Miracle-dz/UniFAR-FTUs huggingface dataset:
Rational Design of Human Metapneumovirus Live Attenuated Vaccine Candidates by Inhibiting Viral mRNA Cap Methyltransferase

ABSTRACT The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2′-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2′-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2′-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. IMPORTANCE Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising vaccine strategy for human paramyxoviruses. However, it remains a challenge to identify an attenuated virus strain that has an optimal balance between attenuation and immunogenicity. Using reverse genetics, we generated a panel of recombinant hMPVs that were specifically defective in ribose 2′-O methyltransferase (MTase) but not G-N-7 MTase. These MTase-defective hMPVs were genetically stable and sufficiently attenuated but retained high immunogenicity. This work highlights a critical role of 2′-O MTase in paramyxovirus replication and pathogenesis and a new avenue for the development of safe and efficacious live attenuated vaccines for hMPV and other human paramyxoviruses.
Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome

Orthotopic liver transplantation (OLT) has been considered the best treatment option for patients with hepatocellular carcinoma (HCC). Because of a steadily increasing waiting time, a noteworthy proportion of patients are excluded from OLT because of tumor progression. A 20% and more dropout rate from the waiting list has recently been reported. In this prospective study, we evaluated the effect of preoperative transarterial chemoembolization (TACE) on preventing tumor progression while on the waiting list in patients meeting current selection criteria (solitary lesion ≤ 5 cm, three lesions ≤ 3 cm). In addition, we analyzed the outcome of a separate group of patients with advanced‐stage HCC outside the selection criteria but with at least 50% tumor reduction after TACE (downstaging) to expand current criteria. Forty‐eight patients met the selection criteria and were eligible for this study. Seven patients are still on the waiting list; 41 underwent OLT. None of these patients had to be removed from the list because of tumor progression after a mean waiting time of 178 days (23 patients ≥180 days). The 1‐, 2‐, and 5‐year intention‐to‐treat survival was 98%, 98%, and 94%. The outcome after OLT was also excellent with 1‐, 2‐, and 5‐year survival rates of 98%, 98%, and 93%. Tumor recurrence occurred only in 1 patient (2.4%). Fifteen patients with advanced‐stage HCC were included in this study. Three developed a tumor progression and had to be removed from the list (20% dropout rate). Despite tumor reduction before OLT, these patients had a significantly less favorable outcome in the intention‐to‐treat analysis as well as in the posttransplantation survival. Tumor recurrence was seen in 30% of patients after OLT. In conclusion, TACE followed by OLT is associated with an excellent outcome in selected patients. Furthermore, TACE is highly efficacious in preventing tumor progression while waiting for OLT. Although TACE reduced tumor preoperatively, it failed to show a beneficial effect on patient survival in advanced‐stage HCCs.
An Overview of Mechanisms of Cry Toxin Resistance in Lepidopteran Insects

Abstract Arthropods have the capacity to evolve resistance to insecticides and insecticidal traits in genetically modified crops. Resistance development among Lepidoptera is a common phenomenon, and a repertoire of resistance mechanisms to various Cry toxins have been identified from laboratory, greenhouse, and field studies in this insect order. Elucidation of such resistance mechanisms is crucial for developing IRM (insect resistance management) strategies to ensure sustainable use of genetically modified crops. This mini review provides a comprehensive overview of mechanisms of resistance that have been reported for lepidopteran pests. This study demonstrated that resistance mechanisms are highly complex, and the most common mechanism of resistance is altered binding sites. It is yet to be established whether all these altered binding sites are regulated by an MAPK signaling pathway, which might suggest a universal mechanism of resistance in lepidopterans.
BP and arterial distensibility in children with primary snoring.

STUDY OBJECTIVE While previous studies have suggested an association between obstructive sleep apnea and cardiovascular complications, the effects of primary snoring in children on daytime systemic BP and arterial distensibility remain unknown. DESIGN AND PATIENTS To determine the effects of primary snoring on BP and peripheral conduit artery distensibility, 30 children with primary snoring were studied at an age of 9.5 +/- 2.8 years (mean +/- SD). Systemic BP was measured using an automated device, while brachioradial arterial distensibility was assessed by measuring pulse wave velocity (PWV), which is inversely related to the square root of distensibility. The results were compared to those of 30 healthy control subjects matched for age, sex, and body size. RESULTS As compared to control subjects, children with primary snoring had significantly higher systolic BP (112 +/- 10 mm Hg vs 105 +/- 8 mm Hg, p = 0.001), diastolic BP (60 +/- 7 mm Hg vs 53 +/- 9 mm Hg, p = 0.004), and mean BP (81 +/- 7 mm Hg vs 71 +/- 8 mm Hg, p < 0.001). Likewise, those with primary snoring had significantly higher PWV (9.7 +/- 1.6 m/s vs 7.9 +/- 2.0 m/s, p = 0.001). Multiple regression identified age, body mass index (BMI), and primary snoring as significant determinants of systemic BP; however, primary snoring is the only significant determinant of PWV. Regardless of the BMI, systemic BP and PWV remained significantly higher in children with primary snoring. CONCLUSION Children with primary snoring have increased daytime systemic BP and reduced arterial distensibility, which may jeopardize long-term cardiovascular health.
[Examination of risk factors for onset of certification of long-term care insurance in community-dwelling older people: AGES project 3-year follow-up study].

