Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Bocavirus VP2 Upregulates IFN-β Pathway by Inhibiting Ring Finger Protein 125–Mediated Ubiquitination of Retinoic Acid–Inducible Gene-I

Precise regulation of innate immunity is crucial for maintaining optimal immune responses against infections. Whereas positive regulation of IFN signaling elicits rapid type I IFNs, negative regulation is equally important in preventing the production of superfluous IFNs that can be hazardous to the host. The positive regulators of IFN pathway are known to be the main targets of viruses to antagonize the innate immune system. Whether viruses target the negative regulators of IFN pathway remains to be fully investigated. In this study, we report that the structural protein VP2 of human Bocavirus modulates IFN pathway by targeting the ring finger protein 125 (RNF125), a negative regulator of type I IFN signaling, which conjugates Lys48-linked ubiquitination to retinoic acid–inducible gene-I (RIG-I) and subsequently leads to the proteasome-dependent degradation of RIG-I. VP2 not only upregulated Sendai virus (SeV)–induced IFNB promoter activity, but also enhanced SeV-induced IFN-β production at both mRNA and protein levels. In agreement, the level of Ser396-phosphorylated IFN regulatory factor 3 stimulated by SeV was enhanced in the presence of VP2. Furthermore, VP2 was demonstrated to physically interact with RNF125, resulting in the reduction of RNF125-mediated ubiquitination and proteasome-dependent degradation of RIG-I. Additional study indicated that endogenous RIG-I degradation was decreased in VP2-expressing cells. Our study delineates a unique phenomenon for aberrant activation of IFN regulatory factor 3 pathway and may represent a new mechanism underlying viral manipulation of the host immune system.
The Dot/Icm Type IV Secretion System of Legionella pneumophila Is Essential for the Induction of Apoptosis in Human Macrophages

ABSTRACT We have previously shown that Legionella pneumophila induces caspase 3-dependent apoptosis in mammalian cells during early stages of infection. In this report, we show that nine L. pneumophila strains with mutations in the dotA, dotDCB, icmT, icmGCD, and icmJB loci are completely defective in the induction of apoptosis, in addition to their severe defects in intracellular replication and pore formation-mediated cytotoxicity. Importantly, all nine dot/icm mutants were complemented for all their defective phenotypes with the respective wild-type loci. We show that the role of the Dot/Icm type IV secretion system in the induction of apoptosis is independent of the RtxA toxin, the dot/icm-regulated pore-forming toxin, and the type II secretion system. However, the pore-forming toxin, which is triggered upon entry into the postexponential growth phase, enhances the ability of L. pneumophila to induce apoptosis. Our data provide the first example of the role of a type IV secretion system of a bacterial pathogen in the induction of apoptosis in the host cell.
Structure of mycobacterial 3′-to-5′ RNA:DNA helicase Lhr bound to a ssDNA tracking strand highlights distinctive features of a novel family of bacterial helicases

Abstract Mycobacterial Lhr is a DNA damage-inducible superfamily 2 helicase that uses adenosine triphosphate (ATP) hydrolysis to drive unidirectional 3′-to-5′ translocation along single-stranded DNA (ssDNA) and to unwind RNA:DNA duplexes en route. ATPase, translocase and helicase activities are encompassed within the N-terminal 856-amino acid segment. The crystal structure of Lhr-(1–856) in complex with AMPPNP•Mg2+ and ssDNA defines a new helicase family. The enzyme comprises two N-terminal RecA-like modules, a winged helix (WH) domain and a unique C-terminal domain. The 3′ ssDNA end binds in a crescent-shaped groove at the interface between the first RecA domain and the WH domain and tracks 5′ into a groove between the second RecA and C domains. A kissing interaction between the second RecA and C domains forms an aperture that demarcates a putative junction between the loading strand tail and the duplex, with the first duplex nucleoside bookended by stacking on Trp597. Intercalation of Ile528 between nucleosides of the loading strand creates another bookend. Coupling of ATP hydrolysis to RNA:DNA unwinding is dependent on Trp597 and Ile528, and on Thr145 and Arg279 that contact phosphates of the loading strand. The structural and functional data suggest a ratchet mechanism of translocation and unwinding coupled to ATP-driven domain movements.
Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism.

