Munkhaastrup7353

Selectively utilizing alternative mechanisms to repair damaged DNA in essential factors deficient cancer facilitates tumor genetic evolution and contributes to treatment resistance. Synthetic lethality strategies provide a novel scenario to anticancer therapy with DNA repair protein mutation, such as glioma with DNA-PKcs-deficiency, a core factor crucial for non-homologous end joining (NHEJ) mediated DNA damage repair. Nevertheless, the clinical significance and molecular mechanisms of synthetic lethality function by interfering tumor DNA replication remain largely unexplored.

Cancer clinic treatment resistance-related replication core factors were identified through bioinformatics analysis and RNA-sequencing and verified in clinical specimens by immunoblotting and in situ Proximity Ligation Analysis (PLA). Then, in vitro and in vivo experiments, including visible single molecular tracking system were performed to determine functional roles, the molecular mechanisms and clinical significance of synthetic tumor evolution and demonstrate the applicability of combined FEN1 and DNA-PKcs targeting in the treatment of glioma.

Our findings highlight an unanticipated synthetic interaction between FEN1/BRCA1/RAD51 and DNA-PKcs when dysfunction leads to incompatible with cell survival under conditions of interrupted replication progression by disrupting addictive alternative tumor evolution and demonstrate the applicability of combined FEN1 and DNA-PKcs targeting in the treatment of glioma.Kidneys are key regulators of phosphate homeostasis. Biallelic mutations of the renal Na+/phosphate cotransporter SLC34A1/NaPi-IIa cause idiopathic infantile hypercalcemia, whereas monoallelic mutations were frequently noted in adults with kidney stones. Genome-wide-association studies identified SLC34A1 as a risk locus for chronic kidney disease. Pathogenic mutations in SLC34A1 are present in 4% of the general population. Here, we characterize a mouse model carrying the 91del7 in-frame deletion, a frequent mutation whose significance remains unclear. Under normal dietary conditions, 12 weeks old heterozygous and homozygous males have similar plasma and urinary levels of phosphate as their wild type (WT) littermates, and comparable concentrations of parathyroid hormone, fibroblast growth factor 23 (FGF-23) and 1,25(OH)2 vitamin D3. Renal phosphate transport, and expression of NaPi-IIa and NaPi-IIc cotransporters, was indistinguishable in the three genotypes. Challenging mice with low dietary phosphate did not result in differences between genotypes with regard to urinary and plasma phosphate. Urinary and plasma phosphate, plasma FGF-23 and expression of cotransporters were similar in all genotypes after weaning. Urinary phosphate and bone mineral density were also comparable in 300 days old WT and mutant mice. In conclusion, mice carrying the 91del7 truncation do not show signs of impaired phosphate homeostasis.Top-level management teams are particularly exposed to stress factors as they frequently have to make important decision under stress. While an existing body of research evidence suggests that stress negatively affects decision-making processes, very little is known about possible strategies to reduce these negative effects. The aim of the current work is to investigate the effect of training self-regulation ability through neurobiofeedback on managers' intertemporal and risky decision making. Twenty-three managers were assigned to the experimental or the control condition. All participants performed, two decisional tasks, before and after a training phase. The tasks were administered through mouse tracker software, in order to measure participants' delay discounting and risk taking propensity on both explicit and implicit choice parameters. During the training phase, the experimental condition received a training protocol based on stress assessment tests via neurobiofeedback signals (i.e., temperature and skin conductance), with the goal of improving self-regulation ability while the control condition was administered a control training. The main result of this study is to have conclusively demonstrated that NBF training increases an individual's ability to self-regulate stress-related psychophysiological phenomena. Consequently, the improved ability to manage one's own reaction to stress enables a reduction in instinctive behavior during a probabilistic choice task.

Epidermolysis bullosa (EB) is a disabling and chronic genodermatosis characterized by mucocutaneous fragility with blister formation after minimal trauma. Severity ranges between very mild forms to extremely severe or lethal subtypes. Depending on disease subtypes, blisters may be localized also in larynx, bladder, esophagus, and most frequent disease complications are malnutrition, chronic anemia, osteoporosis, limb contracture and early development of squamous cell carcinomas. EB is classified into four major groups EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler EB (KEB). No specific treatment is available; however, a multidisciplinary management is mandatory in order to treat the lesions, to prevent complication, and to give a psychological support to the patient and family members.