PURPOSE The purpose of this study was to examine risk factors for certification of long-term care insurance in community dwelling elderly people. METHODS We sent self-completion questionnaires to 24,374 persons (in 5 municipalities) aged 65 years and older and 12,031 responded. Among these participants, we analyzed 9,702 persons who were not requiring care and showed no disability in basic activities of daily living (ADL) at baseline and provided complete data on age and sex. The endpoint was the onset of certification of long-term care insurance. Independent variables from the baseline survey were age, family structure, income, years of education attainment, diseases under treatment, number of medications, fall(s) in 1 year, biting ability, BMI (body mass index), hearing impairment, vision impairment, excretion impairment, the TMIG index of competence, depression, self-rated health, alcohol consumption, smoking, walking time in a day, frequency of going out, frequency of contact with friends, social support, participation in group activity, working and housekeeping. We calculated the hazard ratio (HR) for onset of certification of long-term care insurance using the Cox proportional hazards model of SPSS Ver. 12.0J. RESULTS Among the 9,702 persons, 520 died and 821 had onset of certification of long-term care insurance by October 2006 (follow-up period of 36 months). Age, diseases under treatment, number of medications, fall(s) in 1 year, biting ability, excretion impairment, the TMIG index of competence, depression, self-rated health, walking time in a day, frequency of going out, frequency of contact with friends, participation in group activity, working and housekeeping were significantly related to increased risk of onset of certification of long-term care insurance. CONCLUSION We here were able to clarify risk factors for certification of long-term care insurance. Development of care prevention programs focusing on these factors is now needed.
Lipid metabolism in children with chronic hepatitis C, A preliminary report.

BACKGROUND/AIMS The importance of lipid metabolism in the pathogenesis of chronic hepatitis C has been recognized in recent years. Bearing in mind remote sequelae of chronic hepatitis C in children, it seems reasonable to seek to determine potential risk factors for the development of cirrhosis and carcinogenesis. The aim of the study was to assess lipid metabolism in children with chronic HCV-related hepatitis. METHODOLOGY The study comprised 16 children with chronic hepatitis C and 16 healthy controls. In all the children anthropometric data and after, overnight fasting, serum levels of total bilirubin, AST, ALT, total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides were investigated. In the study group biopsy specimens were assessed. RESULTS Macrovesicular steatosis in numerous hepatocytes was found in 3 children. Total cholesterol level in children with chronic hepatitis was significantly lower than in control group (p < or = 0.05). Mean values of body mass, height, body mass index (BMI), levels of bilirubin, HDL-cholesterol, LDL-cholesterol, triglycerides and HDL/C index did not differ significantly between the two groups. No correlation between lipid parameters and histological markers, hepatic enzymes, patient age, weight, height or BMI was found. CONCLUSIONS Neither obesity nor hyperlipidemia, which are recognized risk factors for steatosis were found in children with HCV-related hepatitis. Lower cholesterol levels in children with chronic HCV infection compared to the controls and only scarce signs of steatosis which were noted could suggest the risk, existing already in such young patients, of developing fatty liver disease with its consequences including cirrhosis and neoplastic disease.
The Efficiency of Gabapentin Therapy in Patients With Lumbar Spinal Stenosis

