Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment experience, burden and unmet needs (TRIBUNE) in MS study: results from five European countries

Background: Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The TRIBUNE study provides a detailed exploration of costs in relation to relapses and disease severity, and assesses the quality of life impact on MS patients in terms of utilities, fatigue and activities of daily living (ADL). Methods: Patients in five European countries (France, Germany, Italy, Spain and the United Kingdom) completed a self-administered web-based questionnaire capturing information on demographics, disease characteristics and severity (EDSS), co-morbidities, relapses, resource consumption, utilities, fatigue, and activities of daily living. Results: In total, 1261 MS patients completed the questionnaire. More than half of the patients (68%) had the relapsing–remitting form of the disease; 87% of the sample reported receiving MS treatments. Costs were higher with advancing disease severity; for mild patients (EDSS score ≤ 3) the costs ranged between €13,534 and €22,461 across countries; for moderate (EDSS score 4 – 6.5) between €28,524 and €43,948; for severe (EDSS ≥ 7) between €39,592 and €65,395. Relapses were also associated with increasing costs; the difference in the cost per patient per year for relapsing–remitting patients with EDSS score ≤ 5 that did experience at least one relapse during the past 12 months and those who did not ranged between €3321 and €9430. The quality of life of patients decreased with disease progression and existence of relapses. Conclusion: The TRIBUNE study provides an important update on the economic burden of MS in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity, and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.
Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase

The effects of creatine (Cr) absence in skeletal muscle caused by a deletion of guanidinoacetate methyltransferase (GAMT) were studied in a knockout mouse model by in vivo31P magnetic resonance (MR) spectroscopy. 31P MR spectra of hindleg muscle of GAMT‐deficient (GAMT–/–) mice showed no phosphocreatine (PCr) signal and instead showed the signal for phosphorylated guanidinoacetate (PGua), the immediate precursor of Cr, which is not normally present. Tissue pH did not differ between wild‐type (WT) and GAMT–/– mice, while relative inorganic phosphate (Pi) levels were increased in the latter. During ischaemia, PGua was metabolically active in GAMT–/– mice and decreased at a rate comparable to the decrease of PCr in WT mice. However, the recovery rate of PGua in GAMT–/– mice after ischaemia was reduced compared to PCr in WT mice. Saturation transfer measurements revealed no detectable flux from PGua to γ‐ATP, indicating severely reduced enzyme kinetics. Supplementation of Cr resulted in a rapid increase in PCr signal intensity until only this resonance was visible, along with a reduction in relative Pi values. However, the PGua recovery rate after ischaemia did not change. Our results show that despite the absence of Cr, GAMT–/– mice can cope with mild ischaemic stress by using PGua for high energy phosphoryl transfer. The reduced affinity of creatine kinase (CK) for (P)Gua only becomes apparent during recovery from ischaemia. It is argued that absence of Cr causes the higher relative Pi concentration also observed in animals lacking muscle CK, indicating an important role of the CK system in Pi homeostasis.
Efficient Infection of Primary Tupaia Hepatocytes with Purified Human and Woolly Monkey Hepatitis B Virus

ABSTRACT The Asian tree shrew, Tupaia belangeri, has been proposed as a novel animal model for studying hepatitis B virus (HBV) infection. Here, we describe a protocol for efficient and reproducible infection of primary tupaia hepatocytes with HBV. We report that human serum interferes with HBV binding to the hepatocytes, thus limiting the maximum multiplicity of infection. Purification of HBV virions by gradient sedimentation greatly enhances virus binding and infectivity. Covalently closed circular DNA was clearly detectable by Southern blot analysis and newly synthesized single-stranded HBV DNA was visible 2 weeks postinoculation. Primary tupaia hepatocytes are also susceptible to infection with the recently discovered woolly monkey hepatitis B virus (WMHBV) but not to woodchuck hepatitis virus infection. Compared to HBV, WMHBV replicated at a higher rate with single-stranded DNA detectable within the first week postinoculation. Primary tupaia hepatocytes should represent a useful system for studying early steps of HBV and WMHBV infection.
Inhibition of Beta Interferon Transcription by Noncytopathogenic Bovine Viral Diarrhea Virus Is through an Interferon Regulatory Factor 3-Dependent Mechanism