BACKGROUND Standard therapy to prevent recurrent venous thromboembolism includes 3 to 12 months of treatment with full-dose warfarin with a target international normalized ratio (INR) between 2.0 and 3.0. However, for long-term management, no therapeutic agent has shown an acceptable benefit-to-risk ratio. METHODS Patients with idiopathic venous thromboembolism who had received full-dose anticoagulation therapy for a median of 6.5 months were randomly assigned to placebo or low-intensity warfarin (target INR, 1.5 to 2.0). Participants were followed for recurrent venous thromboembolism, major hemorrhage, and death. RESULTS The trial was terminated early after 508 patients had undergone randomization and had been followed for up to 4.3 years (mean, 2.1). Of 253 patients assigned to placebo, 37 had recurrent venous thromboembolism (7.2 per 100 person-years), as compared with 14 of 255 patients assigned to low-intensity warfarin (2.6 per 100 person-years), a risk reduction of 64 percent (hazard ratio, 0.36 [95 percent confidence interval, 0.19 to 0.67]; P<0.001). Risk reductions were similar for all subgroups, including those with and those without inherited thrombophilia. Major hemorrhage occurred in two patients assigned to placebo and five assigned to low-intensity warfarin (P=0.25). Eight patients in the placebo group and four in the group assigned to low-intensity warfarin died (P=0.26). Low-intensity warfarin was thus associated with a 48 percent reduction in the composite end point of recurrent venous thromboembolism, major hemorrhage, or death. According to per-protocol and as-treated analyses, the reduction in the risk of recurrent venous thromboembolism was between 76 and 81 percent. CONCLUSIONS Long-term, low-intensity warfarin therapy is a highly effective method of preventing recurrent venous thromboembolism.
Gender differences in 2 clinical trials of adults with attention-deficit/hyperactivity disorder: a retrospective data analysis.

INTRODUCTION Studies show that, in childhood attention-deficit/hyperactivity disorder (ADHD), boys have the combined type with externalizing behaviors more frequently, and girls have the inattentive type with increased internalizing disorders more frequently. METHOD This study explored gender differences in adults with ADHD in 2 large, placebo-controlled, multicenter studies conducted from 2000 to 2001. Information collected included 2 measures of ADHD, multiple psychological measures, general physical symptoms, and treatment response. RESULTS Thirty-four percent of the subjects were female. Women were rated as more impaired on every measure of ADHD symptoms including total Conners' Adult ADHD Rating Scale-Investigator Format (CAARS-INV), total Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS), and most subscales of both measures. More women (75%) had combined type compared with men (62%). Women showed a more complex presentation, with higher scores on the Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Rating Scale for Depression, 17-item version (HAM-D(17)), more sleep problems, and more past DSM-IV Axis I diagnoses. Both sexes displayed substantial impairment on 3 Psychological General Well-Being Schedule factors: tension-anxiety, life satisfaction, and vitality-drive. Women experienced significantly (p = .003) greater rates of emotional dysregulation (37%) versus men (29%) as defined by a cluster of symptoms on the WRAADDS. The emotional dysregulation factor is derived by combining 3 symptoms--temper control, mood lability, and emotional overreactivity--from the Utah Criteria for ADHD in adults. These symptoms are considered associated symptoms in the DSM-IV description of ADHD. Women also experienced greater improvement (p = .011) on this symptom factor. CONCLUSION In contrast to the results from childhood studies, women were more impaired than men on ADHD scales in our study. The higher level of emotional symptoms and more complicated presentation in women may obscure the diagnosis of ADHD. Thus, the assessments of adults with ADHD should include an exploration of the emotional dimensions of the illness.
Justifying the clinical use of fresh frozen plasma - an audit.

