Miracle-dz/UniFAR-FTUs huggingface dataset:
Statin-Induced Inhibition of MCF-7 Breast Cancer Cell Proliferation is Related to Cell Cycle Arrest and Apoptotic and Necrotic Cell Death Mediated by an Enhanced Oxidative Stress

Statins have antiproliferative and anti-tumoral effects in MCF-7 cells. We determined the effect of statins upon MCF-7 cell cycle, toxicity, cell death, reactive oxygen species (ROS) production and mitochondrial membrane potential. Fluvastatin, simvastatin and atorvastatin inhibited cell proliferation. Antiproliferation was associated with a decrease in the DNA synthesis and a cell cycle arrest in the G1 and G2/M phases. A loss in the mitochondrial membrane potential was observed with fluvastatin. Statins induced increase in ROS production that was associated with cell death, which was abrogated by the antioxidant NAC. Our results suggest that the cytotoxic effect observed is mediated by an oxidative stress.
In vivo evidence for progressive activation of parathyroid hormone‐related peptide gene transcription with tumor growth and stimulation of osteoblastic bone formation at an early stage of humoral hypercalcemia of cancer

The present study was undertaken to clarify in vivo the temporal profile of parathyroid hormone‐related peptide (PTHRP) gene expression as well as bone histomorphometric features as a function of tumor growth, using an athymic rat model associated with humoral hypercalcemia of malignancy (HHM). Tumor‐bearing animals exhibited hypercalcemia, hypophosphatemia, and increased circulating levels of PTHRP, and died within 3 weeks. Steady‐state PTHRP mRNA levels and the transcription rate of PTHRP gene in the tumors were markedly increased with tumor growth. RNAse mapping analysis revealed that both upstream and downstream promoters of the human PTHRP gene were utilized in the tumors and became progressively activated with time. Bone histomorphometric analysis showed that osteoclastic bone resorption was progressively increased throughout the course, whereas osteoblastic bone formation was stimulated more than 2‐fold at a very early stage (day 6 after tumor implantation) and then markedly suppressed thereafter on day 12 and day 18 compared with age‐matched control animals. These results provide in vivo evidence that PTHRP gene transcription is progressively activated with tumor growth and that activation of osteoblasts does occur at a very early phase of HHM syndrome in contrast to the marked suppression of bone formation at later stages.
Efficacy and safety of desmoteplase in acute ischemic stroke patients

Background: Pending results from double-blind, multicenter, parallel-group, randomized trials, the benefit and safety of the novel plasminogen activator, desmoteplase remain undetermined. The aim of this meta-analysis was to help evaluate desmoteplase's efficacy and safety. Methods: A thorough search was performed of the Cochrane Library, PubMed, and Embase from the inception of electronic data to March 2017, and double-blind, multicenter, parallel-group, randomized trials were chosen. We conducted a meta-analysis of studies investigating intravenous desmoteplase treatment of acute ischemic stroke patients 3 to 9 hours after symptom onset. Asymptomatic intracerebral hemorrhage, good clinical outcome at 90 days, and reperfusion 4 to 8 hours posttreatment were variables assessing efficacy; symptomatic intracerebral hemorrhage and death rates were measures of safety. Results: Six trials involving 1071 patients thrombolyzed >3 hours postonset were included (600 received intravenous desmoteplase, 471 placebo). Desmoteplase was associated with increased reperfusion (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.10–2.24; P = .01 vs control) and showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.97–1.62; P = .09 vs control), whereas there was no increase in symptomatic intracerebral hemorrhage and death rate with desmoteplase. However, there was no difference in the clinical response at 90 days (OR 1.14; 95% CI, 0.88–1.49; P = .31 vs control). Subgroup analysis showed that desmoteplase 90 &mgr;g/kg (OR 1.53; 95% CI, 1.07–2.21; P = .02 vs control) and 125 &mgr;g/kg (OR 4.07; 95% CI, 1.16–14.24; P = .03 vs control) were associated with an increase in reperfusion. Also, we found desmoteplase 90 &mgr;g/kg showed a tendency to increase asymptomatic intracerebral hemorrhage (OR 1.25; 95% CI, 0.95–1.63; P = .11 vs control). Conclusion: Intravenous desmoteplase is associated with a favorable reperfusion efficacy and acceptable safety in ischemic stroke treatment >3 hours after symptom onset. Well-designed randomized controlled trials with larger patient cohorts and a moderate dose of drugs are needed to further evaluate the true efficacy of desmoteplase in stroke patients. Trial Registration: URL: http://www.crd. york.ac. uk/PROSPERO; PROSPERO registration number: CRD42016037667).
Surgical options for articular defects of the knee

