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Cancer will directly affect the lives of over one-third of the population. The DNA Damage Response (DDR) is an intricate system involving damage recognition, cell cycle regulation, DNA repair, and ultimately cell fate determination, playing a central role in cancer etiology and therapy. Two primary therapeutic approaches involving DDR targeting include: combinatorial treatments employing anticancer genotoxic agents; and synthetic lethality, exploiting a sporadic DDR defect as a mechanism for cancer-specific therapy. Whereas, many DDR proteins have proven "undruggable", Fragment- and Structure-Based Drug Discovery (FBDD, SBDD) have advanced therapeutic agent identification and development. FBDD has led to 4 (with ∼50 more drugs under preclinical and clinical development), while SBDD is estimated to have contributed to the development of >200, FDA-approved medicines. Protein X-ray crystallography-based fragment library screening, especially for elusive or "undruggable" targets, allows for simultaneous generation of hits plus details of protein-ligand interactions and binding sites (orthosteric or allosteric) that inform chemical tractability, downstream biology, and intellectual property. Using a novel high-throughput crystallography-based fragment library screening platform, we screened five diverse proteins, yielding hit rates of ∼2-8% and crystal structures from ∼1.8 to 3.2 Å. We consider current FBDD/SBDD methods and some exemplary results of efforts to design inhibitors against the DDR nucleases meiotic recombination 11 (MRE11, a.k.a., MRE11A), apurinic/apyrimidinic endonuclease 1 (APE1, a.k.a., APEX1), and flap endonuclease 1 (FEN1).

This study tested whether a new training tool, the Exposure Guide (EG), improved in-session therapist behaviors (i.e., indicators of quality) that have been associated with youth outcomes in prior clinical trials of exposure therapy. Six therapists at a community mental health agency (CMHA) provided exposure therapy for 8 youth with obsessive-compulsive disorder (OCD). Using a nonconcurrent multiple baseline design with random assignment to baseline lengths of 6 to 16 weeks, therapists received gold-standard exposure therapy training with weekly consultation (baseline phase) followed by addition of EG training and feedback (intervention phase). The primary outcome was therapist behavior during in-session exposures, observed weekly using a validated coding system. Therapist behavior was evaluated in relation to a priori benchmarks derived from clinical trials. Additional outcomes included training feasibility/acceptability, therapist response to case vignettes and beliefs about exposure, and independent evaluator-rated clinical outcomes. Three therapists reached behavior benchmarks only during the EG (intervention) phase. Two therapists met benchmarks during the baseline phase; one of these subsequently moved away from benchmarks but met them again after starting the EG phase. Across all therapists, the percentage of weeks meeting benchmarks was significantly higher during the EG phase (86.4%) vs. the baseline phase (53.2%). Youth participants experienced significant improvement in OCD symptoms and global illness severity from pre- to posttreatment. Results provide initial evidence that adding the EG to gold-standard training can change in-session therapist behaviors in a CMHA setting.

BackgroundOne mechanism that can explain the link between processed meat consumption and colorectal cancer (CRC) is the production of carcinogenic N-nitroso compounds (NOCs) in the gastrointestinal tract. Oral and gut microbes metabolize ingested proteins (a source of secondary and tertiary amines and amides) and can reduce nitrate to nitrite, generating potentially carcinogenic NOCs.ObjectiveWe evaluated whether nitrate/nitrite in processed meat or water influences the fecal or salivary microbiota.DesignIn this dietary intervention study, 63 volunteers consumed diets high in conventional processed meats for two weeks, switched to diets high in poultry for two weeks, and then consumed phytochemical-enriched conventional processed or low-nitrite processed meat diets for two weeks. During the intervention, they drank water with low nitrate concentrations and consumed a healthy diet with low antioxidants. Then the volunteers drank nitrate-enriched water for 1 week, in combination with one of the four different diets. We measured creatinine-adjusted urinary nitrate levels and characterized the oral and fecal microbiota using 16S rRNA amplicon sequencing.ResultsUsing linear mixed models, we found that, compared to baseline, urinary nitrate levels were reduced during the phytochemical-enriched low-nitrite meat diet (p-value = 0.009) and modestly during the poultry diet (p-value = 0.048). In contrast, urinary nitrate increased after 1-week of drinking nitrate-enriched water (p-value