OBJECTIVE To determine the appropriateness of fresh frozen plasma (FFP), uses in various haematological and clinical disorders, with reference to the British Committee for Standards in Haematology (BCSH) guidelines through an audit. DESIGN Descriptive study. PLACE AND DURATION OF STUDY Department of Haematology and Transfusion Medicine, Shalamar Hospital, Lahore, from June 2001 to June 2004. SUBJECTS AND METHODS The data was collected from June 2001 to June 2004 from the request forms ordered by the clinicians for the transfusion of FFP at the Department of Haematology and Transfusion Medicine, Shlamar Hospital, Lahore. A total of 2075 healthy blood donors donated their whole blood for the preparation of fresh frozen plasma (FFP). All blood donors were screened for anti HCV, HBsAg, VDRL and HIV. Those 2075 FFP units were prepared on high-speed centrifuge and were rapidly stored at -30oC freezer. A total of 587 patients were transfused 2075 units of FFP for various clinical disorders. The percentage of FFP units, transfused appropriately and inappropriately, as defined by BCSH guidelines, was estimated. RESULTS Out of 2075 FFP units, 335 (24.41%) FFP units were transfused to patients suffering from bleeding due to disseminated intravascular coagulation (DIC), 306 (22.30%) units used for massive transfusion and surgical bleeding, 236 (17.20%) units for bleeding due to chronic liver disease, 202 (14.72%) units used to control bleeding due to coagulation factor deficiencies, 84(6.12%) units for thromobotic thrombocytopenic purpura (TTP), 75(5.46%) units prior to liver biopsy to correct prolonged prothrombin time (PT), 72(5.24%) units for haemorrhage due to haemolytic disease of newborn (HDN) and 62(4.51%) units to control bleeding due to warfarin overdosage, 425(60.45%) units used for nutritional support and hypovolaemia replacement, 131(18.63%) units for the reversal of prolonged INR in the absence of bleeding due to warfarin, 92 (13.08%) units used in ICU to correct prolonged PT without bleeding due to Vitamin K deficiency and 55(7.82%) units for chronic liver disease (CLD) to correct prolonged PT and APTT in the absence of bleeding. In summary, 1372 (66.12%) FFP units were appropriately and 703 (33. 88 %) were inappropriately used. CONCLUSION In conclusion, 33.88% FFP was inappropriately used mainly due to lack of awareness of international guidelines and ignorance of risks.
Effects of a music therapy group intervention on enhancing social skills in children with autism.

BACKGROUND Research indicates that music therapy can improve social behaviors and joint attention in children with Autism Spectrum Disorder (ASD); however, more research on the use of music therapy interventions for social skills is needed to determine the impact of group music therapy. OBJECTIVE To examine the effects of a music therapy group intervention on eye gaze, joint attention, and communication in children with ASD. METHOD Seventeen children, ages 6 to 9, with a diagnosis of ASD were randomly assigned to the music therapy group (MTG) or the no-music social skills group (SSG). Children participated in ten 50-minute group sessions over a period of 5 weeks. All group sessions were designed to target social skills. The Social Responsiveness Scale (SRS), the Autism Treatment Evaluation Checklist (ATEC), and video analysis of sessions were used to evaluate changes in social behavior. RESULTS There were significant between-group differences for joint attention with peers and eye gaze towards persons, with participants in the MTG demonstrating greater gains. There were no significant between-group differences for initiation of communication, response to communication, or social withdraw/behaviors. There was a significant interaction between time and group for SRS scores, with improvements for the MTG but not the SSG. Scores on the ATEC did not differ over time between the MTG and SSG. CONCLUSIONS The results of this study support further research on the use of music therapy group interventions for social skills in children with ASD. Statistical results demonstrate initial support for the use of music therapy social groups to develop joint attention.
Influence of thermal and other manufacturing stresses on retinol isomerization in milk and dairy products

An analytical procedure, based upon HPLC, has been used to determine the degree of isomerization of retinol (vitamin A) in various dairy products. In raw milks, which are not subjected to thermal processing, there was no conversion of the predominant all-trans-isomers to cis-isomers in samples from various species. Pasteurized milks with mild heat treatment (high quality milk) had an average 13-cis[ratio ]all-trans ratio of 2·6%, while pasteurized milk treated for 15 s at temperatures ranging from 72 to 76°C had an average ratio of 6·4%. Milk subjected to more severe heat treatments had a higher degree of isomerization (UHT milk, 15·7%; sterilized milk, 33·5%), consistent with increased thermal conversion of the retinol isomers. In pasteurized and UHT cream, the increase in 13-cis-isomer was also a consequence of heat treatment (pasteurized cream, 3·0%; UHT cream, 14·4%). The presence of cis isomers in fermented milk suggests that fermentation processes, directly or indirectly, can induce cis–trans isomerization. In the cheeses analysed, the extent of retinol isomerization ranged from 7·6 to 35·0%. Our results confirm the importance of individual isomers in evaluating the vitamin A status of dairy products.
Serum magnesium levels in asthmatic children during and between exacerbations.

