Persistent Changes Research Articles

Long-term optical imaging of the spinal cord in awake behaving mice.

Advances in optical imaging and fluorescent biosensors enable study of the spatiotemporal and long-term neural dynamics in the brain of awake animals. However, methodological difficulties and fibrosis limit similar advances in the spinal cord. Here, to overcome these obstacles, we combined in vivo application of fluoropolymer membranes that inhibit fibrosis, a redesigned implantable spinal imaging chamber and improved motion correction methods that together permit imaging of the spinal cord in awake behaving mice, for months to over a year. We demonstrated a robust ability to monitor axons, identified a spinal cord somatotopic map, performed months-long imaging in freely moving mice, conducted Ca2+ imaging of neural dynamics in behaving mice responding to pain-provoking stimuli and observed persistent microglial changes after nerve injury. The ability to couple in vivo imaging and behavior at the spinal cord level will drive insights not previously possible at a key location for somatosensory transmission to the brain.

Long-term Radiation Signal Persistence in Urine and Blood: A Two-year Analysis in Non-human Primates Exposed to a 4 Gy Total-Body Gamma-Radiation Dose.

National security concerns regarding radiological incidents, accidental or intentional in nature, have increased substantially over the past few years. A primary area of intense planning is the assessment of exposed individuals and timely medical management. However, exposed individuals who receive survivable radiation doses may develop delayed effects of acute radiation exposure many months or years later. Therefore, it is necessary to identify such individuals and determine whether their symptoms may have been initiated by radiation and require complex medical interventions. We previously developed early response metabolomic biosignatures in biofluids from non-human primates exposed to a total body gamma radiation dose of 4 Gy (up to 60 days). A follow-up of these animals has been ongoing with samples consistently collected every few months for up to 2 years after exposure, providing a unique cohort to determine if a radiation signal persists longer than 2 months. Metabolic fingerprinting in urine and serum determined that exposed animals remain metabolically different from pre-exposure levels and from age-matched controls, and the pre-determined biosignature maintains high sensitivity and specificity. Significant perturbations in tricarboxylic acid intermediates, cofactors and nucleotide metabolism were noted, signifying energetic changes that could be attributed to or perpetuate altered mitochondrial dynamics. Importantly, these animals have begun developing diseases such as hypertension much earlier than their age-matched controls, further emphasizing that radiation exposure may lead to accelerated aging. This NHP cohort provides important information and highlights the potential of metabolomics in determining persistent changes and a radiation-specific signature that can be correlated to phenotype.

Older Age as a Predictor of Ongoing Active Changes in Follow-Up Cardiac Magnetic Resonance in Children with Acute Myocarditis.

Background/Objectives: Cardiac magnetic resonance (CMR) is used to diagnose and monitor the course of acute myocarditis in adults and children. This study aimed to assess the frequency of persistent inflammation at follow-up CMR and to look for predictors of ongoing active changes in CMR in children with myocarditis. Methods: This retrospective study included 31 children (median age 15 years, 68% male) with clinically and CMR-diagnosed acute myocarditis who underwent baseline and follow-up CMR at a median of 6 months. Old and new Lake Louise criteria were compared. Results: A complete resolution of changes was observed in four patients (13%) at follow-up, according to both criteria. Seven patients (23%) presented ongoing active changes, and twenty (64%) showed a persistent scar according to the old Lake Louise criteria. When the new Lake Louise criteria were used, an additional two patients (6%) were found to have persistent active changes instead of a persistent scar. Patients with persistent inflammation (nine patients, 29%) were older than those who showed recovery. None of the patients below 14 years of age presented active changes on their follow-up CMR and all the patients who showed inflammation were between 14 and 17 years old. Conclusions: Pediatric myocarditis can lead to persistent active changes in CMR beyond a 6-month follow-up in over a fifth of patients. The application of new Lake Louise criteria further increases that number compared to the old criteria. The only predictor of persistent inflammatory changes in CMR is older age.

