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The human hippocampus and prefrontal cortex play critical roles in learning and cognition 1,2 , yet the dynamic molecular characteristics of their development remain enigmatic. Here we investigated the epigenomic and three-dimensional chromatin conformational reorganization during the development of the hippocampus and prefrontal cortex, using more than 53,000 joint single-nucleus profiles of chromatin conformation and DNA methylation generated by single-nucleus methyl-3C sequencing (snm3C-seq3) 3 . The remodelling of DNA methylation is temporally separated from chromatin conformation dynamics. Using single-cell profiling and multimodal single-molecule imaging approaches, we have found that short-range chromatin interactions are enriched in neurons, whereas long-range interactions are enriched in glial cells and non-brain tissues. We reconstructed the regulatory programs of cell-type development and differentiation, finding putatively causal common variants for schizophrenia strongly overlapping with chromatin loop-connected, cell-type-specific regulatory regions. Our data provide multimodal resources for studying gene regulatory dynamics in brain development and demonstrate that single-cell three-dimensional multi-omics is a powerful approach for dissecting neuropsychiatric risk loci., Competing Interests: Competing interests J.R.E. serves on the scientific advisory board of Zymo Research. A.D.S. is an employee of Arima Genomics., (© 2024. The Author(s).)

Background: Prevalence of bioprosthetic valve degeneration (BVD) is rising as the use of bioprosthetic aortic valves increases. Detecting early signs of BVD remains a challenge, with conventional imaging methods often failing to identify early deterioration stages. 18F-fuoride positron emission tomography (PET-CT) is an emerging technique that offers promising prospects to detect subclinical BVD. This study aimed to compare early PET parameters of fluoride uptake with echocardiographic hemodynamic parameters and compare outcomes according to anticoagulation in patients who received bioprosthetic valves., Methods: This is a sub-study of the ANTIPRO clinical trial, which involved patients undergoing surgical aortic valve replacement (SAVR) with a porcine bioprosthesis and randomized them into anticoagulated and non-anticoagulated groups. Hemodynamic changes were assessed by transthoracic echocardiography (TTE), while 18F-fluoride PET-CT quantified fluoride uptake and divided the patients in two groups: high-uptake and low-uptake. Mean and maximum gradients by TTE at three years were compared between the two uptake groups. Fluoride uptake was also compared between the anticoagulated and control groups., Results: We found no significant differences in transprosthetic gradients between high-uptake(21.4 ± 8.6 mmHg) and low-uptake(17.3 ± 11.2 mmHg.p = 0.244) PET-defined groups in this specific timeframe. Notably, anticoagulated patients exhibited significantly risk of higher fluoride uptake(OR = 4.34;95%CI:1.04-18.21.p = 0.045)., Conclusions: No association was found between fluoride uptake and hemodynamic evaluation. Anticoagulation was associated with higher fluoride uptake. These findings highlight the emerging role of PET-CT in studying bioprosthetic aortic valves and emphasize the need for extended follow-up to evaluate the impact of anticoagulation on valve degeneration., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption. We further demonstrate that the combination of LIV and RANKL antibody reduces SCI-related bone loss more than each intervention alone. Our findings that LIV is efficacious in maintaining sublesional bone mass suggests that such physical-based intervention approach would be a noninvasive, simple, inexpensive and practical intervention to treat bone loss after SCI. Because the combined administration of LIV and RANKL inhibition better preserved sublesional bone after SCI than either intervention alone, this work provides the impetus for the development of future clinical protocols based on the potential greater therapeutic efficacy of combining non-pharmacological (e.g., LIV) and pharmacological (e.g., RANKL inhibitor or other agents) approaches to treat osteoporosis after SCI or other conditions associated with severe immobilization., Competing Interests: YP, AM, OFA, JSM, JC, JH, AL, JQF, WAB, WQ have nothing to disclose. HMB and WDD are co-founders and managing members of InflamaCORE, LLC and have licensed patents on inflammasome proteins as biomarkers of injury and disease as well as on targeting inflammasome proteins for therapeutic purposes. HMB and WDD are Scientific Advisory Board Members for ZyVersa Therapeutics., (© 2024 Published by Elsevier Inc.)

Background: Evidence on abatacept (ABA) utility for rheumatoid arthritis (RA) - associated interstitial lung disease (ILD) is growing. Clinical trials have shown equivalence in subcutaneous (SC) and intravenous (IV) administration of ABA for articular manifestations. However, this has not been studied in respiratory outcomes., Objective: To compare the effectiveness of ABA in RA-ILD patients according to the route of administration., Methods: National retrospective multicentre study of RA-ILD patients on treatment with ABA. They were divided into 2 groups: a) IV, and b) SC. The following outcomes were analysed from baseline to final follow-up using linear mixed models: a) forced vital capacity (FVC), b) diffusing capacity of the lungs for carbon monoxide (DLCO), c) chest high resolution computed tomography (HRCT), d) dyspnoea, e) RA activity, and f) sparing corticosteroids effect., Results: A total of 397 patients were included (94 IV-ABA and 303 SC-ABA), median follow-up of 24 [10-48] months. After adjustment for possible confounders, FVC and DLCO remained stable during the first 24 months without differences between IV-ABA and SC-ABA (p = 0.6304 and 0.5337). Improvement/ stability of lung lesions in HRCT was observed in 67 % of patients (75 % IV-ABA, 64 % SC-ABA; p = 0.07). Dyspnoea stabilized/ improved in 84 % of patients (90 % IV-ABA, 82 % SC-ABA; p = 0.09). RA - disease activity improved in both groups. No statistically significant differences regarding any of the variables studied between the two groups were found. ABA was withdrawn in 87 patients (21.9 %), 45 % IV-ABA and 37 % SC-ABA (p = 0.29). ILD worsening and articular inefficacy were the most common reasons for ABA discontinuation., Conclusion: In patients with RA-ILD, ABA seems to be equally effective regardless of the route of administration., Competing Interests: Declaration of competing interest Disclosures that may be interpreted as constituting of possible conflict(s) of interest for the study: B. A.-M. received grants/research supports from Abbvie and Roche and had consultation fees/participation in company-sponsored speaker´s bureau from Pfizer, Celgene, Novartis, Sanofi, Janssen, UCB and Lilly, outside the submitted work; N.V.-R. has received fees in company-sponsored speaker's bureau and research supports from AbbVie, Lilly, Celgene, Grünenthal, UCB Pharma, Nordic Pharma, MSD and Rubió; L.C.D.-C has received research supports and participation in company-sponsored speaker's bureau from Abbvie, Janssen, Lilly and Celgene; J.L.M has received fees in company-sponsored speaker's bureau from Boehringer Ingelheim, Bristol-Myers Squibb (BMS) and Galapagos and had consultation fees from Boehringer Ingelheim; G.B has received fees in company-sponsored speaker's bureau from Bristol-Myers Squibb (BMS); A.U.-A. has received grants/research supports from Abbvie, Galápagos, Novartis, GSK, Astrazeneca, Janssen, Pfizer and Amgen; C.F.-D. has received fees in company-sponsored speaker's bureau from: Janssen, Galápagos, Amgen, Bristol Myers Squibb (BMS); I. F.-A. has received grants/research supports from Abbott, MSD, Janssen, and Roche, as well as consultation fees from company sponsored speakers bureaus associated with Abbott, Pfizer, Roche, Sanofi, Celgene, and MSD; S.C. has received research supports from MSD and Pfizer and had consultation fees/participation in company-sponsored speaker's bureau from Amgen, BMS, Eli-Lilly, MSD, Roche, and UCB. S. C. is also assistant professor of the cátedra EPID-Future, funded by UAM-Roche, Universidad Autónoma de Madrid (UAM), Spain; R. B. received grants/research support from AbbVie, MSD, and Roche, and had consultation fees/participation in a company-sponsored speaker's bureau from AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD. The rest of the authors have declared no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite respiratory infections being a leading cause of hospitalization in children with tracheostomy tubes, there are no published guidelines for their diagnosis and management. This study aims to outline the clinical, laboratory and microbiological aspects of pneumonia in these children, along with the antibiotics used and outcomes. Additionally, it seeks to determine pneumonia incidence and associated risk factors., Methods: We conducted a retrospective study using the medical records of tracheostomized children at La Paz University Hospital in Madrid from 2010 to 2021., Results: Thirty-three pneumonia cases were observed in 25 tracheostomized children. Pseudomonas aeruginosa was the predominant bacterium (52%), followed by Escherichia coli , Staphylococcus aureus and Serratia marcescens . The same microorganism isolated in the tracheal aspirate culture during pneumonia was previously isolated in 83% of cases that had a similar culture, with some growth obtained within 7-30 days prior. Multiplex respiratory PCR detected respiratory viruses in 73% of cases tested. Antibiotic treatment was administered in all cases except 1, mostly intravenously (81%), with piperacillin/tazobactam and meropenem being commonly used. Only 1 of the described episodes had a fatal outcome., Conclusions: It is advisable to include coverage for P. aeruginosa , E. coli , S. aureus , and S. marcescens in the empirical antibiotic treatment for pneumonia in tracheostomized children, along with the microorganisms identified in tracheal cultures obtained within 7-30 days prior, if available. A positive PCR for respiratory viruses is often discovered in bacterial pneumonia in tracheostomized children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Introduction: malnutrition is a very frequent problem in oncology patients and may have serious repercussions. Adequate nutritional management is cost-effective in terms of health and survival in this population, but it requires multidisciplinary coordination, specific training, and continuous follow-up. Objective: to validate the applicability and efficacy of a multidisciplinary nutritional support protocol in oncology patients. Methods: a multidisciplinary nutritional protocol was developed for oncology patients, with guidelines for screening and assessment of malnutrition, treatment, re-evaluation, and management of side effects, as well as guidance on supplementation and eating patterns. The protocol would be implemented in various clinical centers, collecting data through a structured questionnaire, registering variables before and after implementation. Results: the protocol and its impact were implemented and evaluated in 39 centers. An improvement in nutritional care was observed, evidenced by an earlier initiation of nutritional assessment and an increase in the number of patients receiving adequate care following the protocol implementation. Problems related to inadequate malnutrition coding in the centers, limited resources, and the need for greater interdepartmental collaboration were identified. Conclusions: the conduct of this study provides insights into how the implementation of a multidisciplinary nutritional support protocol can improve the nutritional care received by patients and informs about the main obstacles to adequate implementation.