ABSTRACT The induction and inhibition of the interferon (IFN) response and apoptosis by bovine viral diarrhea virus (BVDV) has been examined. Here we show that prior infection of cells by noncytopathogenic BVDV (ncp BVDV) fails to block transcriptional responses to alpha/beta IFN. In contrast, ncp BVDV-infected cells fail to produce IFN-α/β or MxA in response to double-stranded RNA (dsRNA) or infection with a heterologous virus (Semliki Forest virus [SFV]). ncp BVDV preinfection is unable to block cp BVDV- or SFV-induced apoptosis. The effects of ncp BVDV infection on the transcription factors controlling the IFN-β induction pathway have been analyzed. The transcription factor NF-κB was not activated following ncp BVDV infection, but ncp BVDV infection was not able to block the activation of NF-κB by either SFV or tumor necrosis factor alpha. Furthermore, ncp BVDV infection did not result in the activation of stress kinases (JNK1 and JNK2) or the phosphorylation of transcription factors ATF-2 and c-Jun; again, ncp BVDV infection was not able to block their activation by SFV. Interferon regulatory factor 3 (IRF-3) was shown to be translocated to the nuclei of infected cells in response to ncp BVDV, although DNA-binding of IRF-3 was not seen in nuclear extracts. In contrast, an IRF-3-DNA complex was observed in nuclear extracts from cells infected with SFV, but the appearance of this complex was blocked when cells were previously exposed to ncp BVDV. We conclude that the inhibition of IFN induction by this pestivirus involves a block to IRF-3 function, and we speculate that this may be a key characteristic for the survival of pestiviruses in nature.
On dative causers in Hungarian

This paper aims at investigating a special, causative use of dative case in Hungarian that has not received much attention in the literature so far. I show that Hungarian dative causers differ from dative causers in the languages of the Balkan Sprachbund, German, or Spanish in important ways. What makes Hungarian dative causers different is that they are not licensed and interpreted via syntactic structure but are lexically determined to be causative given that dative case has a special, causative lexical entry in Hungarian.
Current and future drug targets in fibrosis : 1 focusing on Rho GTPase regulated gene transcription

23 Tissue fibrosis occurs with excessive extracellular matrix (ECM) deposition from 24 myofibroblasts resulting in tissue scarring and inflammation. It is driven by multiple 25 mediators, such as the G-protein coupled receptor ligands lysophosphatidic acid (LPA) 26 and endothelin (ET-1) as well as signaling by transforming growth factor β (TGFβ), 27 connective tissue growth factor (CTGF), and integrins. Fibrosis contributes to 45% of 28 deaths in the developed world. As current therapeutic options for tissue fibrosis are 29 limited and organ transplantation is the only effective treatment for end-stage disease, 30 there is an imminent need for efficacious antifibrotic therapies. This review discusses 31 the various molecular pathways involved in fibrosis. It highlights the Rho GTPase 32 signaling pathway and its downstream gene transcription output through myocardin33 related transcription factor (MRTF) and serum response factor (SRF) as a convergence 34 point for targeting this complex set of diseases. 35 36
Postsurgical Use of Imiquimod 5% Cream in the Prevention of Earlobe Keloid Recurrences: Results of an Open‐Label, Pilot Study

Background Traditional surgical modalities for the management of earlobe keloids are often associated with high recurrence rates. A recent report suggests that imiquimod 5% cream can be effective in the prevention of keloid recurrences after surgical excision. Method To establish the safety and efficacy of imiquimod 5% cream in the prevention of recurrences of excised earlobe keloids. Methods Patients who attended a dermatologic surgery clinic for the treatment of earlobe keloids were recruited into the study. Earlobe keloids underwent parallel shave excision. Imiquimod 5% cream was applied daily for 8 weeks followed by an observation period of 16 weeks. In patients who presented with bilateral earlobe keloids, paired comparisons of imiquimod versus intralesional steroid injections were performed. Results Eight earlobes were treated with imiquimod 5% cream after parallel keloid removal. Twenty-four weeks after surgery, six (75%) remained recurrence free. Four patients underwent bilateral paired comparisons. At the end of the observation period, two patients (50%) remained recurrence free in the imiquimod-treated areas while experiencing recurrences in the intralesional steroid–treated areas. Local irritation secondary to imiquimod application required rest periods in three cases. In all cases, patients were able to resume therapy and completed the study without further complications. Conclusion Although small and uncontrolled, the results of this open-label, pilot study suggest that imiquimod 5% cream may prove to be a reasonably effective adjuvant therapeutic alternative for the prevention of recurrences in excised earlobe keloids.
Bilateral functional thoracic outlet syndrome in a collegiate football player.

