Search

Background: Major depressive disorder (MDD) is a disease that has been increasingly affecting more people worldwide. The dopamine D2 receptor (DRD2), encoded by the DRD2 gene, plays critical roles in the brain, one of which is related to reward processes. Aims: The following systematic review aims to analyze the DRD2/ANKK1 TaqIA (rs1800497) polymorphism’s A1 genotype frequency fluctuation in MDD patients and determine its influence on MDD. Methods: Four databases were searched, and the consequent articles were analyzed following the inclusion criteria per the PECOS strategy, resulting in five selected articles. Results: Interestingly, although two articles showed that the A1 allele presence significantly increases the risk of MDD manifestation, most articles did not find a significant association between this DRD2 gene variant and MDD. Conclusions: Most of the included studies were dated, indicating the need for more studies to address the results’ non-conformity with different populations.

The present work aims to explore Spirulina biomass’ functional and technological marvels and its components, such as C-phycocyanin (C-PC), in modern food systems from a circular economy perspective, evaluating a decade of insights and innovations. This comprehensive review delves into the pivotal studies of the past decade, spotlighting the vital importance of maintaining stability in various food matrices to unleash the full biological impacts. Through the lens of food science intertwined with circular economy principles, this analysis meets health and environmental requisites and explores the harmonious synergy between food systems, economy, and industry. While Spirulina has typically served as a supplement, its untapped potential as a fundamental food ingredient has been unveiled, showcasing its abundant nutritional and functional attributes. Technological hurdles in preserving the vibrant color of C-PC have been triumphantly surmounted through simple temperature control methods or cutting-edge nanotechnology applications. Despite the gap in sensory acceptance studies, the emergence of blue foods introduces groundbreaking functional and innovative avenues for the food industry.

Abstract Real‐time and in‐line transversal monitoring of ionizing radiation beams is a crucial task for several applications which span from medical treatments to particle accelerators in high energy physics. Here a flexible and large area device based on 2D hybrid perovskite thin films (phenylethylammonium lead bromide), fabricated onto a thin flexible polyimide substrate, able to map the transversal beam profile of high energy radiation beams is reported. The performance of this novel tool is here compared with the one offered by standard commercial large‐area technology, namely radiochromic sheets. The great potential of this class of devices is demonstrated by successfully mapping in real‐time a 5 MeV proton beam at fluxes between 108 and 1010 H+ s−1 cm−2, confirming the capability to operate in a radiation‐harsh environment without output signal saturation issues. The versatility and scalability of here proposed detecting system are demonstrated by the development of a multipixel array able to map in real‐time a 40 kVp X‐ray beam spot (dose rate 8 mGy s−1). Perovskite thin film‐based detectors are thus assessed as a very promising class of thin, flexible devices for real‐time, in‐line, large‐area, conformable, reusable, transparent, and low‐cost transversal beam monitoring of different ionizing radiation.

