Miracle-dz/UniFAR-FTUs huggingface dataset:
Vitamin D receptor polymorphisms: are they really associated with type 1 diabetes?

In their interesting paper, Turpeinen et al. (1) studied the effects of polymorphisms of the vitamin D receptor (VDR) gene on the susceptibility to type 1 diabetes mellitus (T1DM) in a large case –control series from the Finnish population. Recent studies have clarified the molecular basis of the immunomodulatory activity of vitamin D which has been observed to inhibit T-cells and cytokine production (2). Moreover, vitamin D deficiency is considered to be associated with increased risk of T1DM (3). The biological effects of vitamin D, by interaction through VDRs and the association between allelic variants of the VDR gene and susceptibility to T1DM, have also been studied (4). To date, published results have been controversial. Studies carried out on European populations – using PCR and Apa I, Bsm I and Taq I restriction enzymes – showed a significantly higher incidence of the genotype AABBtt in type 1 diabetic patients than in normal subjects (5, 6). Turpeinem et al. (1) genotyped for VDRA (Apa I), VDRB (Bsm I) and VDRF (Fok I) single nucleotide polymorphisms using a mini-sequencing reaction. The authors concluded that the single nucleotide polymorphisms analysed are unlikely to be associated with T1DM in the Finnish population. Recently we compared polymorphisms of the VDR gene in a group of T1DM patients (group A) and in a group of normal subjects (group B). Group A consisted of 31 patients followed at our Genoa Centre (21 males, mean age 10 years, range 2–22.5 years) and group B consisted of 36 blood donors (24 males, mean age 33 years, range 20–39.8 years). VDR genotyping was performed using PCR and Bsm I, Apa I and Taq I restriction enzymes, in order to identify alleles A, a, B, b, T and t. VDR gene polymorphisms were compared between patients and controls using the x test and Fisher exact test (Table 1). Our data show that there is no relationship between the VDR gene and T1DM susceptibility, except for a significantly higher frequency of the genotype AaBbTt in controls compared with diabetic patients. Moreover, we observed that the frequency of the genotypes AaBbTT and AABbTt was higher in group A patients than in group B subjects, but not significantly. To our knowledge, this is the first study on an Italian population and, even though the data are from a small series, our experience, in contrast to the Finnish study, does not confirm that polymorphism of the VDR gene has a role in the susceptibility to T1DM.
Is Cheap Talk Effective at Eliminating Hypothetical Bias in a Provision Point Mechanism?

Significant difference between response to real and hypothetical valuation questions is often referred to as hypothetical bias. Some economists have had success with using “cheap talk” (which entails reading a script that explicitly highlights the hypothetical bias problem before participants make any decisions) as a means of generating unbiased responses in a referendum format. In this article, we test the robustness of cheap talk using a voluntary contribution mechanism with a provision point over a wide range of possible payment amounts. Our results confirm the existence of hypothetical bias, and suggest that cheap talk may eliminate hypothetical bias, but only for respondents facing higher payments.
CD19‐Targeted chimeric antigen receptor‐modified T‐cell immunotherapy for B‐cell malignancies

Chimeric antigen receptors (CARs) comprise a tumor‐targeting moiety, often in the form of a single chain variable fragment derived from a monoclonal antibody, fused to one or more intracellular T‐cell signaling sequences. Lymphodepletion chemotherapy followed by infusion of T cells that are genetically modified to express a CD19‐specific CAR is a promising therapy for patients with refractory CD19+ B‐cell malignancies, producing rates of complete remission that are remarkably high in acute lymphoblastic leukemia and encouraging in non‐Hodgkin lymphoma and chronic lymphocytic leukemia. Responses are often durable, although additional studies are needed to define the role of CAR‐T cell immunotherapy in the context of other treatments. CAR‐modified T‐cell immunotherapy can be complicated by cytokine release syndrome and neurologic toxicity, which in most cases are manageable and reversible. Here we review recent clinical trial data and discuss issues for the field.
Plasma Levels of Syndecan-4 (Ryudocan) Are Elevated in Patients with Acute Myocardial Infarction