The impact of leachates from micronized beached plastics of the Mediterranean Sea and Atlantic Ocean on coastal marine ecosystems was investigated by using a multidisciplinary approach. Chemical analysis and ecotoxicological tests on phylogenetically distant species were performed on leachates from the following plastic categories: bottles, pellets, hard plastic (HP) containers, fishing nets (FN) and rapido trawling rubber (RTR). The bacteria Alivibrio fischeri, the nauplii of the crustaceans Amphibalanus amphitrite and Acartia tonsa, the rotifer Brachionus plicatilis, the embryos of the sea urchin Paracentrotus lividus, the ephyrae of the jellyfish Aurelia sp. and the larvae of the medaka Oryzias latipes were exposed to different concentrations of leachates to evaluate lethal and sub-lethal effects. Thirty-one additives were identified in the plastic leachates; benzophenone, benzyl butyl phthalate and ethylparaben were present in all leachates. Ecotoxicity of leachates varied among plastic categories and areas, being RTR, HP and FN more toxic than plastic bottles and pellets to several marine invertebrates. The ecotoxicological results based on 13 endpoints were elaborated within a quantitative weight of evidence (WOE) model, providing a synthetic hazard index for each data typology, before their integrations in an environmental risk index. The WOE assigned a moderate and slight hazard to organisms exposed to leachates of FN and HP collected in the Mediterranean Sea respectively, and a moderate hazard to leachates of HP from the Atlantic Ocean. No hazard was found for pellet, bottles and RTR. These findings suggest that an integrated approach based on WOE on a large set of bioassays is recommended to get a more reliable assessment of the ecotoxicity of beached-plastic leachates. In addition, the additives leached from FN and HP should be further investigated to reduce high concentrations and additive types that could impact marine ecosystem health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Atopic dermatitis (AD), a prevalent chronic inflammatory disease with multifactorial etiology, features epidermal barrier defects and immune overactivation. Synthetic glucocorticoids (GCs) are widely prescribed for treating AD due to their anti-inflammatory actions; however, mechanisms are incompletely understood. Defective local GC signaling due to decreased production of endogenous ligand and/or GC receptor (GR) levels was reported in prevalent inflammatory skin disorders; whether this is a consequence or contributing factor to AD pathology is unclear. To identify the chromatin-bound cell-type-specific GR protein interactome in keratinocytes, we used rapid immunoprecipitation of endogenous proteins and mass spectrometry identifying 145 interactors that increased upon dexamethasone treatment. GR-interacting proteins were enriched in p53/p63 signaling, including epidermal transcription factors with critical roles in AD pathology. Previous analyses indicating mirrored AD-like phenotypes between P63 overexpression and GR loss in epidermis, and our data show an intricate relationship between these transcription factors in human keratinocytes, identifying TP63 as a direct GR target. Dexamethasone treatment counteracted transcriptional up-regulation of inflammatory markers by IL4/IL13, known to mimic AD, causing opposite shifts in GR and P63 genomic binding. Indeed, IL4/IL13 decreased GR and increased P63 levels in cultured keratinocytes and human epidermal equivalents (HEE), consistent with GR down-regulation and increased P63 expression in AD lesions vs normal skin. Moreover, GR knockdown (GR KD ) resulted in constitutive increases in P63, phospho-P38 and S100A9, IL6, and IL33. Also, GR KD culture supernatants showed increased autocrine production of TH2-/TH1-/TH17-TH22-associated factors including IL4, CXCL10, CXCL11, and CXCL8. GR KD HEEs showed AD-like features including hyperplasia and abnormal differentiation, resembling phenotypes observed with GR antagonist or IL4/IL13 treatment. The simultaneous GR/P63 knockdown partially reversed constitutive up-regulation of inflammatory genes in GR KD . In summary, our data support a causative role for GR loss in AD pathogenesis via functional interactions with P63 and autocrine signaling in epidermal keratinocytes., (© 2024. The Author(s).)

Hippocampal seizures mimicking mesial temporal lobe epilepsy cause a profound disruption of the adult neurogenic niche in mice. Seizures provoke neural stem cells to switch to a reactive phenotype (reactive neural stem cells, React-NSCs) characterized by multibranched hypertrophic morphology, massive activation to enter mitosis, symmetric division, and final differentiation into reactive astrocytes. As a result, neurogenesis is chronically impaired. Here, using a mouse model of mesial temporal lobe epilepsy, we show that the epidermal growth factor receptor (EGFR) signaling pathway is key for the induction of React-NSCs and that its inhibition exerts a beneficial effect on the neurogenic niche. We show that during the initial days after the induction of seizures by a single intrahippocampal injection of kainic acid, a strong release of zinc and heparin-binding epidermal growth factor, both activators of the EGFR signaling pathway in neural stem cells, is produced. Administration of the EGFR inhibitor gefitinib, a chemotherapeutic in clinical phase IV, prevents the induction of React-NSCs and preserves neurogenesis., (© 2024 Pastor-Alonso et al.)

