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JOURNAL/nrgr/04.03/01300535-202507000-00032/figure1/v/2024-09-09T124005Z/r/image-tiff A microgravity environment has been shown to cause ocular damage and affect visual acuity, but the underlying mechanisms remain unclear. Therefore, we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under microgravity. After 4 weeks of tail suspension, there were no notable alterations in retinal function and morphology, while after 8 weeks of tail suspension, significant reductions in retinal function were observed, and the outer nuclear layer was thinner, with abundant apoptotic cells. To investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina, proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail suspension. The results showed that the expression levels of fibroblast growth factor 2 (also known as basic fibroblast growth factor) and glial fibrillary acidic protein, which are closely related to Müller cell activation, were significantly upregulated. In addition, Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks, respectively, of simulated weightlessness. These findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.
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This study explores the role of the transcription factor FOXM1 in the initiation and progression of oesophageal squamous cell carcinoma (ESCC). Our findings reveal that FOXM1 is highly expressed in ESCC and correlates with the prognosis of the disease. The relationship between FOXM1 and asparagine synthetase (ASNS) is investigated, and the study demonstrates that FOXM1 activates ASNS, impacting the tumour stemness of ESCC. In this study, we reveal the association between FOXM1 and ESCC development, as well as FOXM1's promotion of migration and proliferation in ESCC cells. The study also highlights FOXM1's regulation of ASNS transcription and the functional role of ASNS in ESCC metastasis and growth. Furthermore, the study explores the impact of FOXM1 and ASNS on ESCC stemness and their potential implications for chemotherapy resistance.
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Aspartato-Amônia Ligase , Movimento Celular , Proliferação de Células , Progressão da Doença , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Proteína Forkhead Box M1 , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Aspartato-Amônia Ligase/genética , Aspartato-Amônia Ligase/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Prognóstico , Animais , Camundongos , Masculino , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carbono-Nitrogênio Ligases com Glutamina como Doadora de N-AmidaRESUMO
Indoor photovoltaics (IPVs) have attracted increasing attention for sustainably powering Internet of Things (IoT) electronics. Sb2S3 is a promising IPV candidate material with a bandgap of ~1.75 eV, which is near the optimal value for indoor energy harvesting. However, the performance of Sb2S3 solar cells is limited by nonradiative recombination, which is dependent on the quality of the absorber films. Additive engineering is an effective strategy to fine tune the properties of solution-processed films. This work shows that the addition of monoethanolamine (MEA) into the precursor solution allows the nucleation and growth of Sb2S3 films to be controlled, enabling the deposition of high-quality Sb2S3 absorbers with reduced grain boundary density, optimized band positions, and increased carrier concentration. Complemented with computations, it is revealed that the incorporation of MEA leads to a more efficient and energetically favorable deposition for enhanced heterogeneous nucleation on the substrate, which increases the grain size and accelerates the deposition rate of Sb2S3 films. Due to suppressed carrier recombination and improved charge-carrier transport in Sb2S3 absorber films, the MEA-modulated Sb2S3 solar cell yields a power conversion efficiency (PCE) of 7.22% under AM1.5 G illumination, and an IPV PCE of 17.55% under 1000 lux white light emitting diode (WLED) illumination, which is the highest yet reported for Sb2S3 IPVs. Furthermore, we construct high performance large-area Sb2S3 IPV minimodules to power IoT wireless sensors, and realize the long-term continuous recording of environmental parameters under WLED illumination in an office. This work highlights the great prospect of Sb2S3 photovoltaics for indoor energy harvesting.
