Miracle-dz/UniFAR-FTUs huggingface dataset:
Drug–diagnostic co-development: challenges and issues

ABSTRACT Diagnostic tests have become increasingly important for optimizing drug use. Ideally, a companion diagnostic test is developed concurrently with a corresponding therapeutic product (co-development). However, the diagnostic test may also be developed to optimize treatment with previously approved therapeutic agents (follow-up-development). In co-development, the effectiveness of an agent in marker-defined patients is confirmed by an enrichment trial design. In follow-up-development, a biomarker is validated by prospective and/or retrospective analyses of unselected design trials. A prospectively designed trial is the gold-standard approach to biomarker validation, but retrospective validation can be used to efficiently determine effective treatments for marker-defined patients. Accumulation and systematization of examples of drug–diagnostic development will aid in the effective development of companion diagnostics.
PENERIMAAN SISTEM E-COMMERCE : PENGARUH KEPERCAYAAN, PERSEPSI MANFAAT DAN PERSEPSI RISIKO

Penerimaan Sistem E-Commerce : Pengaruh Kepercayaan, Persepsi Risiko dan Persepsi Manfaat . Tujuan penelitian ini adalah untuk menguji faktor-faktor yang mempengaruhi minat digunakannya sistem e-commerce dan pengaruhnya terhadap perilaku penggunaan sistem e-commerce . Penelitian ini dilakukan di Fakultas Ekonomi dan Bisnis Universitas Brawijaya Malang dengan menggunakan metode survei. Peneliti memperoleh respon sebanyak 234 orang mahasiswa Jurusan Akuntansi yang menggunakan layanan sistem e- commerce . Peneliti menggunakan Partial Least Square (PLS) untuk menguji data penelitian. Hasil analisis untuk model ini menunjukkan bahwa konstruk minat berpengaruh terhadap perilaku untuk menggunakan layanan e-commerce, serta konstruk kepercayaan dan persepsi manfaat berpengaruh terhadap minat digunakannya layanan sistem e-commerce. Sedangkan konstruk persepsi risiko tidak berpengaruh terhadap minat digunakannya layanan e-commerce. Hal ini berarti bahwa perilaku untuk menggunakan layanan e-commerce dipengaruhi oleh minat, serta variabel minat dipengaruhi oleh persepsi kepercayaan dan persepsi manfaat. Implikasi dari penelitian “ in relevan ” bagi pihak manajemen dan pengembang sistem agar memperhatikan kembali faktor minat, kepercayaan, dan persepsi manfaat dalam menerapkan dan mengembangkan transaksi e-commerce pada sistem jual beli. Kata Kunci : kepercayaan, persepsi risiko, persepsi manfaat, minat, perilaku , e-commerce .
Intra-puparial development of the females of Chrysomya albiceps (Wiedemann) (Diptera, Calliphoridae)

Desenvolvimento intra-pupal de femeas de Chrysomya albiceps (Wiedemann) (Diptera, Calliphoridae) A cronologia e as mudancas morfologicas que ocorrem durante o desenvolvimento intra-pupal de Chrysomya albiceps sao descritos com base em 254 especimes criados em laboratorio. As larvas foram obtidas a partir os ovos postos por uma unica femea. As pre-pupas foram separadas de acordo com a reducao do comprimento larval, o grau de pigmentacao e esclerotizacao da cuticula, depois da formacao das pupas, 10 individuos foram fixados em solucao de Carnoy e conservados em etanol 70%, e 10 individuos foram fixados a cada 3 horas, ate completar as primeiras 24 horas (n = 80), os demais individuos foram fixados a cada seis horas ate a hora 90 (n = 110), quando 54 femeas haviam emergido. As pupas foram imersas em de acido formico a 5% por 48 horas e mantidos em etanol 70%, e entao dissecados e analisados. C. albiceps mostrou quatro estagios intra-pupais, que foram descritos e comparados com aqueles descritos para Musca domestica, Calliphora erythrocephala, Sarcophaga bullata, Cuterebra tenebrosa, Oestrus ovis e Dermatobia hominis. Quatro estagios de desenvolvimento podem ser descritos: (1) apolise da larva-pupa, depois de tres horas; (2) a pupa criptocefalica, depois de seis horas, (3) a pupa fanerocefalica, depois de nove horas, e a pupa farada apos nove horas. O adulto farado esta completamente formado apos 81 horas.
BASAL CELL CARCINOMA: INFLUENCE OF TUMOR SIZE ON MORTALITY AND MORBIDITY

