Miracle-dz/UniFAR-FTUs huggingface dataset:
Prostate-Specific Kallikreins-2 and -4 Enhance the Proliferation of DU-145 Prostate Cancer Cells through Protease-Activated Receptors-1 and -2

A major characteristic of prostate cancer is the elevation of serum levels of prostate-specific antigen (hK3) and hK2, which are tumor markers that correlate with advancing stages of disease. Including hK4, these three kallikrein serine proteases are almost exclusively produced by the prostate. Prostate cancer cells have been recently shown to overexpress protease-activated receptors (PAR), which can be potentially activated by kallikreins and can regulate tumor growth. Here, we show that recombinant hK2 and hK4 activate ERK1/2 signaling of DU-145, PC-3, and LNCaP prostate cancer cells, which express both PAR1 and PAR2. These kallikreins also stimulate the proliferation of DU-145 cells. Pretreatment of hK2 and hK4 with the serine protease inhibitor, aprotinin, blocks the responses in DU-145 cells, and small interfering RNA against PAR1 and PAR2 also inhibits ERK1/2 signaling. To determine which PAR is activated by hK2 and hK4, a cell line that expresses a single PAR, a PAR1 knockout mouse lung fibroblast cell line transfected with PAR1 (KOLF-PAR1) or PAR2 (KOLF-PAR2) was used. hK4 activates both PAR1 and PAR2, whereas hK2 activates PAR2. hK4 generates more phosphorylated ERK1/2 than hK2. These data indicate that prostatic kallikreins (hK2 and hK4) directly stimulate prostate cancer cell proliferation through PAR1 and/or PAR2 and may be potentially important targets for future drug therapy for prostate cancer. (Mol Cancer Res 2008;6(6):1043–51)
Risks of unbalanced progeny at amniocentesis to carriers of chromosome rearrangements: data from United States and Canadian laboratories.

Data on 1,237 prenatal (amniocyte) diagnoses in cases of familial chromosome rearrangements were collated from 79 American and Canadian laboratories. These were added to European data (Daniel et al: Prenatal Diagn 6:315-350, 1986) on 596 reciprocal translocations (rcp) from 71 collaborative laboratories. The total data set was examined for relationships between balanced or unbalanced result and mode of ascertainment, sex of carrier parent, chromosomes involved, and (in cases of reciprocal translocations and pericentric inversions) for potential or actual chromosome imbalance size (% haploid autosome length). Risk rates for unbalanced segregants were markedly dissimilar. These ranged from approximately 50% down to essentially a negligible risk. The risk was approximately 50% for carriers of the following: complex chromosome rearrangements (ccr); insertions (ins); and for 2:2 segregating rcp ascertained by mode 1 (term unbalanced proband) with small imbalance segments. Pooled carriers (either sex) of 2:2 segregating rcp of mode 1 had a risk of 20-25% whereas female Robertsonian (rob) translocation (D;21) carriers and pericentric inversion (pii) carriers of pii with small distal segments had a risk of 10-15%. Pooled 2:2 segregating rcp carriers ascertained by mode 2 (a couple with recurrent miscarriages) and male carriers of rob (D;21) had a risk of 1.5-5%. The risk of unbalanced segregants was 1-2% (in this data) for male and female rob (13;14) carriers and for pooled pericentric inversion carriers. However, for carriers of most "type" (recurrent breakpoints) pii, for all paracentric inversions, and (as expected) for rob not involving 13 or 21, there were no term unbalanced progeny. For 2:2 segregating reciprocal translocations plots were prepared that could be used to determine broad risk groups for carriers of such rcp. In 3:1 segregating rcp there were 3.3 times fewer male than female carriers, whereas there were 1.3 times fewer male carriers in 2:2 segregating rcp. In 2:2 segregating rcp there is little effect on the fertility of male carriers and risks of unbalanced progeny were found to be equal to those for female carriers, whereas in the 3:1 segregating rcp, risks were much less for male as compared to female carriers. This indicates that 3:1 segregating rep are more similar to Robertsonian translocations in their greater effect on the fertility of male carriers. (ABSTRACT TRUNCATED AT 400 WORDS)
Timing should no Longer be an Obstacle to Oocyte Cryopreservation in Patients with Cancer