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Purpose: This study aims to evaluate the diagnostic performance of a machine learning model (ML model) to train junior ophthalmologists in detecting preclinical keratoconus (PKC). Methods: A total of 1,334 corneal topography images (The Pentacam HR system) from 413 keratoconus eyes, 32 PKC eyes and 222 normal eyes were collected. Five junior ophthalmologists were trained and annotated the images with or without the suggestions proposed by the ML model. The diagnostic performance of PKC was evaluated among three groups: junior ophthalmologist group (control group), ML model group and ML model-training junior ophthalmologist group (test group). Results: The accuracy of the ML model between the eyes of patients with KC and NEs in all three clinics (99% accuracy, area under the receiver operating characteristic (ROC) curve AUC of 1.00, 99% sensitivity, 99% specificity) was higher than that for Belin-Ambrósio enhanced ectasia display total deviation (BAD-D) (86% accuracy, AUC of 0.97, 97% sensitivity, 69% specificity). The accuracy of the ML model between eyes with PKC and NEs in all three clinics (98% accuracy, AUC of 0.96, 98% sensitivity, 98% specificity) was higher than that of BAD-D (69% accuracy, AUC of 0.73, 67% sensitivity, 69% specificity). The diagnostic accuracy of PKC was 47.5% (95%CI, 0.5-71.6%), 100% (95%CI, 100-100%) and 94.4% (95%CI, 14.7-94.7%) in the control group, ML model group and test group. With the assistance of the proposed ML model, the diagnostic accuracy of junior ophthalmologists improved with statistical significance (p < 0.05). According to the questionnaire of all the junior ophthalmologists, the average score was 4 (total 5) regarding to the comprehensiveness that the AI model has been in their keratoconus diagnosis learning; the average score was 4.4 (total 5) regarding to the convenience that the AI model has been in their keratoconus diagnosis learning. Conclusion: The proposed ML model provided a novel approach for the detection of PKC with high diagnostic accuracy and assisted to improve the performance of junior ophthalmologists, resulting especially in reducing the risk of missed diagnoses.
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BACKGROUND: Endonucleases play a crucial role in plant growth and stress response by breaking down nuclear DNA. However, the specific members and biological functions of the endonuclease encoding genes in wheat remain to be determined. RESULTS: In this study, we identified a total of 26 TaENDO family genes at the wheat genome-wide level. These genes were located on chromosomes 2 A, 2B, 2D, 3 A, 3B, and 3D and classified into four groups, each sharing similar gene structures and conserved motifs. Furthermore, we identified diverse stress-response and growth-related cis-elements in the promoter of TaENDO genes, which were broadly expressed in different organs, and several TaENDO genes were significantly induced under drought and salt stresses. We further examined the biological function of TaENDO23 gene since it was rapidly induced under drought stress and exhibited high expression in spikes and grains. Subcellular localization analysis revealed that TaENDO23 was localized in the cytoplasm of wheat protoplasts. qRT-PCR results indicated that the expression of TaENDO23 increased under PEG6000 and abscisic acid treatments, but decreased under NaCl treatment. TaENDO23 mainly expressed in leaves and spikes. A kompetitive allele-specific PCR (KASP) marker was developed to identify single nucleotide polymorphisms in TaENDO23 gene in 256 wheat accessions. The alleles with TaENDO23-HapI haplotypes had higher grain weight and size compared to TaENDO23-HapII. The geographical and annual frequency distributions of the two TaENDO23 haplotypes revealed that the elite haplotype TaENDO23-HapI was positively selected in the wheat breeding process. CONCLUSION: We systematically analyzed the evolutionary relationships, gene structure characteristics, and expression patterns of TaENDO genes in wheat. The expression of TaENDO23, in particular, was induced under drought stress, mainly expressed in the leaves and grains. The KASP marker of TaENDO23 gene successfully distinguished between the wheat accessions, revealing TaENDO23-HapI as the elite haplotype associated with improved grain weight and size. These findings provide insights into the evolution and characteristics of TaENDO genes at the genome-wide level in wheat, laying the foundation for further biological analysis of TaENDO23 gene, especially in response to drought stress and grain development.
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Secas , Estresse Fisiológico , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Endonucleases/genética , Endonucleases/metabolismo , Família Multigênica , Regulação da Expressão Gênica de Plantas , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Genoma de Planta , Filogenia , Cromossomos de Plantas/genética , Mapeamento Cromossômico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.
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Astrophotonics aims to transfer photonic technology to the development of compact astronomical instruments. However, light coupling from a multimode fiber, typically adopted in modern observatories, to a single-mode photonic device still poses a challenge. Though a photonic lantern can enable this transition in a low-loss way, it requires that the number of single-mode fibers (SMFs) at the output is the same as the number of guided modes in the multimode fiber, resulting in a cumbersome fan-out of many single-mode devices to be connected. Herein, we invent an active device in a waveguide form called "the mode detangler" (MD). We show that it can adaptively transform a complex light field from a multimode fiber to a single-mode-like spot. In this way, only one single-mode device is required at the end. The path leading to the idea and the theory behind the mode detangling effect is explained, followed by numerical simulations and experimental demonstrations using a few-mode fiber as proof of concept. We believe this device has the potential to address the multimode-to-single-mode conversion challenge in astrophotonics but also sheds light on (de)multiplexing applications regarding spatial mode technology in optical communications.