The cultural heritage sector increasingly integrates augmented and virtual reality (VR) solutions to meet dissemination and interpretation needs for its collections. As research in the field grows, the required entertainment and learning impacts of such applications are rising. This study presents a VR museum that aims to facilitate an understanding of cultural heritage. More specifically, an exhibition was designed, curated and developed in a VR environment based on a framework that encourages the public’s interaction with the artworks and experiential learning through activities that utilize VR functionalities in a meaningful way. This framework was applied in a contemporary art museum where the description of artistic concepts is not always obvious to the general public due to the abstract forms of the artworks or the particularities of different artistic movements. This paper focuses on the application development and three user experience evaluations (museum experts, technical experts and general audience). The results were positive regarding the perceived sense of control, usability and the feelings of the user, including their sense of entertainment. Additionally, the participants valued the educational value of the developed activity types and their usefulness. Moreover, the users were interested in exploring the cultural heritage content available in the exhibition, and they would suggest the application to colleagues or friends.

The role of Bifidobacterium species and microbial metabolites such as short-chain fatty acids (SCFAs) and human milk oligosaccharides in controlling intestinal inflammation and the pathogenesis of obesity and type 1 diabetes (T1D) has been largely studied in recent years. This paper discusses the discovery of signature biomarkers for obesity and T1D based on data from a novel test for profiling several Bifidobacterium species, combined with metabolomic analysis. Through the NUTRISHIELD clinical study, a total of 98 children were recruited: 40 healthy controls, 40 type 1 diabetics, and 18 obese children. Bifidobacterium profiles were assessed in stool samples through an innovative test allowing high taxonomic resolution and precise quantification, while SCFAs and branched amino acids were measured in urine samples through gas chromatography–mass spectrometry (GC-MS). KIDMED questionnaires were used to evaluate the children’s dietary habits and correlate them with the Bifidobacterium and metabolomic profiles. We found that B. longum subs. infantis and B. breve were higher in individuals with obesity, while B. bifidum and B. longum subs. longum were lower compared to healthy individuals. In individuals with T1D, alterations were found at the metabolic level, with an overall increase in the level of the most measured metabolites. The high taxonomic resolution of the Bifidobacterium test used meant strong correlations between the concentrations of valine and isoleucine, and the relative abundance of some Bifidobacterium species such as B. longum subs. infantis, B. breve, and B. bifidum could be observed.

(1) Background: We reviewed a stem cell-derived therapeutic strategy for advanced neovascular age-related macular degeneration (nAMD) using a human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE) monolayer delivered on a coated, synthetic basement membrane (BM)—the patch—and assessed the presence and distribution of hESC-RPE over 5 years following transplantation, as well as functional outcomes. (2) Methods: Two subjects with acute vision loss due to sub-macular haemorrhage in advanced nAMD received the hESC-RPE patch. Systematic immunosuppression was used peri-operatively followed by local depot immunosuppression. The subjects were monitored for five years with observation of RPE patch pigmentation, extension beyond the patch boundary into surrounding retina, thickness of hESC-RPE and synthetic BM and review for migration and proliferation of hESC-RPE. Visual function was also assessed. (3) Results: The two study participants showed clear RPE characteristics of the patch, preservation of some retinal ultrastructure with signs of remodelling, fibrosis and thinning on optical coherence tomography over the 5-year period. For both participants, there was evidence of pigment extension beyond the patch continuing until 12 months post-operatively, which stabilised and was preserved until 5 years post-operatively. Measurement of hESC-RPE and BM thickness over time for both cases were consistent with predefined histological measurements of these two layers. There was no evidence of distant RPE migration or proliferation in either case beyond the monolayer. Sustained visual acuity improvement was apparent for 2 years in both subjects, with one subject maintaining the improvement for 5 years. Both subjects demonstrated initial improvement in fixation and microperimetry compared to baseline, at year 1, although only one maintained this at 4 years post-intervention. (4) Conclusions: hESC-RPE patches show evidence of continued pigmentation, with extension, to cover bare host basement membrane for up to 5 years post-implantation. There is evidence that this represents functional RPE on the patch and at the patch border where host RPE is absent. The measurements for thickness of hESC-RPE and BM suggest persistence of both layers at 5 years. No safety concerns were raised for the hypothetical risk of RPE migration, proliferation or tumour formation. Visual function also showed sustained improvement for 2 years in one subject and 5 years in the other subject.