BACKGROUND Thoracic Outlet Syndrome (TOS) involves compression of the brachial plexus, subclavius artery and vein. Many studies discuss efficacy of surgery and few discuss conservative treatment. It is unknown what specific forms of conservative treatment are best. OBJECTIVE Describe conservative management for TOS using unique exercises. CASE DESCRIPTION A collegiate football player reported numbness/tingling down his right arm after a right brachial plexus stretch injury. Seven months later, he was diagnosed with recurrent cervical traction neuropraxia. Two months later, he reported bilateral symptoms and was diagnosed with functional TOS. The athlete began shoulder strengthening (deltoid, middle trapezius, rhomboids, pectoralis major, latissimus dorsi, biceps, upper trapezius and rotator cuff) and stretching (pectoralis, scalene and upper trapezius) which failed to resolve his symptoms after four weeks. Surgical resection of bilateral first ribs and quitting football was recommended by four physicians. Unique therapeutic exercises developed by the Postural Restoration Institute™ were used to optimize respiration/posture via muscle activation and inhibition. After six weeks, the athlete was asymptomatic and returned to football but still experienced paresthesia with contact. Additional exercises were prescribed and remaining symptoms were abolished. OUTCOMES The Northwick Park Neck Pain Questionnaire was 55.5% at initial and 0% at four weeks and discharge. DISCUSSION Athlete did not demonstrate relief of symptoms from shoulder stretching and strengthening. Intervention designed to optimize respiration/posture by repositioning the pelvis/trunk via specific muscle inhibition and activation resulted in abolishing the athlete's symptoms. Management that aims to optimize respiration via muscle inhibition, activation, and repositioning warrants further research.
Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

The role of endogenous androgens and sex hormone‐binding globulin (SHBG) in ovarian carcinogenesis is poorly understood. Epithelial invasive ovarian cancer (EOC) is a heterogeneous disease and there are no prospective data on endogenous androgens and EOC risk by tumor characteristics (histology, grade, stage) or the dualistic model of ovarian carcinogenesis (i.e. type I vs. type II, leading to less or more aggressive tumors). We conducted a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort evaluating androgens and SHBG and invasive EOC risk by tumor characteristics. Female participants who provided a blood sample and were not using exogenous hormones at blood donation were eligible (n = 183,257). A total of 565 eligible women developed EOC; two controls (n = 1,097) were matched per case. We used multivariable conditional logistic regression models. We observed no association between androgens, SHBG and EOC overall. A doubling of androstenedione reduced risk of serous carcinomas by 21% (odds ratio (OR)log2 = 0.79, 95% confidence interval [CI] = [0.64–0.97]). Moreover, associations differed for low‐grade and high‐grade carcinomas, with positive associations for low‐grade and inverse associations for high‐grade carcinomas (e.g. androstenedione: low grade: ORlog2 = 1.99 [0.98–4.06]; high grade: ORlog2 = 0.75 [0.61–0.93], phet ≤ 0.01), similar associations were observed for type I/II tumors. This is the first prospective study to evaluate androgens, SHBG and EOC risk by tumor characteristics and type I/II status. Our findings support a possible role of androgens in ovarian carcinogenesis. Additional studies exploring this association are needed.
Adsorption–Desorption Characteristics of Lead in Variable Charge Soils