War Reparations, Structural Change, and Intergenerational Mobility

Abstract From 1944 to 1952, largely agrarian Finland had to export, on average, 4% of its yearly GDP in industrial products to the Soviet Union as war reparations. To meet the reparation demands, the Finnish state needed to provide extensive but temporary support to Soviet-assigned industries with insufficient production capacity. This paper documents the long-term impacts of this extensive and temporary industrial policy on industrial and local development and on individual outcomes. Using newly digitized datasets, I show in a difference-in-differences setup that the short-term nonmarket production persistently and significantly increased the employment and production of the manufacturing industries exposed to the policy. These industries plausibly benefited from large initial investments and exposure to export markets associated with the war reparations. The episode further led to local development and structural change, as the more exposed regions became persistently more industrialized. I substantiate these within-Finland results with triple-difference setups employing comparable Norwegian data. I further use Finnish administrative data to study the long-term individual impacts of the episode. Tracking individuals over 30 years, I show that the initial state investments and the persistent change in the local industrial structure increased long-term incomes, led to more educational attainment, and promoted the upward mobility of children and young adults living in the more exposed regions prior to the war reparations period. The observed effects are driven by the more advanced heavy industry, which received the majority of state assistance.

Cognitive and Functional Capacity Assessment of Individuals Who Were Admitted to the Intensive Care Unit Due to COVID-19: A Prospective Cohort Study.

The goal of this study was to identify changes in cognitive and functional capacity after hospital discharge in those infected with COVID-19 who were admitted to the ICU. This is a prospective cohort study carried out with individuals who were admitted to a hospital, from July 2021 to May 2022. The evaluations happened in three moments: at hospital discharge, 30 days after discharge and 90 days after discharge. The instruments applied are the following: handgrip dynamometer, Montreal Cognitive Assessment Basic questionnaire (MoCA-B), Barthel Index (BI), timed up and go test (TUG), hospital anxiety and depressive scale (HADS) and 36-Item Short Form Health Survey questionary (SF-36). 74 individuals were eligible to participate in the study, 25 of which were followed for 90 days. Based on the results of the MoCA-b, there were no relevant cognitive changes after 3 months. According to the Barthel Index applied to each of the evaluations, the percentage of subjects that were classified as independent or minimally dependent was 48%, 92% then 96%, respectively, demonstrating that individuals can achieve a good degree of functional independence after 3 months. Despite that, the SF-36 demonstrated a score below the South Brazilian normal in some domains. The individuals studied did not present persistent cognitive changes after 3 months and functional capacity showed significant improvement during this period. However, when the assessment is about the self-perceived quality of life, the majority of domain values are still below expectations, deserving attention by the health professionals involved.

Exploring the diagnostic yield of family screening and genetic testing in adolescent individuals with pre-clinical phenotypes

Abstract Introduction Family screening and genetic testing are key components in the management strategy of individuals diagnosed with an inherited cardiac condition (ICC). Disease penetrance for most ICCs, notably cardiomyopathies is age dependent, which is why a more permissive approach towards family screening is adopted in young individuals with a pre-clinical phenotype. Study Objectives The main objective of this study was to explore the role of family screening and genetic testing in adolescent subjects with a pre-clinical phenotype has not been formally explored. Methodology Adolescent probands with a pre-clinical phenotype following a national cardiac screening program (BEAT-IT) were offered genetic testing and family screening. Probands with anterior TWI were rescreened at 16 years. Only those with persistent changes were enrolled in the study. Genetic counselling was also offered to probands and relatives. Testing was initially offered to first degree relatives. Cascade testing (clinical and genetic) was also offered to other generations if a screened relative satisfied one or more of these conditions i) phenotype positive, ii) pre-clinical phenotype, iii) clinically relevant genotype. Results 16 probands (mean age 15 years) were identified with a pre-clinical phenotype. All had an abnormal ECG (9=inferior/lateral TWI, 6=anterior TWI, 1=ST depression). A comprehensive evaluation was otherwise normal. Half were gene positive (G+), 4 had clinically relevant genotypes (n=4 inferior/lateral TWI). These were classified as likely pathogenic according to ACMG criteria (n=2 MYH7, n=1 ACTC1, n=1 MYBPC3). 71 family members were subsequently screened (59.2% female, median 43Y [IQR 27] at evaluation, 11.3% <18Y at evaluation, 67.6% first degree relatives). A substantial proportion (n=13, 18.3%) were referred for further evaluation. Two (2/8, 25.0%) were <18Y. An abnormal ECG was the commonest reason for referral (n=9, 12.7%). Three (4.2%) were given a diagnosis (n=2 HCM [both MYH7}, n=1 DCM [ACTC1]). Seven (9.9%) were referred because of an abnormal ECG (n=3 inferolateral TWI, n=2 ventricular ectopics, n=1 anterolateral TWI, n=1 ST depression). Four were G+ and were offered surveillance. Fourteen (19.7%) were offered family screening because of incorporating genetic testing into the study protocol. Genetics altered the evaluation strategy in 16.9% of screened relatives. More in-depth cascade testing identified 6 (8.5%) individuals who needed follow-up (n=1 diagnosis [DCM], n=1 abnormal ECG, n=4 G+). Gene negative individuals (6, 8.5%) were safely reassured and discharged. Conclusion Family screening in adolescent probands with pre-clinical phenotypes offers a reasonable diagnostic yield (4.2% diagnosis, 14.1% surveillance). Incorporating genetic testing into the evaluation protocol offers a more personalized strategy, altering management in a significant proportion of screened relatives (16.9%).