The selection of the optimal methodology for the 3D geometric documentation of cultural heritage is a subject of high concern in contemporary scientific research. As a matter of fact, it requires a multi-source data acquisition process and the fusion of datasets from different sensors. This paper aims to demonstrate the workflow for the proper implementation and integration of geodetic, photogrammetric and laser scanning techniques so that high-quality photorealistic 3D models and other documentation products can be generated for a complicated, large-dimensional architectural monument and its surroundings. As a case study, we present the monitoring of the Mehmet Bey Mosque, which is a landmark in the city of Serres and a significant remaining sample of the Ottoman architecture in Greece. The surveying campaign was conducted in the context of the 2022–2023 annual workshop of the Interdepartmental Program of Postgraduate Studies “Protection Conservation and Restoration of Cultural Monuments” of the Aristotle University of Thessaloniki, and it served as a geometric background for interdisciplinary cooperation and decision-making on the monument restoration process. The results of our study encourage the fusion of terrestrial laser scanning and photogrammetric datasets for the 3D modeling of the mosque, as they supplement each other as regards geometry and texture.

Introduction The Centers for Disease Control and Prevention (CDC) issued a health advisory in response to an outbreak of Fusarium meningitis from exposure to spinal anesthesia for cosmetic surgery performed in Mexico between Jan 1 to May 13, 2023. This paper outlines the neuroendovascular and neurosurgical observations and management of this outbreak at our Comprehensive Stroke Center with a focus on angio‐invasive disease. Methods A retrospective chart review was performed for fungal meningitis patients that presented between April and July 2023. Results There were a total of 12 patients who were found to have fungal meningitis, 11 of whom were included in the final analysis with angio‐invasive Fusarium solani. The mean age was 31.7 ± 7.15. 92% of patients were female. CT and MRI were initially normal in two‐thirds of patients. No cases demonstrated positive growth on fungal cultures. Only (1→3)‐β‐D‐Glucan assays were positive in all patients who were tested. After several patients in this series developed subarachnoid hemorrhage from a ruptured mycotic aneurysm, we proceeded to institute weekly cerebral angiography protocol. This detected moderate to severe vasospasm in 75%, and aneurysms in 58%, with the most common site being the basilar artery. The aneurysms were seen exclusively in the posterior circulation. The average size of aneurysms when first detected was 5.0 ± 3.8 mm. Patients with brain aneurysms were treated with flow diversion in 57% of cases, primary coiling was performed in 14%, and the remaining expired prior to treatment. 14% in our series actually developed another episode of subarachnoid hemorrhage after treatment from a new angiographically confirmed aneurysm. All patients who presented with subarachnoid hemorrhage from mycotic aneurysms have passed or withdrawn care. With regard to vasospasm treatment, 80% had treatment with intra‐arterial verapamil and 40% underwent mechanical angioplasty. We did not perform balloon angioplasty in any case due to concern for rupture of the weakened compromised vessel walls. Finally with regard to cerebrospinal fluid (CSF) diversion; 67% underwent ventriculostomy, and a minority were converted to ventriculoperitoneal shunts. All but one patient received dual antifungal therapy with Amphotericin B and Voriconazole, and 42% were started on every other day intrathecal Amphotericin B. Conclusion We have found that in patients with fusarium meningitis that weekly angiographic surveillance for aneurysms and vasospasm should be performed. Conventional angiography is preferred to computed tomography angiography due to the smaller size of aneurysms. Aneurysms should be primarily coiled prior before flow diversion is attempted, and vasospastic vessels may be mechanically dilated in the setting of vessel wall necrosis.