One of the major challenges for edu-communication research is to analyze the influence of social media on young and adolescent users. This article examines the evaluation of gender inequalities - real and symbolic - in the consumption of social networks such as YouTube and Instagram among young people. Within the framework of a Research & Development & innovation (R&D + i ) project, it presents a discursive-theoretical analysis of how young users of social media perceive the presence and representation of gender on social media and whether such digital representations can be associated with an empowering gender perspective. This study presents results from 14 focus groups ( N  = 83), composed of students aged 12 to 18, drawn from three Spanish Autonomous Communities (Catalonia, the Balearic Islands and the Basque Country). The results show that gender issues arise in participants' conversations, especially among female participants, who perceive the importance of physical appearance on platforms such as Instagram and TikTok. Female participants feel more pressure in terms of appearance and dress compared to male participants. Among male participants there are more expressions of self-affirmation and more mentions related to fun and social prestige. Both male and female participants express concern about the impact of that pressure on younger girls. The influence of social media on self-image is more evident among female participants, who make frequent mention of the importance of self-esteem in relation to beauty standards and exposure to idealized body images. Notably, there were no comments by male participants that acknowledge any influence of social media on their self-image. The findings are in line with existing research and taken as a whole gives rise to concern as to the gender disparities observed in the use of social media, which do not constitute a picture of female empowerment. This research underlines the importance of promoting a respectful and equitable environment in relation to gender equality within digital spaces. Thus, this study provides support for the need to develop and implement edu-communicative initiatives to foster critical thinking around the influence of social media in this context and the evaluation of the impact of such initiatives in future research., Competing Interests: The authors declare that there are no commercial or financial relationships connected with this research that could be constitute a conflict of interest., (Copyright © 2024 Aran-Ramspott, Korres-Alonso, Elexpuru-Albizuri, Moro-Inchaurtieta and Bergillos-García.)

A Point-of-Care system for molecular diagnosis (PoC-MD) is described, combining GaN and CMOS chips. The device is a micro-system for fluorescence measurements, capable of analyzing both intensity and lifetime. It consists of a hybrid micro-structure based on a 32 × 32 matrix addressable GaN microLED array, with square LEDs of 50 µm edge length and 100 µm pitch, with an underneath wire bonded custom chip integrating their drivers and placed face-to-face to an array of 16 × 16 single-photon avalanche diodes (SPADs) CMOS. This approach replaces instrumentation based on lasers, bulky optical components, and discrete electronics with a full hybrid micro-system, enabling measurements on 32 × 32 spots. The reported system is suitable for long lifetime (>10 ns) fluorophores with a limit of detection ~1/4 µM. Proof-of-concept measurements of streptavidin conjugate Qdot™ 605 and Amino PEG Qdot™ 705 are demonstrated, along with the device ability to detect both fluorophores in the same measurement.

Background: Nicotine-containing electronic cigarette (EC) vaping has become popular worldwide, and our understanding of the effects of vaping on stroke outcomes is elusive. Using a rat model of transient middle cerebral artery occlusion, the current exploratory study aims to evaluate the sex-dependent effects of EC exposure on brain energy metabolism and stroke outcomes., Methods: Adult Sprague-Dawley rats of both sexes were randomly assigned to air/EC vapor (5% nicotine Juul pods) exposure for 16 nights, followed by randomization into 3 cohorts. The first cohort underwent exposure to air/EC preceding randomization to transient middle cerebral artery occlusion (90 minutes) or sham surgery, followed by survival for 21 days. During the survival period, rats underwent sensorimotor and Morris water maze testing. Subsequently, brains were collected for histopathology. A second cohort was exposed to air/EC after which brains were collected for unbiased metabolomics analysis. The third cohort of animals was exposed to air/EC and received transient middle cerebral artery occlusion/sham surgery, and brain tissue was collected 24 hours later for biochemical analysis., Results: In females, EC significantly increased ( P <0.05) infarct volumes by 94% as compared with air-exposed rats, 165±50 mm 3 in EC-exposed rats, and 85±29 mm 3 in air-exposed rats, respectively, while in males such a difference was not apparent. Morris water maze data showed significant deficits in spatial learning and working memory in the EC sham or transient middle cerebral artery occlusion groups compared with the respective air groups in rats of both sexes ( P <0.05). Thirty-two metabolites of carbohydrate, glycolysis, tricarboxylic acid cycle, and lipid metabolism were significantly altered ( P ≤0.05) due to EC, 23 of which were specific for females. Steady-state protein levels of hexokinase significantly decreased ( P <0.05) in EC-exposed females; however, these changes were not seen in males., Conclusions: Even brief EC exposure over 2 weeks impacts brain energy metabolism, exacerbates infarction, and worsens poststroke cognitive deficits in working memory more in female than male rats., Competing Interests: Disclosures Dr Raval reports employment by the American Heart Association. The other authors report no conflicts.

Tire wear particles (TWP) are a major source of microplastics in the aquatic environment and the ecological impacts of their leachates are of major environmental concern. Among marine biota, copepods are the most abundant animals in the ocean and a main link between primary producers and higher trophic levels in the marine food webs. In this study, we determined the acute lethal and sublethal effects of tire particle leachates on different life stages of the cosmopolitan planktonic copepod Acartia tonsa. Median lethal concentration (LC 50 , 48 h) ranged from 0.4 to 0.6 g L -1 depending on the life stages, being nauplii and copepodites more sensitive to tire particle leachates than adults. The median effective concentration (EC 50 , 48 h) for hatching was higher than 1 g L -1 , indicating a relatively low sensitivity of hatching to tire particle leachates. However, metamorphosis (from nauplius VI to copepodite I) was notably reduced by tire particle leachates with an EC 50 (48 h) of 0.23 g L -1 and the absence of metamorphosis at 1 g L -1 , suggesting a strong developmental delay or endocrine disruption. Leachates also caused a significant decrease (10-22%) in the body length of nauplii and copepodites after exposure to TWP leachates (0.25 and 0.5 g L -1 ). We tested a battery of enzymatic biomarkers in A. tonsa adult stages, but a sublethal concentration of 50 mg L -1 of tire particle leachates did not cause a statistically significant effect on the measured enzymatic activities. Our results show that tire particle leachates can negatively impact the development, metamorphosis, and survival of planktonic copepods. More field data on concentrations of TWPs and the fate and persistence of their leached additives is needed for a better assessment of the risk of tire particle pollution on marine food webs., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lifelong hippocampal neurogenesis is maintained by a pool of multipotent adult neural stem cells (aNSCs) residing in the subgranular zone of the dentate gyrus (DG). The mechanisms guiding transition of NSCs from the developmental to the adult state remain unclear. We show here, by using nestin-based reporter mice deficient for cyclin D2, that the aNSC pool is established through cyclin D2-dependent proliferation during the first two weeks of life. The absence of cyclin D2 does not affect normal development of the dentate gyrus until birth but prevents postnatal formation of radial glia-like aNSCs. Furthermore, retroviral fate mapping reveals that aNSCs are born on-site from precursors located in the dentate gyrus shortly after birth. Taken together, our data identify the critical time window and the spatial location of the precursor divisions that generate the persistent population of aNSCs and demonstrate the central role of cyclin D2 in this process., (© 2023. The Author(s).)

In industrial applications based on texture classification, efficient and fast classifiers are extremely useful for quality control of industrial processes. The classifier of texture images has to satisfy two requirements: It must be efficient and fast. In this work, a texture unit is coded in parallel, and using observation windows larger than 3×3, a new texture spectrum called Texture Spectrum based on the Parallel Encoded Texture Unit (TS&#95;PETU) is proposed, calculated, and used as a characteristic vector in a multi-class classifier, and then two image databases are classified. The first database contains images from the company Interceramic ®® and the images were acquired under controlled conditions, and the second database contains tree stems and the images were acquired in natural environments. Based on our experimental results, the TS&#95;PETU satisfied both requirements (efficiency and speed), was developed for binary images, and had high efficiency, and its compute time could be reduced by applying parallel coding concepts. The classification efficiency increased by using larger observational windows, and this one was selected based on the window size. Since the TS&#95;PETU had high efficiency for Interceramic ®® tile classification, we consider that the proposed technique has significant industrial applications.

