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Many drugs, both approved and in development, exert their effects through transcription factors. The complexity of the biology of transcriptional regulation, however, presents challenges to the effective design of therapies that directly target transcription factors. This review focuses on the different approaches that are currently pursued in therapeutics and drug discovery aimed at targeting transcription factors and signaling molecules, and their areas of effect in transcription factor biology. A relatively recent approach termed "transcription therapy" has been applied for a number of drugs in development, which may potentially provide a new avenue for targeting transcription factors for therapeutic purposes.
When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.
This study examined the effects of a mixed reality (MR)-based auxiliary training system on visual-motor skill acquisition, with a focus on hitting accuracy and oculomotor performance in novice badminton players. Forty-seven college students without prior badminton experience were randomly assigned to either a Mixed Reality Training (MRT) group or a coach-led Traditional Teaching (TT) group. Both groups received instruction in the forehand long shot over an eight-week intervention period. Pre- and post-intervention assessments evaluated hitting accuracy (successful shots and shots failing to cross the net) and oculomotor parameters, including pupil diameter, saccade velocity, fixation duration, fixation count, and visual attention toward areas of interest. After the intervention, the MRT group exhibited a significant increase in successful shots, whereas the TT group showed no notable improvement in hitting accuracy. Furthermore, the MRT group demonstrated enhanced fixation count and saccade velocity, reflecting greater visual efficiency and attentional control. In contrast, the TT group showed reductions in fixation-related metrics and slower saccades, accompanied by an increase in pupil diameter. These findings indicate that mixed reality (MR) based instructional strategies can effectively enhance attentional engagement and visual-motor coordination in novices, thereby serving as an innovative pedagogical approach for early-stage motor skill acquisition and sports training. Moreover, the immersive virtual coaching system may contribute to more equal opportunities for learning and help reduce educational gaps.
Research suggests that affective temperaments influence adherence to pharmacotherapy; however, this has not been investigated in infertility treatment. Our prospective longitudinal study assessed the impact of affective temperaments on medication adherence during infertility treatments. 179 women presenting at an Assisted Reproduction Centre completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-A) questionnaire before treatment, and the Morisky Medication Adherence Scale (MMAS) six months later. Univariate linear regression assessed whether affective temperaments predict medication adherence; multivariate and interaction models examined the influence of sociodemographic and medical variables on this relationship, and potential moderating effects of age and education. Higher cyclothymic, depressive, irritable, and anxious affective temperament scores predicted significantly poorer adherence to pharmacotherapeutic recommendations (β = -0.122, p < 0.001, β = -0.178, p < 0.001, β = -0.114, p = 0.002, β = -0.071, p = 0.08; respectively). These results remained significant in multivariate models including sociodemographic and medical factors, which did not influence adherence. Increasing age intensified the negative impact of anxious temperament on medication adherence (β = -0.015, p = 0.024). Affective temperaments impact adherence to pharmacotherapeutic recommendations among women experiencing infertility, possibly influencing treatment outcomes. Screening for affective temperaments can identify patients at risk of medication non-adherence. Applying patient-tailored psychological interventions to aid adherence could increase the chances of successful pregnancies.
An injectable HIV drug with a novel mechanism shows remarkable ability to prevent infection.
Quality healthcare requires two critical components: patients' best interests and best decisions to achieve that goal. The first goal is the lodestar, unchanged and unchanging over time. The second component is a more dynamic and rapidly changing paradigm in healthcare. Clinical decision-making has transitioned from an opinion-based paradigm to an evidence-based and data-driven process. A realization that technology and artificial intelligence can bring value adds a third component to the decision process. And the fertility sector is not exempt. The debate about AI is front and centre in reproductive technologies. Launching the transition from a conventional provider-driven decision paradigm to a software-enhanced system requires a roadmap to enable effective and safe implementation. A key nodal point in the ascending arc of AI in the fertility sector is how and when to bring these innovations into the ART routine to improve workflow, outcomes, and bottom-line performance. The evolution of AI in other segments of clinical care would suggest that caution is needed as widespread adoption is urged from several fronts. But the lure and magnitude for the change that these tech tools hold for fertility care remain deeply engaging. Exploring factors that could enhance thoughtful implementation and progress towards a tipping point (or perhaps not) should be at the forefront of any 'next steps' strategy. The objective of this Opinion is to discuss four critical areas (among many) considered essential to successful uptake of any new technology. These four areas include value proposition, innovative disruption, clinical agency, and responsible computing.
