Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of droplet dispersion during non-invasive ventilation, oxygen therapy, nebuliser treatment and chest physiotherapy in clinical practice: implications for management of pandemic influenza and other airborne infections.

BACKGROUND Influenza viruses are thought to be spread by droplets, but the role of aerosol dissemination is unclear and has not been assessed by previous studies. Oxygen therapy, nebulised medication and ventilatory support are treatments used in clinical practice to treat influenzal infection are thought to generate droplets or aerosols. OBJECTIVES Evaluation of the characteristics of droplet/aerosol dispersion around delivery systems during non-invasive ventilation (NIV), oxygen therapy, nebuliser treatment and chest physiotherapy by measuring droplet size, geographical distribution of droplets, decay in droplets over time after the interventions were discontinued. METHODS Three groups were studied: (1) normal controls, (2) subjects with coryzal symptoms and (3) adult patients with chronic lung disease who were admitted to hospital with an infective exacerbation. Each group received oxygen therapy, NIV using a vented mask system and a modified circuit with non-vented mask and exhalation filter, and nebulised saline. The patient group had a period of standardised chest physiotherapy treatment. Droplet counts in mean diameter size ranges from 0.3 to > 10 µm were measured with an counter placed adjacent to the face and at a 1-m distance from the subject/patient, at the height of the nose/mouth of an average health-care worker. RESULTS NIV using a vented mask produced droplets in the large size range (> 10 µm) in patients (p = 0.042) and coryzal subjects (p = 0.044) compared with baseline values, but not in normal controls (p = 0.379), but this increase in large droplets was not seen using the NIV circuit modification. Chest physiotherapy produced droplets predominantly of > 10 µm (p = 0.003), which, as with NIV droplet count in the patients, had fallen significantly by 1 m. Oxygen therapy did not increase droplet count in any size range. Nebulised saline delivered droplets in the small- and medium-size aerosol/droplet range, but did not increase large-size droplet count. CONCLUSIONS NIV and chest physiotherapy are droplet (not aerosol)-generating procedures, producing droplets of > 10 µm in size. Due to their large mass, most fall out on to local surfaces within 1 m. The only device producing an aerosol was the nebuliser and the output profile is consistent with nebuliser characteristics rather than dissemination of large droplets from patients. These findings suggest that health-care workers providing NIV and chest physiotherapy, working within 1 m of an infected patient should have a higher level of respiratory protection, but that infection control measures designed to limit aerosol spread may have less relevance for these procedures. These results may have infection control implications for other airborne infections, such as severe acute respiratory syndrome and tuberculosis, as well as for pandemic influenza infection.
One-year clinical outcome of various doses and pharmacokinetic release formulations of paclitaxel eluted from an erodable polymer - Insight in the Paclitaxel In-Stent Controlled Elution Study (PISCES).

AIMS The one year clinical benefit of various doses and release durations of paclitaxel eluted from an erodable polymer has not been evaluated so far. METHODS AND RESULTS Conor paclitaxel-eluting stents have intra-stent wells in which drug and polymer are deposited. Stents with six different release formulations (dose: 10 microg or 30 microg, duration: 5, 10 or 30 days, direction: mural or bidirectional) were implanted in 6 patient cohorts. Clinical follow-up was conducted at 4 and 12 months. Quantitative angiography and IVUS were performed at 4 months, and additional angiographic and IVUS follow-up were performed for groups D5 (10microg/30days/mural) and D6 (30microg/30days/mural), as they had shown the most favorable results at 4 months. At one year, the lowest major adverse cardiac event rates were observed in the slow release (30 day) group (5.1% in D5 and 6.9% in D6). One-year in-stent late loss was 0.52+/-0.34 mm in D5 and 0.36+/-0.50mm in D6 (p=0.20) while neointimal area was 0.99+/-0.54 mm2 in D5 and 0.77+/-0.92 mm2 in D6 (p=0.42). Corresponding in-stent binary restenosis at one year was 0% and 5.6% respectively (p=0.36). CONCLUSIONS Patients who received the slow release formulation stent had better clinical outcome at one year than those who received the fast release formulation. However, the effect on neointimal suppression requires investigation in a larger population to determine whether the high dose formulation confers an additional clinical benefit.
On Human Disease‐Causing Amino Acid Variants: Statistical Study of Sequence and Structural Patterns