Abstract Adsorption–desorption processes of Pb at contaminated levels in two variable charge soils were investigated. The red soil (RAR) developed on the Arenaceous rock (clayey, mixed siliceous thermic typic Dystrochrept) adsorbed more Pb2+ than the red soil (REQ) derived from the Quaternary red earths (clayey, kaolinitic thermic plinthite Aquult). The maximum adsorption values (Xm ) that were obtained from the simple Langmuir model were 52.6 mmol Pb2+ kg−1 soil and 29.9 mmol Pb2+ kg−1 soil, respectively, for the RAR and REQ. Adsorption of Pb2+ decreased soil pH by 1.10 unit for the RAR soil and 1.21 unit for the REQ soil at the highest loading. The adsorption equilibrium pH of RAR was higher than that of REQ at the same Pb2+ concentration. The distribution coefficient (K d ) of Pb in the soils decreased exponentially with increasing Pb2+ loading. Most of the adsorbed Pb2+ in the soils was not desorbed in the 0.01 mol L−1 NaNO3 solution. After five successive extractions with NaNO3, only 0–11% of the total adsorbed Pb2+ in the RAR soil was desorbed and the corresponding value of the REQ soil was 0–19%, indicating that the RAR soil had a greater affinity for Pb2+ than the REQ soil at the same Pb2+ loading. Different mechanisms might be involved in Pb2+ adsorption/desorption at different levels of Pb2+ loading and between the two soils.
EXPERIENCE WITH TITANIUM CAGES IN ANTERIOR CERVICAL DISCECTOMY AND FUSION.

BACKGROUND Anterior cervical discectomy is a common procedure for treating patients for cervical disc prolapse. This study was conducted to study the surgical outcome and demographic characteristics of patients who were treated for anterior cervical disc prolapse. METHODS Study was conducted in the combined military hospital (CMH) Peshawar. Study interval was 3 years from 1st September, 2011 to 31st August, 2014. Total numbers of patients were 84. Males were 54 (64.28%) and females were 30 (35.71%). All the patients had undergone the procedure of anterior cervical discectomy and fusion with titanium cages (ACDF). All the patients had plain MRI cervical spine done for diagnosis of anterior cervical disc prolapse. RESULTS Total 84 patients were operated. In the patients who complained of brachialgia, 100% improvement was seen after the operation. Three (3.5%) of the patients, who presented with axial neck pain, continued to complain of pain and 2 (2.5%) of the patients complained of pain at the donor site after the operation. One of the patients had dural tear which resulted in subcutaneous cerebrospinal fluid (CSF) accumulation and was treated conservatively with repeated aspiration. Fusion rate was 100% with titanium cages used for fusion after anterior cervical discectomy. No complications were noted after the surgery at 1 year of interval. CONCLUSION Results with titanium cages are expectedly good. Symptoms resolved and fusion rate was 100% at 1 year follow up.
Heat dissipation from a heated square cylinder in an oscillating channel flow

Experiments have been performed to investigate heat dissipation from a heated square cylinder in a channel by oscillating flow. During the experiments, the input power and oscillating amplitude (A) are fixed. The effects of the Reynolds number based on the mean flow velocity (Re = 350 and 540) and the oscillating frequency (0 Hz < f p < 60 Hz) on the heat transfer enhancement are examined. The time-averaged Nusselt number and the Strouhal number were determined for each oscillating condition. The measured Strouhal numbers according to the Reynolds number are compared with the previous results and good agreement is found. The occurrence of the "lock-on" phenomenon is demonstrated for a square cylinder. When the pulsating frequency is in the lock-on regime (fp ~ 2fso), the heat transfer from a square cylinder is dramatically enhanced. The heat transfer enhancement is pronounced as the Reynolds number increases
Helicobacter pylori infection in mother and infant pairs in Anatolia.

BACKGROUND/AIMS The aim of this prospective study was to determine the seroprevalence rates of Helicobacter pylori in mother and infant pairs and to discuss the possible fecal-oral transmission route of Helicobacter pylori infection in the early years of life. METHODS Forty-eight mother-child pairs were followed for 12 months. Helicobacter pylori IgG and hepatitis A virus (HAV) IgG levels were measured in maternal sera, infant sera and breast-milk samples at birth and in breast-milk samples and infant sera at follow-up visits. RESULTS At birth, the rate of Helicobacter pylori positivity was 81.25% in breast-milk and 95.8% in maternal and infant sera. Although there was a decrease in seropositivity in both baby sera and breast-milk at the age of nine months, an increase was observed in the 12th month. Hepatitis A virus IgG was measured to show whether Helicobacter pylori and hepatitis A virus use the same transmission routes. Hepatitis A was positive in all infants' sera, in 95.8% of mothers' sera, and in 68.75% of breast-milk samples. Seropositivity rates in infants whose mothers were seropositive for Helicobacter pylori and hepatitis A virus decreased gradually. There was an increase after the 9th month of life. CONCLUSIONS Helicobacter pylori seroprevalence rates are high in Anatolia. It is possible that the decrease in breastfeeding with increased introduction of supplemental foods may lead to an increased risk of exposure to Helicobacter pylori.
Occult tumor contamination of hematopoietic stem-cell products does not affect clinical outcome of autologous transplantation in patients with metastatic breast cancer.