For dermatological practices, non-standardized conventional photo images are taken and collected as a mixture of variable fields of the image view, including close-up images focusing on designated lesions and long-shot images including normal skin and background of the body surface. Computer-aided detection/diagnosis (CAD) models trained using non-standardized conventional photo images exhibit lower performance rates than CAD models that detect lesions in a localized small area, such as dermoscopic images. We aimed to develop a convolutional neural network (CNN) model for skin image segmentation to generate a skin disease image dataset suitable for CAD of multiple skin disease classification. We trained a DeepLabv3 + -based CNN segmentation model to detect skin and lesion areas and segmented out areas that satisfy the following conditions: more than 80% of the image will be the skin area, and more than 10% of the image will be the lesion area. The generated CNN-segmented image database was examined using CAD of skin disease classification and achieved approximately 90% sensitivity and specificity to differentiate atopic dermatitis from malignant diseases and complications, such as mycosis fungoides, impetigo, and herpesvirus infection. The accuracy of skin disease classification in the CNN-segmented image dataset was almost equal to that of the manually cropped image dataset and higher than that of the original image dataset. Our CNN segmentation model, which automatically extracts lesions and segmented images of the skin area regardless of image fields, will reduce the burden of physician annotation and improve CAD performance.
The question of how to specify the posterior tilt of the tibia during arthroplasty operations remains unclear. The most current opinion is that a design whereby incisions are made in parallel with the individual pre-arthritic posterior tilt will yield better post-operational results. However, the wide range of inter-individual variations of posterior tilt of the tibia and the difficult task of identifying the shaft axis of the tibia through standard lateral radiographs are the main obstacles to this particular method. Therefore, there is a need for another reference line that can be measured with plain radiography and yields less inter-individual variation. The hypothesis of this study was that the angle formed between the anterior metaphyseal line of the proximal tibia and the tibial plateau would prove to be less variable across individuals. Long-shot radiographs of non-rotating lateral tibias of 85 patients aged between 18 and 38 years were analysed. The angle forming between the anterior metaphyseal line of the proximal tibia and the slope of the tibial plateau, and the posterior slope angle was measured by 2 separate observers using the classical method. From the measurements of the posterior slope angle taken with the classical method, 38% (33/85) of the patients were within the ±2-degree range of the mean, and the anterior metaphyseal angle was within ±2 degrees of the mean in 75% (64/85) of the total patients. 44.23% variation (CoV) in posterior slop degrees, 2.73% (CoV) variation in the anterior metaphyseal angle measured by the same researchers. The difference between the percentages of variation was also found to be statistically significant. (z = 15.36, p = 0.000). The anterior metaphyseal angle can be utilized to predict the individual posterior slope. Nevertheless, further large-scale, multicentre studies are needed to establish a mean value for the population.
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Remote drug delivery has become an essential tool for safely delivering medication and vaccines to free-ranging, non-domestic, or dangerous animals. All dart guns currently use a single dart per injection, and it might occasionally be not practical with large animals. Shooting the dart more than once on an animal may cause flight, injury, stress, and ultimately unsuccessful delivery. Furthermore, purchasing many dart guns and hiring and training more staff may be unfeasible in developing countries. Therefore, employing the double-dart injection technique may help reduce the cost of operation, save time for capturing animals, minimize stress and injury, and improve animal welfare. The objectives of this study were to test the possibility of using the double-dart injection technique and optimizing the guidelines for this procedure. A standard brand-calibrated darting rifle was used to deliver the darts to the target board constructed from paper, polypropylene, and ethylene-vinyl acetate foam. The shot stage and shooter were fixed, and the shooting range was 5-20 m. The pressure of the gun was varied according to a company's recommendation. The single dart (control dart) was first shot to the target point, and then the double darts were shot 3 times for each condition. The experiment was done in the field with no wind. The inclusion criteria were that two darts must hit the target and not penetrate the target board deeply. The distances between the control dart and double darts (first and second darts) and between each dart of the double darts were measured, and the standard curve graphs and formulas were created. The results showed that the distance between the control dart and the double darts was shortened as the pressure was increased. All double-dart injections hit the target below the control dart. We were able to create many formulas to predict the optimal gun pressure and aim point for double-dart injection in each shot range. It usually requires more pressure settings than a single-dart injection, particularly the long shot range. It also needs to aim the target point above the original point. Double-dart injection technique can be used efficiently in 5-20 m distance, and it usually requires increasing the pressure from the company's recommendation and adjusting the injecting point.