Statistical analysis was carried out on large set of naturally occurring human amino acid variations, and it was demonstrated that there is a preference for some amino acid substitutions to be associated with diseases. At an amino acid sequence level, it was shown that the disease‐causing variants frequently involve drastic changes in amino acid physicochemical properties of proteins such as charge, hydrophobicity, and geometry. Structural analysis of variants involved in diseases and being frequently observed in human population showed similar trends: disease‐causing variants tend to cause more changes in hydrogen bond network and salt bridges as compared with harmless amino acid mutations. Analysis of thermodynamics data reported in the literature, both experimental and computational, indicated that disease‐causing variants tend to destabilize proteins and their interactions, which prompted us to investigate the effects of amino acid mutations on large databases of experimentally measured energy changes in unrelated proteins. Although the experimental datasets were linked neither to diseases nor exclusory to human proteins, the observed trends were the same: amino acid mutations tend to destabilize proteins and their interactions. Having in mind that structural and thermodynamics properties are interrelated, it is pointed out that any large change in any of them is anticipated to cause a disease.
Theoretical investigation of negative differential conductance regime of silicon nanocrystal single-electron devices

The current-voltage characteristics of metal-insulator-Si quantum dot (QD)-insulator-metal structures are numerically simulated to investigate the design and the possible applications of single-electron devices taking advantage of Coulomb-blockade phenomenon. The simulation technique is based on a physical description of the devices and only requires fundamental quantities of the system but no fitting parameter. One of the originality of this work lies in the accurate calculation of tunneling rates by a perturbation method, which allows us to properly include the effect of a bias voltage on the wave functions in the QD. As a consequence, we show that the bias influence on the wave function may lead to negative-differential-conductance effects depending on the design of the structure.
Bortezomib: friend or foe of hemolytic anemia?

Over the last decade, bortezomib moved in a stepwise fashion from a benchside promise into a bedside reality and is currently an important tool in the treatment of plasma cell disorders. This review focuses on the relationship between bortezomib and hemolytic anemia. In animal models with lupus-like disease, this agent was shown to deplete the auto-reactive plasma cells and serum autoantibody levels. In humans, two isolated reports advocate the efficacy of bortezomib in autoimmune hemolytic anemia, but important concerns remain with data interpretation and length bias. Conversely, bortezomib may be causative of hemolytic anemia, as reported in a cohort of patients with chronic lymphocytic anemia. Concerted efforts of both basic and clinical researchers are necessary to further explore the safety and efficacy of this agent in nonmalignant disorders, including autoimmune disorders and anemias.
Rationally engineered double substituted variants of Yarrowia lipolytica lipase with enhanced activity coupled with highly inverted enantioselectivity towards 2‐bromo phenyl acetic acid esters

Inverting enzyme enantioselectivity by protein engineering is still a great challenge. Lip2p lipase from Yarrowia lipolytica, which demonstrates a low S‐enantioselectivity (E‐value = 5) during the hydrolytic kinetic resolution of 2‐bromo‐phenyl acetic acid octyl esters (an important class of chemical intermediates in the pharmaceutical industry), was converted, by a rational engineering approach, into a totally R‐selective enzyme (E‐value > 200). This tremendous change in selectivity is the result of only two amino acid changes. The starting point of our strategy was the prior identification of two key positions, 97 and 232, for enantiomer discrimination. Four single substitution variants were recently identified as exhibiting a low inversion of selectivity coupled to a low‐hydrolytic activity. On the basis of these results, six double substituted variants, combining relevant mutations at both 97 and 232 positions, were constructed by site‐directed mutagenesis. This work led to the isolation of one double substituted variant (D97A‐V232F), which displays a total preference for the R‐enantiomer. The highly reversed enantioselectivity of this variant is accompanied by a 4.5‐fold enhancement of its activity toward the preferred enantiomer. The molecular docking of the R‐ and S‐enantiomers in the wild‐type enzyme and the D97A‐V232F variant suggests that V232F mutation provides a more favorable stacking interaction for the phenyl group of the R‐enantiomer, that could explain both the enhanced activity and the reversal of enantioselectivity. These results demonstrate the potential of rationally engineered mutations to further enhance enzyme activity and to modulate selectivity. Biotechnol. Bioeng. 2010;106: 852–859. © 2010 Wiley Periodicals, Inc.
Evaluation of relationship between chromosome 22 and p53 gene alterations and the subtype of meningiomas by the interphase-FISH technique.