Cartilage and osteochondral defects of the knee can in most cases be treated with total knee replacement in the elderly population. However, these lesions pose a difficult treatment problem in the younger patient. A number of surgical options are available today to address this increasingly common condition and each has its own indications and limitations. This article reviews debridement and microfracture, fixation, metallic spacing devices, autologous chondrocyte implantation, osteochondral autograft transplantation, fresh cadaveric allografts and osteotomies. In addition, possible future developments are discussed.
Bilateral Hermite Radial Basis Functions for Contour‐based Volume Segmentation

In this paper, we propose a novel contour‐based volume image segmentation technique. Our technique is based on an implicit surface reconstruction strategy, whereby a signed scalar field is generated from user‐specified contours. The key idea is to compute the scalar field in a joint spatial‐range domain (i.e., bilateral domain) and resample its values on an image manifold. We introduce a new formulation of Hermite radial basis function (HRBF) interpolation to obtain the scalar field in the bilateral domain. In contrast to previous implicit methods, bilateral HRBF (B‐HRBF) generates a segmentation boundary that passes through all contours, fits high‐contrast image edges if they exist, and has a smooth shape in blurred areas of images. We also propose an acceleration scheme for computing B‐HRBF to support a real‐time and intuitive segmentation interface. In our experiments, we achieved high‐quality segmentation results for regions of interest with high‐contrast edges and blurred boundaries.
ALGEBRAIC COMBINATORICS

A PSCA( v,t,λ ) is a multiset of permutations of the v -element alphabet { 0 ,. ,v − 1 } such that every sequence of t distinct elements of the alphabet appears in the specified order in exactly λ permutations. For v ⩾ t , let g ( v,t ) be the smallest positive integer λ such that a PSCA( v,t,λ ) exists. Kuperberg, Lovett and Peled proved g ( v,t ) = O ( v t ) using probabilistic methods. We present an explicit construction that proves g ( v,t ) = O ( v t ( t − 2) ) for fixed t ⩾ 4. The method of construction involves taking a permutation representation of the group of projec-tivities of a suitable projective space of dimension t − 2 and deleting all but a certain number of symbols from each permutation. In the case that this space is a Desarguesian projective plane, we also show that there exists a permutation representation of the group of projectivities of the plane that covers the vast majority of 4-sequences of its points the same number of times.
Morphogenesis of the Skin

This excellent monograph by Phillippe Sengel brings together an enormous body of data on the embryonic development of the skin in mammals, birds, and reptiles, and most of the information available on the many chemical factors and tissue interactions which produce these changes. The book is divided into four sections. The first describes the histogenesis of developing skin visible with the light or electron microscope. In addition to the discussion on epidermis, a substantial amount of information is presented about the histogenesis of the dermis, hair and feathers. The second section compiles the data on proliferation of the epidermal cells; the many chemical regulators of cellular division such as chalones, prostaglandins, and epidermal growth factor; and the effect of epidermal-dermal interaction on basal cell mitosis. The section concludes with a superb discussion on the relationship of cellular proliferation to topography, and architecture of the epidermis, hair and feathers. The third part presents the histologic features of cellular differentiation within the epidermis and the identified regulators of cellular differentiation such as dermalepidermal interactions, vitamin A and hydrocortisone. Section four synthesizes the data to show the mechanisms by which these two processes, cellular proliferation and differentiation, combine to form the final product, i.e., the skin of the neonate. The presentation on morphogenesis of the hair and feathers, the author's specialties, are especially complete and well done. The book is excellent in most respects. The author deserves special credit for including sections on the development and formation of the dermis, a forgotten portion of the skin. The author is an expert in the field and is able to present a wide range of data in clear, concise fashion. The book will be of most value to developmental biologists and dermatologists, or other physicians with a particular interest in diseases of keratinocytes and keratinization such as psoriasis or ichthyosis; diseases affecting dermal-epidermal interaction such as epidermolysis bullosa; or hair formation such as monilethrix. The single valid criticism of the book should be directed at the publisher. The author compiled the data on development of the skin up to 1973. He completed and dated his introduction to the monograph in May 1974, but the book was not published until late 1975, almost two years' delay during which time substantial amounts of new data became available. Despite this criticism, the book is worth obtaining for those seeking detailed information on the morphogenesis of the skin. JAMES J. NORDLUND Department of Dermatology Yale University School of Medicine
The effects of low-level laser light exposure on sperm motion characteristics and DNA damage.