Krompecher' coined the term "epithelioma" to describe the indolent ulcerative skin neoplasm we now call basal cell carcinoma. The term "epithelioma" literally means a tumor arising from the epithelium (epithel = derived from epithelium, oma = tumor). Tumors taking origin from the epithelium would include warts, molluscum contagiosum, and seborrheic keratoses. The inclusion of these benign tumors with basal cell carcinoma conveys the mistaken impression that basal cell carcinoma is a relatively benign disorder. Unfortunately, the term epithelioma continues to appear in the literature as a confusing appellation.A review of the literature shows that basal cell carcinoma can be an extremely destructive and aggressive malignancy. '-'' Jackson and Adams collected 33 large and aggressive basal cell carcinomas and compared these to the more commonly encountered basal cell cancers. ' The term they used for these invasive and destructive cancers was "horror tumors. " Their conclusion was that basal cell carcinoma, under certain circumstances, can be an inordinately aggressive tumor. The factors that were associated with a disastrous outcome were large size, neglect, and inadequate treatment. Blewitt reviewed the apparent paradox of the low nietastatic potential of basal cell carcinoma in spite of the sometimes aggressive histology. '' His conclusion was that longstanding tumors, deep invasion, and large size were highly correlated with metastasis and death. Snow et al. demonstrated that basal cell carcinomas showing large size and deep invasion account for 75% of all metastatic basal cell carcinomas. -^ Sahl et al. showed that in tumors larger than 10 cm in diameter the incidence of metastasis and/or fatal outcome was 45%. * It is the readily accessible nature of basal cell carcinoma on the surface of the skin that makes for ease of diagnosis and surveillance. The patient usually becomes aware of the lesion early in the course of evolution of tumor growth and seeks treatment promptly. If treatment is delayed or inadequate, the tumor becomes difficult to manage and may tiltimately becotne impossible to cure. ''
Ephrin B3 interacts with multiple EphA receptors and drives migration and invasion in non-small cell lung cancer

Ephrin receptors (Ephs) are reported to control metastatic signaling of non-small cell lung cancer (NSCLC) and other tumors. Here we show for the first time that blocking expression of the Eph ligand Ephrin B3 inhibits NSCLC cell migration and invasion. We demonstrate that Ephrin B3 directly binds the EphAs EphA2, EphA3, EphA4, and EphA5. EphA2 Ser897 was previously shown to drive migration propensity of tumor cells and our study reveals that EphA2 stays phosphorylated on Ser897 in the Ephrin B3/EphA2 complex in NSCLC cells of different histology. Moreover, we report that within such Ephrin B3/EphA2 complex both Akt Ser 129 and p38MAPK are found indicating a potential to drive migration/proliferation. We also found the EMT marker E-cadherin expression to be maintained or increased upon Ephrin B3 blockade in NSCLC cells. Expression of Ephrin B3 was furthermore analyzed in a cohort of NSCLC stage IA-IB cases (n=200) alongside EphA2 and Ephrin A1. We found that Ephrin B3 was concomitantly expressed with EphA2 and Ephrin A1 with higher Ephrin B3 levels found in non-squamous than in squamous tumors, whereas EphA2 was higher expressed in well-differentiated than in low-differentiated tumors. In the entire NSCLC cohort, Ephrin B3 expression was not linked to patient survival, whereas a high EphA2 expression was associated with improved survival (p=0.03). In conclusion, we show that blocking Ephrin B3 expression inhibits NSCLC proliferation-, migration- and invasion capacity which calls for further studies on interference with Ephrin B3 as a possible therapeutic avenue in this tumor malignancy.
Endocrine‐paracrine cells in pancreatic exocrine carcinomas

Eleven cases of primary pancreatic adenocarcinomas have been investigated histochemically, immunohistochemically and with electron‐microscopy. Endocrine‐paracrine (EP) cells were present in six of these tumours. In one case numerous 5HT‐enterochromaffin cells (EC) of the intestinal type and a few somatostatin immunoreactive D cells were found. Two cases contained insulin‐immunoreactive cells and another case displayed glucagon‐IR elements. In the remaining two cases argyrophilic cells were present. These findings demonstrate that polypeptide hormone or amine production is not restricted to islet cell tumours. It is suggested that both endocrine and exocrine components of the tumours studied might have derived from a common precursor.
Characteristics of Precipitating Convective Systems Accounting for the Summer Rainfall of Tropical and Subtropical South America