Cancer prevention is one of the most pressing challenges that public health needs to face. In this regard, data-driven research is central to assist medical solutions targeting cancer. To fully harness the power of data-driven research, it is imperative to have well-organized machine-readable facts into a knowledge base (KB). Motivated by this urgent need, we introduce the Collaborative Oriented Relation Extraction (CORE) system for building KBs with limited manual annotations. CORE is based on the combination of distant supervision and active learning paradigms and offers a seamless, transparent, modular architecture equipped for large-scale processing. We focus on precision medicine and build the largest KB on 'fine-grained' gene expression-cancer associations-a key to complement and validate experimental data for cancer research. We show the robustness of CORE and discuss the usefulness of the provided KB. Database URL https://zenodo.org/record/7577127., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: To compare the efficacy of TNF inhibitors (adalimumab (ADA) and infliximab (IFX)) vs tocilizumab (TCZ) in patients with refractory cystoid macular edema (CME) due to Behçet's disease (BD)., Methods: Multicenter study of patients with BD-associated CME refractory to conventional and/or biological immunosuppressive drugs. From a cohort of 177 patients treated with anti-TNF and 14 patients treated with TCZ, we selected those with CME at baseline. We analyzed the evolution of macular thickness (main outcome), best-corrected visual acuity (BCVA) and intraocular inflammation (Tyndall and vitritis) from baseline up to 4 years in the 3 groups mentioned., Results: 49 patients and 72 eyes with CME were included. ADA was used in 25 patients (40 eyes), IFX in 15 (21 eyes) and TCZ in 9 (11 eyes). No statistically significant baseline differences were observed between the 3 groups except for a lower basal BCVA in TCZ group and a higher basal degree of intraocular inflammation in ADA group. Most patients from all groups had received several conventional immunosuppressive drugs. In addition, most patients in the group of TCZ had also received anti-TNF agents. Biological therapy was used in monotherapy (n=8) or combined with conventional immunosuppressive drugs (n=41). Macular thickness progressively decreased in the 3 groups, with no signs of CME after 1 year of treatment. Similarly, BCVA improvement and inflammatory intraocular remission was achieved in all groups., Conclusion: Refractory CME associated with BD uveitis can be effectively treated either with ADA, IFX or TCZ. Furthermore, TCZ is effective in patients resistant to anti-TNF therapy., Competing Interests: Declaration of Competing Interest Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: B. Atienza-Mateo received grants/research supports from Abbvie and Roche and had consultation fees/participation in company-sponsored speaker´s bureau from Pfizer, Celgene, Novartis, Sanofi, Janssen, UCB and Lilly. I. Ferraz-Amaro has received grants/research supports from Abbott, MSD, Jansen and Roche and had consultation fees/participation in company-sponsored speaker´s bureau from Abbott, Pfizer, Roche, Sanofi, Sobi, Amgen, Celgene and MSD. D. Prieto-Peña is supported by a research contract from the Carlos III Health Institute of Spain (Río Hortega program, ref. CM20/00006) and has received research support from UCB Pharma, Roche, Sanofi, Pfizer, Jansen, Amgen, AbbVie, Novartis and Lilly. A. Adán received grants/research supports from Abbvie and UCB. M. Cordero-Coma had consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Merck Sharp & Dohme, Allergan and UCB. He also participated in Advisory Boards from Abbvie and Allergan. He also had travel grants from Abbvie, UCB and Allergan. J.M. Nolla received grants/research supports from BMS, Galápagos, Kern, Lilly and UCB. V. Calvo-Río had consultation fees/participation in company-sponsored speaker's bureau from AbbVie, Lilly, MSD, UCB Pharma, Grünenthal Pharma and Celgene. S. Castañeda has received grants/research support from Amgen, MSD and Pfizer, and has received consultation fees in company sponsored speaker's bureau from Amgen, Bristol-Myers-Squibb, Grünenthal Pharma, Janssen, Lilly, MSD, Novartis, Sanofi, Sobi, Stata and UCB. S. Castañeda is also associated professor of the UAM-Roche chair, EPID-Future, Department of Medicine, Universidad Autónoma de Madrid, Madrid, Spain. Miguel A. González-Gay received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker´s bureau from Pfizer, Celgene, Novartis, Roche, Sanofi, and Lilly. R. Blanco received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company-sponsored speaker´s bureau from Abbvie, Pfizer, Roche, BMS, Janssen, Lilly and MSD. No financial disclosure declared: N. Barroso-García, E. Beltrán, M. Hernández-Garfella, L. Martínez-Costa, M. Díaz-Llopis, J.M. Herreras, O. Maíz-Alonso, I. Torre-Salaberri, A. De Vicente-Delmás, D. Díaz-Valle, A. Atanes-Sandoval, F. Francisco, S. Insua, J. Sánchez, R. Almodóvar-González, A. Jiménez-Sosa, O. Ruiz-Moreno, M. Gandía Martínez., (Copyright © 2022. Published by Elsevier Inc.)

With the objective to develop a potential 99m Tc radiopharmaceutical for imaging the androgen receptor (AR) in prostate cancer, four ligands bearing the same pharmacophore derived from the AR antagonist flutamide were prepared, labeled with 99m Tc, and their structures corroborated via comparison with the corresponding stable rhenium analogs. All complexes were obtained with high radiochemical purity. Three of the complexes were highly stable, and, due to their favorable physicochemical properties, were further evaluated using AR-positive and AR-negative cells in culture. All complexes exhibited considerable uptake in AR-positive cells, which could be blocked by an excess of flutamide. The efflux from the cells was moderate. They also showed significantly lower uptakes in AR-negative cells, indicating interactions with the AR receptor. However, the binding affinities were considerably reduced by the coordination to 99m Tc, and the complex that exhibited the best biological behavior did not show sufficient specificity towards AR-positive cells.

Glucocorticoids (GCs) exert potent antiproliferative and anti-inflammatory properties, explaining their therapeutic efficacy for skin diseases. GCs act by binding to the GC receptor (GR) and the mineralocorticoid receptor (MR), co-expressed in classical and non-classical targets including keratinocytes. Using knockout mice, we previously demonstrated that GR and MR exert essential nonoverlapping functions in skin homeostasis. These closely related receptors may homo- or heterodimerize to regulate transcription, and theoretically bind identical GC-response elements (GRE). We assessed the contribution of MR to GR genomic binding and the transcriptional response to the synthetic GC dexamethasone (Dex) using control (CO) and MR knockout (MR EKO ) keratinocytes. GR chromatin immunoprecipitation (ChIP)-seq identified peaks common and unique to both genotypes upon Dex treatment (1 h). GREs, AP-1, TEAD, and p53 motifs were enriched in CO and MR EKO peaks. However, GR genomic binding was 35% reduced in MR EKO , with significantly decreased GRE enrichment, and reduced nuclear GR. Surface plasmon resonance determined steady state affinity constants, suggesting preferred dimer formation as MR-MR > GR-MR ~ GR-GR; however, kinetic studies demonstrated that GR-containing dimers had the longest lifetimes. Despite GR-binding differences, RNA-seq identified largely similar subsets of differentially expressed genes in both genotypes upon Dex treatment (3 h). However, time-course experiments showed gene-dependent differences in the magnitude of expression, which correlated with earlier and more pronounced GR binding to GRE sites unique to CO including near Nr3c1. Our data show that endogenous MR has an impact on the kinetics and differential genomic binding of GR, affecting the time-course, specificity, and magnitude of GC transcriptional responses in keratinocytes., (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

A point-of-care (POC) device is reported for highly sensitive and selective detection of Plasmodium falciparum lactate dehydrogenase (Pf-LDH), a biomarker of malaria infection, based on a single-step magneto-immunoassay, a single-use microfluidic paper device and a customized hand-held fluorescence reader. The single-step magneto-immunoassay consists in a single 5-min incubation of immuno-modified magnetic particles (c-MAb-MPs), biotinylated detection antibody (bd-MAb), and an enzymatic signal amplifier (Poly-HRP). After on-chip MP concentration and washing, signal generation is achieved by adding a fluorescent enzymatic substrate (QuantaRed). Fluorescence signal is measured using a low-cost customized, portable, and sensible fluorescent detector. The POC affords quantitative Pf-LDH detection in <20 min, with a detection limit of 0.92 ng mL -1 (equivalent to 4.6 parasites μL -1 ). Furthermore, Pf-LDH quantitation in clinical samples correlates with that provided by the reference ELISA, is more sensitive than a commercial rapid diagnostic test (RDT) and entails little user intervention. These results show that fluorescent paper-based microfluidic devices can be exploited to simplify magneto-immunoassay handling, taking this type of test closer to the requirements of POC testing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