Purpose Anticancer treatment-related infertility is preventable with oocyte cryopreservation, but this is often not considered a relevant issue, due to lack of knowledge and time. The aim of this study is to prove that adequate organization of an Oncofertility Unit and the use of new protocols for controlled ovarian stimulation (COS) can reduce the time required by the procedure, encouraging consultants and patients to preserve fertility before gonadotoxic treatments. Methods A total of 125 patients diagnosed with malignant tumors were referred to the Oncofertility Unit of San Raffaele Hospital: 52 patients between April 2011 and October 2013 and 73 patients between October 2013 and November 2015. The 2 periods differ in office organization and type of COS protocol used. Results Between the 2 periods, a reduction in the mean number of days required from first counseling to the initiation (6.45 ± 1.058 vs 1.61 ± 0.228) and the end of the COS (17.83 ± 1.227 vs 13.70 ± 0.393) was observed (p<0.0001). No differences exist in the groups between the mean time required to complete COS (11.38 ± 0.360 vs 12.17 ± 0.309; p = 0.11) and mean number of frozen oocytes (8.458 ± 1.060 vs 10.30 ± 0.919; p = 0.22). Furthermore, in the second period, the number of patients who accepted fertility preservation increased (46.15% vs 64.38%; p<0.05). Conclusions Renewed organization of the Oncofertility Unit and the newest random-start COS protocol allowed us to shorten the time for oocyte cryopreservation and start anticancer treatment on time.
El contenido en los medios sociales de los destinos turísticos y la búsqueda de información de los usuarios

espanolEl objeto de este estudio es el analisis comparado de como los destinos turisticos utilizan los medios sociales y que contenidos publican en su estrategia de comunicacion; y como y que buscan los usuarios cuando planifican un viaje. Las metodologias utilizadas son: entrevistas a directores de comunicacion de destinos, encuestas a gestores de medios sociales, analisis de contenido de las publicaciones de los destinos y una encuesta a usuarios. Los resultados muestran ciertas diferencias en los medios sociales utilizados por ambos y en los contenidos publicados por los destinos y buscados por los usuarios, lo cual supone una interesante aportacion para la comunicacion de los destinos turisticos. EnglishThe aim of this study is the comparative analysis of how destinations use social media and what contents publish in their communication strategies and how do users use these social media and what do they look for in there when they organize a trip. The used methodologies are: interviews with communication directors of destinations, surveys to community managers, content analysis of the publications of the destinations and a survey to users. Results show some differences among social media used by both and among the contents published by destinations and looked for users. These results provide interesting insights for the communication of tourist destinations.
Management strategies of non-profit community sport facilities in an era of austerity

ABSTRACT Research Question: This qualitative research explores the impact of austerity on community sport facilities across England (United Kingdom), drawing upon resource dependence theory (RDT) embedded within network theory. Research Methods: In-depth semi-structured interview data were collected from 24 stakeholders related to community sport facilities (n = 12 facility managers, n = 6 regional grant managers, n = 6 national funders both third sector and corporate). The qualitative data were thematically analysed to understand the impact of austerity on how community sport facilities managed their organisations and operations. Results and Findings: The findings from this research offer insight into the challenges that community sport facilities are encountering which have resulted from austerity, and a shrinking of the funding from the central Government to local public services. Furthermore, different community sport facilities have navigated these challenges to maintain sustainability, essentially through adapting network structure and through income dynamism. In addition, using a network theory approach alongside RDT within a sporting context has allowed us to address issues on how network flow and structure impact sustainability and operations within and between organisations. Implications: The article offers managerial recommendations for community sport facility managers, practitioners and policy makers who operate in times of fiscal constraint. It recommends that future sport research utilises and applies both RDT and network theory to examine these changes and the subsequent management strategies adopted to overcome the associated challenges of fiscal constraint.
Neuromuscular features in sprinters with cerebral palsy: case studies based on paralympic classification