Summary Syndecan-4 (ryudocan) is a cell-surface heparan sulfate proteoglycan, which plays an important role in a variety of biological functions including regulation of blood coagulation, cell adhesion, and cell growth. In this study, we measured plasma levels of syndecan-4 in patients with acute myocardial infarction using an enzyme-immunoassay, and found that they were extremely high, with a peak of average (10.5 ± 5.6 ng/ml, 2 weeks after onset), as compared with those in normal subjects (0.078 ± 0.030 ng/ml) (p < 0.001). We also observed a distinct expression of syndecan-4 in the repair region of the damaged cardiac tissues with infarction, but not in intact region, by immunohistochemical analysis. To clarify the mechanism of syndecan-4 induction, we investigated the hypoxia effect on its expression, and found that hypoxia treatment up-regulated the gene expression of syndecan-4 in various types of cells. Taken together, it is suggested that syndecan-4 is induced by hypoxia stimuli in ischemic heart tissues, and may function as a tissue-repair molecule via biological mediators such as heparin-binding growth factors.
Stenotic lesion level did not affect outcomes of carotid endarterectomy

Background Carotid endarterectomy is the established treatment for carotid artery stenosis, and remains the primary surgical option due to its superior outcomes compared to carotid arterial stenting. However, Japanese patients are known to have unfavorable anatomical conditions for carotid endarterectomy, with a relatively higher level of the carotid artery bifurcation than in the Western population. We investigated the outcomes of carotid endarterectomy in our institute and evaluated the procedural quality by comparing patients based on higher or lower lesion levels. Methods The clinical data of 65 patients who underwent carotid endarterectomy were collected retrospectively. The outcomes reviewed included stroke-free survival and stroke-free rate. The patients were divided into a higher group (n = 25) and a lower group (n = 40), based on lesion location in respect of the 2nd cervical vertebral level. Results There was no perioperative death and only one case of stroke in the higher group within 30 days after carotid endarterectomy. At 5 years after carotid endarterectomy, the stroke-free survival rates were 83.4% in the higher group and 87.8% in the lower group, while the stroke-free rates were 96.0% and 94.0%, respectively; there were no significant differences between groups. Conclusions Stenotic lesion level did not affect the outcome or procedural quality of carotid endarterectomy.
Sociodemographic Characteristics, Health, and Success at Obtaining Work among Latino Urban Day Laborers

Background. The purpose of this study was to examine the health and social circumstances, knowledge of and access to health and social services, and success at getting work among urban day laborers. Methods. We conducted an interview survey of 217 men waiting for work at several sites in San Francisco. Results. Day laborers were generally unsuccessful at obtaining work and had less than optimal housing, but supported a number of family members. Over half reported fair or poor health, associated with longer time as a day laborer, poor English proficiency, and financially supporting three or more other people. Awareness of health and social services available to them was low. Discussion. The stress of seeking work daily, separation from family, inadequate housing and lack of health care puts this population at increased risk for disease conditions associated with poor physical and mental health.
Frequency and management of epistaxis in schools

Abstract Study objectives: To investigate the frequency and management of epistaxis in schools. Study design: A postal survey of schools. Results: One hundred and fifty-seven questionnaires were posted out to 41 secondary schools (students aged 11–18 years) and to 116 primary schools (students aged four to 11 years). One hundred and twelve completed questionnaires were returned, 32 from secondary schools and 80 from primary schools. Most schools stated that they encountered a nose bleed once per month. The commonest method of treating a nose bleed was to pinch the top of the nose (an ineffective method), although pinching the bottom of the nose was almost as common. Only a minority of primary and secondary schools (37.5 and 25 per cent, respectively) had a policy for dealing with nose bleeds. Despite many respondents reportedly using an ineffective method, only two stated that they did not feel confident in dealing with nose bleeds. Conclusion: Nose bleeds in school students are common, and management frequently deviates from recommended guidelines.
Bone Mineral Density and Its Relationship to Prolactin Levels in Patients Taking Antipsychotic Treatment