18 F-FDG PET/CT quantification of whole-body tumor burden in lymphoma is not routinely performed because of the lack of fast methods. Although the semiautomatic method is fast, it is not fast enough to quantify tumor burden in daily clinical practice. Our purpose was to evaluate the performance of convolutional neural network (CNN) software in localizing neoplastic lesions in whole-body 18 F-FDG PET/CT images of pediatric lymphoma patients. Methods: The retrospective image dataset, derived from the data pool of the International Atomic Energy Agency (coordinated research project E12017), included 102 baseline staging 18 F-FDG PET/CT studies of pediatric lymphoma patients (mean age, 11 y). The images were quantified to determine the whole-body tumor burden (whole-body metabolic tumor volume [wbMTV] and whole-body total lesion glycolysis [wbTLG]) using semiautomatic software and CNN-based software. Both were displayed as semiautomatic wbMTV and wbTLG and as CNN wbMTV and wbTLG. The intraclass correlation coefficient (ICC) was applied to evaluate concordance between the CNN-based software and the semiautomatic software. Results: Twenty-six patients were excluded from the analysis because the software was unable to perform calculations for them. In the remaining 76 patients, CNN and semiautomatic wbMTV tumor burden metrics correlated strongly (ICC, 0.993; 95% CI, 0.989 - 0.996; P < 0.0001), as did CNN and semiautomatic wbTLG (ICC, 0.999; 95% CI, 0.998-0.999; P < 0.0001). However, the time spent calculating these metrics was significantly (<0.0001) less by CNN (mean, 19 s; range, 11-50 s) than by the semiautomatic method (mean, 21.6 min; range, 3.2-62.1 min), especially in patients with advanced disease. Conclusion: Determining whole-body tumor burden in pediatric lymphoma patients using CNN is fast and feasible in clinical practice., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4-10 ng/mL. All patients underwent PET/CT scanning with 68 Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment ( P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

From the outset of the COVID-19 pandemic we, the nuclear medicine (NM) community, expediently mobilized to enable continuity of essential services to the best of our abilities. For example, we effectuated adapted guidelines for NM standard operating procedures (SOPs) and enacted heightened infection protection measures for staff, patients, and the public, alike. Challenges in radionuclide supply chains were identified and often met. NM procedural volumes declined globally and underwent restoration of varying degrees, contingent upon local contexts. Serial surveys have gauged and chronicled such geographical variance of the impact of COVID-19 on NM service delivery and, though it may be too early to fully understand the long-term consequences of reduced NM services, overall, we can certainly expect that this era adversely affected the management of many patients afflicted with non-communicable diseases. Today we are unquestionably better prepared to face unforeseen outbreaks, but a degree of uncertainty lingers. Which lessons learned will endure in the form of permanent NM pandemic preparedness procedures and protocols? In this spirit, the present manuscript presents a revision of prior recommendations issued mid-pandemic to NM centers, some of which may become mainstays in NM service delivery and implementation. Discussed herein are (1) comparative worldwide survey results of the measurable impact of COVID-19 on the practice of nuclear medicine (2) the definitions of a pandemic and its phases (3) relevant, recently developed or updated guidelines specific to nuclear medicine (4) incidental findings of COVID-19 on hybrid nuclear medicine studies performed primarily for oncologic indications and (5) how pertinent pedagogical methods for medical education, research, and development have been re-invented in a suddenly more virtual world. NM professionals shall indefinitely adopt many of the measures implemented during this pandemic, to enable continuity of essential services while preventing the spread of the virus. Which ones? Practices must remain ready for possible new peaks or variants of the roiling COVID-19 contagion and for the emergence of potential new pathogens that may incite future outbreaks or pandemics. Communications technologies are here to stay and will continue to be used in a broad spectrum of applications, from telemedicine to education, but how best? NM departments must align synergistically with these trends, considering what adaptations to a more virtual professional environment should not only last but be further innovated. The paper aims to provide recent history, analysis, and a springboard for continued constructive dialogue. To best navigate the future, NM must continue to learn from this crisis and must continue to bring new questions, evidence, ideas, and warranted systematic updates to the figurative table., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: The objective of this study was to evaluate the clinical impact PET with 18 F-FDG and 11 C-PIB in patients with dementia in a developing country. Methodology: Retrospective study of the patients referred for the evaluation of dementia to the only PET center in Uruguay. A total of 248 patients were identified, from which 70 patients were included based on the availability of medical history and clinical follow-up. Main outcomes included change in diagnosis, diagnostic dilemma and AD treatment. We evaluated the association of clinical outcomes with PET concordance with baseline diagnosis, diagnostic dilemma, level of education, AD pathology/Non-AD pathology (AD/Non-AD), baseline diagnosis and 11 C-PIB PET result. Results: Baseline clinical diagnosis was concordant with 18 F-FDG and 11 C-PIB PET results in 64.7 and 77.1% of the patients, respectively. Change in diagnosis after PET was identified in 30.0% of the patients and was associated with discordant 18 F-FDG ( p = 0.002) and 11 C-PIB ( p < 0.001) PET results, previous diagnostic dilemma ( p = 0.005), low education ( p = 0.027), Non-AD baseline diagnosis ( p = 0.027), and negative 11 C-PIB PET result ( p < 0.001). Only the last variable remained significant in the multivariate analysis (adjusted p = 0.038). Diagnostic dilemma decreased after PET from 15.7 to 7.1% ( p = 0.11) and was associated with Non-AD diagnosis ( p = 0.002) and negative 11 C-PIB PET result ( p = 0.003). Change in AD treatment after PET occurred in 45.7% of the patients. Conclusion: 18 F-FDG and 11 C-PIB PET had a significant clinical impact in terms of change in diagnosis and treatment in patients with dementia in a developing country, similar to that reported in high-income countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Damian, Portugal, Niell, Quagliata, Bayardo, Alonso and Ferrando.)

Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies., Competing Interests: The authors declare no conflicts of interest.

Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interpreted as evidence for high rates of adult neurogenesis, even at older ages. However, most of these DCX-labeled cells have mature morphology. Furthermore, studies in the adult human DG have not found a germinal region containing dividing progenitor cells. In this Dual Perspectives article, we show that dual antigen retrieval is not required for the detection of DCX in multiple human brain regions of infants or adults. We review prior studies and present new data showing that DCX is not uniquely expressed by newly born neurons: DCX is present in adult amygdala, entorhinal and parahippocampal cortex neurons despite being absent in the neighboring DG. Analysis of available RNA-sequencing datasets supports the view that DG neurogenesis is rare or absent in the adult human brain. To resolve the conflicting interpretations in humans, it is necessary to identify and visualize dividing neuronal precursors or develop new methods to evaluate the age of a neuron at the single-cell level., (Copyright © 2021 the authors.)

Some studies have assessed the expression of dopaminergic dopamine 2 (D2)/3 receptors in prolactinomas and nonfunctioning pituitary adenomas (NFPA) by positron emission tomography/computed tomography (PET/CT) with 11 C-raclopride, proving that this modality can be useful to predict the response to treatment with dopamine agonists. However, the use of 11 C-labeled radiotracers is limited, as it requires a cyclotron in the PET center. 18 F-fallypride is a radiotracer that has proven useful in assessing the expression of D2/3 receptors. As it is labeled with 18 F, it can be produced and transported to distant PET centers. There are no studies on the usefulness of 18 F-fallypride for the evaluation of patients with prolactinomas and NFPA. The aim of this study was to describe the first case series of patients with prolactinomas and NFPA studied with 18 F-fallypride and 11 C-methionine PET/CT to reveal D2/3 expression and amino acid (AA) metabolism. 18 F-fallypride and 11 C-methionine uptake were assessed in a case series of six patients, five with prolactinomas and one with a NFPA, and compared with clinical presentation and follow-up at 6-18 months. All patients presented with macroadenomas, with a wide range of AA metabolism, as revealed by 11 C-methionine PET/CT. 18 F-fallypride PET/CT identified low to moderate/high D2/3 expression in the tumors. The patient that presented low expression of D2/3 in the tumor and high AA metabolism showed a poor response to DA therapy. 18 F-fallypride was able to reveal D2/3 receptor expression in prolactinomas and NFPA, with the advantage of been a more accessible radiotracer in comparison with previous 11 C labeled analogs., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 World Journal of Nuclear Medicine.)