Nail changes in patients receiving systemic isotretinoin therapy

In this study, it was aimed to describe isotretinoin-induced nail changes and increase patients’ treatment compliance. A total of 200 patients diagnosed with acne vulgaris were included in the study. 100 of the patients were started systemic isotretinoin treatment and 100 control patients were receiving topical acne treatment. Age and gender of all of the participants, duration of treatment, total doses per month, and type of nail changes were recorded. Patients with persistent nail changes were followed at the 3rd and 6th months after treatment. A total of 34 patients had nail changes in the isotretinoin group. These changes included onychoschizia (55.9%), leukonychia (11.8%), onychorexis (8.8%), median nail dystrophy (5.9%), pyogenic granulomas (5.9%), chronic paronychia and granulation tissue (5.9%), onycholysis (2.9%) and Beau’s line (2.9%). The rate of nail changes in the isotretinoin group was significantly higher than in the topical treatment group (34% vs. 11%, p:0.001). Isotretinoin increases the risk of nail changes, primarily onychoschizia. The risk of developing nail changes is not associated with treatment duration but is associated with the total cumulative dose. Nail findings induced by isotretinoin are completely reversible.

3D cultivation of non-small-cell lung cancer cell lines using four different methods

PurposeThe aim of this study was to set up reliable and reproducible culture conditions for 3D tumoroids derived from non-small cell lung cancer (NSCLC) cell lines to enable greater opportunity for successful cultivation of patient-derived samples.MethodsFour NSCLC cell lines, two adenocarcinomas (A549, NCI-H1975) and two squamous cell carcinomas (HCC-95, HCC-1588), were first cultured in traditional 2D settings. Their expected expression profiles concerning TTF-1, CK7, CK5, and p40 status were confirmed by immunohistochemistry (IHC) before the generation of 3D cultures. Tumoroids were established in the hydrogel GrowDex®-T, Nunclon™ Sphera™ flasks, BIOFLOAT™ plates, and Corning® Elplasia® plates. Western blot was used to verify antigen protein expression. Hematoxylin-eosin staining was used to evaluate the cell morphology in the 2D and 3D cultures. Mutational analysis of KRAS and EGFR by PCR on extracted DNA from 3D tumoroids generated from cells with known mutations (A549; KRAS G12S mutation, NCI-H1975; EGFR L858R/T790M mutations).ResultsWe successfully established 3D cultures from A549, NCI-H1975, HCC-95, and HCC-1588 with all four used cultivation methods. The adenocarcinomas (A549, NCI-H1975) maintained their original IHC features in the tumoroids, while the squamous cell carcinomas (HCC-95, HCC-1588) lost their unique markers in the cultures. PCR analysis confirmed persistent genetic changes where expected.ConclusionThe establishment of tumoroids from lung cancer cell lines is feasible with various methodologies, which is promising for future tumoroid growth from clinical lung cancer samples. However, analysis of relevant markers is a prerequisite and may need to be validated for each model and cell type.

Fostering trust - a qualitative outcome study of psychodynamic group and individual psychotherapy for refugees with PTSD.