Despite the evolution of runner performance in athletes with cerebral palsy (CP), little is known about neuromuscular parameters of sprinters from different classes, especially related to power output, muscular imbalances and asymmetry indexes in lower limbs. The aim of this study was to assess muscle power, muscular imbalance and asymmetry in sprinters with CP. Four male sprinters with CP (age, 18 to 27 years; body mass, 58.5 to 72.8 kg; height, 161.5 to 174 cm) classified as T38, T37, T36, T35 according to International Paralympic Committee functional classification, performed vertical counter movement jump and squat jump on force plate and isokinetic torque evaluations in both limbs. The concentric peak torque (PT) was measured at 60°/sec, 120°/sec and 180°/sec and PT eccentric at 60°/sec and 120°/sec. The asymmetry indexes, conventional and functional ratios were assessed. the results showed that athletes with more severe impairments (T35 and T36) showed worse performance to muscle power, more muscular imbalance and higher asymmetry in PT between limbs (> 10%). The exception was T37 athlete, who presented the better performance for all variables. it is concluded that CP athletes with more severe impairments showed lower jumping performance and torque production of knee extensors and flexors, they showed greater asymmetries between limbs. Finally, considering the results of T37 athlete, it seems that the athletic training for a longer period can reverse part of the neuromuscular impairments caused by CP.
Acute or Chronic? Within‐Host Models with Immune Dynamics, Infection Outcome, and Parasite Evolution

There is ample theoretical and experimental evidence that virulence evolution depends on the immune response of the host. In this article, we review a number of recent studies that attempt to explicitly incorporate the dynamics of the immune system (instead of merely representing it by a single black box parameter) in models for the evolution of parasite virulence. A striking observation is that the type of infection (acute or chronic) is invariably considered to be a constraint that model assumptions have to satisfy rather than as a potential outcome of the interaction of the parasite with its host’s immune system. We argue that avoiding making assumptions about the type of infection will lead to a better understanding of infectious diseases, even though a number of fundamental and technical problems remain. Dynamical modeling of the immune system opens a wide range of perspectives: for understanding how the immune system eradicates a parasite (which it does for most pathogens but not for all, HIV being a notorious example of a virus that is not completely eliminated), for studying multiple infections through concomitant immunity, for understanding the emergence and evolution of the immune system in animals, and for evolutionary epidemiology in general (e.g., predicting evolutionary consequences of new therapies and public health policies). We conclude by discussing new approaches based on embedded (or nested) models and identify future perspectives for the modeling of infectious diseases.
Towards using blockchain technology for eHealth data access management

eHealth is a technology that is growing in importance over time, varying from remote access to Medical Records, such as Electronic Health Records (EHR), or Electronic Medical Records (EMR), to real-time data exchange from different on-body sensors coming from different patients. With this huge amount of critical data being exchanged, problems and challenges arise. Privacy and confidentiality of this critical medical data are of high concern to the patients and authorized persons to use this data. On the other hand, scalability and interoperability are also important problems that should be considered in the final solution. This paper illustrates the specific problems and highlights the benefits of the blockchain technology for the deployment of a secure and a scalable solution for medical data exchange in order to have the best performance possible.
A study on knowledge, attitude, and practice regarding mental health illnesses in Amdanga block, West Bengal