Abstract: Antipsychotic treatment is frequently associated with elevated prolactin levels. Raised prolactin levels have been linked with osteoporosis. The objective of this study is to determine whether patients taking antipsychotics show reduced bone mineral density (BMD), and whether this is associated with prolactin levels. BMD (standardized as z scores) was compared using dual x-ray absorptiometry of the lumbar spine and hip in patients taking antipsychotics (n = 102, mean age: 46.0, SD: 13.1, 47% male, median treatment duration: 3.0 years) to matched reference controls. Levels of prolactin, markers of bone metabolism, and risk factors for osteoporosis were measured. Mean BMD was not significantly reduced, other than the total spine score for black males (mean z score: −0.88, P = 0.00001). BMD was correlated with body mass index but there was no correlation with prolactin. BMD was not correlated with prolactin levels and showed no clinically significant reduction. The low BMD in black males warrants further investigation.
Collagenolytic enzymes in human neoplasms.

A variety of human neoplasms were examined for their ability to produce collagenolytic enzymes in culture. Some types of tumors of epithelial origin demonstrated a very high frequency of collagenolytic activity, while neoplasms of mesenchymal origin, nonneoplastic tissues, and other types of epithelial neoplasms only rarely produced collagenase. In particular, tumors of the colon and carcinomas of both squamous and basal cell origin displayed a high frequency of activity. Tumor collagenases from several different sources were isolated and examined for their mode of attack on native collagen, pH optima, and inhibition of activity by EDTA, cysteine, and pooled human serum. Tumor enzymes appear to be similar to the collagenases isolated from normal human skin by these criteria.
Utilizing Mixed Methods in Psychological Research

Along with the emergence of a strong community of qualitative researchers in the past few decades, a sharp dichotomy has emerged between them and the traditionally quantitative community of scholars in social and behavioral sciences. Mixed methods research has achieved popularity as a reaction to this dichotomy of approaches. It has provided an integrative and multiapproach alternative, consisting of systematic and formal ways of conceptualizing research questions and research designs, data collection and analysis, inference-making, and quality audits. Following a review of historical examples of utilizing both qualitative and quantitative methods in psychological research, we discuss the main characteristics of four families of mixed methods research designs: Sequential, parallel, conversion, and fully integrated. Within each family of designs, examples are provided to demonstrate various possibilities in terms of types of research questions (preplaned, emergent), data sources (different samples, same/sub samples, multilevel), data collection and analysis techniques, and interpretation/integration of the findings. Conceptual and practical issues are discussed in relation to assessing the quality and transferability of inferences in mixed methods. The chapter is concluded by suggesting that mixed methods provide a highly eclectic and flexible possibility to answer research questions that require research methodology beyond the traditional qualitative or quantitative mono approaches. Keywords: mixed methods (qualitative and quantitative); humanistic research methodology; sequential mixed design; parallel mixed design; conversion mixed design; fully integrated mixed design
Inhibition of the Human Respiratory Syncytial Virus Small Hydrophobic Protein and Structural Variations in a Bicelle Environment