To report the experience on a therapeutic education plan of an Italian reference center for epidermolysis bullosa in the last 30years.

In our study we included all patients with EB from 1990to the ted with recessive DEB; only 1 patient died for squamous cell carcinoma at the age of 16.

An adequate management of EB patients require a multidisciplinary approach with an educational plan to guarantee an appropriate treatment and to support and accompany patients and their families since birth along life. The dynamic educational plan adopted in our hospital showed good clinical and psychological outcome in our population, allowing adherence to treatment, reducing the frequency of complications and improving life expectancy and quality of life.

An adequate management of EB patients require a multidisciplinary approach with an educational plan to guarantee an appropriate treatment and to support and accompany patients and their families since birth along life. The dynamic educational plan adopted in our hospital showed good clinical and psychological outcome in our population, allowing adherence to treatment, reducing the frequency of complications and improving life expectancy and quality of life.Videos, especially short videos, have become an increasingly important source of information in these years. However, many videos spread on video sharing platforms are misleading, which have negative social impacts. Therefore, it is necessary to find methods to automatically identify misleading videos. In this paper, three categories of features (content features, uploader features and environment features) are proposed to construct a convolutional neural network (CNN) for misleading video detection. The experiment showed that all the three proposed categories of features play a vital role in detecting misleading videos. Our proposed approach that combines three categories of features achieved the best performance with the accuracy of 0.90 and the F1 score of 0.89. It also outperformed other baselines such as SVM, k-NN, decision tree and random forest models by more than 22%.

Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethicists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the potential for utopian or dystopian distortions. Thus, it is important to understand how this technology is portrayed to the public.

To investigate how brain organoids are displayed to the public, we conducted a systematic review of media literature indexed in the Nexis Uni database from 2013-2019. News and media source articles passing exclusion criteria (n = 93) were scored to evaluate tone and relevant themes. Themes were validated with a pilot sample before being applied to the dataset. Thiated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids.

Given the power that media have to inform or misinform the public, it is important this literature provides an accurate and balanced reflection of the therapeutic potential and associated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids.Optical homodyne detection is widely adopted in continuous-variable quantum key distribution for high-rate field measurement quadratures. Besides that, those detection schemes have been being implemented for single-photon statistics characterization in the field of quantum tomography. In this work, we propose a discrete-variable quantum key distribution (DV-QKD) implementation that combines the use of phase modulators for high-speed state of polarization (SOP) generation, with a conjugate homodyne detection scheme which enables the deployment of high speed QKD systems. The channel discretization relies on the application of a detection threshold that allows to map the measured voltages as a click or no-click. Our scheme relies also on the use of a time-multiplexed pilot tone-quantum signal architecture which enables the use of a Bob locally generated local oscillator and opens the door to an effective polarization drift compensation scheme. Besides that, our results shows that for higher detection threshold values we obtain a very low quantum bit error rate (QBER) on the sifted key. Nevertheless, due to huge number of discarded qubits the obtained secure key length abruptly decreases. From our results, we observe that optimizing the detection threshold and considering a system operating at 500 MHz symbol generation clock, a secure key rate of approximately 46.9 Mbps, with a sifted QBER of [Formula see text] over 40 km of optical fiber. This considering the error correction and privacy amplification steps necessary to obtain a final secure key.

The trial investigates the efficacy of internet-based cognitive behavioral therapy (iCBT) in improving health-related QoL in patients with endometriosis, which is a chronic gynecological condition affecting up to 15% of people with female-assigned reproductive organs. find more Endometriosis is stress-related and comes with various physical symptoms such as pelvic pain and infertility. It has a substantial impact on health-related quality of life (QoL), and mind-body interventions seem promising in reducing the psychological burden.

This is a monocentric randomized-controlled trial recruiting 120 patients with endometriosis. The intervention consists of eight iCBT modules focusing on psychoeducation, cognitive restructuring, pacing, and emotion regulation. Participants will receive written feedback from a trained therapist weekly. The comparator is a waitlist control group. All participants will be followed up 3 months after the intervention, and the intervention group will additionally be followed up 12 months after the intervention.