Background: Refugees and asylum-seekers have an elevated risk of mental health issues, such as depression and posttraumatic stress. Qualitative outcome studies can contribute by offering insight into patients' experiences of what they find beneficial and how they undergo the process of recovery. This study aligns with the small body of qualitative research focusing on refugees' perspectives of psychotherapeutic treatment for PTSD.Objective: This study investigates and compares the treatment experiences of refugees with posttraumatic stress disorder (PTSD) in psychoanalytic group therapy (PAGT) and individual psychodynamic therapy (PDT) within an outpatient context in Sweden.Method: 10 former patients were interviewed using a semi-structured interview schedule. Data were analysed and interpreted according to the principles of grounded theory.Results: The findings reveal distinct categories for each treatment modality, being reborn for PDT and building a home for PAGT. Being reborn involved persistent intrapersonal change and lasting improvement in posttraumatic symptoms. Building a home involved a sense of belonging, support and temporary relief from posttraumatic symptoms. Participants from both treatment modalities underscored the significance of cultivating trust in therapeutic relationships.Conclusions: The study emphasises the necessity for tailored therapeutic approaches, contributing valuable insights to the limited research on effective mental health interventions for this population.

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

BackgroundBreast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.MethodsPlasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.ResultsBefore initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.ConclusionPostmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

An educational intervention study on mandatory reporting of intimate partner violence: changes in knowledge and attitudes among healthcare providers

BackgroundIntimate partner violence (IPV) is a major public health concern. Healthcare providers can play a crucial role in reporting cases of IPV or suspected IPV injuries to the police or the criminal justice system, commonly referred to as mandatory reporting. However, mandatory reporting of intimate partner violence (MR-IPV) is a debated topic that can pose complex challenges for healthcare providers. This underscores the importance of training programs to ensure that healthcare providers can fulfill their MR-IPV obligations.MethodsWe developed an educational intervention on MR-IPV and assessed its impact on healthcare providers’ knowledge and attitudes. The study used a pre- and post-test design with three measurement points: baseline (T0), immediately after the intervention (T1), and six months later (T2). The intervention was conducted at a university college in Norway, with data collected between October 2022 and May 2023. The intervention was delivered to 37 healthcare providers who were currently part-time students in mental healthcare. Changes in knowledge and attitudes between T0 and T1, and T0 and T2 were analyzed through nonparametric tests on related samples using the Marginal homogeneity (Stuart–Maxwell) test. Risk differences (RD), along with their corresponding 95% confidence intervals (CI), were calculated for selected categories.ResultsThe number of participants knowing the MR law increased from 2.9% at baseline to 62.9% at T1 (RD = 0.60, 95% CI: 0.41—0.79) and to 31.4% at T2 (RD = 0.29, 95% CI: 0.11–0.46). The number of participants reporting knowing relevant criteria increased from 0.0% at baseline to 68.6% at T1 (RD = 0.69, 95% CI: 0.50–0.87) and to 34.3% at T2 (RD = 0.34, 95% CI: 0.16—0.53). We observed several persistent changes in healthcare providers' attitudes towards MR, including finding MR to be a useful instrument and generally complying with MR requirements.ConclusionsThe findings suggest that this educational intervention can have a positive impact on healthcare providers' attitudes and compliance with MR-IPV. Before the intervention, few participants reported knowing the MR law and its application criteria, demonstrating the importance of continuous learning and evidence-based training programs.

Longitudinal Assessment of Nasopharyngeal Biomarkers Post-COVID-19: Unveiling Persistent Markers and Severity Correlations.

SARS-CoV-19 infection provokes a variety of symptoms; most patients present mild/moderate symptoms, whereas a small proportion of patients progress to severe illness with multiorgan failure accompanied by metabolic disturbances requiring ICU-level care. Given the importance of the disease, researchers focused on identifying severity-associated biomarkers in infected patients as well as markers associated with patients suffering long-COVID. However, little is known about the presence of biomarkers that remain a few years after SARS-CoV-2 infection once the patients fully recover of the symptoms. In this study, we evaluated the presence of persistent biomarkers in the nasopharyngeal tract two years after SARS-Cov-2 infection in fully asymptomatic patients, taking into account the severity of their infection (mild/moderate and severe infections). In addition to the direct identification of several components of the Coronavirus Infection Pathway in those individuals that suffered severe infections, we describe herein 371 proteins and their associated canonical pathways that define the different adverse effects of SARS-CoV-2 infections. The persistence of these biomarkers for up to two years after infection, along with their ability to distinguish the severity of the infection endured, highlights the surprising presence of persistent nasopharyngeal exudate changes in fully recovered patients.

