identified: zone 1 with constant SD absolute error; zone 2 with constant SD relative error. Goodness-of-fit tests confirmed that identified PDF models are valid and superior to Gaussian models used so far in the literature. Conclusions: The proposed methodology allows to derive realistic models of SMBG error PDF. These models can be used in several investigations of present interest in the scientific community, for example, to perform in silico clinical trials to compare SMBG-based with nonadjunctive CGM-based insulin treatments.
A Bivalent Vaccine Based on a Replication-Incompetent Influenza Virus Protects against Streptococcus pneumoniae and Influenza Virus Infection

ABSTRACT Streptococcus pneumoniae is a major causative pathogen in community-acquired pneumonia; together with influenza virus, it represents an important public health burden. Although vaccination is the most effective prophylaxis against these infectious agents, no single vaccine simultaneously provides protective immunity against both S. pneumoniae and influenza virus. Previously, we demonstrated that several replication-incompetent influenza viruses efficiently elicit IgG in serum and IgA in the upper and lower respiratory tracts. Here, we generated a replication-incompetent hemagglutinin knockout (HA-KO) influenza virus possessing the sequence for the antigenic region of pneumococcal surface protein A (PspA). Although this virus (HA-KO/PspA virus) could replicate only in an HA-expressing cell line, it infected wild-type cells and expressed both viral proteins and PspA. PspA- and influenza virus-specific antibodies were detected in nasal wash and bronchoalveolar lavage fluids and in sera from mice intranasally inoculated with HA-KO/PspA virus, and mice inoculated with HA-KO/PspA virus were completely protected from lethal challenge with either S. pneumoniae or influenza virus. Further, bacterial colonization of the nasopharynx was prevented in mice immunized with HA-KO/PspA virus. These results indicate that HA-KO/PspA virus is a promising bivalent vaccine candidate that simultaneously confers protective immunity against both S. pneumoniae and influenza virus. We believe that this strategy offers a platform for the development of bivalent vaccines, based on replication-incompetent influenza virus, against pathogens that cause respiratory infectious diseases. IMPORTANCE Streptococcus pneumoniae and influenza viruses cause contagious diseases, but no single vaccine can simultaneously provide protective immunity against both pathogens. Here, we used reverse genetics to generate a replication-incompetent influenza virus carrying the sequence for the antigenic region of pneumococcal surface protein A and demonstrated that mice immunized with this virus were completely protected from lethal doses of infection with either influenza virus or Streptococcus pneumoniae. We believe that this strategy, which is based on a replication-incompetent influenza virus possessing the antigenic region of other respiratory pathogens, offers a platform for the development of bivalent vaccines.
Emergency cesarean section and blood transfusions in patients with severe anemia-Our experience

Introduction: Anemia in pregnancy is a ubiquitous problem, more so in the developing countries. Many of the changes that accompany blood loss appear later, rather than sooner, because obstetric patients are usually young fit adults with an expanded blood volume. In such cases, the needs for blood transfusions mainly depend on the clinical condition rather than the preoperative value of the hemoglobin (Hb) and blood loss. This is usually due to the tolerance of these chronic anemia patients to the accompanying blood loss. Aim: This study was aimed to see how frequently the patients actually received blood perioperatively. Material and Methods: This was a retrospective analysis of patients who underwent emergency cesarean sections. A total of 303 patients underwent emergency cesareans with Hb 8 g%. Patients in each group were studied regarding the perioperative blood transfusion, any multiple units received, and complications encountered Results: In Group I, blood transfusion done in 88% cases fell drastically to 30% in Group II and 20% in Group III. No significant complications were noted and all patients were discharged without any morbidity. Conclusions: The lower cutoff value of Hb level for an emergency surgery remains a big enigma, which needs further evaluation. Clinical judgment in conjunction with the monitoring of tissue oxygen delivery determines the individual patient's transfusion trigger, and not the use of categorical magic number. Parturient women tend to have lower hematocrit values due to physiological changes and dilutional effect, but they still can tolerate this chronic anemia without any ill effects. This may be one of the reasons for the reduced need for blood transfusion in our study and also for the successful outcome in spite of severe anemia.
Continuous Glucose Monitoring in Older Adults With Type 1 and Type 2 Diabetes Using Multiple Daily Injections of Insulin: Results From the DIAMOND Trial