The objective of this study was to determine the effects of low-level laser light exposure on the motility of spermatozoa and on DNA damage. Thirty-three semen samples were collected for routine analysis and were classified as normospermic, oligospermic, or asthenospermic. After routine semen analysis was performed, residual semen was divided into treated and control aliquots. Treated samples were exposed to a 30-second infrared laser pulse of 50 mW/cm(2) at 905 nm, a wavelength thought to increase light-sensitive cytochrome c oxidase in the mitochondrial electron transport chain. Samples were then incubated at 37°C, and aliquots were analyzed at 30 minutes and 2 hours using computerassisted semen analysis. After incubation, 250 μL of each sample was frozen at 280°C until DNA fragmentation analysis by flow cytometry. A significant increase in motility, most prominent in oligospermic and asthenospermic samples (85% increase), was observed 30 minutes after the treatment (P < .0001). No significant increase in DNA damage compared with control samples was observed. Significant changes in sperm motion kinetics were observed. Low-level laser light exposure appears to have a positive short-term effect on the motility of treated spermatozoa and did not cause any increase in DNA damage measured at 2 hours. We conclude that some cases of asthenospermia may be related to mitochondrial dysfunction. The implications of this study in terms of future clinical applications needs further investigation.
Epistemik İnanç Ölçeği: Türkçeye Uyarlama, Geçerlik ve Güvenirlik Çalışması

Bu arastirmanin amaci, Schraw, Bendixen, ve Dunkle (2002), tarafindan gelistirilen epistemik inanc olceginin Turkceye uyarlama, guvenirlik ve gecerlik calismasini yapmaktir. Genel tarama modellerinden kesitsel tarama modeline gore tasarlanan arastirmanin calisma grubunu 2015-2016 ogretim yili guz doneminde Usak ve Dumlupinar Universitelerinin Egitim Fakultelerinde ogrenim goren toplam 530 ogretmen adayi olusturmustur. Olcegin yapi gecerliliginin tespit edilmesi icin once acimlayici sonra da dogrulayici faktor analizi yapilmistir. Orijinal halinde "uzman otoritesi", "kesin bilgi", "hizli ogrenme", "basit bilgi" ve "dogustan yetenek" boyutlarindan ve 28 maddeden olusan olcegin, yapilan acimlayici faktor analizi sonucunda "bilgiye erisim ve edinme sureci", "kesin bilgi", "dogustan yetenek" ve "basit bilgi" seklinde 4 boyuttan ve 15 maddeden olustugu tespit edilmistir. Bu haliyle olcegin, toplam varyansin % 52,22 sini acikladigi ve epistemolojik inanclarin cok boyutlu yapisini ortaya koydugu tespit edilmistir. Olcegin guvenirligi icin Cronbach’s alpha degeri hesaplanarak ,78 bulunmustur. Olcegin Turkce surumunun kulturel uyum duzeyini belirlemek icin yapilan dogrulayici faktor analizi sonucunda ise olcegin uyumlu oldugu gorulmustur. Son haliyle, olcegin gecerli ve guvenilir oldugu sonucuna ulasilmistir.
Herc5, an Interferon-induced HECT E3 Enzyme, Is Required for Conjugation of ISG15 in Human Cells*