Profiling muscle transcriptome in mice exposed to microgravity using gene set enrichment analysis

Space exploration’s advancement toward long-duration missions prompts intensified research on physiological effects. Despite adaptive physiological stability in some variables, persistent changes affect genome integrity, immune response, and cognitive function. Our study, utilizing multi-omics data from GeneLab, provides crucial insights investigating muscle atrophy during space mission. Leveraging NASA GeneLab’s data resources, we apply systems biology-based analyses, facilitating comprehensive understanding and enabling meta-analysis. Through transcriptomics, we establish a reference profile of biological processes underlying muscle atrophy, crucial for intervention development. We emphasize the often-overlooked role of glycosylation in muscle atrophy. Our research sheds light on fundamental molecular mechanisms, bridging gaps between space research and terrestrial conditions. This study underscores the importance of interdisciplinary collaboration and data-sharing initiatives like GeneLab in advancing space medicine research.

Synaptic weight dynamics underlying memory consolidation: Implications for learning rules, circuit organization, and circuit function

Systems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site. This simple principle naturally leads to a speed-accuracy tradeoff in systems consolidation and provides insight into how the circuit mitigates the stability-plasticity dilemma of storing new memories while preserving core features of older ones. Furthermore, it imposes two constraints on the circuit. First, the plasticity rule at the late-learning site must stably support a continuum of possible outputs for a given input. We show that this is readily achieved by heterosynaptic but not standard Hebbian rules. Second, to turn off the consolidation process and prevent erroneous changes at the late-learning site, neural activity in the early-learning area must be reset to its baseline activity. We provide two biologically plausible implementations for this reset that propose functional roles in stabilizing consolidation for core elements of the cerebellar circuit.

COVID-19 related cognitive, structural and functional brain changes among Italian adolescents and young adults: a multimodal longitudinal case-control study

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting-state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in ECdelta (i.e., the difference in EC values pre- and post-COVID-19) and Volumetricdelta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that ECdelta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in Volumetricdelta between groups (p = 0.041). The reduced ECdelta in the left amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19.

Persistently Elevated High‐Latitude Ocean Temperatures and Global Sea Level Following Temporary Temperature Overshoots

AbstractAs exceeding the 1.5°C level of global warming is likely to happen in the near future, understanding the response of the ocean‐climate system to temporarily overshooting this warming level is of critical importance. Here, we apply the Adaptive Emissions Reduction Approach to the Earth System Model GFDL‐ESM2M to conduct novel overshoot scenarios that reach 2.0, 2.5 and 3.0°C of global warming before returning to 1.5°C over the time period of 1861–2500. We also perform a complementary scenario that stabilizes global temperature at 1.5°C, allowing to isolate impacts caused by the temperature overshoots alone, both during their peaks and after their reversals. The simulations indicate that substantial residual ocean surface warming persists in the high latitudes after the overshoots, with most notable regional anomalies occurring in the North Atlantic (up to +3.1°C in the 3°C overshoot scenario compared to the 1.5°C stabilization scenario) and the Southern Ocean (+1.2°C). The residual warming is primarily driven by the recoveries of the Atlantic and Southern Ocean meridional overturning circulation and associated increases in ocean heat transport. Excess subsurface heat storage in low and mid‐latitudes prevents steric sea level rise (SLR) from reverting to 1.5°C stabilization levels in any overshoot scenario, with steric sea level remaining up to 32% higher in the 3°C overshoot scenario on centennial time scales. Both peak impacts and persistent changes after overshoot reversal bear significant implications for future assessments of coastlines, regional climates, marine ecosystems, and ice sheets.