Introduction Rapid expansion of mechanical thrombectomy and swift manufacturing development has translated into significant evolution of large bore catheter technology. The objective of this study was to evaluate the association among diverse structural components of large bore aspiration catheters on procedural performance. Methods Retrospective analysis of a prospectively maintained mechanical thrombectomy consortium (SVIN Registry) treated with stand‐alone contact aspiration for the first pass in the MCA M1 or intracranial ICA occlusions from 2012‐2021. Catheters were stratified based on construction materials, tip technology, catheter sizing, and catheter lining. Factors associated with first pass effect (FPE ‐ first‐pass eTICI2c‐3 reperfusion) as well as speed of clot engagement were analyzed. Results We identified 983 patients with proximal occlusion and aspiration as the first pass technique. FPE was observed in 34% and associated with age (OR:1.016;95%CI:1.006‐1.027), cardioembolic stroke etiology (OR:1.685;95%CI:1.77 ‐2.41), MCA M1(OR:2.737;95%CI:1.091 ‐1.867), non‐general anesthesia (OR:0.546;95%CI:0.389 ‐0.767), as well as with 0.070” (OR:2.038;95%CI:1.099 ‐3.779) and 0.088” (OR:3.899;95%CI:1.582 ‐9.606) distal catheter inner diameter in the adjusted analysis. Median time from arterial access to clot contact was 17 minutes with faster times observed in younger patients (OR:0.986;95%CI:0.975 ‐0.996) as well as with the use of aspiration catheters with shorter length of distal outer hydrophilic coating (18‐30cm) on multivariable regression (OR:0.303; 95%CI:0.113‐0.816). Conclusion Larger aspiration catheter distal inner diameter was associated with higher rates of FPE. Aspiration catheters with reduced distal tip hydrophilic coating were associated with faster arterial access to clot contact time.

Abstract EFSA Strategy 2027 outlines the need for fit‐for‐purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the ‘Draft framework for protocol development for EFSA's scientific assessments’ published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub‐questions is proposed: the ‘APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross‐cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub‐questions, including uncertainty analysis. Five possible approaches to answering individual (sub‐)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi‐formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and – not covered in this guidance – generating empirical evidence ex novo. The guidance is complemented by a standalone ‘template’ for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.

In this perspective paper, we argue for incorporating personal narratives in positive psychology interventions for chronic pain. Narratives refer to the telling and retelling of events. Narratives detail accounts of events and provide rich, in-depth information on human interactions, relationships, and perspectives. As such, narratives have been used to understand people’s experiences with pain and pain coping mechanisms—as well as to facilitate therapeutic outcomes. Furthermore, narrative research has shown that narration can help restore and promote relief, calm, hope, self-awareness, and self-understanding in chronic pain sufferers. Positive psychology interventions have been successful in improving the lives of people living with chronic pain, but these psychology interventions do not typically incorporate personal narratives. Still, narrative, and positive psychology scholarship foci overlap, as both aim to enhance people’s quality of life, happiness, and well-being, and to promote the understanding of psychosocial strengths and resources. In this article, we provide a rationale for incorporating personal narratives as an agentic form of positive psychology intervention. To that aim, we outline areas of convergence between positive psychology and narrative research and show how combining positive psychology exercises and narration can have additive benefits for pain sufferers. We also show how integrating narration in positive psychology intervention research can have advantages for healthcare research and policy.

IntroductionNeurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study).MethodsIn this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal-Wallis test followed by the Dunn procedure to test for differences in practices among world regions.ResultsWe analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority of respondents reported having a dedicated neuro-ICU (67% overall; highest in North America: 82%; and lowest in Oceania: 14%).ConclusionThe PRINCE Study results suggest that there is significant variability in the delivery of neurocritical care. The study also shows it is feasible to undertake international collaborations to gather global data about the practice of neurocritical care.

A dead individual of Metamasius hemipterus (Linnaeus, 1758) was collected by a citizen scientist in Athens, Greece from a hand of imported bananas. The equatorial origin of the fruit as well as the extensive growth of a fungus on the specimen, both suggest an unintentional introduction as a contaminant. Nevertheless, this record highlights the valu-able contribution of citizen scientists in the study of alien species. Although the species is not presently considered as established in the country, citizen-science initiatives in order to raise awareness and monitor its presence are ongoing.

Radio frequency (RF) energy harvesting and wireless power transmission (WPT) technologies —both near-field and far-field—have attracted significant interest for wireless applications and RFID systems. We already utilize near-field WPT products in our life and it is expected that RF EH and far-field WPT systems can drive the future low-power wireless systems. In this article, we initially present a brief historical overview of these technologies. The main technical challenges of rectennas and WPT transmitters are discussed. Furthermore, this paper presents the recent advances on the development of these technologies, including the possibility of powering RFID systems through the millimeter wave power from 5G networks, the trends in flexible rectennas design and the technological developments on the simultaneous wireless information and power transfer (SWIPT).

This paper is devoted to the problem of the thermal fracture of a functionally graded coating (FGC) on a homogeneous substrate (H), i.e., FGC/H structures. The FGC/H structure was subjected to thermo-mechanical loadings. Systems of interacting cracks were located in the FGC. Typical cracks in such structures include edge cracks, internal cracks, and edge/internal cracks. The material properties and fracture toughness of the FGC were modeled by formulas based on the rule of mixtures. The FGC comprised two constituents, a ceramic on the top and a metal as a homogeneous substrate, with their volume fractions determined by a power law function with the power coefficient λ as the gradation parameter for the FGC. For this study, the method of singular integral equations was used, and the integral equations were solved numerically by the mechanical quadrature method based on the Chebyshev polynomials. Attention was mainly paid to the determination of critical loads and energy release rates for the systems of interacting cracks in the FGCs in order to find ways to increase the fracture resistance of FGC/H structures. As an illustrative example, a system of three edge cracks in the FGC was considered. The crack shielding effect was demonstrated for this system of cracks. Additionally, it was shown that the gradation parameter λ had a great effect on the fracture characteristics. Thus, the proposed model provided a sound basis for the optimization of FGCs in order to improve the fracture resistance of FGC/H structures.

The rapid development of technology in today’s times make business’ survival a rather complex task. It is therefore necessary for the specialized organization and administration of each company to differentiate and strengthen its competitive advantages. Gamification is an established practice in many business domains and can enforce employees to engage in business processes and change aspects of their behavior. Even though numerous gamification patterns that are described in literature have been used so far by businesses to various working environments, the outcomes were not the best possible that we would expect in terms of their right utilization to business non-game contexts. Thus, there is need for concise gamification patterns that can offer right guidance to game designers in business. Gamification design patterns can provide a distilled knowledge of techniques of how to design object-oriented software. This paper aims to address this gap in existing literature by describing new gamification design patterns, classifying them according to specific criteria and providing new information to this research domain. Our study is a descriptive literature review and is based on review of previous works. This descriptive literature review tries to give a better understanding by proposing new gamification design patterns in the continuously evolving research domain of gamification design patterns.

This study seeks to identify the strategic and operational factors necessary for the effective operation of the International Olympic Academy (IOA), and of the National Olympic Academies (NOAs). It applies Resource Dependence Theory (RDP) and Inter-organizational Relationships Theory (IOR) to the institutional environment of the NOAs. A set of exploratory semi-structured interviews were conducted with key stakeholders from the International Olympic Committee (IOC), IOA, NOAs and Academics. A thematic analysis of the interview data provided themes to be incorporated into a questionnaire conducted with NOA directors and NOC officials focusing on relationships of the NOAs with other organisations and the implications for their autonomy. The nature of the field of NOA activity and its environment, is such that, for many NOAs, it is beset by an imbalance of power. This is reflected in the resource dependency of many NOAs on, in particular, NOCs and ultimately the IOC for legitimacy, human, financial and physical resources. The paper highlights a number of ways in which these relationships might be modified for the benefit of all the organisations involved.