ISG15 is an interferon (IFN)-α/β-induced ubiquitin-like protein that is conjugated to cellular proteins during innate immune responses to viral and bacterial infections. A recent proteomics study identified 158 human proteins targeted for ISG15 conjugation, including the ISG15 E1 and E2 enzymes (Ube1L and UbcH8, respectively) and a HECT E3 enzyme, Herc5. Like the genes encoding Ube1L and UbcH8, expression of Herc5 was also induced by IFN-β, suggesting that Herc5 might be a component of the ISG15 conjugation system. Consistent with this, small interfering RNAs targeting Herc5 had a dramatic effect on overall ISG15 conjugation in human cells, abrogating conjugation to the vast majority of ISG15 target proteins in vivo. In addition, co-transfection of plasmids expressing ISG15, Ube1L, UbcH8, and Herc5 resulted in robust ISG15 conjugation in non-IFN-treated cells, while the active-site cysteine mutant of Herc5 or a mutant lacking the RCC1 repeat region did not support ISG15 conjugation. These results demonstrate that Herc5 is required for conjugation of ISG15 to a broad spectrum of target proteins in human cells.
Genetic studies of affective disorders: should we be starting with childhood onset probands?

OBJECTIVE The objective of this study is to test whether the presence of childhood onset affective disorder identifies families with increased incidence and severity of affective disorders. METHOD Family history information was collected on the first and second degree relatives and first cousins age > or = 15 years of 22 children with bipolar affective disorder, 54 children with major depressive disorder, and 31 psychiatrically normal children. RESULTS Compared with the relatives of normal children, relatives identified through children with bipolar affective disorder or major depressive disorder had elevated rates of affective disorders and increased severity of affective disorders as judged by earlier age of onset and increased suicide attempts. Segregation analyses could reject purely environmental transmission of illness. CONCLUSION Ascertaining families through childhood onset affective disorder probands identifies extended pedigrees with high incidence and severity of affective disorders. These families may be more appropriate for genetic analyses than are families of adult probands.
Detection and Positioning of Overlapped Sounds in a Room Environment

The description of the acoustic activity in a room environment has to face the problem of overlapped sounds, i.e. those which occur simultaneously. That problem can be tackled by carrying out some kind of source signal separation followed by the detection and recognition of the identity of each of the overlapped sounds. An alternative approach relies on modeling all possible overlapping combinations of acoustic events. For a spatial scene description, there is still the need of assigning each of the detected acoustic events to one of the estimated source positions. Both detection approaches are tested in our work for the case of two simultaneous sources, one of which is speech, and an array of three microphones. Blind source separation based on the deflation method and null steering beamforming are used for signal separation. Also a position assignment system is developed and tested in the same experimental scenario. It is based on the above mentioned beamformer and takes the decision based on a likelihood ratio. Both signal-level fusion and likelihood fusion are tried to combine the information from the two pairs of microphones. The reported experimental results illustrate the possibilities of the various implemented techniques.
Numerical taxonomy of some nocardioform bacteria.

Summary: A collection of 283 nocardioform bacteria was studied by means of 241 tests which included many biochemical, physiological and nutritional characters. The results were subjected to computer analysis in which two coefficients of association and two cluster-analysis techniques were used. Single linkage and average linkage cluster analysis gave almost identical results, but with the simple matching coefficient a few strains were grouped together on the basis of shared negative correlations. With the matching coefficient 15 clusters were formed whereas with the similarity coefficient there were 18. In each analysis the seven major clusters corresponded to (1) Nocardia asteroides, (2) Nocardia caviae, (3) Nocardia brasiliensis, (4) Actinomadura madurae, (5) Actinomadura pelletieri, (6) Oerskovia turbata, (7) the rhodochrous complex. The data revealed many new characters which could be weighted for identification. The clusters and subgroups were therefore readily distinguished from one another by several unrelated phenotypic characters.
The combined electrophysiological effects of lignocaine and sotalol in canine isolated cardiac Purkinje fibres are rate‐dependent