An Integrated Depok Smart City Evaluation

Given the complicated pressures brought on by the fast pace of urbanization, innovative and long-lasting solutions to the issues arising from urban expansion are needed. To ensure a greater standard of life for their citizens and make sustainable growth one of their long-term goals, cities will need to make more inventive, persistent, and successful changes to their infrastructure. Nonetheless, smart cities require complex solutions to problems involving ICT, economics, government, social issues, the environment, and transportation. The sustainability of smart cities is now a topic that academics, environmental policymakers, and governmental organizations are more interested in. Depok's smart city must be evaluated to determine its capacity to fulfill the desired vision to help implement the Movement Towards 100 Smart Cities. This study offers an evaluation approach for the Depok smart city. Three indices were used to construct an integrated evaluation approach: the IMD Smart City Index 2023, The Cities of the Future Index, and the Global Power City Index. None of the indexes' results include all six of the Depok Smart City's necessary dimensions. Thus, the advice was to merge the three indices into an integrated evaluation approach for evaluating the six primary dimensions of the Depok Smart City. The results of this study also offer a sample measurement statement according to Depok Smart City. Furthermore, follow-up actions that the government or stakeholders can take to improve Depok's smart city performance include implementing the integrated matrix indicators and evaluating their validity and relevance in the real world.

Forecasting the Mediterranean Sea marine heatwave of summer 2022

Abstract. Early warning of marine heatwaves requires short-term forecasts to provide precise information on timings, local-scale coverage, and intensities of coming events. Here, we describe our successful efforts to track the onset, peak, and decay of the Mediterranean Sea marine heatwave of summer 2022 with the Copernicus MedFS short-term (10 d) forecast system. First, we show that the 2022 event eclipses the economically and ecologically damaging event of 2003 in terms of marine heatwave (MHW) activity (a measure of intensity and duration). Forecasts of MHW area and activity provide a means of basin-wide validation, highlighting the capability of MedFS to capture regional behaviour. On local scales, we found that the MHW occurrence in the Ligurian Sea and Gulf of Taranto, two regions of economic and ecological importance, was also reliably forecast. Encouragingly, we note that the forecast has demonstrated skill in capturing not just the season-long MHW cycle but also breaks in MHW persistence and abrupt changes in local activity. Subseasonal forecasts do not yet demonstrate the capacity to predict MHW response to short-lived weather patterns, but this study confirms that short-term forecasts, at least in the Mediterranean Sea, can fill this gap.

Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction-associated steatohepatitis, have emerged as the most prevalent liver diseases worldwide. Currently, lifestyle modification is the foremost guideline-recommended management strategy for MASLD. However, it remains unclear which detrimental signals persist in MASLD even after disease remission. Thus, we aimed to examine the persistent changes in liver transcriptomic profiles following this reversal. Male C57BL/6J mice were divided into three groups: Western diet (WD) feeding, chow diet (CD) feeding, or diet reversal from WD to CD. After 16 weeks of feeding, RNA sequencing was performed on the mice's livers to identify persistent alterations characteristic of MASLD. Additionally, RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were utilized. WD-induced MASLD triggered persistent activation of the DNA damage response (DDR) and its primary transcription factor, P53, long after the resolution of the hepatic phenotype through dietary reversal. Elevated levels of P53 might promote apoptosis, thereby exacerbating metabolic dysfunction-associated steatohepatitis, as they strongly correlated with hepatocyte ballooning, an indicator of apoptosis activation. Moreover, P53 knockout in mice led to downregulated expression of apoptosis signaling in the liver. Mechanistically, P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease (AEN). Consistently, P53, AEN, and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary reversal. The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to WD. Our findings provide new insights into the mechanisms of MASLD relapse, highlighting DDR signaling as a promising target to prevent MASLD recurrence.

Vascular changes in the retinal capillary network in fellow eye of the patients with central retinal artery occlusion.

We aimed to evaluate the retinal vascular changes in the superficial and deep retinal vascular networks in the fellow eye of patients with central retinal artery occlusion (CRAO) and compare them with controls using optical coherence tomography angiography (OCT-A). In a cross-sectional study, 27 patients with CRAO and 189 normal controls were included. Ophthalmic examination and OCT-A images were performed on all participants. The total vascular density of the superficial capillary network in the 6-mm scan was significantly lower in the fellow eye of patients with CRAO than in the control group (p = 0.02). No significant difference was observed in the FAZ area of the affected eyes and their fellow eyes compared with the controls. Total vascular density at 300 microns around the fovea was lower in the fellow eye compared with the control group (p = 0.034). The retinal vascular network changes in the fellow eyes of patients with CRAO suggest that persistent microvascular changes may be present before the onset of CRAO. This finding indicates that such changes could serve as an early diagnostic window for systemic vascular changes before catastrophic vascular events occur.