Introdução: Os Beta-lactâmicos (BL) são amplamente usados contra bactérias, as quais podem ter resistência por meio da produção de Beta-lactamase. Para isso dispõe-se de Beta-lactâmicos + Inibidor da Beta-lactamase: a Piperacilina-Tazobactam, por exemplo, inibe a enzima que degrada o BL. Dentre as reações adversas a esse antimicrobiano, a mielotoxicidade é pouco comum; há relatos de 1-4% de frequência da população geral. Objetivo: Relatar caso de efeito adverso raro do uso da Piperacilina-Tazobactam e contribuir para comunidade científica. Método: Relato de caso realizado no Hospital Heliópolis-SP, após aplicação do Termo de Comprometimento Livre e Esclarecido. Resultados: Masculino, 40 anos, queixa de edema, hiperemia e dor no membro inferior direito (MID), associado a febre e náuseas. Ao exame físico, área hiperemiada, não delimitada, dolorosa, edemaciada, se estendendo da perna até metade da coxa e prejudicando o movimento. Paciente é internado para tratamento de celulite com Oxacilina, apresentando reação de hipersensibilidade e necessidade de troca para Daptomicina. Após 5 dias, evoluiu com piora da infecção, associando-se Piperacilina-Tazobactam para cobertura de germes gram negativos. Após 15 dias, de tratamento com Piperacilina-Tazobactam, inicia febre, sem piora clínica e com neutropenia intensa (80/mm³), anemia (HB:10,9 mg/dl) e plaquetopenia (132 mil cels/mm³). Optado por suspensão das drogas e manutenção da internação hospitalar para avaliar evolução. Paciente evolui com ascensão das linhagens hematológicas para níveis normais, resolução da febre e melhora de lesão em MID, recebendo alta hospitalar. Conclusão: O uso frequente de antimicrobianos, requer conhecimento sobre farmacocinética, farmacodinâmica e farmacovigilância, tal qual dos beta lactâmicos, deve ser acompanhado da ciência das possíveis reações adversas, sendo que até mesmo as mais raras podem estar presentes no uso cotidiano dessa classe. Ao se deparar com uma evolução incomum de mielotoxicidade durante o tratamento de uma infecção, é necessário avaliar a gravidade da doença no momento e os riscos e benefícios da suspensão dos antimicrobianos em uso. No caso relatado, com a interrupção da Piperacilina-Tazobactam, a celulite não se exacerbou e a mielotoxicidade se resolveu, prevenindo um desfecho de maior gravidade que poderia decorrer da intensa pancitopenia.

X-ray detection for personal dosimetry requires sensitive, stable and non-toxic materials. At the same time, scalability onto large-area and flexible substrates is emerging as a desirable property. To satisfy these requirements, novel materials to be employed as the active layer of direct X-ray detectors are needed. In this search for easy-processability, large area, efficient and non-toxic materials for direct X-ray detection, we assess the performance of a layered metal-organic chalcogenide [AgSePh]∞, recently proposed as representative of a novel excitonic semiconductors platform. Here we demonstrate that [AgSePh]∞ can be successfully applied as direct ionizing radiation detecting layer, reaching sensitivities up to (180 ± 10) μC Gy−1 cm−2 and competitive limit of detection down to (100 ± 30) nGy s−1. Moreover, it offers good stability and reproducibility of detection after 100 Gy of irradiation and upon bending to a curvature radius of 5 mm.

Background Many interventions, especially those linked to open science, have been proposed to improve reproducibility in science. To what extent these propositions are based on scientific evidence from empirical evaluations is not clear. Aims The primary objective is to identify Open Science interventions that have been formally investigated regarding their influence on reproducibility and replicability. A secondary objective is to list any facilitators or barriers reported and to identify gaps in the evidence. Methods We will search broadly by using electronic bibliographic databases, broad internet search, and contacting experts in the field of reproducibility, replicability, and open science. Any study investigating interventions for their influence on the reproducibility and replicability of research will be selected, including those studies additionally investigating drivers and barriers to the implementation and effectiveness of interventions. Studies will first be selected by title and abstract (if available) and then by reading the full text by at least two independent reviewers. We will analyze existing scientific evidence using scoping review and evidence gap mapping methodologies. Results The results will be presented in interactive evidence maps, summarized in a narrative synthesis, and serve as input for subsequent research. Review registration This protocol has been pre-registered on OSF under doi https://doi.org/10.17605/OSF.IO/D65YS

Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 gene variants’ frequencies across populations with MDD, evaluating their impact on clinical characteristics and treatment response. We comprehensively searched five databases, identifying 240 articles, of which only nine within the last decade met our inclusion criteria. Except for one study that achieved 74.28% of STROPS items, the rest met at least 75% of GRIPS and STROPS guidelines for quality and bias risk assessment. The CYP2C19’s *1 allele, the *1/*1 genotype, and the NM phenotype, considered as references, were generally more frequent. Other CYP2C19 polymorphism frequencies exhibit significant variability across different populations. Some studies associated variants with MDD development, a more extended history of depression, prolonged depressive episodes, and symptom severity, while others reported no such association. Some studies confirmed variants’ effects on escitalopram and citalopram metabolism but not that of other drugs, such as sertraline, venlafaxine, and bupropion. Treatment tolerability and symptom improvement also varied between studies. Despite some common findings, inconsistencies highlight the need for further research to clarify the role of these polymorphisms in MDD and optimize treatment strategies.