ABSTRACT The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by the human respiratory syncytial virus (hRSV). SH protein has a single α-helical transmembrane (TM) domain that forms pentameric ion channels. Herein, we report the first inhibitor of the SH protein channel, pyronin B, and we have mapped its binding site to a conserved surface of the RSV SH pentamer, at the C-terminal end of the transmembrane domain. The validity of the SH protein structural model used has been confirmed by using a bicellar membrane-mimicking environment. However, in bicelles the α-helical stretch of the TM domain extends up to His-51, and by comparison with previous models both His-22 and His-51 adopt an interhelical/lumenal orientation relative to the channel pore. Neither His residue was found to be essential for channel activity although His-51 protonation reduced channel activity at low pH, with His-22 adopting a more structural role. The latter results are in contrast with previous patch clamp data showing channel activation at low pH, which could not be reproduced in the present work. Overall, these results establish a solid ground for future drug development targeting this important viroporin. IMPORTANCE The human respiratory syncytial virus (hRSV) is responsible for 64 million reported cases of infection and 160,000 deaths each year. Lack of adequate antivirals fuels the search for new targets for treatment. The small hydrophobic (SH) protein is a 64-amino-acid polypeptide encoded by hRSV and other paramyxoviruses, and its absence leads to viral attenuation in vivo and early apoptosis in infected cells. SH protein forms pentameric ion channels that may constitute novel drug targets, but no inhibitor for this channel activity has been reported so far. A small-molecule inhibitor, pyronin B, can reduce SH channel activity, and its likely binding site on the SH protein channel has been identified. Black lipid membrane (BLM) experiments confirm that protonation of both histidine residues reduces stability and channel activity. These results contrast with previous patch clamp data that showed low-pH activation, which we have not been able to reproduce.
Monte Carlo Modeling of a Siemens Primus 6 MV Photon Beam Linear Accelerator

Monte Carlo calculation method is considered to be the most accurate method for dose calculation in radiotherapy. The purpose of this study is to examine the accuracy of the radiotherapy dose calculations calculated by treatment planning computer system in water by comparison with Monte Carlo model. Monte Carlo model for the photon-beam output from the Primus linear accelerator was validated by plotting the energy spectrum of photon beam and calculating the percentage depth dose (PDD) and beam profiles for the 5 x 5 cm 2 and 10 x 10 cm 2 field sizes. BEAMnrc and the DOSXYZnrc codes were used to perform all dose calculation in this project. The simulated PDD and beam profile obtained were compared with that calculated using treatment planning system (TPS). Good agreement was found between calculated PDD and beam profile using Monte Carlo simulation and TPS calculation with maximum dose difference of 2% for PDD and 6 % for beam profiles. The results showed that the different components of the simulated primus linear accelerator were accurately modeled using Mote Carlo simulation. In conclusion, the BEAMnrc and DOSXYZnrc codes package have very good accuracy in calculating dose distribution for 6 MV photon beam and it can be considered as a promising method for patient dose calculations.
Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease.

BACKGROUND Attentional deficits are described in the consensus clinical criteria for the operationalized diagnosis of dementia with Lewy bodies (DLB) as characteristic of the condition. In addition, preliminary studies have indicated that both attentional impairments and fluctuation of attentional impairments are more marked in patients with DLB than in patients with Alzheimer disease (AD), although neuropsychological function has not previously been examined in a large prospective cohort with confirmed diagnostic accuracy against postmortem diagnosis. METHODS A detailed evaluation of attention and fluctuating attention was undertaken in 155 patients with dementia (85 with DLB and 80 with AD) from a representative hospital dementia case register and 35 elderly controls using the Cognitive Drug Research Computerized Assessment System for Dementia Patients computerized neuropsychological battery. Operationalized clinical diagnosis was made using the consensus criteria for DLB and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD. High levels of sensitivity and specificity have been achieved for the first 50 cases undergoing postmortem examination. RESULTS The groups were well matched for severity of cognitive impairments, but the AD patients were older (mean age, 80 vs 78 years) and more likely to be female (55% vs 40%). Patients with DLB were significantly more impaired than patients with AD on all measures of attention and fluctuating attention (for all comparisons, t > or = 2.5, P<.001), and patients from both dementia groups were significantly more impaired than elderly controls for all comparisons other than cognitive reaction time, which was significantly more impaired in DLB patients than controls but was comparable in controls and AD patients. There were, however, significant associations between the severity of cognitive impairment and the severity of both attentional deficits and fluctuations in attention. CONCLUSIONS This large prospective study confirms that slowing of cognitive processing, attention, and fluctuations of attention are significantly more pronounced in DLB and AD patients, although fluctuating attention is common in patients with moderate-to-severe AD. Deficits of cognitive reaction time appear to be specific to DLB, except in severe dementia. A detailed evaluation of attentional performance could make an important contribution to differential diagnosis, although the results need to be interpreted within the context of the overall severity of cognitive deficits.
z ∼ 4 Hα EMITTERS IN THE GREAT OBSERVATORIES ORIGINS DEEP SURVEY: TRACING THE DOMINANT MODE FOR GROWTH OF GALAXIES