Objective: The objective was to determine the effectiveness of real-time continuous glucose monitoring (CGM) in adults ≥ 60 years of age with type 1 (T1D) or type 2 (T2D) diabetes using multiple daily insulin injections (MDI). Methods: A multicenter, randomized trial was conducted in the United States and Canada in which 116 individuals ≥60 years (mean 67 ± 5 years) with T1D (n = 34) or T2D (n = 82) using MDI therapy were randomly assigned to either CGM (Dexcom™ G4 Platinum CGM System® with software 505; n = 63) or continued management with self-monitoring blood glucose (SMBG; n = 53). Median diabetes duration was 21 (14, 30) years and mean baseline HbA1c was 8.5 ± 0.6%. The primary outcome, HbA1c at 24 weeks, was obtained for 114 (98%) participants. Results: HbA1c reduction from baseline to 24 weeks was greater in the CGM group than Control group (−0.9 ± 0.7% versus −0.5 ± 0.7%, adjusted difference in mean change was −0.4 ± 0.1%, P < .001). CGM-measured time >250 mg/dL (P = .006) and glycemic variability (P = .02) were lower in the CGM group. Among the 61 in the CGM group completing the trial, 97% used CGM ≥ 6 days/week in month 6. There were no severe hypoglycemic or diabetic ketoacidosis events in either group. Conclusion: In adults ≥ 60 years of age with T1D and T2D using MDI, CGM use was high and associated with improved HbA1c and reduced glycemic variability. Therefore, CGM should be considered for older adults with diabetes using MDI.
A Monomeric Uncleaved Respiratory Syncytial Virus F Antigen Retains Prefusion-Specific Neutralizing Epitopes

ABSTRACT Respiratory syncytial virus (RSV) is the leading infectious cause of severe respiratory disease in infants and a major cause of respiratory illness in the elderly. There remains an unmet vaccine need despite decades of research. Insufficient potency, homogeneity, and stability of previous RSV fusion protein (F) subunit vaccine candidates have hampered vaccine development. RSV F and related parainfluenza virus (PIV) F proteins are cleaved by furin during intracellular maturation, producing disulfide-linked F1 and F2 fragments. During cell entry, the cleaved Fs rearrange from prefusion trimers to postfusion trimers. Using RSV F constructs with mutated furin cleavage sites, we isolated an uncleaved RSV F ectodomain that is predominantly monomeric and requires specific cleavage between F1 and F2 for self-association and rearrangement into stable postfusion trimers. The uncleaved RSV F monomer is folded and homogenous and displays at least two key RSV-neutralizing epitopes shared between the prefusion and postfusion conformations. Unlike the cleaved trimer, the uncleaved monomer binds the prefusion-specific monoclonal antibody D25 and human neutralizing immunoglobulins that do not bind to postfusion F. These observations suggest that the uncleaved RSV F monomer has a prefusion-like conformation and is a potential prefusion subunit vaccine candidate. IMPORTANCE RSV is the leading infectious cause of severe respiratory disease in infants and a major cause of respiratory illness in the elderly. Development of an RSV vaccine was stymied when a clinical trial using a formalin-inactivated RSV virus made disease, following RSV infection, more severe. Recent studies have defined the structures that the RSV F envelope glycoprotein adopts before and after virus entry (prefusion and postfusion conformations, respectively). Key neutralization epitopes of prefusion and postfusion RSV F have been identified, and a number of current vaccine development efforts are focused on generating easily produced subunit antigens that retain these epitopes. Here we show that a simple modification in the F ectodomain results in a homogeneous protein that retains critical prefusion neutralizing epitopes. These results improve our understanding of RSV F protein folding and structure and can guide further vaccine design efforts.
A Robotic Biopsy Device for Capsule Endoscopy

This paper introduces a robotic biopsy device for capsule endoscopes. The proposed device consists of three modules for the complete process of biopsy, which includes monitoring the intestinal wall by a tissue monitoring module (TMM), aligning onto a polyp by an anchor module (AM), and sampling of the polyp tissue by a biopsy module (BM). The TMM utilizes a trigonal mirror as well as an on-board camera; since the TMM continuously takes images through lateral apertures, an operator such as a medical doctor is able to anchor the capsule endoscope onto the polyp and biopsy it with the visual feedback in real-time. When the operator finds a polyp using the TMM and the frontal camera of a capsule endoscope, then the AM is used to approach the polyp for biopsy. When the AM is in use, outriggers are extruded by shape-memory-alloy (SMA) springs, which results in the swelling of capsule endoscope body. In addition, an alignment module, which is a part of the AM, rotates the body of the capsule endoscope such that the biopsy razor can be aligned onto the polyp. Then, the BM excises a part of the polyp and seals the aperture, and the capsule endoscope continues exploring the intestine. The concept and working principles of the proposed device are introduced in this paper and are verified by a prototype that successfully integrates the three modules.
A Novel Picornavirus Associated with Gastroenteritis