In this study, we investigated the relationship between genetic alterations such as chromosome 22 aneuploidy and p53 gene deletion, and the pathological types of meningioma of typical and aggressive forms. Thirty-four meningiomas (23 typical and 11 aggressive) were examined by application of fluorescence in situ hybridization (FISH) with chromosome 22 specific alpha satellite probe and a combination of p53 locus specific and chromosome 17 centromere specific alpha satellite probes, to evaluate the chromosome 22 aneuploidy and gain or loss of p53 gene along with chromosome 17. The results showed that, although chromosome 22 aneuploidy was seen in 7 out of 23 typical (30.4%) and 4 out of 11 aggressive meningiomas (36.3%), no p53 deletion was detected in typical meningiomas, and p53 deletion was detected in 3 out of 11 aggressive meningiomas (1 atypical and 2 malignant), which had recurrence. There were no simultaneous occurrences of p53 gene deletions between typical and aggressive meningiomas. The present findings indicate that the loss of chromosome 22 may be involved with tumorogenesis of typical and aggressive meningiomas, while p53 gene deletions may be involved with malignant progression and recurrence in the aggressive meningiomas.
Phenotypic psychiatric characterization of children with Williams syndrome and response of those with ADHD to methylphenidate treatment

Williams syndrome (WS) is associated with cognitive deficits, special behavioral phenotype, and high rates of psychiatric disorders. The aims of the present study were: (1) To compare the rates of psychiatric disorders and repetitive behaviors in children with WS to children with idiopathic developmental disability (DDs); (2) To longitudinally assess the change in psychiatric disorders during adolescence in WS; (3) To assess retrospectively the effectiveness and safety of methylphenidate (MPH) treatment in WS children with ADHD. The study consisted of a cohort of 38 children and adolescents (age 13.1 ± 5.2 years) with WS and a sample of age‐matched DDs (age 15.0 ± 3.1 years). A current follow‐up evaluation was conducted after 5.6 ± 1.6 years for 25 subjects (65.8%) of the WS cohort. The rate of most psychiatric disorders was found similar in children with WS and DD controls. Specific phobia, especially from noises, obsessive–compulsive symptoms (e.g., aggressive obsessions and repetitive questions), and stereotypic behaviors (e.g., glancing), were more common in WS than DDs. In a longitudinal follow‐up of the WS children, we found a decrease in the rate of anxiety disorders. In addition, a clinically significant improvement was reported in 72.2% of WS children with ADHD following MPH treatment. Sadness/unhappiness was the most common side effect associated with MPH treatment in WS, occurring in 2/3 of treated individuals. The present study further elucidates the neuropsychiatric phenotype of WS. Our results also suggest that MPH treatment for ADHD in WS warrants future prospective controlled trials. © 2011 Wiley Periodicals, Inc.
Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs

Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected with the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV-2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus.
Chronic ethanol consumption impairs receptor‐mediated endocytosis of formaldehyde‐treated albumin by isolated rat liver endothelial cells