Abstract Organic semiconductors are a promising material candidate for X‐ray detection. However, the low atomic number (Z) of organic semiconductors leads to poor X‐ray absorption thus restricting their performance. Herein, the authors propose a new strategy for achieving high‐sensitivity performance for X‐ray detectors based on organic semiconductors modified with high –Z heteroatoms. X‐ray detectors are fabricated with p‐type organic semiconductors containing selenium heteroatoms (poly(3‐hexyl)selenophene (P3HSe)) in blends with an n‐type fullerene derivative ([6,6]‐Phenyl C71 butyric acid methyl ester (PC70BM). When characterized under 70, 100, 150, and 220 kVp X‐ray radiation, these heteroatom‐containing detectors displayed a superior performance in terms of sensitivity up to 600 ± 11 nC Gy−1 cm−2 with respect to the bismuth oxide (Bi2O3) nanoparticle (NP) sensitized organic detectors. Despite the lower Z of selenium compared to the NPs typically used, the authors identify a more efficient generation of electron‐hole pairs, better charge transfer, and charge transport characteristics in heteroatom‐incorporated detectors that result in this breakthrough detector performance. The authors also demonstrate flexible X‐ray detectors that can be curved to a radius as low as 2 mm with low deviation in X‐ray response under 100 repeated bending cycles while maintaining an industry‐standard ultra‐low dark current of 0.03 ± 0.01 pA mm−2.

X-ray detection for personal dosimetry requires sensitive, stable and non-toxic materials. At the same time, scalability onto large-area and flexible substrates is emerging as a desirable property. To satisfy these requirements, novel materials to be employed as the active layer of direct X-ray detectors are needed. In this search for easy-processability, large area, efficient and non-toxic materials for direct X-ray detection, we assess the performance of a layered metal-organic chalcogenide [AgSePh]∞, recently proposed as representative of a novel excitonic semiconductors platform. Here we demonstrate that [AgSePh]∞ can be successfully applied as direct ionizing radiation detecting layer, reaching sensitivities up to (180 ± 10) μC Gy−1 cm−2 and competitive limit of detection down to (100 ± 30) nGy s−1. Moreover, it offers good stability and reproducibility of detection after 100 Gy of irradiation and upon bending to a curvature radius of 5 mm.

Introduction: Following consumers’ demand for healthier alternatives, Spirulina biomass has been included as a functional ingredient in different types of food as a sustainable alternative to improve physicochemical characteristics and nutritional aspects in the diet. This study aimed to explore the use of Spirulina biomass (SB) and residual biomass (RB) obtained after C-phycocyanin (C-PC) extraction in the production of wheat bread (WB).Methods: The dough rheology, texture, color, nutritional aspects, and bioaccessibility of the different manufactured bread samples were accessed to achieve this goal.Results and Discussion: This is the first research to exploit RB. It was possible to replace 3% of wheat flour for SB or RB in bread-making; this substitution did not impact the rheological characteristics of the dough, even though the pH increased with the addition of SB or RB (5.63 and 5.70, respectively). SB and RB addition improved bread volume and enhanced the nutritional profile, increasing the antioxidant capacity (DPPH and FRAP) compared to WB. Heavy metals (Ni, Cd, and Pb) were not found in any of the samples (