We present evidence for strong Hα emission in galaxies with spectroscopic redshifts in the range of 3.8 < z < 5.0 over the Great Observatories Origins Deep Survey fields. Among 74 galaxies detected in the Spitzer IRAC 3.6 and 4.5 μm bands, more than 70% of the galaxies show clear excess at 3.6 μm compared to the expected flux density from stellar continuum only. We provide evidence that this 3.6 μm excess is due to Hα emission redshifted into the 3.6 μm band, and classify these 3.6 μm excess galaxies to be Hα emitter (HAE) candidates. The selection of HAE candidates using an excess in broadband filters is sensitive to objects whose rest-frame Hα equivalent width (EW) is larger than 350 Å. The Hα inferred star formation rates (SFRs) of the HAEs range between 20 and 500 M☉ yr−1 and are a factor of ∼6 larger than SFRs inferred from the UV continuum. The ratio between the Hα luminosity and UV luminosity of HAEs is also on average larger than that of local starbursts. Possible reasons for such strong Hα emission in these galaxies include different dust extinction properties, young stellar population ages, extended star formation histories, low metallicity, and a top-heavy stellar initial mass function. Although the correlation between UV slope β and LHα/LUV raises the possibility that HAEs prefer a dust extinction curve which is steeper in the UV, the most dominant factor that results in strong Hα emission appears to be star formation history. The Hα EWs of HAEs are large despite their relatively old stellar population ages constrained by spectral energy distribution fitting, suggesting that at least 60% of HAEs produce stars at a constant rate. Under the assumption that the gas supply is sustained, HAEs are able to produce ≳ 50% of the stellar mass density that is encompassed in massive (M* > 1011 M☉) galaxies at z ∼ 3. This “strong Hα phase” of star formation plays a dominant role in galaxy growth at z ∼ 4, and they are likely progenitors of massive red galaxies at lower redshifts.
Neoadjuvant chemotherapy is the better treatment option in some patients with stage IIIc to IV ovarian cancer.

Ignace Vergote, University Hospitals Leuven, Leuven, Belgium Claes G. Trope, Norwegian Radium Hospital, Oslo, Norway Frederic Amant, University Hospitals Leuven, Leuven, Belgium Tom Ehlen, University of British Columbia, Vancouver, British Columbia, Canada Nick S. Reed, Gartnavel General Hospital and Beatson Oncology Center, Glasgow, United Kingdom Antonio Casado, Hospital Universitario San Carlos, Madrid, Spain
Nonverbal Social Skills of Adults with Mild Intellectual Disability Diagnosed with Depression

Depression is one of the most common psychiatric disorders in adults with intellectual disability (ID), yet little is known about depressive behaviors in an ID population. This study examined the nonverbal social skills of 18 adults with mild ID diagnosed with depression and a matched sample of adults with mild ID without depression. Nonverbal social skills were coded from videotapes of actual social interactions. Results indicate that adults with mild ID diagnosed with depression evidence a profile of maladaptive nonverbal social skills including limited body movement, a restricted range of facial expressions, infrequent smiling, speaking in a flat and quiet voice, and taking a long time to respond to the questions or comments of a social partner. Findings from this study have implications for enhancing the early detection and diagnosis of depression and guiding theories of and treatments for depression in an ID population.