Abstract Neuromarketing exploits neuroimaging techniques so as to reinforce the predictive power of conventional marketing tools, like questionnaires and focus groups. Electroencephalography (EEG) is the most commonly encountered neuroimaging technique due to its non-invasiveness, low-cost, and its very recent embedding in wearable devices. The transcription of brainwave patterns to consumer attitude is supported by various signal descriptors, while the quest for profitable novel ways is still an open research question. Here, we suggest the use of sample covariance matrices as alternative descriptors, that encapsulate the coordinated neural activity from distinct brain areas, and the adoption of Riemannian geometry for their handling. We first establish the suitability of Riemannian approach for neuromarketing-related problems and then suggest a relevant decoding scheme for predicting consumers’ choices (e.g., willing to buy or not a specific product). Since the decision-making process involves the concurrent interaction of various cognitive processes and consequently of distinct brain rhythms, the proposed decoder takes the form of an ensemble classifier that builds upon a multi-view perspective, with each view dedicated to a specific frequency band. Adopting a standard machine learning procedure, and using a set of trials (training data) in conjunction with the associated behavior labels (“buy”/ “not buy”), we train a battery of classifiers accordingly. Each classifier is designed to operate in the space recovered from the inter-trial distances of SCMs and to cast a rhythm-depended decision that is eventually combined with the predictions of the rest ones. The demonstration and evaluation of the proposed approach are performed in 2 neuromarketing-related datasets of different nature. The first is employed to showcase the potential of the suggested descriptor, while the second to showcase the decoder’s superiority against popular alternatives in the field.

The ability to quickly discover reliable hits from screening and rapidly convert them into lead compounds, which can be verified in functional assays, is central to drug discovery. The expedited validation of novel targets and the identification of modulators to advance to preclinical studies can significantly increase drug development success. Our SaXPyTM (“SAR by X-ray Poses Quickly”) platform, which is applicable to any X-ray crystallography-enabled drug target, couples the established methods of protein X-ray crystallography and fragment-based drug discovery (FBDD) with advanced computational and medicinal chemistry to deliver small molecule modulators or targeted protein degradation ligands in a short timeframe. Our approach, especially for elusive or “undruggable” targets, allows for (i) hit generation; (ii) the mapping of protein–ligand interactions; (iii) the assessment of target ligandability; (iv) the discovery of novel and potential allosteric binding sites; and (v) hit-to-lead execution. These advances inform chemical tractability and downstream biology and generate novel intellectual property. We describe here the application of SaXPy in the discovery and development of DNA damage response inhibitors against DNA polymerase eta (Pol η or POLH) and apurinic/apyrimidinic endonuclease 1 (APE1 or APEX1). Notably, our SaXPy platform allowed us to solve the first crystal structures of these proteins bound to small molecules and to discover novel binding sites for each target.

The combined use of social media, open data, and Artificial Intelligence has the potential to support practitioners and empower patients/citizens living with persistent pain, both as local and online communities. Given the wide availability of digital technology today, both practitioners and interested individuals can be connected with virtual communities and can support each other from the comfort of their homes. Digital means may represent new avenues for exploring the complexity of the pain experience. Online interactions of patients, data on effective treatments, and data collected by wearable devices may represent an incredible source of psychological, sociological, and physiological pain-related information. Digital means might provide several solutions that enhance inclusiveness and motivate patients to share personal experiences, limiting the sense of isolation in both rural and metropolitan areas. Building on the consensus of the usefulness of social media in enhancing the understanding of persistent pain and related subjective experiences via online communities and networks, we provide relevant scenarios where the effectiveness and efficiency of healthcare delivery might be improved by the adoption of the digital technologies mentioned above and repeated subsequently. The aim of this perspective paper is to explore the potential of open data, social media, and Artificial Intelligence in improving the prevention and management of persistent pain by adopting innovative non-biomedical approaches.