Service is assumed important in table tennis because an effective service may allow the serving player to control over the game; hence, the aim of this study was to determine the contribution of arm segment rotations towards ball impact during forehand service. Sixteen shake-hand grip collegiate table tennis athletes had participated in the study. It was revealed that by increasing the radial deviation angular velocity will increase the ball and racket velocities during drop shot service. Furthermore, it was revealed that increasing the wrist palmar flexion and radial deviation will enhance the racket velocity at impact during long shot service. However, it was recommended to the players not to concern on racket speed and arm segment rotations during contact phase as it could not accelerate the ball at impact during long shot service. Although it was the same forehand service, different length of flight ball lead to different contributions of arm segment rotations towards ball impact. The present findings highlight several better postures to increase racket and ball speed at impact during forehand long shot and drop shot services among advanced and intermediate players. Other ranked players may find this study useful as a fundamental understanding on kinematics serving arm.
The propensity to make risky choices has a genetic component, and recent studies have identified several specific genes that contribute to this trait. Since risk-taking often appears irrational or maladaptive, the question arises how (or if) natural selection favors risk-taking. Here we show, using a stochastic simulation of selection between two hypothetical species, "R" (risk-seeking) and "A" (risk-averse) that, when expected reproductive fitness of the individual is unaffected by the making of the risky choice (winnings balanced by losses) natural selection (taken to the point of extinction) favors the risk-averse species. However, the situation is entirely reversed if offspring are permitted to inherit a small fraction of the parent's increased or decreased fitness acquired through risk-taking. This seemingly Lamarckian form of inheritance actually corresponds to the human situation when property or culture are transmitted in families. In the presence of this "cultural inheritance", the long-shot risk-taking species was overwhelmingly favored, even when 90% of individuals were rendered sterile by a losing choice. Given this strong effect in a minimal model, it is important to consider the co-evolution of genes and culture when interpreting the genetics of risk-taking. This conclusion applies, in principle, to any species where parental resources can directly affect the fecundity of offspring. It might also be relevant to the effects of epigenetic inheritance, if the epigenetic state of zygotes can be affected by parental experiences.
Increased risk taking may explain the link between bad moods and self-defeating behavior. In Study 1, personal recollections of self-defeating actions implicated bad moods and resultant risky decisions. In Study 2, embarrassment increased the preference for a long-shot (high-risk, high-payoff) lottery over a low-risk, low-payoff one. Anger had a similar effect in Study 3. Study 4 replicated this and showed that the effect could be eliminated by making participants analyze the lotteries rationally, suggesting that bad moods foster risk taking by impairing self-regulation instead of by altering subjective utilities. Studies 5 and 6 showed that the risky tendencies are limited to unpleasant moods accompanied by high arousal; neither sadness nor neutral arousal resulted in destructive risk taking.
This paper argues that Edward B. Lewis served as a type of independent academic radiation LNT-cancer risk assessment-stalking horse for the BEAR Genetics Panel, a task for which he had no expertise or experience (e.g. radiation, leukemia, epidemiology and statistical modelling). His efforts produced an insufficiently documented, strongly biased, and high-profile paper in Science (May 17, 1957), whose principal conclusions had not been proven, he asserted privately, in writing. This inconclusive perspective was well camouflaged in the published paper by means of sophisticated wordsmithing. At the time his academic department head George Beadle came to chair the BEAR Genetics Panel in the summer of 1956, the Beadle-inspired-Lewis LNT activity acquired an urgency when a study of 70,000 offspring from survivors of the A-bombs failed to show genetic damage after a decade of careful study, undercutting Panel recommendations. With Beadle's guidance, the Lewis effort redirected the Panel's focus from the atomic bomb genetic damage study, which had acrimoniously disrupted Panel relationships and priorities, to more immediate disciplinary/professional opportunities with concerns about fallout, leukemia risks and a new cancer causation role for mutation. The serious limitations of the Lewis paper affected neither its publication in Science nor its receiving an editorial endorsement, possibly due to influence by powerful Panel members, such as Bentley Glass, one of only six senior editors for Science. The Science publication restored, even though improperly, the scientific and moral initiatives of the Panel and led directly to multiple high level LNT recommendations for cancer risk assessment based on the Precautionary Principle, which Lewis asserted, and which remains in place today in essentially all countries. The present paper explores how such a scientific long-shot and quasi-stalking horse, who was unsupported by BEAR Panel members during the withering criticism prompted by his Science article, nevertheless endured in the pursuit of his LNT goal, becoming strikingly successful in achieving a global cancer risk assessment revolution which remains in place.