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Background: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings. Methods: Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system. Conclusions: The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation.
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Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) represent a promising novel treatment for castration-resistant prostate cancer (CRPC) with encouraging results. However, the combination targets in CRPC remain largely unexplored. N6-methyladenosine (m6A) has been shown to play a crucial role in cancer progression and DNA damage response. Here, we observed a higher overall level of m6A and a downregulation of Fat mass and obesity-associated protein (FTO), which correlated with unfavorable clinicopathological parameters in prostate cancer (PCa). Functionally, reduced FTO promotes PCa growth, while overexpression of FTO has the opposite effect. Mechanistically, FOXO3a was identified as the downstream target of FTO in PCa. FTO downregulates the expression of FOXO3a in an m6A-dependent manner, leading to the degradation of its mRNA. Importantly, DNA damage can degrade FTO through the ubiquitination pathway. Finally, we found that overexpression of FTO can enhance the effect of PARPi on PCa. Therefore, our findings may provide insight into novel therapeutic approaches for CRPC.
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Air moisture is a valuable and omnipresent resource of fresh water. However, traditional water collectors come with an enduring problem of the water-release step, which requires special devices and additional energy to remove the water from the adsorbent, such as heat, sunlight, or both. Herein, we report the first composite conical hollow hydrogel to harvest water from aerial humidity. This hollow hydrogel device can rapidly collect water from humid air to a saturation point, whereupon it automatically and continually releases fresh water at room temperature. The entire water collection and release process doesn't require any external assistance. As an exemplary demonstration, positioning the hollow hydrogel device next to a plant turns into an individualized system for irrigation. Since the device is biodegradable, it eventually decomposes and becomes an organic fertilizer after the water supply is not required. For long-term application, the water-release process can be monitored in real time by an electronic device to indicate the amount of collected water. The hollow hydrogel combines the humidity-absorbing capacity with autonomous water release that carries the potential for harvesting water from humidity to address the shortage of fresh water, especially in arid locations where other sources of water are scarce or inaccessible.
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Acetaminophen (APAP) overdose-induced acute liver injury (ALI) is characterized by extensive oxidative stress, and the clinical interventions for this adverse effect remain limited. Astilbin is an active compound found in the rhizome of Smilax glabra Roxb. with anti-inflammatory and antioxidant activities. Due to its low oral bioavailability, astilbin can accumulate in the intestine, which provides a basis for the interaction between astilbin and gut microbiota (GM). In the present study we investigated the protective effects of astilbin against APAP-induced ALI by focusing on the interaction between astilbin and GM. Mice were treated with astilbin (50 mg·kg-1·d-1, i.g.) for 7 days. After the last administration of astilbin for 2 h, the mice received APAP (300 mg/kg, i.g.) to induce ALI. We showed that oral administration of astilbin significantly alleviated APAP-induced ALI by altering the composition of GM and enriching beneficial metabolites including hydroxytyrosol (HT). GM depletion using an "antibiotics cocktail" or paraoral administration of astilbin abolished the hepatoprotective effects of astilbin. On the other hand, administration of HT (10 mg/kg, i.g.) caused similar protective effects in APAP-induced ALI mice. Transcriptomic analysis of the liver tissue revealed that HT inhibited reactive oxygen species and inflammation-related signaling in APAP-induced ALI; HT promoted activation of the Nrf2 signaling pathway to combat oxidative stress following APAP challenge in a sirtuin-6-dependent manner. These results highlight that oral astilbin ameliorates APAP-induced ALI by manipulating the GM and metabolites towards a more favorable profile, and provide an alternative therapeutic strategy for alleviating APAP-induced ALI.
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Mitochondria are central actors in diverse physiological phenomena ranging from energy metabolism to stress signaling and immune modulation. Accumulating scientific evidence points to the critical involvement of specific mitochondrial-associated events, including mitochondrial quality control, intercellular mitochondrial transfer, and mitochondrial genetics, in potentiating the metastatic cascade of neoplastic cells. Furthermore, numerous recent studies have consistently emphasized the highly significant role mitochondria play in coordinating the regulation of tumor-infiltrating immune cells and immunotherapeutic interventions. This review provides a comprehensive and rigorous scholarly investigation of this subject matter, exploring the intricate mechanisms by which mitochondria contribute to tumor metastasis and examining the progress of mitochondria-targeted cancer therapies.