This paper aims at examining interpersonal income and consumption inequality within the Attica Metropolitan Region, which includes Athens, the largest metropolis of Greece. It also aims to make comparisons between Attica and the rest of the country. The analysis is based on income and consumption microdata from Greek Household Budget Surveys (HBS) over the period 2008-2019, encapsulating the period from the commencement of the economic crisis until the year before the outset of the COVID-19 pandemic. Results indicate that income inequalities are systematically higher than consumption inequalities. From a spatial comparative perspective, the results show that the Attica Metropolitan Region exhibits a higher degree of income and consumption inequality relative to the rest of the country. Furthermore, the economic crisis increased income inequality in Athens and in the rest of the country, while consumption expenditure inequality increased in the Athens metropolitan area only. Finally, the distance between socio-economic groups, which stands as a measure of the degree of social polarization, increased during the economic crisis. However, this does not hold true for consumption inequality. Overall, the analysis demonstrates the sensitivity of inequality outcomes to the selection of the welfare indicator (income or consumption), as well as a number of noticeable differences in inequality outcomes between the Metropolitan region of Attica and the rest of the country. The paper unveils facets of inequality which necessitate the implementation of more people and place-targeted policies aimed at more inclusive and balanced welfare conditions in metropolitan regions and across the country.

Variants within the Retinitis Pigmentosa GTPase regulator (RPGR) gene are the predominant cause of X-Linked Retinitis Pigmentosa (XLRP), a common and severe form of inherited retinal disease. XLRP is characterised by the progressive degeneration and loss of photoreceptors, leading to visual loss and, ultimately, bilateral blindness. Unfortunately, there are no effective approved treatments for RPGR-associated XLRP. We sought to investigate the efficacy of RPGRORF15 gene supplementation using a clinically relevant construct in human RPGR-deficient retinal organoids (ROs). Isogenic RPGR knockout (KO)-induced pluripotent stem cells (IPSCs) were generated using established CRISPR/Cas9 gene editing methods targeting RPGR. RPGR-KO and isogenic wild-type IPSCs were differentiated into ROs and utilised to test the adeno associated virus (AAV) RPGR (AAV-RPGR) clinical vector construct. The transduction of RPGR-KO ROs using AAV-RPGR successfully restored RPGR mRNA and protein expression and localisation to the photoreceptor connecting cilium in rod and cone photoreceptors. Vector-derived RPGR demonstrated equivalent levels of glutamylation to WT ROs. In addition, treatment with AAV-RPGR restored rhodopsin localisation within RPGR-KO ROs, reducing mislocalisation to the photoreceptor outer nuclear layer. These data provide mechanistic insights into RPGRORF15 gene supplementation functional potency in human photoreceptor cells and support the previously reported Phase I/II trial positive results using this vector construct in patients with RPGR-associated XLRP, which is currently being tested in a Phase III clinical trial.

The AIAG established the MSA, 4th Edition, as an international guideline to determine if the selected measurement system is capable and can be used for the intended purpose. The MSA guideline provides a practical basis for decision-making and is applied in both scientific and industrial contexts. In addition to the MSA, the Guide to the Expression of Uncertainty in Measurement (GUM) has standardized the determination of measurement uncertainties at an international level. This paper provides a practical example of using a surface comparator to demonstrate the limitations of the MSA for roughness parameters. Additionally, it presents a new method for assessing the capability of a measuring system for roughness measurements by considering the aspects from MSA and GUM. This work considers all information, distinguishing between existing and experimentally generated data. The experimental investigations for the application of the new method were carried out using a confocal laser scanning measuring microscope. The approach presents a new practical opportunity for both science and industry.