PURPOSE To determine whether occult tumor contamination of autologous bone marrow or peripheral-blood progenitor cells (PBPC) influences clinical outcome after high-dose chemotherapy in patients with stage IV breast cancer. PATIENTS AND METHODS We used an immunocytochemical assay capable of detecting one tumor cell in 5 x 10(5) hematopoietic cells to analyze bone marrow and/or PBPC collections obtained from 57 consecutive women with chemotherapy-sensitive metastatic breast cancer who received high-dose chemotherapy. The influence of occult tumor on time to progression, overall survival, and first site of recurrence (old or new) was studied. RESULTS Twenty-three of 57 (40%) patients received bone marrow (n=6) or peripheral-blood progenitor collections (n=17) that contained microscopic cancer. Median time to progression and overall survival were 9 and 22 months in patients who did not receive infused tumor cells, compared with 10 and 24 months, respectively, in those who received occult tumor (P=not significant [NS]). Worse survival, but not time to progression, was observed in six patients who received > or = 2/100,000 tumor cells. Regardless of whether occult tumor was infused, the majority of relapses occurred in prior, rather than new sites of disease. Three patients who received stem-cell products contaminated by microscopic breast cancer remain free from progression at 21+, 47+, and 52+ months. CONCLUSION Microscopic tumor was frequently detected by immunocytochemistry in hematopoietic stem-cell products, but did not predict for inferior treatment outcome in this cohort of patients with metastatic breast cancer. Quantitative information regarding infused tumor burden may have prognostic significance.
Polysubstance use among frequent marijuana users: an examination of John Henryism Active Coping, psychiatric symptoms, and family social support among African American incarcerated men

Abstract Incarcerated African American men who use marijuana are vulnerable to polysubstance use, which is associated with greater risk for negative health and psychosocial outcomes than marijuana use alone. It is imperative to understand risk and protective factors for polysubstance use among this vulnerable population to inform the development of culturally tailored substance use interventions. The current study examined the association between John Henryism Active Coping (JHAC), family social support, psychiatric symptoms, and polysubstance use among African American incarcerated men who frequently use marijuana. Results indicated that higher John Henryism Active Coping (JHAC) is associated with decreased likelihood of engaging in polysubstance use, while psychiatric symptoms are associated with increased likelihood of polysubstance use. Incorporating elements of JHAC into concurrent mental health and substance use treatment may reduce risk for overdose and reincarceration among African American incarcerated men upon release into the community.
Henoch-Schönlein purpura nephritis.

Henoch-Schonlein purpura (HSP) is a systemic vasculitic disorder first reported by Heberden in 1806. The association of purpura and joint pain was described by Schonlein in 1837, who termed it “peliosis rheumatica. ” Henoch added a description of four children with skin lesions associated with
Hierarchical visible-light-response Ag/AgCl@TiO2 plasmonic photocatalysts for organic dye degradation

A plasmonic photocatalyst of Ag/AgCl@TiO2 nanoparticles (NPs) was directly prepared by a one-step sonochemical method. Both Ag NPs and AgCl were co-deposited on TiO2 NPs to form Ag@TiO2 and Ag/AgCl@TiO2 using the method. Due to the localized surface plasmonic effects of Ag NPs, the visible-light absorbance of the Ag/AgCl@TiO2 photocatalyst was dramatically increased and the photocatalytic activity to decompose Rhodamine B was much improved under visible light. In addition, due to the advantages of the sonochemical approach, only a very small amount of Ag is required to obtain a high photocatalytic activity in the plasmonic catalyst. The mechanism for the enhancement of the visible-light-driven photocatalytic activities was also analyzed.