Naturally colored fermented foods currently represent the trend toward a global demand for healthier products. This work produced naturally blue and green ice creams using C-phycocyanin (C-PC) and spirulina residual biomass (RB). The ice creams were assessed based on microbiological analysis, color stability over 6 months, antioxidant activity before and after in vitro digestion, and sensory evaluation. Considering the microorganisms that must be analyzed in accordance with Brazilian legislation, no growth was detected during the storage period. L*, a*, and b* were maintained according to the expected colors. The blue color was intoned over the shelf life (SC-PC *b −9.46 to −19.44 and MC-PC *b from −9.87 to −18.04). The antioxidant activity of the fermented ice creams SC-PC and SRB increased from 15.4 to 41.3 and from 15.3 to 38.0 µM TE/g, respectively, after bioaccessibility analysis. The C-PC ice cream’s appearance received the highest rating, with 70.26% of volunteers expressing a strong preference, highlighting its attractiveness. However, there were no significant differences compared to control samples in the global acceptance. The RB ice cream presented lower results for flavor but moderate acceptance. Thus, these fermented ice creams presented color stability over 6 months, and their antioxidant activity increased after in vitro digestion, highlighting their biological potential.

Abstract Background Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies. Main body Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin. Short conclusion The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.

Abstract This study reports on a novel, flexible, proton beam detector based on mixed 3D–2D perovskite films deposited by solution onto thin plastic foils. The 3D–2D mixture allows to obtain micrometer‐thick and highly uniform films that constitute the detector's active layer. The devices demonstrate excellent flexibility with stable electric transport properties down to a bending radius of 3.1 mm. The detector is characterized under a 5 MeV proton beam with fluxes in the range [4.5 × 105 – 1.4 × 109] H+ cm−2 s−1, exhibiting a stable response to repetitive irradiation cycles with sensitivity up to (290 ± 40) nC Gy−1mm−3 and a limit of detection down to (72±2) µGy s−1. The detector radiation tolerance is also assessed up to a total of 1.7 × 1012 protons impinging on the beam spot area, with a maximum variation of the detector's response of 14%.

Background. Monoamine oxidase (MAO) is involved in several biological processes associated with well-being and mental health, and alterations in its function might directly impact various mental disorders. Some mental disorders concomitantly occur in individuals with clinical characteristics, such as substance abuse and diabetes. Objective. To analyze the functional MAOA uVNTR polymorphism genotype frequency in an older adult population with diabetes mellitus/arterial hypertension and associate this frequency with clinical characteristics impacting daily life. Methodology. Older adults diagnosed with diabetes mellitus, systemic arterial hypertension, or both (DM/SAH) were selected and had their MAOA gene genotyped for uVNTR polymorphism. The revised Beck Depression Inventory (BDI) and a questionnaire were also applied to determine their mental health and clinical characteristics. Results. The allelic variants detected among the participants were the 2R, 3R, 4R, and 3R/4R heterozygous genotypes. Genotypes solely containing the 3R allele had patients who marked yes for smoking and alcoholism, and only those with the 3R genotypes (female 3R/3R homozygote or male 3R∗ hemizygote) were significant. Although not statistically significant, only 3R and 3R/4R genotypes presented cases of severe depression per the revised BDI interpretations. Conclusion. The MAOA uVNTR polymorphism’s low-activity 3R allele presence in an older adult population diagnosed with DM/SAH may represent a risk for developing substance use (alcohol and smoking) dependence.

Background: Cesarean scar pregnancy (CSP) is a pregnancy in the scar area or “niche” from a prior hysterotomy, usually from a cesarean section. Currently, there is no consensus on the best management of CSP. A recent proposed treatment consists in placing a cervical ripening double-balloon catheter in the uterus under ultrasound guidance. Methods: In this systematic review on cervical ripening double-balloon catheter (CRDBC) treatment for CSP, we performed a literature search in electronic databases (Scopus, PubMed, MEDLINE, and Cochrane Library), from their inception until April 2023. The review was written following PRISMA guidelines for systematic reviews. Results: We identified 30 studies, and we finally analyzed 5 studies that met the inclusion criteria (one case report, two retrospective case series studies, a retrospective cohort study, and a retrospective multicentric case series). The total of pregnancies treated with CRDBC is 71, of which 8 (11%) were cervical pregnancies. The gestational age at treatment ranges from 5 + 0 to 10 + 1 gestational weeks, with variable human chorionic gonadotropin (hCG) levels (433–64.700 IU/mL). Most of the patients (73%) received adjuvant systemic methotrexate (MTX) and the catheter dwell time ranges from 1 to 5 days. Treatment was successful in all the patients. Maternal complications, defined as the need for transfusion, vaginal bleeding resulting in readmission, or requiring further treatment occurred in a small number of patients (4.2%). Conclusions: CRDBC was successful in the treatment of early CSPs. The effectiveness and safety of this minimally invasive method is testified to a small rate of maternal complications. Further prospective studies are warranted to explore this treatment modality. The study was registered on INPLASY (https://inplasy.com/), registration number: INPLASY202390070 (doi: 10.37766/inplasy2023.9.0070).