Objective: Identification of imaging prognostic parameters for early therapy personalisation to reduce treatment-related morbidity in paediatric Hodgkin lymphoma (HL). Our aim was to evaluate quantitative markers from baseline 2-[18F]fluoro-2-deoxy-d-glucose PET/CT as prognostic factors for treatment outcomes. Another goal was assessing the prognostic value of Deauville score at interim PET/CT., Methods: Twenty-one patients were prospectively enrolled. Median age was 12 years (range 6-17); 13 were female. Patients underwent PET/CT for disease staging (bPET), at the end of two cycles of chemotherapy (iPET) and after chemotherapy. A total of 173 lesions were segmented from bPET. We calculated 51 texture features for each lesion. Total metabolic tumour volume and total lesion glycolysis from bPET were calculated for response prediction at iPET. Univariate and multivariate analyses were used for optimal cut-off values to separate responders at iPET according to the Deauville score., Results: We identified four texture features as possible independent predictors of treatment outcomes at iPET. The areas under the ROC for univariate analysis were 0.89 (95% CI, 0.75-1), 0.82 (95% CI, 0.64-1), 0.79 (95% CI, 0.59-0.99) and 0.89 (95% CI, 0.75-1). The survival curves for patients assigned Deauville scores 1, 2, 3 and X were different from those assigned a score 4, with 4-year progression free-survival (PFS) rates of 85 versus 29%, respectively (P = 0.05)., Conclusions: We found four textural features as candidates for predicting early response to chemotherapy in paediatric patients with HL. The Deauville score at iPET was useful for differentiating PFS rates., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry., Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m 2 ) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA., Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01- 0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015-0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (-0.03-0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA., Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients.

Objectives: Clinicians often face the challenge of providing effective and safe therapy for pregnant women with uveitis. Certolizumab pegol (CZP) differs from other anti-TNFα agents due to its limited placental transfer. In this study we assessed the efficacy of CZP in pregnant women with uveitis. We also provided information on outcomes of pregnant women and neonates exposed to CZP., Methods: We carried out a multicentre study of women with uveitis who received CZP during pregnancy and their neonates. The main visual outcomes were visual acuity (VA), intraocular inflammation and corticosteroid-sparing effect. Pregnancy outcomes, maternal and neonatal infections and congenital malformations were also assessed., Results: We studied 14 women (23 affected eyes); mean age of 34.3±5.5 years. The underlying diseases were spondyloarthritis (n=7), idiopathic (n=2), and Vogt-Koyanagi-Harada, rheumatoid arthritis, juvenile idiopathic arthritis, punctate inner choroidopathy and Behçet's disease (1 each). The patterns of ocular involvement were anterior (n=10), posterior (n=2), intermediate (n=1), panuveitis (n=1). Cystoid macular oedema was present in one patient (1 eye). Uveitis was bilateral in nine cases and chronic in seven patients. CZP was started before getting pregnant in ten patients and after conceiving in four. All patients achieved or maintained ocular remission throughout pregnancy. Fifteen healthy infants were born. Only one woman presented a mild infection during pregnancy. Neither infections nor malformations were observed in neonates after a follow-up of 6 months. Six infants were breastfed and all of them received scheduled vaccinations without complications., Conclusions: Certolizumab pegol is effective and safe in women with uveitis during pregnancy.

Objective: The aim is to analyze the usefulness of pre-operative COVID-19 screening to detect asymptomatic patients, the capability of our patient selection algorithm to detect patients with more advanced tumors and the results of colorectal cancer surgery managed with a multimodal approach. We propose the use of a preoperative patient selection algorithm to prioritize the surgical treatment of patients with worse oncological prognosis and lower perioperative risk in situations of health system saturation., Material and Methods: Prospective descriptive study including 71 patients operated on for colorectal cancer during COVID-19's high incidence period. A division was made into two periods of time that were later compared with the aim of assessing whether the scale used identified those patients with lower surgical risk and higher oncological priority for their priority scheduling., Results: Post-operative severe acute respiratory syndrome coronavirus 2 infection occurred in one patient (1.4%). Pre-operative polymerase chain reaction detected one asymptomatic patient (3%). Tumor stage was ≥ IIIA in 39% and node positive in 39% of patients in the first period, while 26% and 21% in the second period, respectively (p = 0.320; p = 0.179), without increasing the surgical stay or complications. Median hospital stay was 5 days. Grades III and IV morbidity were 4.4% and 1.4%., Conclusion: The use of an algorithm and Patient Selection Scale can detect patients with more advanced tumors to be operated before. Multimodal management/ERAS have a role in achieving short stay and low morbidity.

Objective: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD)., Methods: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect., Results: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2)., Conclusion: ABA may be an effective and safe treatment for patients with RA-ILD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To evaluate the response to hepatitis B virus (HBV) vaccine in patients on biological therapy. Adults with autoimmune inflammatory diseases on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included. Hepatitis B surface antibody (anti-HBs) was measured by ELISA before and after vaccination. Seroconversion was considered when an anti-HBs titer > 10 mIU/mL was achieved. The effect of treatment on the immunoprotective state was studied. The response was compared with that obtained in patients on synthetic disease modifying anti-rheumatic drugs (DMARDs) and healthy controls. A total of 187 patients on biologicals, 48 on synthetic DMARDs, and 49 on healthy controls were analyzed. More than 80% of patients on biologics responded to the vaccine but required more boosters and second vaccine series. Patients who achieved seroconversion were younger than those who did not (47.10 ± 12.99 vs. 53.18 ± 10.54 years, p = 0.012). Being on etanercept or golimumab was associated with seroconversion, while being on rituximab was not. Seroconversion was achieved in 93.75% of patients on synthetic DMARDs and 97.96% of healthy controls. The seroconversion rate in the biologics group was lower than in the synthetic DMARD group (p = 0.043) and tended to be lower than in the healthy group (p = 0.056). In patients on biological therapy, a high rate of HBV vaccine response can be achieved when a complete vaccination schedule is administered. Vaccination while not on biological agents reduces the requirement for boosters and revaccination. Key points: • Patients on biological therapy can achieve high rates of immune response to HBV vaccine when complete vaccination schedules are administered. • However, to achieve such a high seroconversion rate, more boosters and second vaccination series are required. • This supports the proposal already made to provide HBV vaccination to all patients with an autoimmune inflammatory disease after the diagnosis is made and not when the use of a biological treatment is under consideration.

Background/Objective : Impaired Inhibitory Control (IC) is a core feature of psychotic disorders and is related with impaired social functioning in people experiencing psychosis. Despite research showing the benefits of mindfulness over IC in the general population, no study has assessed its effects on IC in psychoses. The aim of our study was to assess the effectiveness of a mindfulness-based intervention combined with integrated rehabilitation treatment in a sample of people diagnosed of psychotic disorders. Method : Fifty-six patients diagnosed with psychotic disorder were recruited and randomly allocated either to integrated rehabilitation treatment or integrated rehabilitation treatment enhanced with 26 mindfulness group sessions. Measures comprised PANSS interview, MAAS scale, and Stroop Color Word Test (SCWT). The primary outcome variable was the performance in the non-congruent trials of the SCWT. Results : There were no differences between groups at baseline. At post-treatment patients allocated to mindfulness group increased their scores in non-congruent trials of SCWT and in MAAS. At post-treatment mindfulness group scored higher than integrated rehabilitation treatment in MAAS. Conclusions : Data suggest that mindfulness added to integrated rehabilitation treatment may improve IC in psychosis. Results are convergent with prior works about the effect of mindfulness over cognitive performance in general population., (© 2020 Asociación Española de Psicología Conductual. Published by Elsevier España, S.L.U.)