Study Design. Randomized controlled study. Objectives. To investigate the efficacy of treatment with gabapentin on the clinical symptoms and findings in patients with lumbar spinal stenosis (LSS). Summary of Background Data. LSS is a syndrome resulting from the narrowing of the lumbar nerve root canal, spinal canal, and intervertebral foramen, causing compression of the spinal cord. The most significant clinical symptom in patients with LSS is neurologic intermittent claudication (NIC). Gabapentin, which has been used in the treatment of neuropathic pain, may be effective in the treatment of symptoms associated with LSS. Methods. Fifty-five patients with LSS, who had NIC as the primary complaint, were randomized into 2 groups. All patients were treated with therapeutic exercises, lumbosacral corset with steel bracing, and nonsteroidal anti-inflammatory drugs. The treatment group received gabapentin orally in addition to the standard treatment. Results. Gabapentin treatment resulted in an increase in the walking distance better than what was obtained with standard treatment (P = 0.001). Gabapentin-treated patients also showed improvements in pain scores (P = 0.006) and recovery of sensory deficit (P = 0.04), better than could be attained with the standard treatment. Conclusion. Based on the results of our pilot study, extensive clinical studies are warranted to investigate the role of gabapentin in the management of symptomatic LSS.
The Relationship of Patient Population and Nurses’ Certification Statuses on Nurses’ Practices in Preparing Families for the End of Life

While nurses usually prepare family for the patients’ final days, little is known about how this is done. The purpose of this study was to describe nurses’ beliefs and practices concerning family preparation for dying, focusing on strategies, tailoring, timing, and content of preparation. Nurses’ preparatory practices were compared by patient population (hospice or palliative care) and the nurses’ certification status. A descriptive, comparative survey was conducted. All registered nurse members of the Hospice and Palliative Nurses Association who met the inclusion criteria (N = 2706) were invited, and 1434 (53.1%) participated. Nurses believe families can be prepared and identified trust and repetition as important strategies. There are significant differences based on population regarding nurses’ beliefs about preparation, strategies, tailoring, timing, and content. Tailoring differed based on certification status. This information can be compared with what is known about family preparatory needs to develop preparatory interventions that are tailored to patient and family characteristics. Revisiting the similarities and differences in the practice of nurses in hospice and palliative care is important as the specialty continues to mature to ensure that adequate education and proper criteria for certification are being provided for all hospice and palliative care nurses.
Sperm motility after the addition of prostaglandin F2α to the landrace boar diluted semen.

Prostaglandin F2α (PGF2α) has been used to improve reproductive performance in swine. The objective of this study was to investigated whether the sperm motility from Landrace boars improves when PGF2α (Dinolytic®; 5 mg PGF2α /ml) was added to diluted semen. Boars from one large production unit, were manually collected; semen was either enriched with PGF2α (group 1, n=18), either untreated (group 2, n=16). Total volume of semen collected, percent of motility and number of obtained doses were recorded. Only boars from the first group (with PGF2α supplemented semen) showed motility over 80% and even 100%. The untreated semen showed motility values around 65-70%.
Genome damage in testicular seminoma patients seven years after radiotherapy

Abstract Purpose: Testicular seminoma cancer incidence has significantly increased over the last few decades, and although it is successfully treated by radiotherapy, long-term health risks are still unclear. The aim of the study was to show long-term genome damage in patients with seminoma after radiotherapy. Materials and methods: Chromosome aberration (CA) and micronucleus (MN) assays seven years after radiotherapy with a total dose of 25 Gy were conducted in 10 testicular seminoma patients aged 23–49 years and results were compared with 10 healthy control subjects matched for age and smoking status. Results: Although mean CA frequency did not deviate from control values, significantly increased frequencies of dicentrics, double minutes, and ring chromosomes were detected in seminoma patients. MN frequency in binuclear lymphocytes of patients was similar to controls (4.60/1000 vs. 5.82/1000, respectively). Significantly higher MN frequency was detected in mononuclear lymphocytes of patients than in controls (2.55/1000 vs. 0.73/1000, respectively). Average percentage of centromere-positive MN was 62.6% in seminoma patients. Conclusion: This study shows the persistence of unstable CA in seminoma patients seven years after radiotherapy and the relevance of long-term follow up. MN frequency in mononuclear lymphocytes was shown to be relevant biomarker of long-term genome damage.
The effect of wiping on skin resurfacing in a pig model using a high energy pulsed CO2 laser system.