AbstractTen years of Tropical Rainfall Measuring Mission precipitation radar data are used to study the physical properties of the precipitating cloud systems that account for the summer rainfall of tropical and subtropical South America. Radar echoes in the continental subtropics tend to be of an intensely convective nature, especially at the eastern foothills of the Andes where diurnally forced deep convective cells of small horizontal scale form when moist low-level flow is driven toward the foothills in connection with a midlatitude disturbance. As the disturbance moves east over the La Plata basin, nocturnal convective systems of larger horizontal scale with wide stratiform regions occur in a zone of general convergence. Precipitation in the continental tropics is generally produced by convective systems with greater stratiform composition. At the northeastern foothills of the central Andes, radar echoes of nocturnal convective systems of medium to large horizontal scale occur where moist low-level f.
Assessing Citizens' Adoption of a Transactional E-Government System: Validation of the Extended Decomposed Theory of Planned Behavior (DTPB)

The study explores the adoption of an electronic government (e-government) system called online PAN card registration system (OPCRS) in context of India. The study validates the extended decomposed theory of planned behaviour (DTPB) to understand the impact of some of its factors on the citizen’s intention to adopt this system. The proposed research model is validated using the data collected from 377 respondents from six selected cities covering all different locations of India. The data is analysed using AMOS 22.0. The empirical findings of the proposed research model indicated the significant relationships of all proposed hypotheses. The study also provides its limitations, future research directions, and implications for theory and practice toward the end.
Renal Artery Stenosis as Cause of End-stage Renal Disease To Dilate Always or Sometimes ?

Renal artery stenosis (RAS) is a narrowing (usually > 70%-75% to be functionally significant) (1) of one or both main renal arteries or their major branches. This is to be distinguished from renovascular hypertension, which is hypertension caused by renal artery stenosis. Atherosclerosis accounts for 90 percent of cases of atherosclerotic renal artery stenosis (ARAS) and usually involves the ostium and proximal third of the main renal artery and the perirenal aorta. Ostial lesions may represent an extension of an aortic plaque or may be an isolated lesion. The term ischemic nephropathy has been used to describe progressive renal failure due to RAS. However, ischemia is a rate of blood flow that is insufficient to meet the metabolic demands of the organ, thereby leading to tissue hypoxia. There is little evidence that ischemic nephropathy is caused by tissue hypoxia per se. It is therefore proposed that the term ischemic nephropathy be replaced with chronic azotemic renovascular disease (2).
Separation and some properties of the major proteins of the human erythrocyte membrane.

A fractionation procedure is described which allows the isolation of three major human erythrocyte membrane proteins. Their isolation involves three sequential extraction procedures followed by gel filtration in 1% sodium dodecyl sulphate and preparative gel electrophoresis. All three proteins can be isolated from a single preparation. One of the proteins is the erythrocyte sialoglycoprotein, for which no C- or N-terminal residues were found. The other two proteins, which have not previously been isolated, have subunit molecular weights of 74000 and 93000 and contain 9 and 7% carbohydrate respectively. These glycoproteins have blocked N-terminal residues and show similarities in their chemical properties. Preparations derived from blood-group O erythrocytes contain no N-acetylgalactosamine, but similar preparations from blood-group A erythrocytes do contain this sugar. These three proteins cannot easily be solubilized by gentle aqueous procedures and represent about half of the erythrocyte ;ghost' protein. They carry a large proportion of the cell-surface carbohydrate.
Evaluation of acetylcholinesterase activity and behavioural alterations induced by ketamine in an animal model of schizophrenia

Objective Cognitive deficits in schizophrenia play a crucial role in its clinical manifestation and seem to be related to changes in the cholinergic system, specifically the action of acetylcholinesterase (AChE). Considering this context, the aim of this study was to evaluate the chronic effects of ketamine in the activity of AChE, as well as in behavioural parameters involving learning and memory. Methods The ketamine was administered for 7 days. A duration of 24 h after the last injection, the animals were submitted to behavioural tests. The activity of AChE in prefrontal cortex, hippocampus and striatum was measured at different times after the last injection (1, 3, 6 and 24 h). Results The results indicate that ketamine did not affect locomotor activity and stereotypical movements. However, a cognitive deficit was observed in these animals by examining their behaviour in inhibitory avoidance. In addition, an increase in AChE activity was observed in all structures analysed 1, 3 and 6 h after the last injection. Differently, serum activity of AChE was similar between groups. Conclusion Chronic administration of ketamine in an animal model of schizophrenia generates increased AChE levels in different brain tissues of rats that lead to cognitive deficits. Therefore, further studies are needed to elucidate the complex mechanisms associated with schizophrenia.
A Microtiter Plate-Based Assay for Inhibitors of Penicillin-Binding