Electric power line equipment such as insulators, cut-out-switches, and lightning-arresters play important roles in ensuring a safe and uninterrupted power supply. Unfortunately, their continuous exposure to rugged environmental conditions may cause physical or electrical defects in them which may lead to the failure to the electrical system. In this paper, we present an automatic real-time electrical equipment detection and defect analysis system. Unlike previous handcrafted feature-based approaches, the proposed system utilizes a Convolutional Neural Network (CNN)-based equipment detection framework, making it possible to detect 17 different types of powerline insulators in a highly cluttered environment. We also propose a novel rotation normalization and ellipse detection method that play vital roles in the defect analysis process. Finally, we present a novel defect analyzer that is capable of detecting gunshot defects occurring in electrical equipment. The proposed system uses two cameras; a low-resolution camera that detects insulators from long-shot images, and a high-resolution camera which captures close-shot images of the equipment at high-resolution that helps for effective defect analysis. We demonstrate the performances of the proposed real-time equipment detection with up to 93% recall with 92% precision, and defect analysis system with up to 98% accuracy, on a large evaluation dataset. Experimental results show that the proposed system achieves state-of-the-art performance in automatic powerline equipment inspection.
Instagram selfies and groupies symbolize social media users' public display of narcissism. From an evolutionary psychological perspective on the renovated hierarchy of fundamental human motives and needs, this study examined the interaction effects of Instagram photo types (selfies, group selfies, long-shot photos taken by others, and neutral photos) and Instagram peer viewers' individual difference factors (intrasexual competition [ISC] for mates, need for popularity [NfP], loneliness, and need to belong [NtB]) on intersexual attraction. A randomized between-subjects experiment ( N = 110) was executed to see how the interaction affects the intention to date the target opposite-sex person. Multiple regression analyses confirm the moderating effects of ISC for mates, NfP, loneliness, and NtB on dating desire, among heterosexual/bisexual males exposed to female Instagram photos. Viewer characteristics moderate the influence of the potential mate's photo types on perception and dating desirability. This study makes theoretical contributions to the literature on evolutionary psychology of narcissism and the renovated pyramid of primary needs. With regard to practical implications for online dating apps/social networking sites, neutral photos are more effective to appeal to men who feel lonely and have higher need for belonging and popularity, whereas group selfies are more appealing to men who have lower ISC for mate, NtB, and NfP.
Extensive evaluations for intermittent gross hematuria, including selective renal arteriograms, failed to reveal the etiology of bleeding in 2 whtie patients. Sickle cell preparation and hemoglobin electrophoresis, obtained as long shot tests, revealed sickle cell trait in both patients. Both patients were treated successfully with low doses of epsilon aminocaproic acid. Sickle cell prepration and hemoglobin electrophoresis should be included in the evaluation of every patient, white or black, with unexplained hematuria.
We provide a database containing shot scale annotations (i.e., the apparent distance of the camera from the subject of a filmed scene) for more than 792,000 image frames. Frames belong to 124 full movies from the entire filmographies by 6 important directors: Martin Scorsese, Jean-Luc Godard, Béla Tarr, Federico Fellini, Michelangelo Antonioni, and Ingmar Bergman. Each frame, extracted from videos at 1 frame per second, is annotated on the following scale categories: Extreme Close Up (ECU), Close Up (CU), Medium Close Up (MCU), Medium Shot (MS), Medium Long Shot (MLS), Long Shot (LS), Extreme Long Shot (ELS), Foreground Shot (FS), and Insert Shots (IS). Two independent coders annotated all frames from the 124 movies, whilst a third one checked their coding and made decisions in cases of disagreement. The CineScale database enables AI-driven interpretation of shot scale data and opens to a large set of research activities related to the automatic visual analysis of cinematic material, such as the automatic recognition of the director's style, or the unfolding of the relationship between shot scale and the viewers' emotional experience. To these purposes, we also provide the model and the code for building a Convolutional Neural Network (CNN) architecture for automated shot scale recognition. All this material is provided through the project website, where video frames can also be requested to authors, for research purposes under fair use.