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OBJECTIVES: Inflexibility of thought and behaviour is a transdiagnostic feature of many neuropsychiatric disorders and presents several empirical measurement challenges. Here, we developed and validated the Flexibility in Daily Life scale (FIDL); a novel, self-report questionnaire, which captures expressions of cognitive and behavioural flexibility in daily life and is sensitive to natural shifts in these processes across the adult lifespan. METHODS: The FIDL was developed using a deductive scale development approach, which aimed to capture common themes within the flexibility literature and across diagnoses (e.g. insistence on sameness, preference for routines). Following multidisciplinary consensus, an initial 37-item questionnaire was submitted for validation in an online sample of 295 healthy adult participants (19-78 years). RESULTS: Exploratory factor analysis produced a revised 21-item version comprising five factors, labelled: Repetition, Switching, Predictability/Control, Routine, and Thoughts/Beliefs. Internal consistency reliability was good-to-strong for the total FIDL score and moderate-to-strong for individual subscales. Convergent validity was established between the FIDL and an existing measure of cognitive flexibility. Critically, the FIDL total score evinced a U-shaped relationship with age, whereby flexibility was lower at the younger and older tails of the lifespan and greater in middle age. The same U-shaped trajectory emerged for the Repetition, Routine, and Thoughts/Beliefs factors. CONCLUSIONS: Overall, the FIDL is a valid and reliable multidimensional measure of flexibility, which upholds a clearly defined factor structure and good psychometric properties. It promises to be a valuable clinical and research tool to assess the natural fluctuations in flexibility across the lifespan and departures thereof.
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A proportion of patients still need mechanical circulatory support (MCS) during the transcatheter aortic valve replacement (TAVR) because of intraoperative hemodynamic instability. However, the outcomes of patients with different MCS type during TAVR are still controversial. A total of 538 patients who underwent TAVR procedure in four centers were included. The time-related outcomes and their predictors of patients who did not have MCS (MCS-, n = 498) were compared with those who underwent emergency MCS (eMCS+, n = 18) and prophylactic MCS (pMCS+, n = 22). We evaluated the association between different MCS groups and all-cause mortality using conditional landmark analysis with Cox regression. There was a significant increase in 30-day mortality in the eMCS+ group (plog-rank < 0.001) and no significant difference in 31-day to 1-year mortality among the groups (plog-rank = 0.789). A significant improvement in the left ventricular ejection fraction was observed in the pMCS+ group at 1 year after TAVR. Emergency MCS was independently associated with 30-day mortality, as well as 1-year mortality. Prophylactic MCS showed good clinical outcomes and might be considered for high-risk patients. Further studies are needed to investigate the predictors that lead to MCS usage and long-term mortality in TAVR patients with MCS.
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Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extra-terminal domain (BET) protein family, which plays a crucial role in recognizing acetylated lysine residues in chromatin. The abnormal expression of BRD4 contributes to the development of various human malignant tumors, including head and neck squamous cell carcinoma (HNSCC). Recent studies have shown that BRD4 inhibition can effectively prevent the proliferation and growth of HNSCC. However, the specific role and mechanism of BRD4 in HNSCC are not yet fully clarified. This article will briefly summarize the critical role of BRD4 in the pathogenesis of HNSCC and discuss the potential clinical applications of targeting BRD4 in HNSCC therapy. We further inquiry the challenges and opportunities for HNSCC therapies based on BRD4 inhibition, including BRD4 inhibitor combination with conventional chemotherapy, radiotherapy, and immunotherapy, as well as new strategies of BRD4-targeting drugs and BRD4 proteolysis-targeting chimeras (PROTACs). Moreover, we will also offer outlook on the associated challenges and future directions of targeting BRD4 for the treatment of patients with HNSCC.