The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges for the delivery of high-quality obstetric services to both SARS-CoV-2 positive and negative women. The initial epidemiological pressure, especially in the most affected areas of China and Italy, led the local health services to defining care pathways based on the organizational and logistical availability of the moment. Currently, some aspects of clinical care practices and the management of women with suspected or confirmed SARS-CoV-2 virus infection are well established. The aim of this review article is to provide an outline of the suggested organization of obstetric units during the COVID-19 pandemic, and to mention the challenges we had to face at our institution.

Abstract Background In-depth analysis of regulation networks of genes aberrantly expressed in cancer is essential for better understanding tumors and identifying key genes that could be therapeutically targeted. Results We developed a quantitative analysis approach to investigate the main biological relationships among different regulatory elements and target genes; we applied it to Ovarian Serous Cystadenocarcinoma and 177 target genes belonging to three main pathways (DNA REPAIR, STEM CELLS and GLUCOSE METABOLISM) relevant for this tumor. Combining data from ENCODE and TCGA datasets, we built a predictive linear model for the regulation of each target gene, assessing the relationships between its expression, promoter methylation, expression of genes in the same or in the other pathways and of putative transcription factors. We proved the reliability and significance of our approach in a similar tumor type (basal-like Breast cancer) and using a different existing algorithm (ARACNe), and we obtained experimental confirmations on potentially interesting results. Conclusions The analysis of the proposed models allowed disclosing the relations between a gene and its related biological processes, the interconnections between the different gene sets, and the evaluation of the relevant regulatory elements at single gene level. This led to the identification of already known regulators and/or gene correlations and to unveil a set of still unknown and potentially interesting biological relationships for their pharmacological and clinical use.

Major Depressive Disorder (MDD) is a disabling and particularly persistent mental disorder that is considered to be a priority public health problem. The active human dopamine transporter (DAT), which is encoded by the SLC6A3 gene, regulates the dopamine concentration in the synaptic cleft. In this sense, this neurotransmitter is primordial in modulating human emotions. This systematic review aims to verify the SLC6A3 (DAT1) 3′UTR VNTR (rs28363170) gene variant’s SS (9R/9R) genotype and S (9R) allele frequency fluctuation and its influence on the modulation of pharmacotherapy in MDD. For this purpose, we searched different databases, and after applying the eligibility criteria, six articles were selected. Studies have shown an association between the SS (9R/9R) genotypic and S (9R) allelic presence with the risk of developing MDD, in addition to influencing the decrease in response to antidepressant therapy. However, despite the findings, disagreements were observed between other studies. For this reason, further studies with the SLC6A3 3′UTR VNTR (rs28363170) variant in different populations are necessary to understand this polymorphism’s role in the onset of this disease.