Receptor‐mediated endocytosis (RME) by a scavenger receptor on sinusoidal liver endothelial cells (LECs) for formaldehyde‐treated bovine serum albumin (f‐Alb) has previously been shown to be impaired following chronic ethanol consumption. These studies were initially performed by in situ perfusion, making it difficult to determine the point in the process at which RME is affected. Therefore, it was the purpose of this study to use isolated LECs to begin elucidating at what point in the process chronic ethanol consumption affects RME. Initial studies showed that degradation at the single‐cell level were similarly decreased at levels that had been observed for in situ studies, suggesting that the ethanol effects can be repeated using isolated LECs, making them useful for in vitro studies. Binding studies with 125I‐formaldehyde–treated bovine serum albumin (125I–f‐Alb) demonstrated there was a slight, but significantly different, decrease in binding by LECs from ethanol‐fed rats when compared with pair‐fed or chow‐fed rats. However, the affinity of these receptors was not different between these groups. In contrast, a defect in the initial stages of receptor‐ligand internalization was indicated as less surface‐bound ligand was internalized and subsequently degraded in cells from the ethanol‐treated animals as compared with controls. Additionally, once the data were adjusted for the amount of ligand internalized, the degradation of the internalized ligand was only slightly impaired. These results indicate that chronic ethanol feeding impairs the process of RME by the liver; the major cause of this impairment appears to be caused by a decreased ability of these cells to internalize all of the surface‐bound ligand, with a minimal defect in postinternalization events.
Reduction of fresh‐frozen plasma use through a daily survey and education program

In an attempt to reverse a tendency toward the inordinate use of fresh‐ frozen plasma (FFP), the Transfusion Committee in a large tertiary care hospital distributed guidelines based on those derived at a Consensus Development Conference at the National Institutes of Health in 1984. In addition, the use of FFP was surveyed daily and supplemented by a one‐ on‐one educational program for the attending and house staffs. In 2 years, these steps resulted in a 77 percent decrease in the number of units of FFP transfused.
B and T Lymphocyte Attenuator Mediates Inhibition of Tumor-Reactive CD8+ T Cells in Patients After Allogeneic Stem Cell Transplantation

Allogeneic stem cell transplantation (allo-SCT) can cure hematological malignancies by inducing alloreactive T cell responses targeting minor histocompatibility antigens (MiHA) expressed on malignant cells. Despite induction of robust MiHA-specific T cell responses and long-term persistence of alloreactive memory T cells specific for the tumor, often these T cells fail to respond efficiently to tumor relapse. Previously, we demonstrated the involvement of the coinhibitory receptor programmed death-1 (PD-1) in suppressing MiHA-specific CD8+ T cell immunity. In this study, we investigated whether B and T lymphocyte attenuator (BTLA) plays a similar role in functional impairment of MiHA-specific T cells after allo-SCT. In addition to PD-1, we observed higher BTLA expression on MiHA-specific CD8+ T cells compared with that of the total population of CD8+ effector-memory T cells. In addition, BTLA’s ligand, herpes virus entry mediator (HVEM), was found constitutively expressed by myeloid leukemia, B cell lymphoma, and multiple myeloma cells. Interference with the BTLA–HVEM pathway, using a BTLA blocking Ab, augmented proliferation of BTLA+PD-1+ MiHA-specific CD8+ T cells by HVEM-expressing dendritic cells. Notably, we demonstrated that blocking of BTLA or PD-1 enhanced ex vivo proliferation of MiHA-specific CD8+ T cells in respectively 7 and 9 of 11 allo-SCT patients. Notably, in 3 of 11 patients, the effect of BTLA blockade was more prominent than that of PD-1 blockade. Furthermore, these expanded MiHA-specific CD8+ T cells competently produced effector cytokines and degranulated upon Ag reencounter. Together, these results demonstrate that BTLA–HVEM interactions impair MiHA-specific T cell functionality, providing a rationale for interfering with BTLA signaling in post-stem cell transplantation therapies.
1170 consecutive hysterectomies: indications and pathology