OBJECTIVE To determine, if possible, whether magnesium deficiency exists in children with asthma during acute attacks and between exacerbations. SETTING Emergency Department Clinic and Outpatient Pediatric Clinic of Jordan University of Science and Technology, Irbid. METHODS A total of 174 known asthmatic children who presented to the emergency department in acute attack (group 1) and 94 asthmatic children who presented to outpatient clinics for follow-up of asthma (group 2) had their serum magnesium levels assayed and compared with 232 patients without asthma (controls; group 3). Exclusion criteria were history of renal disease, cardiac disease, malabsorption, diuretic use, alcoholism, and pregnancy. RESULTS There were no differences between study groups, although male patients had a slightly lower level of magnesium than female patients. CONCLUSION After removing the confounder of sex, serum magnesium levels in asthmatic children during acute attacks and between exacerbations are not significantly different from those of controls.
Endocrine aspects of the 22q11.2 deletion syndrome

Hormonal disorders are common in patients with a 22q11.2 deletion. While hypoparathyroidism was the first endocrine disturbance documented in the DiGeorge syndrome, growth hormone deficiency, hypothyroidism, and hyperthyroidism are now known to occur in patients with a 22q11.2 deletion. This review briefly summarizes our current understanding of the spectrum of endocrinological manifestations of the 22q11.2 deletion and proposes guidelines for appropriate screening and management of endocrine disorders in patients with a 22q11.2 deletion.
Structure elucidation of two new xanthone derivatives from the marine fungus Penicillium sp. (ZZF 32#) from the South China Sea

Two new xanthones, 8‐(methoxycarbonyl)‐1‐hydroxy‐9‐oxo‐9H‐xanthene‐3‐carboxylic acid (1) and dimethyl 8‐methoxy‐9‐oxo‐9H‐xanthene‐1, 6‐dicarboxylate (2) and one known xanthone methyl 8‐hydroxy‐6‐methyl‐9‐oxo‐9H‐xanthene‐1‐carboxylate (3) were isolated from the culture broth of the mangrove fungus Penicillium sp. (ZZF 32#) collected from the South China Sea. Their structures were established by comprehensive analysis of one‐dimensional (1D) and two‐dimensional (2D) NMR data. The structure of compound 3 was confirmed by X‐ray crystallography, which led to the suggestion that janthinone (4) might have the same structure as 3. Compounds 1–3 were inactive against KB or KBv200 cells during cytotoxicity evaluations. Copyright © 2008 John Wiley & Sons, Ltd.
Oxidative stress markers in young hemodialysis patients - a pilot study.

AIMS Studies in young hemodialysis patients without significant comorbidities might increase the understanding of incipient vascular pathology in uremia. We investigated whether a specific pattern of oxidative stress markers with potential prognostic significance could be identified in this population. MATERIAL AND METHODS We performed a cross-sectional matched case control study of 25 young hemodialysis patients (age 18 - 40 years) without known comorbidity factors. Patients were matched pairwise to healthy controls, and markers of oxidative stress were analyzed for associations with surrogate parameters of vascular structure and function. RESULTS Oxidized low-density lipoproteins (OxLDL) were similar in patients and controls whereas conjugated dienes were increased in the very low-density lipoproteins (VLDL) fraction (20 +/- 6 vs. 12 +/- 5 micromol/l, p < 0.0001), but not in the low-density lipoproteins (LDL) fraction (16 +/- 6 vs. 18 +/- 6 micromol/l). Superoxide dismutase (SOD) activity was diminished in patients (1,117 +/- 151 vs. 1,299 +/- 88 U/g Hb, p < 0.0001), but there was no difference in glutathione peroxidase (GPx) activity. Oxidative stress expressed as the ratio of oxidized and reduced glutathione (GSSG/GSH) was increased in patients (0.25 +/- 0.18 vs. 0.13 +/- 0.04, p = 0.0048). Intima-media thickness (IMT) of the common carotid artery (0.70 +/- 0.12 vs. 0.62 +/- 0.08 mm, p = 0.0007) was significantly increased, and postischemic peak flow (PIPF) by venous occlusion plethysmography was severely diminished in patients (632 +/- 319 vs. 1,057 +/- 543% of basal flow, p < 0.0001). None of the markers of oxidative stress was independently associated with IMT or PIPF or a significant discriminator between patients and controls by multivariate regression. CONCLUSIONS In this pilot study of exclusively young patients on hemodialysis, oxidative stress markers were of limited clinical value in identifying young patients at risk for vascular complications.
Red blood cell distribution width and ischaemic stroke