Background: The discourse of mental health is getting its due attention after all these years in India. A major threat to the mental health system is the demand side factors, namely, knowledge, attitude, and practice (KAP) of the general population toward this. In spite of growing concern regarding mental health in India, this kind of study to assess the mental health status has been very few in India, more so in West Bengal. Objectives: With this background, this study was carried out with the objectives to validate the Community Attitude to Mental Illness (CAMI), to assess the different sociodemographic factors among the study population, to assess the KAP regarding mental illness among the study population. Methods: It was an observational, descriptive study with cross-sectional design done at Amdanga Community Development Block, North 24 Parganas, West Bengal, India, in 2015-16. Questionnaire validation to assess the KAP was the primary objective with obtaining the descriptive data were the second one. CAMI questionnaire was used which was validated for the given area by validation methods such as Cronbach's alpha and structural equation modeling. The resultant questionnaire was used in the field on adult population after a single-stage survey design to collect 730 samples. Results: The test statistics showed that the questionnaire was reasonably valid after a few tweakings. SEM identified well-define domains in the attitude part. 94.9% says that they are willing to live with a people with mental illness. 14.9% has actually done so. Health-care seeking behavior shows that 19.2% will go to a GP in case of any mental illness. Furthermore, attitude toward mental illness showed mixed picture as also knowledge. This study correlated with various studies of developing countries and it was seen that these population showed markedly different attitudes for probability of the patients getting cured than many other countries. Furthermore, stigma was gradually decreasing, as evident from various other studies. Conclusion: This study will provide valuable insights into the cognitive and affective aspect of mental illness among these population and thus help in implementing better policies in this regard, as this is fast becoming the talk of the day.
Recovery after contraction of white muscle fibres from the dogfish Scyliorhinus canicula.

Recovery after contraction of white muscle fibres of dogfish was investigated using 31P-NMR and measurements of heat production. The muscle fibres were stimulated to perform either a single isometric tetanus or a series of brief isometric tetani; the NMR measurements showed that approximately half of the phosphocreatine (PCr) was used. The period of activity was followed by a recovery period without stimulation. Both NMR and heat measurements agreed in showing that recovery was very slow, requiring at least 60 min for PCr resynthesis and for the production of recovery heat. The NMR results showed that changes in intracellular pH and in the concentrations of PCr and intracellular phosphate (Pi) had very similar time courses. Intracellular pH moved in the alkaline direction during the period of activity and then returned monotonically during recovery. The non-phosphate buffer power was 13.0 +/- 3.1 mmol l-1 intracellular water per pH unit (N = 4, mean +/- S.E.M.). The results are consistent with the view that oxidative processes resynthesize PCr during recovery, which is slow because of the low mitochondrial content of these muscle fibres.
Anti‐Hu paraneoplastic syndrome presenting with brainstem‐cerebellar symptoms and Lambert–Eaton myasthenic syndrome

Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50‐year‐old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. Pulmonary X‐ray findings, class IIIb sputum cytology, and positive anti‐Hu antibody established the diagnosis of PNS associated with small‐cell lung cancer (SCLC). Two cycles of combined chemotherapy resulted in shrinkage of the lung tumor together with complete recovery of neurological symptoms and disappearance of anti‐Hu antibody. Relapse of SCLC 4 months later with re‐appearance of anti‐Hu antibody required additional chemotherapy and irradiation. Eight months later, when multiple liver metastasis of SCLC was noticed, muscular weakness with positive waxing phenomenon compatible with Lambert–Eaton myasthenic syndrome (LEMS) developed. Postmortem examinations revealed residual SCLC in the primary lung, and massive liver metastasis with generalized lymph node involvement, but no tumors in the CNS. In the cerebellum, there was a slight loss of Purkinje cells with torpedo formation but without apparent lymphocytic infiltration. The present PNS was unique in that the relapse of SCLC was accompanied by the appearance of anti‐Hu antibody, and that initial signs of brainstem‐cerebellar symptoms, encephalopathy and autonomic failure were replaced by LEMS coinciding with the tumor recurrence.
ANALISIS EFISIENSI PERBANKAN NASIONAL BERDASARKAN UKURAN BANK: PENDEKATAN DATA ENVELOPMENT ANALYSIS

This study evaluates the performance of the technical efficiency of banks in Indonesia during the period 2008-2009 based on the size of the banks using Data Envelopment Analysis approach (DEA). Empirical findings indicate that a large bank with economies of scale (economics of scale) in its operations have a better level of efficiency compared with medium and small banks. Economies of scale benefit the banks with lower average cost per-unit with an increasingly large amount of the loan. Efficiency level for banks that have not reached an optimum level can do the repair potential (potential improvement) by increasing the output and or lower the input to the reference (benchmarking) on the bank efficient
Changes in physical activity measured by accelerometry following initiation of DMARD therapy in rheumatoid arthritis.