Graves' orbitopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD). Our aim was to assess the efficacy and safety of Tocilizumab (TCZ) in GO refractory to conventional therapy. This was an open-label multicenter study of glucocorticoid-resistant GO treated with TCZ. The main outcomes were the best-corrected visual acuity (BVCA), Clinical Activity Score (CAS) and intraocular pressure (IOP). These outcome variables were assessed at baseline, 1st, 3rd, 6th and 12th month after TCZ therapy onset. The severity of GO was assessed according to the European Group on Graves' Orbitopathy (EUGOGO). We studied 48 (38 women and 10 men) patients (95 eyes); mean age ± standard deviation 51 ± 11.8 years. Before TCZ and besides oral glucocorticoids, they had received IV methylprednisolone ( n = 43), or selenium ( n = 11). GO disease was moderate ( n =29) or severe ( n = 19) and dysthyroid optic neuropathy (DON) ( n = 7). TCZ was used in monotherapy ( n = 45) or combined ( n = 3) at a dose of 8 mg/kg IV every four weeks ( n = 43) or 162 mg/s.c. every week ( n = 5). TCZ yielded a significant improvement in all of the main outcomes at the 1st month that was maintained at one year. Comparing the baseline with data at 1 year all of the variables improved; BCVA (0.78 ± 0.25 vs. 0.9 ± 0.16; p = 0.0001), CAS (4.64 ± 1.5 vs. 1.05 ± 1.27; p = 0.0001) and intraocular pressure (IOP) (19.05 ± 4.1 vs. 16.73 ± 3.4 mmHg; p = 0.007). After a mean follow-up of 16.1 ± 2.1 months, low disease activity (CAS ≤ 3), was achieved in 88 eyes (92.6%) and TCZ was withdrawn in 29 cases due to low disease activity ( n = 25) or inefficacy ( n = 4). No serious adverse events were observed. In conclusion, TCZ is a useful and safe therapeutic option in refractory GO treatment.

The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healthcare workers and 42 healthcare workers exposed to LDIR. Hospital staff exposed to LDIR presented a redox imbalance in blood that seems to correlate with dose. Workers from the Nuclear Medicine Unit were the most affected group with the lowest value of plasma antioxidant response and the highest value of plasma thiobarbituric acid reactive substances, TBARS (indicator of lipid peroxidation) of all four groups. Cumulative personal dose equivalent positively correlated with nitrites and negatively correlated with total antioxidant capacity in blood. The diet of healthcare workers from Nuclear Medicine Unit had higher ORAC values than the diet of non-exposed. Therefore, occupational exposure to LDIR, especially for the Nuclear Medicine Unit, seems to produce an imbalanced redox status in blood that would correlate with cumulative personal dose equivalent.

A population of neural stem cells (NSCs) dwelling in the dentate gyrus (DG) is able to generate neurons throughout adult life in the hippocampus of most mammals. These NSCs generate also astrocytes naturally and are capable of generating oligodendrocytes after gene manipulation. It has been more recently shown that adult hippocampal NSCs after epileptic seizures as well as subventricular zone NSCs after stroke can give rise to reactive astrocytes (RAs). In the hippocampus, the induction of seizures triggers the conversion of NSCs into reactive NSCs (React-NSCs) characterized by a drastic morphological transformation, abnormal migration, and massive activation or entry into the cell cycle to generate more React-NSCs that ultimately differentiate into RAs. In the search for tools to investigate the properties of React-NSCs, we have explored the LPA 1 -green fluorescent protein (GFP) transgenic line of mice in which hippocampal NSCs are specifically labeled due to the expression of lysophosphatidic acid receptor 1 (LPA 1 ). We first addressed the validity of the transgene expression as true marker of LPA 1 expression and then demonstrated how, after seizures, LPA 1 -GFP labeled exclusively React-NSCs for several weeks. Then React-NSCs lost LPA 1 -GFP expression as neurons of the granule cell layer started to express it. Finally, we used knockout for LPA 1 transgenic mice to show that LPA 1 plays a functional role in the activation of React-NSCs. Thus, we confirmed that LPA 1 -GFP expression is a valid tool to study both NSCs and React-NSCs and that the LPA 1 pathway could be a target in the intent to preserve NSCs after seizures., (Copyright © 2020 Valcárcel-Martín, Martín-Suárez, Muro-García, Pastor-Alonso, Rodríguez de Fonseca, Estivil-Torrús and Encinas.)

We aimed to assess the efficacy of biologic therapy in refractory non-Multiple Sclerosis (MS) Optic Neuritis (ON), a condition more infrequent, chronic and severe than MS ON. This was an open-label multicenter study of patients with non-MS ON refractory to systemic corticosteroids and at least one conventional immunosuppressive drug. The main outcomes were Best Corrected Visual Acuity (BCVA) and both Macular Thickness (MT) and Retinal Nerve Fiber Layer (RNFL) using Optical Coherence Tomography (OCT). These outcome variables were assessed at baseline, 1 week, and 1, 3, 6 and 12 months after biologic therapy initiation. Remission was defined as the absence of ON symptoms and signs that lasted longer than 24 h, with or without an associated new lesion on magnetic resonance imaging with gadolinium contrast agents for at least 3 months. We studied 19 patients (11 women/8 men; mean age, 34.8 ± 13.9 years). The underlying diseases were Bechet's disease ( n = 5), neuromyelitis optica ( n = 3), systemic lupus erythematosus ( n = 2), sarcoidosis ( n = 1), relapsing polychondritis ( n = 1) and anti-neutrophil cytoplasmic antibody -associated vasculitis ( n = 1). It was idiopathic in 6 patients. The first biologic agent used in each patient was: adalimumab ( n = 6), rituximab ( n = 6), infliximab ( n = 5) and tocilizumab ( n = 2). A second immunosuppressive drug was simultaneously used in 11 patients: methotrexate ( n = 11), azathioprine ( n = 2), mycophenolate mofetil ( n = 1) and hydroxychloroquine ( n = 1). Improvement of the main outcomes was observed after 1 year of therapy when compared with baseline data: mean ± SD BCVA (0.8 ± 0.3 LogMAR vs. 0.6 ± 0.3 LogMAR; p = 0.03), mean ± SD RNFL (190.5 ± 175.4 μm vs. 183.4 ± 139.5 μm; p = 0.02), mean ± SD MT (270.7 ± 23.2 μm vs. 369.6 ± 137.4 μm; p = 0.03). Besides, the median (IQR) prednisone-dose was also reduced from 40 (10-61.5) mg/day at baseline to. 2.5 (0-5) mg/day after one year of follow-up; p = 0.001. After a mean ± SD follow-up of 35 months, 15 patients (78.9%) achieved ocular remission, and 2 (10.5%) experienced severe adverse events. Biologic therapy is effective in patients with refractory non-MS ON.

A miniature internet of things (IoT)-based point-of-care testing (PoCT) fluorescence reader, able to perform both intensity and time-resolved measurements of different fluorescent tags, is presented. This low cost platform has been conceived for performing tests in low-resource and remote settings, displaying versatile performance and yet simple operation. It consists on an external case of 43 × 30 × 42 mm 3 (built in a 3D-printer) where all the elements are fixed, including some basic optics (3 lenses and 2 filters), a laser diode and a custom designed Single-Photon Avalanche Diodes (SPADs) camera. Both, the laser and the camera are controlled by a Field Programmable Gate Array (FPGA) with IoT capabilities. The PoCT was validated by detecting Plasmodium antigen in a fluorescent enzyme-linked immunosorbent assay (ELISA) using a fluorescence substrate. The results were compared to those provided in parallel by two commercial fluorescent plate readers. As it will be shown, the PoCT fluorescent readout was more sensitive than its colorimetric counterpart. Furthermore, the PoCT displayed similar signal trends and levels of detection than the bulkier and more expensive commercial fluorescence plate readers. These results demonstrate that the PoCT platform developed could bring the performance of central laboratory assay techniques closer to the end-user level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD)., Methods: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups., Results: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042)., Conclusion: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up., (© 2019, American College of Rheumatology.)