1 The frequency‐dependent electrophysiological effects of lignocaine, sotalol, and their combination were studied in dog isolated cardiac Purkinje fibres, both at various constant rates of stimulation and following abrupt changes in pacing cycle length. 2 The combined effect of 18 μm lignocaine and 30 μm sotalol selectively lengthened duration of premature action potentials evoked at a diastolic interval of 40 ms (from 172.2 ± 5.4 to 201.7 ± 4.9 ms, n = 6, P > 0.01) without significantly changing the durations of action potentials evoked at the basic cycle length of 500 ms (259.1 ± 7.7 vs 251.9 ± 3.9 ms, n = 11). 3 The combination of lignocaine with sotalol, like lignocaine alone, displayed a use‐dependent depression of and revealed a slow component for a recovery of (τ = 173.5 ± 16.0 ms, n = 5). 4 The kinetics for restitution of action potential duration were also slowed by the combination of the two dwo drugs (τf = 173.6 ± 16.7, before, vs 268.5 ± 8.5 ms, after; n = 5, P > 0.01), while the maximum action potential duration attained in this relation was not increased as it was by sotalol alone. 5 Lignocaine, therefore, appeared to inhibit the sotalol‐induced lengthening of action potential duration at slow pacing rates and at long diastolic intervals. The combination of lignocaine with sotalol also completely abolished the occurrence of sotalol‐induced early afterdepolarizations. 6 Finally, sotalol alone moderately increased the range of premature action potential durations, while the combination of the two drugs significantly decreased this parameter. 7 These findings indicate that the combination of lignocaine with sotalol may provide important, and unique, beneficial electrophysiological alterations that might be expected to provide enhanced antiarrhythmic efficacy in patients.
Burnout, hopelessness and suicide risk in medical doctors.

OBJECTIVES The aim of the present study was to investigate the association between burnout and hopelessness in medical doctors. MATERIALS AND METHODS We conducted an investigation of 133 medical doctors working either in a hospital setting or in general practice to explore the relationship between the level of burnout and hopelessness, a psychometric marker for suicide risk. The participants were administered the Oldenburg Burnout Inventory (OBI) and Beck's Hopelessness Scale (BHS). RESULTS Burnout is an important issue in mediating the level of hopelessness. Doctors with high hopelessness had higher scores on the disengagement factor (2.61±0.47 vs 2.14±0.41; t131=-4.37; p<0.001; Cohen D=1.07), and on the exhaustion factor (2.68±0.65 vs 2.19±0.54; t131=-3.39; p<0.001; Cohen D=0.82) than doctors with low hopelessness. A multivariate regression analysis confirmed that disengagement and exhaustion are significant predictors of the BHS scores. CONCLUSIONS People in charge of workers' health should pay particular attention to the level of burnout in doctors, intervene with changes in the work environment and evaluate the impact of such procedures.
Sentences in the Wild

The goal of this work is to recognise phrases and sentences being spoken by a talking face, with or without the audio. Unlike previous works that have focussed on recognising a limited number of words or phrases, we tackle lip reading as an open-world problem – unconstrained natural language sentences, and in the wild videos. Our key contributions are: (1) a ‘Watch, Listen, Attend and Spell’ (WLAS) network that learns to transcribe videos of mouth motion to characters; (2) a curriculum learning strategy to accelerate training and to reduce overfitting; (3) a ‘Lip Reading Sentences’ (LRS) dataset for visual speech recognition, consisting of over 100,000 natural sentences from British television. The WLAS model trained on the LRS dataset surpasses the performance of all previous work on standard lip reading benchmark datasets, often by a significant margin. This lip reading performance beats a professional lip reader on videos from BBC television, and we also demonstrate that if audio is available, then visual information helps to improve speech recognition performance.
Variability in Potency Among Commercial Preparations of Berberine

ABSTRACT Berberine is an isoquinoline alkaloid plant extract that is widely available as a dietary supplement in the United States and has demonstrated efficacy in the treatment of type 2 diabetes mellitus and dyslipidemia. Because of its increased use and purported pharmacological properties, potential variations in product quality could pose a barrier to berberine's safety and effectiveness in clinical practice. Thus, this study evaluated the potency of dietary supplements containing berberine available in the U.S. commercial market. Fifteen unique dietary supplements containing berberine were purchased through U.S. dietary supplement vendors. For each product, berberine was extracted from 3 unique capsules and analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Percentage content based on the product label claim was determined for each product. The average berberine content across the products was found to be 75% ± 25% of the product label claim, with product potency ranging from 33% to 100%. Nine of the 15 tested products (60%) failed to meet the potency standards of 90% to 110% of labeled content claim, as commonly required of pharmaceutical preparations by the U.S. Pharmacopeial Convention. Evaluation of the relationship between product cost and the measured potency failed to demonstrate an association between quality and cost. Variability in product quality may significantly contribute to inconsistencies in the safety and effectiveness of berberine. In addition, the quality of the berberine product cannot be inferred from its cost.