PBP2a, the molecular determinant for high level β-lactam resistance in 19 Methicillin-resistant Staphylococcus aureus (MRSA), is intrinsically resistant to most β20 lactam antibiotics. The development and characterization of new inhibitors targeting 21 PBP2a would benefit from an effective and convenient assay for inhibitor binding. This 22 study was directed towards the development of a fluorescently detected β-lactam binding 23 assay for PBP2a from MRSA. Biotinylated ampicillin and biotinylated cephalexin were 24 tested as tagging reagents for fluorescence detection using a strepavidin-HRP conjugate. 25 Both bound surprisingly well to PBP2a, with binding constants of 1.6 ± 0.4 μM and 13.6 ± 26 0.8 μM respectively. Two forms of the assay were developed, a one step direct 27 competition form of the assay and a two step indirect competition form of the assay, and 28 both forms of the assay gave comparable results. This assay was then used to 29 characterize PBP2a binding to ceftobiprole which gave results consistent with previous 30 studies of ceftobiprole-PBP2a binding. This assay was also demonstrated for screening 31 for PBP2a inhibitors by screening a set of thirteen randomly selected β-lactams for 32 PBP2a inhibition at 750 μM. Meropenem was observed to give substantial inhibition in 33 this screen, and a follow-up titration experiment determined its KI app to be 480 ± 70 μM. 34 The availability of convenient and sensitive microtiter-plate based assays for the 35 screening and characterization of PBP2a inhibitors is expected to facilitate the discovery 36 and development of new PBP2a inhibitors for use in combating the serious public health 37 problem posed by MRSA. 38 39 on M ay 5, 2021 by gest httpaac.asm . rg/ D ow nladed fom
Causes of death in geriatric patients: a cross-cultural study.

BACKGROUND The elderly are living longer and causes of death are shifting. At the same time, autopsy rate is at, or near, its lowest in history, compounded by an even lower interest in geriatric autopsies. Thus, the prevalent cause of death in this age group remains poorly studied. METHODS In a retrospective study, the autopsy protocols of 440 70-year-old or older patients from the Houston Veterans Affairs Hospital and 321 80-year-old or older patients from the II*Institute of Pathology in Prague (Czech Republic) were reviewed in order to establish a correct cause of death. The autopsy diagnosis was correlated with the prosectors' description of pathological findings in the protocol. In questionable cases or discrepancies, the patient's clinical chart and/or the histological autopsy slides were also reviewed. RESULTS The distribution of death by infections and cardiac disorders each accounted for one-third of all deaths. Congestive heart failure prevailed in the over 80-year-olds, and myocardial infarcts prevailed in the younger patients. The number of deaths due to malignancy dropped from 25% in those 70-79 years old to about 10% in the elder patients. Central nervous system disorders were frequent as an underlying disease, but were not common as a cause of death. The findings were similar in both series, thus supporting their accuracy. CONCLUSION Our findings bring into question the accuracy of reported causes of death in the elderly. With increasing age, differences appear in the levels of mortality and morbidity for various disease categories. This study underlines the need for more baseline data for older people which can be obtained only by more and well-performed autopsies.
Alternative splicing of RGS8 gene changes the binding property to the M1 muscarinic receptor to confer receptor type‐specific Gq regulation