Background: Major depressive disorder (MDD) is a disease that has been increasingly affecting more people worldwide. The dopamine D2 receptor (DRD2), encoded by the DRD2 gene, plays critical roles in the brain, one of which is related to reward processes. Aims: The following systematic review aims to analyze the DRD2/ANKK1 TaqIA (rs1800497) polymorphism's A1 genotype frequency fluctuation in MDD patients and determine its influence on MDD. Methods: Four databases were searched, and the consequent articles were analyzed following the inclusion criteria per the PECOS strategy, resulting in five selected articles. Results: Interestingly, although two articles showed that the A1 allele presence significantly increases the risk of MDD manifestation, most articles did not find a significant association between this DRD2 gene variant and MDD. Conclusions: Most of the included studies were dated, indicating the need for more studies to address the results' non-conformity with different populations. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) affects over 300 million people globally and has a multifactorial etiology. The CYP2C19 enzyme, involved in metabolizing certain antidepressants, can influence treatment response. Following the PRISMA protocol and PECOS strategy, this systematic review assessed the variation in common CYP2C19 gene variants' frequencies across populations with MDD, evaluating their impact on clinical characteristics and treatment response. We comprehensively searched five databases, identifying 240 articles, of which only nine within the last decade met our inclusion criteria. Except for one study that achieved 74.28% of STROPS items, the rest met at least 75% of GRIPS and STROPS guidelines for quality and bias risk assessment. The CYP2C19's *1 allele, the *1/*1 genotype, and the NM phenotype, considered as references, were generally more frequent. Other CYP2C19 polymorphism frequencies exhibit significant variability across different populations. Some studies associated variants with MDD development, a more extended history of depression, prolonged depressive episodes, and symptom severity, while others reported no such association. Some studies confirmed variants' effects on escitalopram and citalopram metabolism but not that of other drugs, such as sertraline, venlafaxine, and bupropion. Treatment tolerability and symptom improvement also varied between studies. Despite some common findings, inconsistencies highlight the need for further research to clarify the role of these polymorphisms in MDD and optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Real‐time and in‐line transversal monitoring of ionizing radiation beams is a crucial task for several applications which span from medical treatments to particle accelerators in high energy physics. Here a flexible and large area device based on 2D hybrid perovskite thin films (phenylethylammonium lead bromide), fabricated onto a thin flexible polyimide substrate, able to map the transversal beam profile of high energy radiation beams is reported. The performance of this novel tool is here compared with the one offered by standard commercial large‐area technology, namely radiochromic sheets. The great potential of this class of devices is demonstrated by successfully mapping in real‐time a 5 MeV proton beam at fluxes between 108 and 1010 H+ s−1 cm−2, confirming the capability to operate in a radiation‐harsh environment without output signal saturation issues. The versatility and scalability of here proposed detecting system are demonstrated by the development of a multipixel array able to map in real‐time a 40 kVp X‐ray beam spot (dose rate 8 mGy s−1). Perovskite thin film‐based detectors are thus assessed as a very promising class of thin, flexible devices for real‐time, in‐line, large‐area, conformable, reusable, transparent, and low‐cost transversal beam monitoring of different ionizing radiation. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 12 (CDK12) is a serine/threonine kinase involved in the regulation of RNA polymerase II and in the transcription of a subset of genes involved in the DNA damage response. CDK12 is one of the most mutated genes in ovarian carcinoma. These mutations result in loss-of-function and can predict the responses to PARP1/2 inhibitor and platinum. To investigate the role of CDK12 in ovarian cancer, CRISPR/Cas9 technology was used to generate a stable CDK12 knockout (KO) clone in A2780 ovarian carcinoma cells. This is the first report on a CDK12 null cell line. The clone had slower cell growth and was less clonogenic than parental cells. These data were confirmed in vivo, where CDK12 KO transplanted cells had a much longer time lag and slightly slower growth rate than CDK12-expressing cells. The slower growth was associated with a higher basal level of apoptosis, but there were no differences in the basal level of autophagy and senescence. While cell cycle distribution was similar in parental and knockout cells, there was a doubling in DNA content, with an almost double modal number of chromosomes in the CDK12 KO clone which, however did not display any increase in γH2AX, a marker of DNA damage. We found partial down-regulation of the expression of DNA repair genes at the mRNA level and, among the down-regulated genes, an enrichment in the G2/M checkpoint genes. Although the biological features of CDK12 KO cells are compatible with the function of CDK12, contrary to some reports, we could not find any difference in the sensitivity to cisplatin and olaparib between wild-type and CDK12 KO cells.