OBJECTIVE The aim of this study was to assess changes in habitual physical activity levels in response to DMARD therapy in RA patients. METHODS Eighteen drug-naive RA patients were prospectively assessed at baseline and following 3 months of DMARD therapy for habitual physical activity by accelerometry, disease activity using the clinical disease activity index (CDAI) and functional disability using the modified HAQ (mHAQ). Baseline physical activity was also compared with an equal number of healthy control participants matched for age, sex and BMI. RESULTS Following 3 months of DMARD therapy, in parallel with significant improvements in CDAI scores (P < 0.001) and HAQ scores (P < 0.001), accelerometry measures in the RA cohort showed that the average activity counts in sedentary thresholds decreased (P = 0.012), while average activity counts within higher-intensity thresholds increased (P = 0.039). Multiple regression analysis showed that the change in moderate activity was associated with a decrease in CRP (β = - 0.922, P = 0.026) while the decrease in sedentary activity and increase in moderate activity were associated with decreased morning stiffness of the joints (β = 0.694, P = 0.035 and β = -0.927, P = 0.024, respectively). At baseline, RA patients were less physically active than control participants in the morning (P = 0.048) and in the late afternoon (P = 0.016), but these diurnal differences were no longer significant after the DMARD intervention. CONCLUSION These findings suggest that accelerometry may potentially be a viable objective method of assessing changes in physical disability in response to various disease-modifying drugs.
Engineering a lysosomal enzyme with a derivative of receptor-binding domain of apoE enables delivery across the blood–brain barrier

To realize the potential of large molecular weight substances to treat neurological disorders, novel approaches are required to surmount the blood–brain barrier (BBB). We investigated whether fusion of a receptor-binding peptide from apolipoprotein E (apoE) with a potentially therapeutic protein can bind to LDL receptors on the BBB and be transcytosed into the CNS. A lysosomal enzyme, α-L-iduronidase (IDUA), was used for biological and therapeutic evaluation in a mouse model of mucopolysaccharidosis (MPS) type I, one of the most common lysosomal storage disorders with CNS deficits. We identified two fusion candidates, IDUAe1 and IDUAe2, by in vitro screening, that exhibited desirable receptor-mediated binding, endocytosis, and transendothelial transport as well as appropriate lysosomal enzyme trafficking and biological function. Robust peripheral IDUAe1 or IDUAe2 generated by transient hepatic expression led to elevated enzyme levels in capillary-depleted, enzyme-deficient brain tissues and protein delivery into nonendothelium perivascular cells, neurons, and astrocytes within 2 d of treatment. Moreover, 5 mo after long-term delivery of moderate levels of IDUAe1 derived from maturing red blood cells, 2% to 3% of normal brain IDUA activities were obtained in MPS I mice, and IDUAe1 protein was detected in neurons and astrocytes throughout the brain. The therapeutic potential was demonstrated by normalization of brain glycosaminoglycan and β-hexosaminidase in MPS I mice 5 mo after moderate yet sustained delivery of IDUAe1. These findings provide a noninvasive and BBB-targeted procedure for the delivery of large-molecule therapeutic agents to treat neurological lysosomal storage disorders and potentially other diseases that involve the brain.
Potential role of dendritic cells for progression of atherosclerotic lesions

Atherosclerosis is a lipid related chronic inflammatory disease in which immune mechanisms play a pivotal part. Its lesion is filled with large numbers of immune cells. In 1995 dendritic cells (DCs) were identified in atherosclerotic plaques and thought to play an important part in atherogenesis. DCs express MHCI and ll, HLA-DR, CD1a, ICAM-1 and VCAM1 on their surfaces, and this explains their unique ability to activate naive T cells. The risk factors for atherosclerosis are the factors for DCs’ activation and migration. Mature DCs are capable of presenting antigen to T cells, which play an important part in progression of disease. Statin and diltiazem have been shown to protect endothelial function by suppressing the function of DCs and play an important part in preventing atherosclerosis.