Objective: An analysis of consecutive hysterectomies during 1997-99 exploring the relationship between histological findings, operation performed and clinical indication was conducted to observe any trends. Methods: A retrospective review of histology reports for hysterectomies performed in a large district teaching hospital. Results: The rate of hysterectomy for women aged over 25 years was 23 per 10,000 women. Menstrual disturbance including endometriosis was the indication in 45%, pelvic tumours including fibroids in 21%, prolapse in 17% and malignant or pre-malignant conditions in 15%; 1% were performed in relation to childbirth. 79% were total abdominal hysterectomies, 4% subtotal and 17% vaginal. 50% included removal of both ovaries and in 8% omentectomy was also performed. The uterus was histologically normal in 20% of abdominal hysterectomies, the rate rising to 70% for vaginal hysterectomies. Conclusions: The rate of hysterectomy has not changed over the past 15 years, despite the introduction of alternative medical and surgical therapies for managing menstrual problems and fibroids. There may have been a greater proportion performed for malignant and premalignant conditions and genital tract prolapse. There were fewer specimens with no evidence of pathology than is often suggested.
The evaluation of the sentinel node successfully conducted in a case of malignant melanoma of the vagina.

BACKGROUND The sentinel node biopsy has been established as a standard procedure in many types of cancer. To date, only one case was reported for successful detection of the sentinel node using a radiopharmaceutical-directed mapping technique in malignant melanoma of the vagina. CASE An 81-year-old woman developed malignant melanoma arising from the lower third of the vagina. She underwent local resection of the tumor and exploration of the sentinel node using blue dye. The sentinel node was detected successfully in the groin, and was negative for metastasis. Intra-cavity irradiation was given as an adjuvant therapy. CONCLUSION In view of relative ease and minimal trauma, sentinel node mapping could be a routine procedure in malignant melanoma arising from the vagina or vulva.
Neurones in commissural nucleus tractus solitarii required for full expression of the pulmonary C fibre reflex in rat.

1. The pulmonary C fibre reflex, triggered by activating pulmonary C fibre endings in the lung, consists of rapid shallow breathing (which may be preceded by apnoea), bradycardia, and hypotension. The purpose of this work was to identify proximal synapses in this reflex. From pilot data, we hypothesized that neurones in a discrete region of the commissural nucleus in the nucleus tractus solitarii (NTS) are required for full expression of the pulmonary C fibre reflex. Studies were carried out in urethane‐anaesthetized, unilaterally vagotomized, spontaneously breathing rats, in which diaphragm electromyogram, arterial pressure, and blood gases were measured. Phenyldiguanide (PDG) was injected in the right atrium to elicit the pulmonary C fibre reflex. Unilateral NTS injections were made through multibarrelled pipettes containing DL‐homocysteic acid (DLH) to mimic the reflex, cobalt chloride to reversibly impair the reflex, and/or dye to mark the injection sites. 2. PDG (5‐16 micrograms kg‐1) injected in the right atrium of twenty‐six rats produced the classic pulmonary C fibre reflex: a vagally mediated, rapid onset of rapid shallow breathing, bradycardia and hypotension. 3. Injection of DLH (3‐12 nl of 20 mM for a total of 60‐240 pmol) in the dorsomedial aspect of the commissural nucleus of the NTS in thirty rats mimicked the pulmonary C fibre reflex, producing rapid shallow breathing, hypotension, and a slight bradycardia. 4. Interruption of neuronal transmission by injecting cobalt chloride (15‐30 nl of 100 mM) in the site where DLH produced rapid shallow breathing, reversibly impaired the rapid shallow breathing and bradycardia produced by right atrial injections of PDG in fifteen rats. The commissural region where DLH produced rapid shallow breathing and cobalt impaired the pulmonary C fibre reflex extended from 720‐1100 microns caudal to the obex, 30‐200 microns lateral to mid‐line, and 200‐600 microns ventral to the dorsal surface of the brain stem within the NTS. 5. Taken together, the results suggest that neurones within a discrete region in the dorsomedial commissural nucleus in caudal NTS are required for full expression of the pulmonary C fibre reflex.