Objectives: Describe patients with noninfectious aortitis and their response to treatment in a regional hospital., Methods: Review of patients with noninfectious aortitis, diagnostic technique used and immunosuppressive therapy received., Results: We report 8 patients (7 women and one man) diagnosed with aortitis by positron emission tomography (PET). The mean age was 69years (interquartile range [IQR] 62-72.2). Three months of treatment with tocilizumab improved symptoms, erythrocyte sedimentation rate and C-reactive protein level (P<.001 and P<.012, respectively) in the 6 patients in whom it was used., Conclusions: Tocilizumab was an effective and safe treatment in those patients diagnosed with aortitis refractory to steroids and conventional immunosuppressive therapy., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Guidelines recommend true whole-body 18 F-FDG PET/CT scans from vertex to toes in pediatric lymphoma patients, although this suggestion has not been validated in large clinical trials. The objective of the study was to evaluate the incidence and clinical impact of lesions outside the "eyes to thighs" regular field of view (R-FOV) in 18 F-FDG PET/CT staging (sPET) and interim (iPET) scans in pediatric lymphoma patients. Methods: True whole-body sPET and iPET scans were prospectively obtained in pediatric lymphoma patients (11 worldwide centers). Expert panel central review of sPET and iPET scans were evaluated for lymphoma lesions outside the R-FOV and clinical relevance of these findings. Results: A total of 610 scans were obtained in 305 patients. The sPET scans did not show lesions outside the R-FOV in 91.8% of the patients, whereas in 8.2% patients the sPET scans demonstrated lesions also outside the R-FOV (soft tissue, bone, bone marrow, and skin); however, the presence of these lesions did not change the clinical stage of any patient and did not affect treatment decision. Among the 305 iPET scans, there were no new positive 18 F-FDG-avid lesions outside the R-FOV, when compared with their paired sPET scans. A single lesion outside the R-FOV on iPET occurred in 1 patient (0.3%), with the primary lesion diagnosed in the femur on sPET that persisted on iPET. Conclusion: The identification of additional lesions outside the R-FOV (eyes to thighs) using 18 F-FDG PET/CT has no impact in the definition of the clinical stage of disease and minimal impact in the treatment definition of patients with pediatric lymphoma. As so, R-FOV for both sPET and iPET scans could be performed., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

The aim of this study was quantitative comparison between 68 Ga-Gallgas positron emission tomography (PET) and 99m Tc-Technegas single photon emission computed tomography (SPECT) for lung ventilation function assessment in patients with moderate-to-severe obstructive pulmonary disease and to identify image-derived texture features correlating to the physiologic parameters. Five patients with moderate-to-severe chronic obstructive pulmonary disease with PET and SPECT lung ventilation scans were selected for this study. Threshold-based segmentations were used to compare ventilated regions between both imaging techniques. Histograms of both scans were compared to reveal main differences in distributions of radiotracers. Volumes of segmentation as well as 50 textural features measured in the pulmonary region were correlated to the forced expiratory volume in 1 s (FEV1) as the relevant physiological variable. A better peripheral distribution of the radiotracer was observed in PET scans for three out of five patients. A segmentation threshold of 27% and 31% for normalized scans, for PET and SPECT respectively, was found optimal for volume correlation with FEV1. A high correlation (Pearson correlation coefficient >0.9) was found between 16 texture features measured from SPECT and 7 features measured from PET and FEV1. Quantitative measurements revealed different tracer distribution in both techniques. These results suggest that tracer distribution patterns may depend on the cause of the pulmonary obstruction. We found several texture features measured from SPECT to correlate to FEV1., Competing Interests: There are no conflicts of interest.

Time-resolved fluorescence measurement is extraordinarily powerful in the analysis of substances due to its effectiveness in eliminating measurement artifacts. Some fluorescence measurements are still conducted on CMOS chips with the decay times determined after reading the data off the chip and fitting the fluorescence decay histogram. We present a novel approach in which an analog CMOS chip divides the fluorescence decay time into slices and classifies the photons according to their arrival times at a CMOS SPAD sensor. The chip was fabricated in a 1P6M 0.18 μm HV-CMOS process. The slice timings can be tailored from 168 ps to 4.9 ns, covering most fluorescence decay times. 9 timing windows are generated per pixel that count up to 13 b each, with a resolution of 0.16 mV/photon, for a maximum output voltage of 1.3 V, in an area of 150 μm × 50 μm. Here, we report on the first practical application of this circuit, which integrates an array of 5 pixels in a single chip and has an excitation light and a microfluidic chip of up to 3 channels. This system could determine the decay time of quantum dots in 20 nl of solution. Thus, this paper could help in the development of a point-of-care device based on time-resolved fluorescence.

Dental pulp stem cells (DPSCs) have the capacity to give rise to cells with neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult genetically unmodified human DPSCs cultured in Neurocult TM (Stem Cell Technologies), a cell culture medium without serum which can be alternatively supplemented for the expansion and/or differentiation of adult neural stem cells (NSCs). Our results show that non-genetically modified human adult DPSCs cultured with Neurocult NS-A proliferation supplement generated neurosphere-like dentospheres expressing the NSC markers Nestin and glial fibrillary acidic protein (GFAP), but also the vascular endothelial cell marker CD31. Remarkably, 1 month after intracranial graft into athymic nude mice, human CD31+/CD146+ and Nestin+ DPSC-derived cells were found tightly associated with both the endothelial and pericyte layers of brain vasculature, forming full blood vessels of human origin which showed an increased laminin staining. These results are the first demonstration that DPSC-derived cells contributed to the generation of neovasculature within brain tissue, and that Neurocult and other related serum-free cell culture media may constitute a fast and efficient way to obtain endothelial cells from human DPSCs.

In this work, two oligophenyleneimines type pentamers with terminal aldehydes, designated as DAFCHO (4,4'-((((((2,5-bis(octyloxy)-1,4-phenylene)bis(methanylylidene))bis(azanyl ylidene))bis(9H-fluorene-7,2-diyl))bis(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy) benzaldehyde)) and FDACHO (4,4'-((((((2,5-bis(octyloxy)-1,4-phenylene)bis(methanylylidene))bis (azanylylidene))bis(4,1-phenylene))bis(azanylylidene))bis(methanylylidene))bis(2,5-bis(octyloxy) benzaldehyde)) were synthesized by mechanochemistry method using 2,5-bis(octyloxy) terephtal aldehyde and 2,7-diaminofluorene or 1,4-phenylenediamine. All compounds were spectroscopically characterized using ¹H and 13 C-NMR, FT-IR and mass spectrometry MALDITOF. The optical properties of the compounds were analyzed by UV-vis spectroscopy using different solvents. We observed that DAFCHO and FDACHO exhibit interesting photochromic properties when they are dissolved in chloroform and exposed to sunlight for 3, 5 and 10 min. The value of the energy band gap was calculated from the absorption spectra without irradiation E gap(optical) . It was 2.50 eV for DAFCHO in chloroform solution, and it decreased to 2.34 eV when it is in films. For FDACHO, it was 2.41 eV in solution and 2.27 eV in film. HOMO (Highest Occupied Molecular Orbital), LUMO (Lowest Unoccupied Molecular Orbital) and E gap(electrochemical) values were obtained by electrochemical studies. The results indicate that the compounds can be considered as organic semiconductors since their values are 2.35 eV for DAFCHO and 2.06 eV for FDACHO. The structural and electronic properties of the compounds were corroborated with a DFT (Density Functional Theory) study.

We describe the integration of techniques and technologies to develop a Point-of-Care for molecular diagnosis PoC-MD, based on a fluorescence lifetime measurement. Our PoC-MD is a low-cost, simple, fast, and easy-to-use general-purpose platform, aimed at carrying out fast diagnostics test through label detection of a variety of biomarkers. It is based on a 1-D array of 10 ultra-sensitive Single-Photon Avalanche Diode (SPAD) detectors made in a 0.18 μm High-Voltage Complementary Metal Oxide Semiconductor (HV-CMOS) technology. A custom microfluidic polydimethylsiloxane cartridge to insert the sample is straightforwardly positioned on top of the SPAD array without any alignment procedure with the SPAD array. Moreover, the proximity between the sample and the gate-operated SPAD sensor makes unnecessary any lens or optical filters to detect the fluorescence for long lifetime fluorescent dyes, such as quantum dots. Additionally, the use of a low-cost laser diode as pulsed excitation source and a Field-Programmable Gate Array (FPGA) to implement the control and processing electronics, makes the device flexible and easy to adapt to the target label molecule by only changing the laser diode. Using this device, reliable and sensitive real-time proof-of-concept fluorescence lifetime measurement of quantum dot Qdot TM 605 streptavidin conjugate is demonstrated.