RGS proteins constitute a large family that modulates heterotrimeric G‐protein signaling. We previously showed that RGS8 suppressed Gq signaling in a receptor type‐specific manner. To elucidate molecular mechanisms underlying receptor‐specific attenuation by RGS8, we examined whether RGS8 can interact with certain G‐protein‐coupled receptors. By pull‐down assay, we showed that RGS8 directly binds to the third intracellular (i3) loop of M1 and M3 muscarinic acetylcholine receptors (mAChRs). The binding of RGS8S, a splice variant with a different N‐terminus, was weaker. RGS8 could bind specifically to the C‐terminal part of M1i3 (containing amino acids of 304–353 of i3 of human M1‐mAChR), but RGS8S could not. Moreover, deletion of the N‐terminal 9 amino acids and substitution of both Arg‐8 and Arg‐9 of RGS8 with Ala resulted in reduced binding to M1i3. BRET experiments revealed that RGS8 actually interacts with M1‐mAChR, but RGS8S does not interact in the living cells. The RGS8 mutant, which had less binding ability to M1i3, showed a reduced inhibitory function of Gq signaling through M1‐mAChR. These results demonstrated that RGS8 can directly interact with M1‐mAChR via its N‐terminus and the i3 loop of the receptor, and this binding must play an essential role in receptor‐specific suppression by RGS8.
Children of the Closet

ABSTRACT This research examined whether a parent's non-disclosure of his or her homosexual or bisexual orientation within the family unit negatively affects self-esteem and anxiety in children, as measured in adulthood. Thirty-six subjects indicated that they had not known of their parent's sexual orientation until an average age of sixteen for the children of lesbian or bisexual mothers, and twenty-two for the children of gay or bisexual fathers. This group's scores on the Rosenberg Self-Esteem Scale, the Marlowe Crowne Social Desirabilty Scale and the State-Trait Anxiety Scale were compared to scores obtained by sixty-three participants who did not have a homosexual/bisexual parent. The number of years a secretive environment surrounded the child was measured, as were participants' attitudes about the secret sexual identity. Although the study did not find that adults previously raised with a closeted parent had significantly higher levels of anxiety or lower levels of self-esteem, results indicated that those who had been raised as children with non-disclosed lesbian mothers showed a significantly higher level of self-esteem than participants with heterosexual parents. Implications of the findings for the targeted population are discussed.
Mitigating wind noise in outdoor microphone signals using a singular spectral subspace method

Wind noise is one of the major concerns of outdoor microphone signal acquisition. Filtering and removal of wind noise are known to be difficult due to its broadband and time varying nature. This paper proposes the use of singular spectrum analysis to address the problem of microphone wind noise removal and/or separation. The paper is presented from the context of reducing microphone wind noise when deploying outdoor acoustic sensing in smart city applications and soundscapes monitoring. But concepts and methods can be generalized beyond its original scope. The method includes two complementary stages, namely decomposition and reconstruction. The first stage decomposes mixed signals in eigen-subspaces, selects and groups the principal components according to their contributions to wind noise and wanted signals in the singular spectrum domain. The second stage is used to reconstruct the signals back to the time domain, resulting in the separation of wind noise and wanted signals. Following a brief review of the wind noise removal problem, this paper presents the algorithm and some experimental results, and discusses the potentials of the singular spectrum analysis for microphone wind noise reduction.
Mycobacterium tuberculosis Transmission in a Country with Low Tuberculosis Incidence: Role of Immigration and HIV Infection

ABSTRACT Immigrants from high-burden countries and HIV-coinfected individuals are risk groups for tuberculosis (TB) in countries with low TB incidence. Therefore, we studied their role in transmission of Mycobacterium tuberculosis in Switzerland. We included all TB patients from the Swiss HIV Cohort and a sample of patients from the national TB registry. We identified molecular clusters by spoligotyping and mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) analysis and used weighted logistic regression adjusted for age and sex to identify risk factors for clustering, taking sampling proportions into account. In total, we analyzed 520 TB cases diagnosed between 2000 and 2008; 401 were foreign born, and 113 were HIV coinfected. The Euro-American M. tuberculosis lineage dominated throughout the study period (378 strains; 72.7%), with no evidence for another lineage, such as the Beijing genotype, emerging. We identified 35 molecular clusters with 90 patients, indicating recent transmission; 31 clusters involved foreign-born patients, and 15 involved HIV-infected patients. Birth origin was not associated with clustering (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.73 to 3.43; P = 0.25, comparing Swiss-born with foreign-born patients), but clustering was reduced in HIV-infected patients (aOR, 0.49; 95% CI, 0.26 to 0.93; P = 0.030). Cavitary disease, male sex, and younger age were all associated with molecular clustering. In conclusion, most TB patients in Switzerland were foreign born, but transmission of M. tuberculosis was not more common among immigrants and was reduced in HIV-infected patients followed up in the national HIV cohort study. Continued access to health services and clinical follow-up will be essential to control TB in this population.