ABSTRACT A novel picornavirus genome was sequenced, showing 42.6%, 35.2%, and 44.6% of deduced amino acid identities corresponding to the P1, P2, and P3 regions, respectively, of the Aichi virus. Divergent strains of this new virus, which we named salivirus, were detected in 18 stool samples from Nigeria, Tunisia, Nepal, and the United States. A statistical association was seen between virus shedding and unexplained cases of gastroenteritis in Nepal (P = 0.0056). Viruses with approximately 90% nucleotide similarity, named klassevirus, were also recently reported in three cases of unexplained diarrhea from the United States and Australia and in sewage from Spain, reflecting a global distribution and supporting a pathogenic role for this new group of picornaviruses.
The Interaction between Herpes Simplex Virus 1 Tegument Proteins UL51 and UL14 and Its Role in Virion Morphogenesis

ABSTRACT To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) tegument protein UL51 promotes viral replication, we screened for viral proteins that interact with UL51 in infected cells. Affinity purification of tagged UL51 in HSV-1-infected Vero cells was coupled with immunoblotting of the purified UL51 complexes with various antibodies to HSV-1 virion proteins. Subsequent analyses revealed that UL51 interacted with another tegument protein, UL14, in infected cells. Mutational analyses of UL51 showed that UL51 amino acid residues Leu-111, Ile-119, and Tyr-123 were required for interaction with UL14 in HSV-1-infected cells. Alanine substitutions of these UL51 amino acid residues reduced viral replication and produced an accumulation of unenveloped and partially enveloped nucleocapsids in the cytoplasm at levels comparable to those of UL51-null, UL14-null, and UL51/UL14 double-null mutations. In addition, although UL51 and UL14 colocalized at juxtanuclear domains in HSV-1-infected cells, the amino acid substitutions in UL51 produced aberrant localization of UL51 and UL14. The effects of these substitutions on localization of UL51 and UL14 were similar to those of the UL51-null and UL14-null mutations on localization of UL14 and UL51, respectively. These results suggested that the interaction between UL51 and UL14 was required for proper localization of these viral proteins in infected cells and that the UL51-UL14 complex regulated final viral envelopment for efficient viral replication. IMPORTANCE Herpesviruses contain a unique virion structure designated the tegument, which is a protein layer between the nucleocapsid and the envelope. HSV-1 has dozens of viral proteins in the tegument, which are thought to facilitate viral envelopment by interacting with other virion components. However, although numerous interactions among virion proteins have been reported, data on how these interactions facilitate viral envelopment is limited. In this study, we have presented data showing that the interaction of HSV-1 tegument proteins UL51 and UL14 promoted viral final envelopment for efficient viral replication. In particular, prevention of this interaction induced aberrant accumulation of partially enveloped capsids in the cytoplasm, suggesting that the UL51-UL14 complex acted in the envelopment process but not in an upstream event, such as transport of capsids to the site for envelopment. This is the first report showing that an interaction between HSV-1 tegument proteins directly regulated final virion envelopment.
The Receptor Binding Domain of the New Middle East Respiratory Syndrome Coronavirus Maps to a 231-Residue Region in the Spike Protein That Efficiently Elicits Neutralizing Antibodies

ABSTRACT The spike (S) protein of the recently emerged human Middle East respiratory syndrome coronavirus (MERS-CoV) mediates infection by binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). Here we mapped the receptor binding domain in the S protein to a 231-amino-acid fragment (residues 358 to 588) by evaluating the interaction of spike truncation variants with receptor-expressing cells and soluble DPP4. Antibodies to this domain—much less so those to the preceding N-terminal region—efficiently neutralize MERS-CoV infection.
Trapping of a mie sphere by acoustic pulses: effects of pulse length

The acoustic counterpart of optical tweezers shows great promise as a single-particle manipulator using a highly focused acoustic beam. Understanding the dependence of the trapping performance of the acoustic beam on the acoustic pulse length may facilitate its development and extend the applications. Herein, we propose a ray-based model for the time-course simulation of instantaneous forces exerted on single Mie spheres by highly focused acoustic pulses of arbitrary lengths. The simulations considered single fat/lipid spheres with a density of 950 kg/m3 and speed of sound of 1450 m/s, suspended in water and located on the beam axis. Simulation was used to establish the spatial and temporal pressure data of pulsed acoustic fields transmitted from a 100-MHz transducer with a half-power bandwidth of 50% and an f-number of 1. The instantaneous intensity vectors were calculated to represent rays for estimating forces exerted by consecutive wave¿particle interactions. The results suggest that short acoustic pulses can exert negative forces pulling spheres beyond the focus in the direction opposite to that of wave propagation. Varying the excitation pulse duration has no effect on the region where the exerted forces are averagely negative. Lengthening the excitation pulse duration rapidly increases the amplitude of the average force. A smaller sphere experiences a greater average force when the spatial length of a transmitted acoustic pulse is comparable to the sphere diameter. The amplitude of the instantaneous force can be maximized as long as the acoustic pulse length is longer than the sphere diameter. Regulating the relation between acoustic pulse length and sphere size may be advantageous in particle sorting applications.