The red blood cell distribution width (RDW) is a measure of red blood cell (RBC) size heterogeneity, which is easily calculated by dividing the SD of erythrocyte volumes for the mean corpuscular volume. Recent reporter suggested that, besides haematological diseases and anaemia, many human disorders may be closely associated with the elevated RDW. A literature review has revealed the RDW may be closely related to the development of ischaemic stroke, carotid artery atherosclerosis and cerebral embolism. Higher RDW could independently predict adverse outcomes in patients in these conditions.
Response to Interferon-α in Chronic Hepatitis B With and Without Precore Mutant Strain Detected by Mutation Site–specific Assay

Goals: We investigated whether the presence of precore mutant (stop codon mutation at codon 28) affects the response to interferon-α in patients with chronic hepatitis B. Background: Mutations of hepatitis B virus (HBV) may influence the response to treatment. The association of precore mutant with the response to interferon is controversial. Study: Thirty-one Japanese patients with hepatitis B e antigen–positive chronic hepatitis were treated with natural interferon-α. HBV DNA with the precore mutation was assayed in serum using a mutation site–specific assay before and after treatment. Results: Before treatment, precore mutant was detected in 22 cases (group A) and not detected in 9 cases (group B). Serum HBV DNA level before treatment was not different between the 2 groups. At the end of treatment, serum HBV DNA was decreased to undetectable levels in 13% (4 of 31). Six months after treatment, the percentage of cases with loss of hepatitis B e antigen and a decrease in the transaminase level to within the normal range was significantly higher in group B than in group A (67%, 18%, P = 0.015). Conclusions: Chronic hepatitis without precore mutant strain before treatment is more responsive to IFN-α.
Correlation Between Polyphenol Oxidase (PPO) Activity and Total Phenolic Contents in Crocus sativus L. Corms During Dormancy and Sprouting Stages

Purification and characterization of polyphenol oxidase (PPO) enzyme and determination of total phenolic contents during dormancy and sprouting stages in Crocus sativus corms were performed. PPO enzyme was purified by ammonium sulfate precipitation and ion-exchange chromatography using DEAE-Sephadex A25 and two isoenzymes were obtained on the SDS-PAGE, which corresponded to molecular weights of 70 and 54 kDa. The Km values of the enzyme were 4.87 and 2.12 mM for l-DOPA in dormancy and waking stages, respectively. Also, enzyme showed higher Vmax values of 0.026 (ΔOD.min-1) in dormancy compared with the value of 0.019 (ΔOD.min-1) in waking corms. Results showed an inverse correlation between phenolic contents and PPO activity. Accordingly, it can be concluded that as plant progressed through sprouting stage, in contrast to polyphenol oxidase activity, there was a significant increase in total amount of phenolic compounds, as determined by Folin-Ciocalteu method and water and aqueous ethanol extractions. Abbreviations used: PPO: Polyphenol Oxidase, DEAE-Sephadex: Diethylaminoethyl Sephadex, SDS-PAGE: Sodium Dodecyl Sulfate- Polyacrylamide Gel Electrophoresis, DOPA: Dihydroxyphenylalanine, PEG: Polyethylene Glycol
A Single Case Narrative of Spirituality Following Aphasia from Traumatic Brain Injury: Findings about Forgiveness and Freedom Using WELLHEAD and SHALOM

Rehabilitation has neglected the spirituality of people with aphasia, a neurogenic impairment of language for communication and thought processes. Aphasia reduces scope for adjustment processes where words are normal currency, such as forgiveness and reconciliation. A single case narrative was generated from a case series exploring the feasibility of spiritual health assessment in aphasia. The individual had traumatic brain injury, with the primary symptom of aphasia, giving the first detailed account of its kind. The WELLHEAD spirituality toolkit provided a structured interview approach, exploring spirituality in terms of ‘meaning and purpose’ within four dimensions, WIDE, LONG, HIGH and DEEP, incorporating patient-reported outcome measures and goal-setting, with feedback interviews. Spiritual Health and Life Orientation Measure (SHALOM) generated a comparator spiritual health assessment. The quantitative feedback measures and self-reported outcomes were complemented by detailed qualitative interview transcripts subject to systematic thematic analysis in NVivo. The findings were co-constructed and systematically verified. This non-religious narrative evidenced the accessibility, acceptability, and impact of the resources. Self-forgiveness was paramount for freedom to journey into the unknown beyond self with ‘Calm’, towards helping others and accepting help. Religion, Faith and Belief were reconceptualised. Forgiveness of self and others was integral and instrumental in recovery, offering avenues for further investigation and application.