BACKGROUND The impact of wiping in laser skin resurfacing has not been systematically studied. METHODS We examined the effects of wiping during single- and multiple-pass high energy pulsed CO2 laser skin resurfacing in a farm pig. Consequences of wiping were evaluated with regard to depth of residual thermal damage, tissue necrosis, and fibroplasia. Also, the impact of wiping on gross wound healing was observed. Wounds were followed for 21 days and biopsies were obtained on postoperative days 0, 1, and 21. RESULTS Immediate postoperative biopsies of single-pass wounds showed equivalent residual thermal damage regardless of wiping; in contrast, biopsies from multiple-pass sites without wiping showed more extensive and variable residual thermal damage than wiped sites. On postoperative day one, single pass sites without wiping were grossly less erythematous than wiped sites, and biopsies showed less extensive necrosis and inflammation. In contrast, multiple pass sites without wiping were grossly more erythematous than corresponding wiped sites, and biopsies revealed significantly increased and variable necrosis. After 21 days, multiple pass sites without wiping were grossly more erythematous and showed a thicker band of fibroplasia microscopy. CONCLUSIONS For single pass wounds, not wiping decreased the level of wounding. In contrast, not wiping in multiple pass wounds significantly increased the depth and variability of residual thermal damage and necrosis, resulting in prolonged healing.
Comparison of Degradative Ability, Enzymatic Activity, and Palatability of Aquatic Hyphomycetes Grown on Leaf Litter

Stream fungi have the capacity to degrade leaf litter and, through their activities, to transform it into a more palatable food source for invertebrate detritivores. The objectives of the present study were to characterize various aspects of fungal modification of the leaf substrate and to examine the effects these changes have on leaf palatability to detritivores. Fungal species were grown on aspen leaves for two incubation times. Leaves were analyzed to determine the weight loss, the degree of softening of the leaf matrix, and the concentrations of ATP and nitrogen associated with leaves. The activities of a protease and 10 polysaccharide-degrading enzymes produced by each fungus were also determined. Most fungi caused similar changes in physicochemical characteristics of the leaves. All fungi exhibited the capability to depolymerize pectin, xylan, and cellulose. Differences among fungi were found in their capabilities to produce protease and certain glycosidases. Leaf palatability was assessed by offering leaves of all treatments to larvae of two caddisfly shredders (Trichoptera). Feeding preferences exhibited by the shredders were similar and indicated that they perceived distinct differences among fungi. Two fungal species were highly consumed, some moderately and others only slightly. No relationships were found between any of the fungal characteristics measured and detritivore feeding preferences. Apparently, interspecific differences among fungi other than parameters associated with biomass or degradation of structural polysaccharides influence fungal palatability to caddisfly detritivores.
Clinical value to quantitate hematogones in Chinese childhood acute lymphoblastic leukemia by flow cytometry analysis

Past studies have shown hematogones (HGs) become prominent in recovery phase after chemotherapy or hematopoietic stem cell transplantation, but still need further researches including different age, centers, and races to prove. So we provide relevant information regarding the clinical impact of this methodology in monitoring the response to treatment.
Identification of Protective Epitopes by Sequencing of the Major Outer Membrane Protein Gene of a Variant Strain ofChlamydia psittaci Serotype 1 (Chlamydophila abortus)

ABSTRACT Protective monoclonal antibodies (MAbs) to the major outer membrane protein (MOMP) of species of the family Chlamydiaceae, which is the primary vaccine candidate antigen, recognize nonlinear epitopes conferred by the oligomeric conformation of the molecule. Protective MAbs failed to recognize oligomeric MOMP of the variant strain LLG, which bears amino acid substitutions in variable segments (VSs) 1, 2, and 4, and competed with monomer-specific MAbs mapping to these VSs in reference strain 577. The results suggest that multiple sites located in the three VSs contribute to the epitope of protective MAbs.
Structural engineering of a phage lysin that targets Gram-negative pathogens

Bacterial pathogens are becoming increasingly resistant to antibiotics. As an alternative therapeutic strategy, phage therapy reagents containing purified viral lysins have been developed against Gram-positive organisms but not against Gram-negative organisms due to the inability of these types of drugs to cross the bacterial outer membrane. We solved the crystal structures of a Yersinia pestis outer membrane transporter called FyuA and a bacterial toxin called pesticin that targets this transporter. FyuA is a β-barrel membrane protein belonging to the family of TonB dependent transporters, whereas pesticin is a soluble protein with two domains, one that binds to FyuA and another that is structurally similar to phage T4 lysozyme. The structure of pesticin allowed us to design a phage therapy reagent comprised of the FyuA binding domain of pesticin fused to the N-terminus of T4 lysozyme. This hybrid toxin kills specific Yersinia and pathogenic E. coli strains and, importantly, can evade the pesticin immunity protein (Pim) giving it a distinct advantage over pesticin. Furthermore, because FyuA is required for virulence and is more common in pathogenic bacteria, the hybrid toxin also has the advantage of targeting primarily disease-causing bacteria rather than indiscriminately eliminating natural gut flora.