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Abstractï¼ Background: Depression is a pervasive and often undetected mental health condition, which poses significant challenges for early diagnosis due to its silent and subtle nature. OBJECTIVE: To evaluate exhaled volatile organic compounds (VOCs) as non-invasive biomarkers for the detection of depression using a virtual surface acoustic wave sensors array (VSAW-SA). METHODS: A total of 245 participants were recruited from the Hangzhou Community Health Service Center, including 38 individuals diagnosed with depression and 207 control subjects. Breath samples were collected from all participants and subjected to analysis using VSAW-SA. Univariate and multivariate analyses were employed to assess the relationship between volatile organic compounds (VOCs) and depression. The findings revealed that the responses of virtual sensor ID 14, 44, 59, and 176, which corresponded respectively to ethanol, trichloroethylene or isoleucine, octanoic acid or lysine, and an unidentified compound, were sensitive to depression. Taking into account potential confounders, these sensor responses were utilized to calculate a depression detection indicator. RESULTS: It has a sensitivity of 81.6% and a specificity of 81.6%, with an area under the curve (AUC) of 0.870 (95% CI=0.816-0.923). CONCLUSIONS: Exhaled VOCs as non-invasive biomarkers of depression could be detected by a VSAW-SA. Large-scale cohort studies should be conducted to confirm the potential ability of the VSAW-SA to diagnose depression. .
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A straightforward copper-catalyzed deborodeuteration of arylboronic acids and borates was achieved, employing the cost-effective deuterium source D2O. This protocol demonstrates wide substrate applicability, exceptional deuterium incorporation efficiency, and favorable tolerance for various functional groups. Therefore, this approach offers a mild option for further applications in valuable deuterium molecule synthesis.
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BACKGROUND: Cognitive impairment presents in both adolescent-onset(ado-OP) and adult-onset psychosis(adu-OP). Age and neurodevelopmental factors likely contribute to cognitive differences. This study aimed to characterize cognitive functions in ado-OP compared to adu-OP in a clinical population with drug-naive first-episode psychosis(FEP). METHODS: A total of 788 drug-naive patients with FEP and 774 sex- and age-matched healthy controls(HCs) were included. Participants were divided into four groups by whether they were under or over 21 years of age: adolescent-onset FEP(ado-FEP, n = 380), adult-onset FEP(adu-FEP, n = 408), adolescent HC(ado-HC, n = 334), and adult HC(adu-HC, n = 440). Comprehensive cognitive assessments were performed using the MATRICS Cognitive Consensus Battery(MCCB), covers six cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning, and problem-solving. Data analyses were conducted using correlation analyses and binary logistic regression. RESULTS: The patterns of cognitive domain differences between ado-FEP and adu-FEP were found to be similar to those between ado-HC and adu-HC, whereas cognitive impairments appeared to be more pronounced in patients with adu-OP than ado-OP. The mazes subtest had the maximum effect size(ES) in the FEP(ES = 0.37) and HC(ES = 0.30) groups when comparing the adolescent and adult groups. Cognitive subtests were mostly significantly correlated with negative symptoms, especially for adolescents with FEP, in which all the subtests were significantly correlated with negative symptoms in the ado-FEP group. Better performance in the domains of spatial cognition and problem-solving abilities was more likely in the ado-FEP group than in the adu-FEP group. CONCLUSIONS: These findings suggest cognitive differences between adolescents and adults but similar patterns of affected domains in HCs and patients with FEP. Therefore, the development of targeted cognitive interventions tailored to the specific needs of different age groups appears warranted.
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BACKGROUND: Populations of Olea europaea subsp. europaea var. sylvestris, the ancestor of cultivated olives, are scattered across the Mediterranean Basin. However, after millennia of possible hybridization with cultivated varieties, the genetic identity of many of these populations remain questionable. In the southern Levant, the plausible primary domestication center of olives, many of the naturally growing olive (NGOs) are considered feral, having developed from nearby olive groves. Here, we investigated the genetic identity of NGOs population in the Carmel region, hypothesizing that their specific location, which limit anemophily, provided an opportunity for the persistence of genuine var. sylvestris. RESULTS: We mapped more than 1,000 NGOs on the Kurkar ridge along the Carmel coast, within and outside the residential area of Atlit and used simple sequence repeats of 14 loci to assess the spatial genetic structure of 129 NGOs. Genetic diversity parameters and genetic distances between NGO and cultivated olives, as well as phenotypic and morphometric analyses of their oil content and pits, respectively, indicated the presence of a genuine var. sylvestris population. However, NGOs within the residential area of Atlit and old settlements showed an intermediate admix genetic structure, indicating on hybridization with local varieties, a consequence of their proximity to cultivated trees. CONCLUSIONS: Integrating the results of genetic and phenotypic analyses we provide crucial evidence of the presence of a genuine var. sylvestris population in the southern Levant, in close geographical proximity to archaeological sites with the earliest evidence of olive exploitation in the ancient world. We supplement the results with recommendations for a conservation program that combines municipal requirements and the urgent need to preserve the largest population of var. sylvestris in the southern Levant.